Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis

array:25 ["pii" => "S0021755717306344" "issn" => "00217557" "doi" => "10.1016/j.jped.2017.03.005" "estado" => "S300" "fechaPublicacion" => "2017-11-01" "aid" => "512" "copyright" => "Sociedade Brasileira de Pediatria" "copyrightAnyo" => "2017" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "J Pediatr (Rio J). 2017;93:639-48" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 708 "formatos" => array:3 [ "EPUB" => 84 "HTML" => 347 "PDF" => 277 ] ] "Traduccion" => array:1 [ "pt" => array:20 [ "pii" => "S2255553617300794" "issn" => "22555536" "doi" => "10.1016/j.jpedp.2017.07.002" "estado" => "S300" "fechaPublicacion" => "2017-11-01" "aid" => "512" "copyright" => "Sociedade Brasileira de Pediatria" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "J Pediatr (Rio J). 2017;93:639-48" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 914 "formatos" => array:3 [ "EPUB" => 91 "HTML" => 594 "PDF" => 229 ] ] "pt" => array:13 [ "idiomaDefecto" => true "cabecera" => "Artigo Original" "titulo" => "Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis" "tienePdf" => "pt" "tieneTextoCompleto" => "pt" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "639" "paginaFinal" => "648" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Variantes no gene da interleucina 8 e a resposta a broncodilatadores inalatórios na fibrose cística" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "pt" => true ] "contienePdf" => array:1 [ "pt" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4239 "Ancho" => 3276 "Tamanyo" => 668369 ] ] "descripcion" => array:1 [ "pt" => "Associação das variantes rs4073 e rs2227306 da IL‐8 (interleucina‐8) à resposta a broncodilatadores inalatórios em pacientes com fibrose cística. A. Associação entre o volume expiratório forçado no 1° segundo (VEF1) da capacidade vital forçada (CVF) e rs4073, modelo dominante e duas mutações identificadas no gene do RTFC (regulador da condutância transmembrana da fibrose cística) pertencente às classes I, II e/ou III (grupo RTFC‐B) (p=0,028; pc–0,112). (AA +AT) n=39; média de 4,77±8,95; mediana de 4 (variação de −9 a 48). (TT) n=21; média de 0,86±5,42; mediana de −1 (variação de −6 a 15). B. Associação da proporção VEF1/CVF à variante rs4073, modelo superdominante e grupo RTFC‐B (p=0,029; pc=0,116). (TT) n=30; média de 0,86±7,36; mediana de 0 (variação de −12 a 23). (AT) n=29; média de 4,76±7,58; mediana de 4 (variação de −9 a 32). C. Associação do fluxo expiratório forçado de 50% (FEF50%) da CVF à variante rs4073, modelo dominante e grupo RTFC‐B (p=0,046; pc=0,184). (AA+AT) n=37; média de 17,38±24,18; mediana de 16 (variação de −20 a 89). (TT) n=21; média de 4,95±20,80; mediana de −2 (variação de −19 a 55). D. Associação do FEF50% à variante rs2227306, modelo dominante e grupo RTFC‐B (p=0,050; pc=0,083). (CC) n=15; média de 1,47±17,22; mediana de 0 (variação de −20 a 29). (CT+TT) n=44; média de 15,84±25,04; mediana de 10,50 (variação de −28 a 89). E. Associação do FEF50% à variante rs2227306, modelo superdominante e grupo RTFC‐B (p=0,033; pc=0,083). (CC+TT) n=33; média de 6,06±20,27; mediana de 4 (variação de −20 a 55). (CT) n=23; média de 19,96±26,43; mediana de 19 (variação de −28 a 89). F. Associação do fluxo expiratório forçado de 75% (FEF75%) da CVF à variante rs4073, modelo codominante independentemente das mutações identificadas no gene do RTFC (grupo RTFC‐A) (p=0,044; pc=0,058). 1 ≠ 3. (AA) n=28; média de 29,93±39,98; mediana de 30 (variação de −47 a 142). (AT) n=42; média de 24,81±53,57; mediana de 14 (variação de −58 a 235). (TT) n=28; média de 9,14±36,95; mediana de 2,5 (variação de −35 a 119). G. Associação do FEF75% à variante rs4073, modelo dominante e grupo RTFC‐B (p=0,024; pc=0,096). (AA+AT) n=38; média de 33±55,23; mediana de (variação de −27 a 235). (TT) n=21; média de 5,43±35,93; mediana de 2 (variação de −35 a 119). H. Associação do FEF75% à variante rs4073, modelo dominante e grupo RTFC‐A (p=0,034; pc=0,058). (AA+AT) (n=70; média de 26,86±48,34; mediana de 18 (variação de −58 a 235). (TT) n=28; média de 9,14±36,95; mediana de 2,5 (variação de −35 a 119). I. Associação do FEF75% à variante rs4073, modelo recessivo e grupo RTFC‐A (p=0,040; pc=0,058). (AA) n=28; média de 29,93±39,98; mediana de 30 (variação de −47 a 142). (AT+TT) n=70; média de 18,54±47,95; mediana de 10 (variação de −58 a 235). J. Associação do FEF entre 25 e 75% (FEF25‐75%) da CVF à variante rs4073, modelo codominante e grupo RTFC‐B (p=0,012; pc=0,024). TT ≠ AA e AT. (AA) n=9; média de 25,78±23,14; mediana de 30 (variação de −21 a 57). (AT) n=29; média de 18,38±29,04; mediana de 14 (variação de −33 a 117). (TT) n=21; média de 2,14±23,74; mediana de 0 (variação de −51 a 65). K. Associação do FEF25‐75% à variante rs4073, modelo dominante e grupo RTFC‐B (p=0,007; pc=0,024). (AA+ATT) n=38; média de 20,13±27,64; mediana de 18,50 (variação de −33 a 117). (TT) n=23; média de 2,14±23,74; mediana de 0 (variação de −51 a 65). L. Associação do FEF25‐75% à variante rs4073, modelo dominante e grupo RTFC‐A (p=0,029; pc=0,100). (AA+AT) n=82; média de 15,48±27,20; mediana de 15 (variação de −40 a 117). (TT) n=33; média de 5,94±27,33; mediana de 0 (variação de −51 a 76). M. Associação do FEF25‐75% à variante rs4073, modelo recessivo e grupo RTFC‐B (p=0,047; pc=0,063). (AA) n=9; média de 25,78±23,14; mediana de 30 (variação de −21 a 57). (AT+TT) n=50; média de 11,56±27,89; mediana de 8 (variação de −51 a 117). O ponto corresponde aos valores medianos e a barra corresponde a intervalo de confiança de 95%." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Larissa Lazzarini Furlan, José Dirceu Ribeiro, Carmen Sílvia Bertuzzo, João Batista Salomão Junior, Dorotéia Rossi Silva Souza, Fernando Augusto Lima Marson" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Larissa Lazzarini" "apellidos" => "Furlan" ] 1 => array:2 [ "nombre" => "José Dirceu" "apellidos" => "Ribeiro" ] 2 => array:2 [ "nombre" => "Carmen Sílvia" "apellidos" => "Bertuzzo" ] 3 => array:2 [ "nombre" => "João Batista" "apellidos" => "Salomão Junior" ] 4 => array:2 [ "nombre" => "Dorotéia Rossi Silva" "apellidos" => "Souza" ] 5 => array:2 [ "nombre" => "Fernando Augusto Lima" "apellidos" => "Marson" ] ] ] ] ] "idiomaDefecto" => "pt" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S0021755717306344" "doi" => "10.1016/j.jped.2017.03.005" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755717306344?idApp=UINPBA000049" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255553617300794?idApp=UINPBA000049" "url" => "/22555536/0000009300000006/v1_201711030110/S2255553617300794/v1_201711030110/pt/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S002175571630170X" "issn" => "00217557" "doi" => "10.1016/j.jped.2017.05.003" "estado" => "S300" "fechaPublicacion" => "2017-11-01" "aid" => "515" "copyright" => "Sociedade Brasileira de Pediatria" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "J Pediatr (Rio J). 2017;93:649-54" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1150 "formatos" => array:3 [ "EPUB" => 76 "HTML" => 762 "PDF" => 312 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Neonatal screening: 9% of children with filter paper thyroid-stimulating hormone levels between 5 and 10μIU/mL have congenital hypothyroidism" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "649" "paginaFinal" => "654" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Triagem neonatal: 9% das crianças com TSH em papel filtro entre 5 e 10 μUI/mL têm hipotireoidismo congênito" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1162 "Ancho" => 1628 "Tamanyo" => 89204 ] ] "descripcion" => array:1 [ "en" => "Flowchart of the screening for congenital hypothyroidism from April 2003 to September 2009." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Flávia C. Christensen-Adad, Carolina T. Mendes-dos-Santos, Maura M.F. Goto, Letícia E. Sewaybricker, Lília F.R. D'Souza-Li, Gil Guerra-Junior, André M. Morcillo, Sofia Helena V. Lemos-Marini" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Flávia C." "apellidos" => "Christensen-Adad" ] 1 => array:2 [ "nombre" => "Carolina T." "apellidos" => "Mendes-dos-Santos" ] 2 => array:2 [ "nombre" => "Maura M.F." "apellidos" => "Goto" ] 3 => array:2 [ "nombre" => "Letícia E." "apellidos" => "Sewaybricker" ] 4 => array:2 [ "nombre" => "Lília F.R." "apellidos" => "D'Souza-Li" ] 5 => array:2 [ "nombre" => "Gil" "apellidos" => "Guerra-Junior" ] 6 => array:2 [ "nombre" => "André M." "apellidos" => "Morcillo" ] 7 => array:2 [ "nombre" => "Sofia Helena V." "apellidos" => "Lemos-Marini" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S2255553617300824" "doi" => "10.1016/j.jpedp.2017.08.001" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255553617300824?idApp=UINPBA000049" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002175571630170X?idApp=UINPBA000049" "url" => "/00217557/0000009300000006/v1_201711050042/S002175571630170X/v1_201711050042/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S0021755717305247" "issn" => "00217557" "doi" => "10.1016/j.jped.2017.01.006" "estado" => "S300" "fechaPublicacion" => "2017-11-01" "aid" => "509" "copyright" => "Sociedade Brasileira de Pediatria" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "J Pediatr (Rio J). 2017;93:632-8" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 862 "formatos" => array:3 [ "EPUB" => 85 "HTML" => 516 "PDF" => 261 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Do infants with cow's milk protein allergy have inadequate levels of vitamin D?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "pt" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "632" "paginaFinal" => "638" ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Lactentes com alergia à proteína do leite de vaca apresentam níveis inadequados de vitamina D?" ] ] "contieneResumen" => array:2 [ "en" => true "pt" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1546 "Ancho" => 2076 "Tamanyo" => 80368 ] ] "descripcion" => array:1 [ "en" => "Frequencies of vitamin D sufficiency levels in infants with cow's milk protein allergy and in the control group, treated at an outpatient clinic in a university hospital, Recife, PE, Brazil (2013–2015). a Fisher's exact test." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cristiane M. Silva, Silvia A. da Silva, Margarida M. de C. Antunes, Gisélia Alves Pontes da Silva, Emanuel Sávio Cavalcanti Sarinho, Katia G. Brandt" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Cristiane M." "apellidos" => "Silva" ] 1 => array:2 [ "nombre" => "Silvia A. da" "apellidos" => "Silva" ] 2 => array:2 [ "nombre" => "Margarida M. de C." "apellidos" => "Antunes" ] 3 => array:2 [ "nombre" => "Gisélia Alves Pontes da" "apellidos" => "Silva" ] 4 => array:2 [ "nombre" => "Emanuel Sávio Cavalcanti" "apellidos" => "Sarinho" ] 5 => array:2 [ "nombre" => "Katia G." "apellidos" => "Brandt" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "pt" => array:9 [ "pii" => "S2255553617300678" "doi" => "10.1016/j.jpedp.2017.06.006" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "pt" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255553617300678?idApp=UINPBA000049" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755717305247?idApp=UINPBA000049" "url" => "/00217557/0000009300000006/v1_201711050042/S0021755717305247/v1_201711050042/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "639" "paginaFinal" => "648" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Larissa Lazzarini Furlan, José Dirceu Ribeiro, Carmen Sílvia Bertuzzo, João Batista Salomão Junior, Dorotéia Rossi Silva Souza, Fernando Augusto Lima Marson" "autores" => array:6 [ 0 => array:3 [ "nombre" => "Larissa Lazzarini" "apellidos" => "Furlan" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "José Dirceu" "apellidos" => "Ribeiro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Carmen Sílvia" "apellidos" => "Bertuzzo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "João Batista" "apellidos" => "Salomão Junior" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] ] ] 4 => array:3 [ "nombre" => "Dorotéia Rossi Silva" "apellidos" => "Souza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "f" "identificador" => "aff0030" ] ] ] 5 => array:4 [ "nombre" => "Fernando Augusto Lima" "apellidos" => "Marson" "email" => array:1 [ 0 => "fernandolimamarson@hotmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:6 [ 0 => array:3 [ "entidad" => "Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Pediatria, Campinas, SP, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Genética Médica, Campinas, SP, Brazil" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Faculdade de Medicina de São José do Rio Preto, Hospital Universitário, Departamento de Pediatria, São José do Rio Preto, SP, Brazil" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Faculdade de Medicina de São José do Rio Preto, Hospital Universitário, Departamento de Pneumologia Pediátrica, São José do Rio Preto, SP, Brazil" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Faculdade de Medicina de São José do Rio Preto, Centro de Pesquisa de Bioquímica e Biologia Molecular, Departamento de Biologia Molecular, São José do Rio Preto, SP, Brazil" "etiqueta" => "f" "identificador" => "aff0030" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Variantes no gene da interleucina 8 e a resposta a broncodilatadores inalatórios na fibrose cística" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4239 "Ancho" => 3284 "Tamanyo" => 641459 ] ] "descripcion" => array:1 [ "en" => "Association of rs4073 and rs2227306 variants of IL-8 (interleukin-8) with the response to inhaled bronchodilators in cystic fibrosis patients. (A) Association between forced expiratory volume in 1s (FEV1) of forced vital capacity (FVC) and rs4073, dominant model and two identified mutations in the CFTR gene (cystic fibrosis transmembrane regulator) belonging to classes I, II, and/or III (CFTR-B group) (p=0.028; pc=0.112). (AA+AT) n=39; mean of 4.77±8.95; median of 4 (ranging from −9 to 48). (TT) n=21; mean of −0.86±5.42; median of −1 (ranging from −6 to 15). (B) Association of FEV1/FVC ratio with rs4073, over-dominant model and CFTR-B group (p=0.029; pc=0.116). (AA+TT) n=30; mean of 1.17±7.36; median of 0 (ranging from −12 to 23). (AT) n=29; mean of 4.76±7.58; median of 4 (ranging from −9 to 32). (C) Association of forced expiratory flow of 50% (FEF50%) of FVC with rs4073, dominant model, and CFTR-B group (p=0.046; pc=0.184). (AA+AT) n=37; mean of 17.38±24.18; median of 16 (ranging from −20 to 89). (TT) n=21; mean of 4.95±20.8; median of −2 (ranging from −19 to 55). (D) Association of FEF50% with rs2227306, dominant model, and CFTR-B group (p=0.05; pc=0.083). (CC) n=15; mean of 1.47±17.22; median of 0 (ranging from −20 to 29). (CT+TT) n=44; mean of 15.84±25.04; median of 10.5 (ranging from −28 to 89). (E) Association of FEF50% with rs2227306, over-dominant model, and CFTR-B group (p=0.033; pc=0.083). (CC+TT) n=33; mean of 6.06±20.27; median of 4 (ranging from −20 to 55). (CT) n=23; mean of 19.96±26.43; median of 19 (ranging from −28 to 89). (F) Association of forced expiratory flow of 75% (FEF75%) of FVC with rs4073, co-dominant model regardless of identified mutations in the CFTR gene (CFTR-A group) (p=0.044; pc=0.058). 1≠3. (AA) n=28; mean of 29.93±39.98; median of 30 (ranging from −47 to 142). (AT) n=42; mean of 24.81±53.57; median of 14 (ranging from −58 to 235). (TT) n=28; mean of 9.14±36.95; median of 2.5 (ranging from −35 to 119). (G) Association of FEF75% with rs4073, dominant model, and CFTR-B group (p=0.024; pc=0.096). (AA+AT) n=38; mean of 33±55.23; median of 16 (ranging from −27 to 235). (TT) n=21; mean of 5.43±35.93; median of 2 (ranging from −35 to 119). (H) Association of FEF75% with rs4073, dominant model, and CFTR-A group (p=0.034; pc=0.058). (AA+AT) n=70; mean of 26.86±48.34; median of 18 (ranging from −58 to 235). (TT) n=28; mean of 9.14±36.95; median of 2.5 (ranging from −35 to 119). (I) Association of FEF75% with rs4073, recessive model, and CFTR-A group (p=0.04; pc=0.058). (AA) n=28; mean of 29.93±39.98; median of 30 (ranging from −47 to 142). (AT+TT) n=70; mean of 18.54±47.95; median of 10 (ranging from −58 to 235). (J) Association of FEF between 25% and 75% (FEF25–75%) of FVC with rs4073, co-dominant model and CFTR-B group (p=0.012; pc=0.024). TT≠AA and AT. (AA) n=9; mean of 25.78±23.14; median of 30 (ranging from −21 to 57). (AT) n=29; mean of 18.38±29.04; median of 14 (ranging from −33 to 117). (TT) n=21; mean of 2.14±23.74; median of 0 (ranging from −51 to 65). (K) Association of FEF25–75% with rs4073, dominant model, and CFTR-B group (p=0.007; pc=0.024). (AA+ATT) n=38; mean of 20.13±27.64; median of 18.5 (ranging from −33 to 117). (TT) n=23; mean of 2.14±23.74; median of 0 (ranging from −51 to 65). (L) Association of FEF25–75% with rs4073, dominant model, and CFTR-A group (p=0.029; pc=0.1). (AA+AT) n=82; mean of 15.48±27.2; median of 15 (ranging from −40 to 117). (TT) n=33; mean of 5.94±27.33; median of 0 (ranging from −51 to 76). (M) Association of FEF25–75% with rs4073, recessive model, and CFTR-B group (p=0.047; pc=0.063). (AA) n=9; mean of 25.78±23.14; median of 30 (ranging from −21 to 57). (AT+TT) n=50; mean of 11.56±27.89; median of 8 (ranging from −51 to 117). The dot corresponds to median values and the bar corresponds to the 95% confidence interval." ] ] ] "textoCompleto" => "IntroductionThe response to inhaled bronchodilators (BD) in cystic fibrosis (CF) (OMIM: n. 219700) is quite variable and depends on the cystic fibrosis transmembrane regulator (CFTR) genotype, pulmonary symptoms, and mainly, on variants in the modifier genes, such as the beta-2-adrenergic receptor (ADRB2).<a class="elsevierStyleCrossRef" href="#bib0155">1</a> So far, only a few studies have investigated such response.Mutations in the CFTR gene cause CF, due to deficiency, dysfunction, or absence of the CFTR protein.<a class="elsevierStyleCrossRef" href="#bib0160">2</a> CF is characterized by a continuous cycle of chronic airway inflammation, which can be exacerbated by interleukin-8 (IL-8), a key pro-inflammatory mediator. IL-8 is responsible for initiating and increasing the inflammatory response in the presence of specific pathogens, causing activation and migration of neutrophils from peripheral blood to tissues.<a class="elsevierStyleCrossRef" href="#bib0165">3</a> Chronic airway inflammation is the final common pathway of lung injury. It is responsible for increased vascular permeability, contributing to interstitial, alveolar, and airway edema.The treatment of CF lung disease includes anti-inflammatory drugs, inhaled corticosteroids, antibiotics, mucolytic, hypertonic saline, and physiotherapy. Among the possible therapies, there is little evidence supporting the role of BD in CF.<a class="elsevierStyleCrossRefs" href="#bib0170">4,5</a> However, BD is often prescribed for a longer period due to wheezing and dyspnea episodes in CF.<a class="elsevierStyleCrossRef" href="#bib0180">6</a> BD reduces the liberation of mediators, which are responsible for recruiting and activating inflammatory cells, activating cholinergic neurotransmission and improving vascular permeability. It also increases mucociliary clearance, leading to reduced lung inflammation.<a class="elsevierStyleCrossRef" href="#bib0185">7</a> The response to BD depends, in part, on the CFTR protein, which interacts with the ADRB2 protein to promote broncodilatation.<a class="elsevierStyleCrossRef" href="#bib0190">8</a> Spirometry is the primary method to assess lung function, severity and progression of the disease, as well as response to BD.Intense neutrophil inflammation and low bronchial hyperresponsiveness are commonly observed characteristics in CF.<a class="elsevierStyleCrossRef" href="#bib0195">9</a> Moreover, the response of genetic variants to BD is little known.<a class="elsevierStyleCrossRef" href="#bib0155">1</a> The role of IL-8 in the neutrophilic component of CF lung disease can be pointed out. Genes that might be associated with the severity of CF and possibly with the response to BD have been reported in the present study and in the literature.<a class="elsevierStyleCrossRefs" href="#bib0155">1,10–12</a> The IL-8 gene should be highlighted, as it has a direct influence on lung inflammation and can be effective in the response to BD. Therefore, this study compared the rs4073, rs2227306, and rs2227307 IL-8 gene variants with the response to BD in CF patients, using spirometry.MethodsPatientsA cross-sectional study was conducted in 186 CF patients, selected in two university referral centers (Medical School of São José do Rio Preto and Universidade Estadual de Campinas) for CF treatment, from 2013 to 2015. The study was approved by the Research Ethics Committee of the Universidade Estadual de Campinas, Brazil (under No. 528/2008). All participants were informed of the study and signed an informed consent form. For patients under the age of 18, the informed consent form was signed by the parents or guardians. The study followed the recommendations of the Declaration of Helsinki.The diagnosis of CF was confirmed by the presence of two altered concentrations of sodium and chloride in sweat (chloride level higher than 60mEq/L). Furthermore, no patient underwent initial immunoreactive trypsinogen (IRT) measurement. In a group of 91 patients, there were two mutations in the CFTR gene belonging to classes I, II, and/or III (associated with greater disease severity, due to the absence or non-functionality of the CFTR protein)<a class="elsevierStyleCrossRef" href="#bib0215">13</a>; 60 patients did not present an identified mutation of the CFTR gene, or had two mutations belonging to classes IV, V, or VI; and 35 patients had a mutation in the CFTR gene belonging to classes I, II, or III, and a non-identified mutation, or belonging to classes IV, V, or VI (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Clinical variablesThe following variables were analyzed: clinical scores (Shwachman-Kulczycki, Kanga, and Bhalla); body mass index (BMI) for patients older than 18 years, using the formula BMI=weight/(height)2, the Anthro program version 3.0.1 (World Health Organization [WHO], 2006) was used for children under five years of age and the Anthro Plus version 1.0.2 (World Health Organization [WHO], 2007) was used for patients aged between five and 18 years; patient's age and age at diagnosis; first clinical symptom (one general symptom, pulmonary and digestive symptoms); period until the first colonization with Pseudomonas aeruginosa; microorganisms identified in the routine sputum culture (mucoid and non-mucoid P. aeruginosa, Achromobacter xylosoxidans, Burkolderia cepacia, and Staphylococcus aureus); transcutaneous arterial hemoglobin oxygen-saturation (SaO2); spirometry; and comorbidities (nasal polyps, osteoporosis, meconium ileus, diabetes mellitus, and pancreatic insufficiency).Spirometry was performed in patients over seven years of age, using the CPFS/D spirometer (MedGraphics – Saint Paul, Minnesota, USA). Data were recorded in the PF BREEZE software version 3.8B for Windows 95/98/NT (American Thoracic Society), and assessed in percentage predicted values for: forced vital capacity (FVC), forced expiratory volume in 1s (FEV1), FEV1/FVC ratio, forced expiratory flow at 25% of FVC (FEF25%), forced expiratory flow at 50% of FVC (FEF50%), forced expiratory flow at 75% of FVC (FEF75%), forced expiratory flow between 25% and 75% of FVC (FEF25–75%), maximum forced expiratory flow (FEFmax), and expiratory reserve volume (ERV). Spirometry data were shown in percentage of the predicted value according to the Polgar and Promadhat (1971), Pereira et al. (2007), and Duarte et al. (2007) equations.<a class="elsevierStyleCrossRefs" href="#bib0220">14–16</a>In all patients undergoing spirometry, the test was performed before and 15min after administration of BD (albuterol – C13H21NO3 [400mg]). Patients under BD therapy were instructed to interrupt the medication eight hours prior to spirometry, if they were under short-acting BD treatment; and 48hours, if they were under long-acting BD treatment. The post-BD percentage change was used for the statistical analysis. The BD response criteria, defined as an increase of >12% and 200mL of initial FEV1, was used as a second model to evaluate the association between the IL-8 gene variants and BD response.DNA extraction and genotypingGenomic DNA was extracted from peripheral blood samples using standard phenol-chloroform method and quantified by GE NanoVue™ spectrophotometer (GE Healthcare Biosciences – Pittsburgh, USA). In this study, the final sample concentration was set at 50ng/μL.Mutations of the CFTR gene were analyzed by polymerase chain reaction (PCR; F508del) followed by enzymatic digestion (G542X, R1162X, R553X, G551D, and N1303K). Other mutations in the CFTR gene were identified by sequencing or with the use of the SALSA Multiplex Ligation-dependent Probe Amplification (MPLA method) Kit P091-C1 CFTR-MRC-Holland S4X, 2183A>G, 1717-G>A, I618T with MegaBace1000® (GE Healthcare Biosciences – Pittsburgh, USA), and ABI3500 (Applied Biosystems – Thermo Fisher Scientific – São Paulo, Brazil).<a class="elsevierStyleCrossRef" href="#bib0235">17</a>IL-8 gene variants were analyzed by PCR followed by restriction enzyme digestion. For the rs4073 variant, the primers 5′-CCA TCA TGA TAG CAT CTG TA-3′ and 5′-CCA CAA TTT GGT GAA TTA TTA A-3′, and the AseI restriction enzyme were used; for the rs2227306 variant, primers 5′-CTC TAA CTC TTT ATA TAG GAA TT-3′ and 5′-GAT TGA TTT TAT CAA CAG GCA-3′, as well as the EcoRI restriction enzyme; and for the rs2227307 variant, primers 5′-TAA AGG TTT GAT CAA TAT AGA-3′ and 5′-CTT CCT TCT AAT TCCA ATA TG-3′, as well as the ScrFI restriction enzyme.<a class="elsevierStyleCrossRefs" href="#bib0240">18,19</a> The products of the enzymatic restriction were submitted to electrophoresis on a 12% polyacrylamide gel, or 4% agarose gel,<a class="elsevierStyleCrossRefs" href="#bib0240">18,19</a> and stained with Red® gel.Statistical analysisStatistical analyses were performed using Statistical Package for the Social Sciences version 22.0 (SPSS Inc. – Chicago, USA). The GPower software version 3.1.9.2<a class="elsevierStyleCrossRef" href="#bib0250">20</a> was used to calculate the sample power, considering the genotype of the analyzed variants and adopting power for value above 80%. The following conditions were applied to calculate the sample power: analysis of variance test, in place of Kruskal–Wallis test considering that analysis of variance is a stronger test (effect size=0.25, α=0.05, power=0.80, numerator degree of freedom=2, number of groups=3, ideal n=158); two-tailed Mann–Whitney test (effect size=0.5, α=0.05, power=0.80, allocation ratio N2/N1=1, ideal n=134); chi-squared test (effect size=0.3, α=0.05, power=0.80, degree of freedom=2, ideal n=108).The Mann–Whitney and Kruskal–Wallis tests were used for the comparison between different genotypes and groups of IL-8 gene variants and the response to BD. In case of significant differences between the groups for the Kruskal–Wallis test, further identification and evaluation of the differences between genotypes were performed with MedCalc® software for Windows, version 16.1 (MedCalc® Software – Ostend, Belgium).The chi-squared test and Fisher's exact test were used for the comparison between different genotypes and groups of IL-8 gene variants, as well as the response to BD, defined as an increase of >12% and 200mL of initial FEV1.For the identification of mutations in the CFTR gene, patients were analyzed based on two contexts: CFTR-A, all CF patients, regardless of gene mutations (n=186 patients); and CFTR-B, patients with two mutations belonging to classes I, II, and/or III (n=91 patients). As for the variants, four analysis models were adopted: (i) co-dominant (Kruskal–Wallis test); (ii) recessive (Mann–Whitney test); (iii) dominant (Mann–Whitney test); (iv) over-dominant (Mann–Whitney test), applied in association with clinical variables. For all analyses, the alpha value was set at 0.05.For analysis of the Hardy–Weinberg equilibrium (HWE), the Online Encyclopedia software for Genetic Epidemiology Studies (OEGE) was used.The false discovery rate (FDR) test was applied to correct the multiple test comparison. FDR is an approach to the multiple comparisons problem. Instead of controlling the chance of any false, FDR controls the expected proportion of false positives among supra threshold voxels. A FDR threshold is determined from the observed p-value distribution, and hence is adaptive to the amount of signal in the data.<a class="elsevierStyleCrossRef" href="#bib0255">21</a> The p-value and corrected p-value (pc) were shown in the manuscript. The linkage disequilibrium analysis was performed in Haploview software version 4.2.ResultsClinical and laboratory data of CF patients are described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> describes the genotype and allele frequency of IL-8 gene variants. <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows the data with p-values and corrected p-values for association of the three IL-8 gene variants, considering the four models of analysis proposed and the genotype of the CFTR gene.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia>The rs2227307 variant was not associated with response to BD in any of the studied models; in turn, rs2227306 was associated with FEF50% for patients with CC genotype (dominant model; p=0.05; pc=0.083) and CT genotype (over-dominant model; p=0.033; pc=0.083) in the CFTR-B group (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>D and E).Special emphasis should be given to the rs4073 variant, which was associated with the following spirometry variables: FEV1, FEV1/FVC ratio, FEF50% FEF75%, and FEF25–75%. The lowest response to BD was observed for the TT genotype (dominant model) and patients of the CFTR-B group to FEV1 (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A), FEF50% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C), FEF75% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>G), and FEF25–75% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>K). The same was observed for the CFTR-A group for FEF75% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>H) and FEF25–75% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>L). In the co-dominant analysis, the TT genotype presented a lower response to BD for FEF75% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>F) and FEF25–75% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>J), respectively, in the CFTR-A and CFTR-B groups. For the marker FEV1/FVC, the AT genotype in patients from the CFTR-B group showed lower response to BD (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B). Finally, in patients from the CFTR-A and CFTR-B groups the AA genotype (recessive model) for rs4073 showed higher response to BD for FEF75% (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>I) and FEF25–75%, respectively (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>M).The haplotype distribution for the IL-8 gene variants is presented in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.For the comparison between IL-8 gene variants and the response to BD, defined as an increase of >12% and 200mL of initial FEV1, no positive association was found (p>0.05).DiscussionThe influence of different IL-8 gene variants in the clinical severity of CF has been previously demonstrated.<a class="elsevierStyleCrossRef" href="#bib0260">22</a> This study showed the association of different IL-8 gene variants and their modulation to BD response, assessing the impact of the drug on pulmonary function. The variability of responses to BD is determined by multiple factors, such as inflammation and pulmonary obstruction,<a class="elsevierStyleCrossRef" href="#bib0265">23</a> bacteria,<a class="elsevierStyleCrossRef" href="#bib0270">24</a> and lung symptoms,<a class="elsevierStyleCrossRef" href="#bib0275">25</a> as well as modifier genes.<a class="elsevierStyleCrossRef" href="#bib0280">26</a> However, no studies so far have investigated the role of IL-8 as a pro-inflammatory mediator of CF and its relationship to BD, and whether the IL-8 gene variants may explain the individual response to BD in CF. It is believed that the short-acting and long-acting beta-2-agonists may be beneficial for CF patients with positive bronchial hyperresponsiveness.<a class="elsevierStyleCrossRef" href="#bib0180">6</a>In progressive lung diseases, different markers have been assessed; the use of BD appears to provide better response to FEF25–75%, when compared with other markers, which indicates involvement of smaller caliber airways in CF.<a class="elsevierStyleCrossRef" href="#bib0285">27</a> In the present study, in agreement with the reference literature, an association was observed between the rs4073 variant and the FEF25–75% marker in the dominant (for both CFTR-A and CFTR-B groups), co-dominant (CFTR-B group), and recessive models (CFTR-B group). There was improvement in several other markers of spirometry for rs4073, such as FEV1, FEV1/FVC, FEF50%, and FEF75%, which shows impact on breathing patterns of patients.The study by Hillian et al. (2008) found an association of rs2227307 and rs4073 IL-8 gene variants and severity of pulmonary disease.<a class="elsevierStyleCrossRef" href="#bib0290">28</a> In that study, patients were divided into two cohorts: (1) homozygous F508del patients; (2) patients with other genotypes of the CFTR gene. In cohort 1, the rs4073, rs2227306, and rs2227543 variants were not associated with lung disease, and an association was observed for rs22227307, regardless of gender. In cohort 2, the rs4073 and rs2227306 variants were associated with lung disease severity in males. Thus, the gender of the patient, genotype of the CFTR gene, and modifier genes may modulate the severity of the lung disease.<a class="elsevierStyleCrossRef" href="#bib0290">28</a> In this study, the rs2227307 genotype did not have an impact on the variability of the response to BD. This suggests that although this genotype is associated with lung disease in homozygous F508del patients, its response to BD is not relevant.The target of BD is the ADRB2 protein, which is expressed in the airway smooth muscle. Variants of ADRB2 are associated with response to the medication. Although this protein has been widely studied in asthma, it was very seldom studied in CF. The effectiveness of the response to BD and inhaled corticosteroids to manage airway inflammation in asthma has been confirmed, and depends on the Arg16Gly (rs1042713; c.46A>G) and Glu27Gln (rs1042714; c.79C>G) ADRB2 gene variants.<a class="elsevierStyleCrossRef" href="#bib0295">29</a> The Gln27Glu variant confers resistance to the ADRB2 protein in BD response. The 46*G and 79*G alleles are protective against asthma, reducing the risk by 27%.<a class="elsevierStyleCrossRef" href="#bib0295">29</a> Both variants of the G allele induce changes in the regulation of the receptor due to increased susceptibility to protein degradation. This study found that the Arg16Gly and Gln27Glu ADRB2 gene variants influence the response to BD in CF. In spirometry and in other markers of severity, the Arg16Gly variant showed a positive association, unlike Gln27Glu. The Arg/Arg genotype for the Arg16Gly variant was associated with better values of FEV1 and FEF25–75%. The response to BD in the analyses of haplotype was positive in the absence of Gly16Gly and Glu27Glu genotypes for FEV1/FVC ratio.Variants of ADRB2, diffusing capacity of the lungs for carbon monoxide, alveolar capillary membrane conductance, volume of blood in the alveolar capillary, and SaO2 were evaluated in the response to BD in 18 patients and 20 healthy controls, before and after the administration of salbutamol (30, 60, and 90min). Healthy subjects showed no changes in markers assessed for the Glu27Glu variant. However, in CF, this variant influenced the response to BD: the best response was found in the presence of at least one allele 27Glu. There was a difference in pulmonary diffusion and peripheral SaO2 according to the variation of the ADRB2 gene at position 27, and the dosage of the drug should be prescribed according to this variation.<a class="elsevierStyleCrossRef" href="#bib0300">30</a>Most studies focus on the ADRB2 gene variants in the response to BD. However, this study demonstrated that, even indirectly, the IL-8 gene variants (and possibly in other genes, which modulate the inflammatory lung response) may potentiate or minimize the effect of BD and also influence the response to the medication.Regarding the HWE, as previously discussed by this group,<a class="elsevierStyleCrossRef" href="#bib0260">22</a> two variants (rs4073 and rs2227306) were not in balance. It is important to remember that the HWE assumes an ideal population, without the interference of evolutionary factors. However, in genes as those involved in immunity, inflammation, and infection control, the HWE imbalance may appear secondarily associated with the selection mechanisms that favored a particular allele that can bring a more effective response. The disequilibrium does not invalidate the association study since the groups are part of the same population.The limitations of the present study include (i) cross-sectional dataset (BD response was evaluated at a single time); (ii) numerous missing data considering the problems to achieve information in the records; (iii) whether BD response differs based on baseline FEV1, mainly in health subjects; (iv) potential confounders to the results, such as disease severity, current therapies, medication adherence, and adequate pulmonary function test effort.In conclusion, IL-8 gene variants (rs2227306 and specially rs4073) can be associated with the response to BD during spirometry. This drug may be an alternative for the treatment of the disease, mostly among patients with airways of smaller caliber. Studies involving dosage and combinations of drugs should be further conducted, in order determine the best treatment according to CF patient genotype, the CFTR gene, as well as modifier genes.FundingFALM: Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for supporting the researches #2011/12939-4, #2011/18845-1, #2015/12183-8, and #2015/12858-5; Fundo de Apoio à Pesquisa, ao Ensino e à Extensão da Universidade Estadual de Campinas for supporting the research #0648/2015; JDR: FAPESP for supporting the research #2011/18845-1 and #2015/12183-8. LLF: FAPESP for supporting the research #2013/19052-0.Conflicts of interestThe authors declare no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres935732" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec909678" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres935733" "titulo" => "Resumo" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec909677" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Clinical variables" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "DNA extraction and genotyping" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack315964" "titulo" => "Acknowledgements" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-08-02" "fechaAceptado" => "2017-01-09" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec909678" "palabras" => array:4 [ 0 => "CFTR" 1 => "Disease severity" 2 => "Interleukin 8" 3 => "Lung function" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec909677" "palabras" => array:4 [ 0 => "CFTR" 1 => "Gravidade da doença" 2 => "Interleucina 8" 3 => "Função pulmonar" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveInterleukin 8 protein promotes inflammatory responses, even in airways. The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators. Thus, this study analyzed the interleukin 8 variants (rs4073, rs2227306, and rs2227307) and their association with the response to inhaled bronchodilators in cystic fibrosis patients. MethodsAnalysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction. The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann–Whitney and Kruskal–Wallis tests. The analysis included all cystic fibrosis patients, and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III. ResultsThis study included 186 cystic fibrosis patients. There was no association of the rs2227307 variant with the response to inhaled bronchodilators. The rs2227306 variant was associated with FEF50% in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene. The rs4073 variant was associated with spirometry markers in four genetic models: co-dominant (FEF25–75% and FEF75%), dominant (FEV1, FEF50%, FEF75%, and FEF25–75%), recessive (FEF75% and FEF25–75%), and over-dominant (FEV1/FVC). ConclusionsThis study highlighted the importance of the rs4073 variant of the interleukin 8 gene, regarding response to inhaled bronchodilators, and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "ObjetivoA proteína interleucina 8 promove respostas inflamatórias, o que inclui sua atuação nas vias aéreas. A presença de variantes no gene da interleucina 8 causa respostas inflamatórias alteradas e possivelmente respostas variadas ao uso de broncodilatadores inalatórios. Assim, este estudo analisou as variantes da interleucina 8 (rs4073, rs2227306, rs2227307) e sua associação à resposta a broncodilatadores inalatórios em pacientes com fibrose cística. MétodosFoi feita análise das variantes genéticas da interleucina 8 por restriction fragment length polymorphism da reação em cadeia da polimerase. A associação entre os marcadores da espirometria e a resposta a broncodilatadores inalatórios foi feita pelos testes de Mann-Whitney e Kruskal-Wallis. A análise incluiu todos os pacientes com fibrose cística e posteriormente pacientes com duas mutações no gene cystic fibrosis transmembrane conductance regulator pertencentes às Classes I a II. ResultadosEste estudo incluiu 186 pacientes com fibrose cística. Não houve associação da variante rs2227307 à resposta a broncodilatadores inalatórios. A variante rs2227306 foi associada a FEF50% no grupo dominante e no grupo com duas mutações identificadas no gene cystic fibrosis transmembrane conductance regulator. A variante rs4073 foi associada a marcadores da espirometria em quatro modelos genéticos: codominante (FEF25-75% e FEF75%), dominante (VEF1, FEF50%, FEF75% e FEF25-75%), recessivo (FEF75% e FEF25-75%) e overdominante (VEF1/CVF). ConclusõesEste estudo destaca, principalmente, a importância da variante rs4073 do gene da interleucina 8, na resposta a broncodilatadores inalatórios, concomitantemente ao genótipo das mutações no gene cystic fibrosis transmembrane conductance regulator." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Furlan LL, Ribeiro JD, Bertuzzo CS, Salomão Junior JB, Souza DR, Marson FA. Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis. J Pediatr (Rio J). 2017;93:639–48." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "Study conducted at Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 4239 "Ancho" => 3284 "Tamanyo" => 641459 ] ] "descripcion" => array:1 [ "en" => "Association of rs4073 and rs2227306 variants of IL-8 (interleukin-8) with the response to inhaled bronchodilators in cystic fibrosis patients. (A) Association between forced expiratory volume in 1s (FEV1) of forced vital capacity (FVC) and rs4073, dominant model and two identified mutations in the CFTR gene (cystic fibrosis transmembrane regulator) belonging to classes I, II, and/or III (CFTR-B group) (p=0.028; pc=0.112). (AA+AT) n=39; mean of 4.77±8.95; median of 4 (ranging from −9 to 48). (TT) n=21; mean of −0.86±5.42; median of −1 (ranging from −6 to 15). (B) Association of FEV1/FVC ratio with rs4073, over-dominant model and CFTR-B group (p=0.029; pc=0.116). (AA+TT) n=30; mean of 1.17±7.36; median of 0 (ranging from −12 to 23). (AT) n=29; mean of 4.76±7.58; median of 4 (ranging from −9 to 32). (C) Association of forced expiratory flow of 50% (FEF50%) of FVC with rs4073, dominant model, and CFTR-B group (p=0.046; pc=0.184). (AA+AT) n=37; mean of 17.38±24.18; median of 16 (ranging from −20 to 89). (TT) n=21; mean of 4.95±20.8; median of −2 (ranging from −19 to 55). (D) Association of FEF50% with rs2227306, dominant model, and CFTR-B group (p=0.05; pc=0.083). (CC) n=15; mean of 1.47±17.22; median of 0 (ranging from −20 to 29). (CT+TT) n=44; mean of 15.84±25.04; median of 10.5 (ranging from −28 to 89). (E) Association of FEF50% with rs2227306, over-dominant model, and CFTR-B group (p=0.033; pc=0.083). (CC+TT) n=33; mean of 6.06±20.27; median of 4 (ranging from −20 to 55). (CT) n=23; mean of 19.96±26.43; median of 19 (ranging from −28 to 89). (F) Association of forced expiratory flow of 75% (FEF75%) of FVC with rs4073, co-dominant model regardless of identified mutations in the CFTR gene (CFTR-A group) (p=0.044; pc=0.058). 1≠3. (AA) n=28; mean of 29.93±39.98; median of 30 (ranging from −47 to 142). (AT) n=42; mean of 24.81±53.57; median of 14 (ranging from −58 to 235). (TT) n=28; mean of 9.14±36.95; median of 2.5 (ranging from −35 to 119). (G) Association of FEF75% with rs4073, dominant model, and CFTR-B group (p=0.024; pc=0.096). (AA+AT) n=38; mean of 33±55.23; median of 16 (ranging from −27 to 235). (TT) n=21; mean of 5.43±35.93; median of 2 (ranging from −35 to 119). (H) Association of FEF75% with rs4073, dominant model, and CFTR-A group (p=0.034; pc=0.058). (AA+AT) n=70; mean of 26.86±48.34; median of 18 (ranging from −58 to 235). (TT) n=28; mean of 9.14±36.95; median of 2.5 (ranging from −35 to 119). (I) Association of FEF75% with rs4073, recessive model, and CFTR-A group (p=0.04; pc=0.058). (AA) n=28; mean of 29.93±39.98; median of 30 (ranging from −47 to 142). (AT+TT) n=70; mean of 18.54±47.95; median of 10 (ranging from −58 to 235). (J) Association of FEF between 25% and 75% (FEF25–75%) of FVC with rs4073, co-dominant model and CFTR-B group (p=0.012; pc=0.024). TT≠AA and AT. (AA) n=9; mean of 25.78±23.14; median of 30 (ranging from −21 to 57). (AT) n=29; mean of 18.38±29.04; median of 14 (ranging from −33 to 117). (TT) n=21; mean of 2.14±23.74; median of 0 (ranging from −51 to 65). (K) Association of FEF25–75% with rs4073, dominant model, and CFTR-B group (p=0.007; pc=0.024). (AA+ATT) n=38; mean of 20.13±27.64; median of 18.5 (ranging from −33 to 117). (TT) n=23; mean of 2.14±23.74; median of 0 (ranging from −51 to 65). (L) Association of FEF25–75% with rs4073, dominant model, and CFTR-A group (p=0.029; pc=0.1). (AA+AT) n=82; mean of 15.48±27.2; median of 15 (ranging from −40 to 117). (TT) n=33; mean of 5.94±27.33; median of 0 (ranging from −51 to 76). (M) Association of FEF25–75% with rs4073, recessive model, and CFTR-B group (p=0.047; pc=0.063). (AA) n=9; mean of 25.78±23.14; median of 30 (ranging from −21 to 57). (AT+TT) n=50; mean of 11.56±27.89; median of 8 (ranging from −51 to 117). The dot corresponds to median values and the bar corresponds to the 95% confidence interval." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "n, sample size; CFTR, cystic fibrosis transmembrane regulator." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genotype \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group of patients \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">–/– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">29.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="6" align="left" valign="middle">Patients without known mutation in the CFTR gene, or with one or two classes IV, V or VI CFTR mutations</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">V562I/– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I507V/– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D110H/V232H \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G576A/R668C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">p.Glu528G>A/TG11-5T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="10" align="left" valign="middle">Patients with one classes I, II or III CFTR mutation, and one non-identified mutation or IV, V or VI CFTR mutation</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X/– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/3272-26A>G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/P205S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X/P205S \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X/R334W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3120+1G>A/L206W \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">622-2A>G/711+1G>T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">R1162X/- \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X/I618T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="4" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/F508del \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">49 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="22" align="left" valign="middle">Patients with two classes I, II, and/or III CFTR mutations (CFTR-B group)</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/G542X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/N1303K \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/R1162X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/R553X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/1584-18672pbA>G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/c.1717-1G>A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3120+1G>A/R1066C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/2183AA>G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/2184insA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/6B to 16 exon duplication \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/G85E \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/S549R (T>G) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/S4X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X/2183AA>G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X/R1162X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A561E/A561E \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/R1066C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">R1070Q; S466X/G542X \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del/1812-1G>A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2183AA>G/2183AA>G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3120+1G>A/3120+1G>A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1581575.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "All patients assessed in this study have been included (CFTR-A group)." ] ] ] "descripcion" => array:1 [ "en" => "Distribution of cystic fibrosis patients for the CFTR genotype and classes of identified mutations.<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a>" ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "SaO2, transcutaneous arterial hemoglobin oxygen-saturation; FVC, forced vital capacity; FEV1, forced expiratory volume in 1s of FVC; FEF25%, forced expiratory flow at 25% of FVC; FEF50%, forced expiratory flow at 50% of FVC; FEF75%, forced expiratory flow at 75% of FVC; FEF25–75%, average forced expiratory flow between 25% and 75% of FVC; FEFmax, maximum forced expiratory flow; ERV, expiratory reserve volume. Spirometry data are shown in percentage of the predicted value. All evaluated patients are described." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Distribution<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gender (male) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">92/186 (49.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Ethnicity (White) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">169/180 (93.9%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">169; 201.41±171.98; 143 (7 to 932) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Onset of symptoms (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">159; 38.23±114.03; 3 (0 to 720) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diagnosis (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">171; 87.90±158.39; 20 (0 to 833) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Onset of digestive symptoms (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">140; 41.2±112.61; 3 (0 to 720) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Onset of pulmonary symptoms (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">156; 46.33±123.64; 6 (0 to 720) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Body mass index (Kg/m2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">178; 17.28±4.08; 16.28 (6.5 to 35.67) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nasal polyposis (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28/162 (17.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Diabetes mellitus (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">32/164 (19.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Osteoporosis (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25/162 (15.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pancreatic insufficiency (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">130/162 (80.2%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Meconium ileus (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23/162 (14.2%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1st Pseudomonas aeruginosa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">121; 103.03±171.74; 31 (0 to 872)<a class="elsevierStyleCrossRef" href="#tblfn0015">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mucoid P. aeruginosa (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">74/173 (42.8%)<a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Non-mucoid P. aeruginosa (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99/173 (57.2%)<a class="elsevierStyleCrossRef" href="#tblfn0020">c</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Achromobacter xylosoxidans (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17/174 (9.8%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Burkolderia cepacia (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25/174 (14.4%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Staphylococcus aureus (presence) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">131/174 (75.3%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">SaO2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">159; 94.87±4.28; 96 (66 to 99) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bhalla score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">113; 8.9±5.77; 8 (0 to 25) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kanga score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">118; 18.78±5.82; 17.5 (10 to 40) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Shwachman-Kulczycki score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">143; 65.97±16.78; 65 (20 to 95) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">142; 72.13±23.86; 77 (19 to 126) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">141; 60.99±25.75; 63 (17 to 116) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV1/FVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">144; 79.08±14.99; 81 (39 to 113) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEF25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">119; 61.28±31.71; 60 (7 to 138) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEF50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">119; 46.2±31.25; 40 (3 to 126) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEF75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">116; 36.32±28.77; 27.5 (4 to 142) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEF25–75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">140; 47.16±32.51; 39 (5 to 150) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEFMax \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">114; 75.54±25.59; 73.5 (25 to 137) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ERV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">112; 80.96±52.39; 69 (3 to 248) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Response to inhaled bronchodilator</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">117; 1.74±8.19; 1 (−17 to 32) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">117; 3.51±8.0; 3 (−12 to 48) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEV1/FVC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">111; 2.14±7.43; 2 (−19 to 32) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEF25% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99; 9.99±24.41; 5 (−45 to 110) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEF50% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99; 13.08±26.06; 9 (−41 to 114) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEF75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99; 20.93±46.47; 16 (−64 to 235) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEF25–75% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">99; 12.28±27.77; 9.5 (−51 to 117) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FEFMax \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">116; 2.63±14.48; 3 (−42 to 69) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ERV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100; 23.04±101.08; 0 (−90 to 670) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1581577.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "The data with categorical distribution are presented as follows: n of variable/n total (percentage); data with numeric distribution are presented as follows: sample size; mean±standard deviation; median (minimum to maximum)." ] 1 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "b" "nota" => "Missing values for first P. aeruginosa correspond to cystic fibrosis patients that never presented a P. aeruginosa positive culture." ] 2 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "c" "nota" => "One cystic fibrosis patient showed a positive culture for P. aeruginosa, with negative values for P. aeruginosa antigen specific IgG and the patient was excluded for the frequency estimation." ] ] ] "descripcion" => array:1 [ "en" => "Descriptive analysis of clinical and laboratory markers of cystic fibrosis patients." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "IL-8, interleukin 8; %, percentage; χ2, chi-square; af, absolute frequency." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variants \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genotype \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number (%) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Allele \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number (af) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">χ2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">p-Value<a class="elsevierStyleCrossRef" href="#tblfn0025">a</a> \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">rs4073</td><td class="td" title="table-entry " align="left" valign="top">AA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">54 (29.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">187 (0.51) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle">3.94</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle"><0.05</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">79 (42.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">183 (0.49) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52 (28.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">370 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">185 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">rs2227306</td><td class="td" title="table-entry " align="left" valign="top">CC \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70 (38) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">C \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">211 (0.57) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle">8.21</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle"><0.05</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">71 (38.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">157 (0.43) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">43 (23.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">368 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">184 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="7" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="4" align="left" valign="top">rs2227307</td><td class="td" title="table-entry " align="left" valign="top">GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31 (17.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">G \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">139 (0.39) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle">1.48</td><td class="td" title="table-entry " rowspan="3" align="left" valign="middle">>0.05</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77 (43.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">217 (0.61) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70 (39.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">356 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">178 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1581574.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">rs4073/rs2227306/rs2227307 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Frequency \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Percentage (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CC GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CC GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CC TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CT GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CT GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CT TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA TT GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA TT GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA TT TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT CC GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT CC TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT CT GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT CT TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT TT GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT TT GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT TT TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CC GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CC GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CC TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CT GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CT GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CT TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT TT GG \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT TT GT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT TT TT \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">177 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">100 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1581576.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "a" "nota" => "χ2 and p-values refer to the calculation of Hardy–Weinberg equilibrium. Significant data are shown in bold type. There was weak correlation among the IL-8 gene variants in the cystic fibrosis patients enrolled in the study. There is no linkage disequilibrium." ] ] ] "descripcion" => array:1 [ "en" => "Distribution of genotypes, alleles and haplotype of IL-8 gene variants (rs4073, rs2227306 and rs2227307) in cystic fibrosis patients." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib0155" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F.A.L. Marson" 1 => "C.S. Bertuzzo" 2 => "A.F. Ribeiro" 3 => "J.D. Ribeiro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2466-12-50" "Revista" => array:6 [ "tituloSerie" => "BMC Pulm Med" "fecha" => "2012" "volumen" => "12" "paginaInicial" => "50" "paginaFinal" => "59" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22950544" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0160" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The cystic fibrosis transmembrane conductance regulator: an intriguing protein with pleiotropic functions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A. Vankeerberghen" 1 => "H. Cuppens" 2 => "J.J. Cassiman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Cyst Fibros" "fecha" => "2002" "volumen" => "1" "paginaInicial" => "13" "paginaFinal" => "29" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15463806" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0165" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Essential involvement of interleukin-8 (IL-8) in acute inflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A. Harada" 1 => "N. Sekido" 2 => "T. Akahoshi" 3 => "T. Wada" 4 => "N. Mukaida" 5 => "K. Matsushima" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Leukoc Biol" "fecha" => "1994" "volumen" => "56" "paginaInicial" => "559" "paginaFinal" => "564" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7964163" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0170" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Inhaled bronchodilators for cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Halfhide" 1 => "H.J. Evans" 2 => "J. Couriel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2005" "volumen" => "19" "paginaInicial" => "CD003428" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0175" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung function testing in preschool-aged children with cystic fibrosis in the clinical setting" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C.L. Gangell" 1 => "G.L. Hall" 2 => "S.M. Stick" 3 => "P.D. Sly" 4 => "C.F. Arest" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/ppul.21192" "Revista" => array:6 [ "tituloSerie" => "Pediatr Pulmonol" "fecha" => "2010" "volumen" => "45" "paginaInicial" => "419" "paginaFinal" => "433" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20425849" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0180" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "WITHDRAWN: inhaled bronchodilators for cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C. Halfhide" 1 => "H.J. Evans" 2 => "J. Couriel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/14651858.CD003428.pub3" "Revista" => array:5 [ "tituloSerie" => "Cochrane Database Syst Rev" "fecha" => "2016" "volumen" => "2" "paginaInicial" => "CD003428" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26866910" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0185" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biochemical basis of asthma therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.J. Barnes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1074/jbc.R110.206466" "Revista" => array:6 [ "tituloSerie" => "J Biol Chem" "fecha" => "2011" "volumen" => "286" "paginaInicial" => "32899" "paginaFinal" => "32905" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21799015" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0190" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of CFTR gene mutation with bronchial asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "N. Maurya" 1 => "S. Awasthi" 2 => "P. Dixit" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Indian J Med Res" "fecha" => "2012" "volumen" => "135" "paginaInicial" => "469" "paginaFinal" => "478" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22664493" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0195" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Regamey" 1 => "L. Tsartsali" 2 => "T.N. Hilliard" 3 => "O. Fuchs" 4 => "H.L. Tan" 5 => "J. Zhu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2011-200585" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2012" "volumen" => "67" "paginaInicial" => "164" "paginaFinal" => "170" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22008188" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0200" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CFTR mutations and GSTM1 and GSTT1 deletions in Brazilian cystic fibrosis patients" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C.S. Lima" 1 => "M.M. Ortega" 2 => "F.A.L. Marson" 3 => "R. Zulli" 4 => "A.F. Ribeiro" 5 => "C.S. Bertuzzo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Bras Pneumol" "fecha" => "2012" "volumen" => "38" "paginaInicial" => "50" "paginaFinal" => "56" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22407040" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0205" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The ACE gene D/I polymorphism as a modulator of severity of cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "F.A. Marson" 1 => "C.S. Bertuzzo" 2 => "T.D. Hortencio" 3 => "J.D. Ribeiro" 4 => "L.C. Bonadia" 5 => "A.F. Ribeiro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2466-12-41" "Revista" => array:5 [ "tituloSerie" => "BMC Pulm Med" "fecha" => "2012" "volumen" => "12" "paginaInicial" => "41" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22874010" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0210" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Polymorphisms in the glutathione pathway modulate cystic fibrosis severity: a cross-sectional study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F.A. Marson" 1 => "C.S. Bertuzzo" 2 => "A.F. Ribeiro" 3 => "J.D. Ribeiro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1471-2350-15-27" "Revista" => array:5 [ "tituloSerie" => "BMC Med Genet" "fecha" => "2014" "volumen" => "15" "paginaInicial" => "27" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24593045" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0215" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Personalized drug therapy in cystic fibrosis: from fiction to reality" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F.A. Marson" 1 => "C.S. Bertuzzo" 2 => "J.D. Ribeiro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Curr Drug Targets" "fecha" => "2015" "volumen" => "16" "paginaInicial" => "1007" "paginaFinal" => "1017" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25438972" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0220" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary function testing in children: techniques and standards" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "G. Polgar" 1 => "V. Promadhat" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "1971" "editorial" => "WB Saunders Company" "editorialLocalizacion" => "Philadelphia (PA)" ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0225" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "New reference values for forced spirometry in white adults in Brazil" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "C.A. Pereira" 1 => "T. Sato" 2 => "S.C. Rodrigues" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Bras Pneumol" "fecha" => "2007" "volumen" => "33" "paginaInicial" => "397" "paginaFinal" => "406" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17982531" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0230" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Validation of new Brazilian predicted values for forced spirometry in Caucasians and comparison with predicted values obtained using other reference equations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.A. Duarte" 1 => "C.A. Pereira" 2 => "S.C. Rodrigues" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Bras Pneumol" "fecha" => "2007" "volumen" => "33" "paginaInicial" => "527" "paginaFinal" => "535" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18026650" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0235" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.C. Bonadia" 1 => "F.A. Marson" 2 => "J.D. Ribeiro" 3 => "I.A. Paschoal" 4 => "M.C. Pereira" 5 => "A.F. Ribeiro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.gene.2014.02.040" "Revista" => array:6 [ "tituloSerie" => "Gene" "fecha" => "2014" "volumen" => "540" "paginaInicial" => "183" "paginaFinal" => "190" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24583165" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0240" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association study suggests opposite effects of polymorphisms within IL-8 on bronchial asthma and respiratory syncytial virus bronchiolitis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A. Heinzmann" 1 => "I. Ahlert" 2 => "T. Kurz" 3 => "R. Berner" 4 => "K.A. Deichmann" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2004.06.038" "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2004" "volumen" => "114" "paginaInicial" => "671" "paginaFinal" => "676" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15356575" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0245" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Haplotypes in the interleukin 8 gene and their association with chronic periodontitis susceptibility" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.M. Scarel-Caminaga" 1 => "Y.J. Kim" 2 => "A.C. Viana" 3 => "K.M. Curtis" 4 => "S.C. Corbi" 5 => "P.M. Sogumo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10528-010-9407-3" "Revista" => array:6 [ "tituloSerie" => "Biochem Genet" "fecha" => "2011" "volumen" => "49" "paginaInicial" => "292" "paginaFinal" => "302" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21188496" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0250" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "GPower 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. Faul" 1 => "E. Erdfelde" 2 => "A.G. Lang" 3 => "A. Buchner" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Behav Res Methods" "fecha" => "2007" "volumen" => "39" "paginaInicial" => "175" "paginaFinal" => "191" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17695343" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0255" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Discovering the false discovery rate" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Y. Benjamini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J R Stat Soc Ser B (Stat Method)" "fecha" => "2010" "volumen" => "72" "paginaInicial" => "405" "paginaFinal" => "416" ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0260" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "IL8 gene as modifier of cystic fibrosis: unraveling the factors which influence clinical variability" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "L.L. Furlan" 1 => "F.A. Marson" 2 => "J.D. Ribeiro" 3 => "C.S. Bertuzzo" 4 => "J.B. Salomão Junior" 5 => "D.R. Souza" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00439-016-1684-4" "Revista" => array:6 [ "tituloSerie" => "Hum Genet" "fecha" => "2016" "volumen" => "135" "paginaInicial" => "881" "paginaFinal" => "894" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27209008" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0265" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of blood eosinophils and plasma periostin with FEV1 response after 3-month inhaled corticosteroid and long-acting beta2-agonist treatment in stable COPD patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.Y. Park" 1 => "H. Lee" 2 => "W. Koh" 3 => "S. Kim" 4 => "I. Jeong" 5 => "H.K. Koo" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Int J Chronic Obstruct Pulm Dis" "fecha" => "2016" "volumen" => "11" "paginaInicial" => "23" "paginaFinal" => "30" ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0270" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biomarkers of progression of chronic obstructive pulmonary disease (COPD)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.G. Shaw" 1 => "A. Vaughan" 2 => "A.G. Dent" 3 => "P.E. O’Hare" 4 => "F. Goh" 5 => "R.V. Bowman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3978/j.issn.2072-1439.2014.11.33" "Revista" => array:6 [ "tituloSerie" => "J Thorac Dis" "fecha" => "2014" "volumen" => "6" "paginaInicial" => "1532" "paginaFinal" => "1547" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25478195" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0275" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of age and sex on response to asthma therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.M. Dunn" 1 => "E. Lehman" 2 => "V.M. Chinchilli" 3 => "R.J. Martin" 4 => "H.A. Boushey" 5 => "E. Israel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201503-0426OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2015" "volumen" => "192" "paginaInicial" => "551" "paginaFinal" => "558" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26068329" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0280" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A genome-wide association study of bronchodilator response in asthmatics" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Q.L. Duan" 1 => "J. Lasky-Su" 2 => "B.E. Himes" 3 => "W. Qiu" 4 => "A.A. Litonjua" 5 => "A. Damask" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/tpj.2013.5" "Revista" => array:6 [ "tituloSerie" => "Pharmacogenomics J" "fecha" => "2014" "volumen" => "14" "paginaInicial" => "41" "paginaFinal" => "47" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23508266" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0285" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pulmonary function parameters and use of bronchodilators in patients with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L.H. Muramatu" 1 => "R. Stirbulov" 2 => "W.C. Forte" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Bras Pneumol" "fecha" => "2013" "volumen" => "39" "paginaInicial" => "48" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23503485" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0290" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Modulation of cystic fibrosis lung disease by variants in interleukin-8" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A.D. Hillian" 1 => "D. Londono" 2 => "J.M. Dunn" 3 => "K.A. Goddard" 4 => "R.G. Pace" 5 => "M.R. Knowles" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/gene.2008.42" "Revista" => array:6 [ "tituloSerie" => "Genes Immun" "fecha" => "2008" "volumen" => "9" "paginaInicial" => "501" "paginaFinal" => "508" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18563170" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0295" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Systematic review and meta-analysis of the association between β2-adrenoceptor polymorphisms and asthma: a HuGE review" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Thakkinstian" 1 => "M. McEvoy" 2 => "C. Minelli" 3 => "P. Gibson" 4 => "B. Hancox" 5 => "D. Duffy" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Epidemiol" "fecha" => "2005" "volumen" => "162" "paginaInicial" => "201" "paginaFinal" => "211" ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0300" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influence of genetic variation of the β2-adrenergic receptor on lung diffusion in patients with cystic fibrosis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B.R. Traylor" 1 => "C.M. Wheatley" 2 => "T.T. Skrentny Jr." 3 => "W.T. Foxx-Lupo" 4 => "H. Phan" 5 => "A.E. Patanwala" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.pupt.2011.06.001" "Revista" => array:6 [ "tituloSerie" => "Pulm Pharmacol Ther" "fecha" => "2011" "volumen" => "24" "paginaInicial" => "610" "paginaFinal" => "616" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21703359" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack315964" "titulo" => "Acknowledgements" "texto" => "To Luciana Montes Rezende, Luciana Cardoso Bonadia, and Stephanie Villa-Nova for their technical support during DNA extraction and identification of mutations of the CFTR gene. To Marcela Augusta de Souza Pinhel, Michele Lima Gregório, Rafael Fernandes Ferreira, Graciele Domitila Tenani, and Heloisa Cristina Caldas for their technical support during standardization of IL-8 genotyping. To Maria Ângela Gonçalves de Oliveira Ribeiro for conducting pulmonary function tests (LAFIP/Ciped/Unicamp). To Rafaella Maionchi Pereira Martins for her technical support to determine clinical scores. To Maria de Fátima Corrêa Pimenta Servidoni for promoting a link between both Universities." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/00217557/0000009300000006/v1_201711050042/S0021755717306344/v1_201711050042/en/main.assets" "Apartado" => array:4 [ "identificador" => "10179" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/00217557/0000009300000006/v1_201711050042/S0021755717306344/v1_201711050042/en/main.pdf?idApp=UINPBA000049&text.app=https://jped.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755717306344?idApp=UINPBA000049"]

Statistics

Original article

Variantes no gene da interleucina 8 e a resposta a broncodilatadores inalatórios na fibrose cística

Larissa Lazzarini Furlana, José Dirceu Ribeirob, Carmen Sílvia Bertuzzoc, João Batista Salomão Juniord,e, Dorotéia Rossi Silva Souzaf, Fernando Augusto Lima Marsonb,c,

Corresponding author

fernandolimamarson@hotmail.com

Corresponding author.

a Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brazil

b Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Pediatria, Campinas, SP, Brazil

c Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Genética Médica, Campinas, SP, Brazil

d Faculdade de Medicina de São José do Rio Preto, Hospital Universitário, Departamento de Pediatria, São José do Rio Preto, SP, Brazil

e Faculdade de Medicina de São José do Rio Preto, Hospital Universitário, Departamento de Pneumologia Pediátrica, São José do Rio Preto, SP, Brazil

f Faculdade de Medicina de São José do Rio Preto, Centro de Pesquisa de Bioquímica e Biologia Molecular, Departamento de Biologia Molecular, São José do Rio Preto, SP, Brazil

Read

2581

Times
was read the article

1267

Total PDF

1314

Total HTML

Share statistics

 array:25 [
  "pii" => "S0021755717306344"
  "issn" => "00217557"
  "doi" => "10.1016/j.jped.2017.03.005"
  "estado" => "S300"
  "fechaPublicacion" => "2017-11-01"
  "aid" => "512"
  "copyright" => "Sociedade Brasileira de Pediatria"
  "copyrightAnyo" => "2017"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "J Pediatr &#40;Rio J&#41;. 2017;93:639-48"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 708
    "formatos" => array:3 [
      "EPUB" => 84
      "HTML" => 347
      "PDF" => 277
    ]
  ]
  "Traduccion" => array:1 [
    "pt" => array:20 [
      "pii" => "S2255553617300794"
      "issn" => "22555536"
      "doi" => "10.1016/j.jpedp.2017.07.002"
      "estado" => "S300"
      "fechaPublicacion" => "2017-11-01"
      "aid" => "512"
      "copyright" => "Sociedade Brasileira de Pediatria"
      "documento" => "article"
      "crossmark" => 1
      "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
      "subdocumento" => "fla"
      "cita" => "J Pediatr &#40;Rio J&#41;. 2017;93:639-48"
      "abierto" => array:3 [
        "ES" => true
        "ES2" => true
        "LATM" => true
      ]
      "gratuito" => true
      "lecturas" => array:2 [
        "total" => 914
        "formatos" => array:3 [
          "EPUB" => 91
          "HTML" => 594
          "PDF" => 229
        ]
      ]
      "pt" => array:13 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Artigo Original</span>"
        "titulo" => "Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis"
        "tienePdf" => "pt"
        "tieneTextoCompleto" => "pt"
        "tieneResumen" => array:2 [
          0 => "en"
          1 => "pt"
        ]
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "639"
            "paginaFinal" => "648"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "pt" => array:1 [
            "titulo" => "Variantes no gene da interleucina 8 e a resposta a broncodilatadores inalat&#243;rios na fibrose c&#237;stica"
          ]
        ]
        "contieneResumen" => array:2 [
          "en" => true
          "pt" => true
        ]
        "contieneTextoCompleto" => array:1 [
          "pt" => true
        ]
        "contienePdf" => array:1 [
          "pt" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 4239
                "Ancho" => 3276
                "Tamanyo" => 668369
              ]
            ]
            "descripcion" => array:1 [
              "pt" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Associa&#231;&#227;o das variantes rs4073 e rs2227306 da <span class="elsevierStyleItalic">IL&#8208;8</span> &#40;interleucina&#8208;8&#41; &#224; resposta a broncodilatadores inalat&#243;rios em pacientes com fibrose c&#237;stica&#46; A&#46; Associa&#231;&#227;o entre o volume expirat&#243;rio for&#231;ado no 1&#176; segundo &#40;VEF<span class="elsevierStyleInf">1</span>&#41; da capacidade vital for&#231;ada &#40;CVF&#41; e rs4073&#44; modelo dominante e duas muta&#231;&#245;es identificadas no gene do <span class="elsevierStyleItalic">RTFC</span> &#40;regulador da condut&#226;ncia transmembrana da fibrose c&#237;stica&#41; pertencente &#224;s classes I&#44; II e&#47;ou III &#40;grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;028&#59; p<span class="elsevierStyleSup">c</span>&#8211;0&#44;112&#41;&#46; &#40;AA &#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#59; m&#233;dia de 4&#44;77<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;95&#59; mediana de 4 &#40;varia&#231;&#227;o de &#8722;9 a 48&#41;&#46; &#40;TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; m&#233;dia de 0&#44;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;42&#59; mediana de &#8722;1 &#40;varia&#231;&#227;o de &#8722;6 a 15&#41;&#46; B&#46; Associa&#231;&#227;o da propor&#231;&#227;o VEF1&#47;CVF &#224; variante rs4073&#44; modelo superdominante e grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;029&#59; pc<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;116&#41;&#46; &#40;TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#59; m&#233;dia de 0&#44;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;36&#59; mediana de 0 &#40;varia&#231;&#227;o de &#8722;12 a 23&#41;&#46; &#40;AT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#59; m&#233;dia de 4&#44;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;58&#59; mediana de 4 &#40;varia&#231;&#227;o de &#8722;9 a 32&#41;&#46; C&#46; Associa&#231;&#227;o do fluxo expirat&#243;rio for&#231;ado de 50&#37; &#40;FEF<span class="elsevierStyleInf">50&#37;</span>&#41; da CVF &#224; variante rs4073&#44; modelo dominante e grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;046&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;184&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&#59; m&#233;dia de 17&#44;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#44;18&#59; mediana de 16 &#40;varia&#231;&#227;o de &#8722;20 a 89&#41;&#46; &#40;TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; m&#233;dia de 4&#44;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#44;80&#59; mediana de &#8722;2 &#40;varia&#231;&#227;o de &#8722;19 a 55&#41;&#46; D&#46; Associa&#231;&#227;o do FEF<span class="elsevierStyleInf">50&#37;</span> &#224; variante rs2227306&#44; modelo dominante e grupo <span class="elsevierStyleItalic">RTFC&#8208;B</span> &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;050&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;083&#41;&#46; &#40;CC&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#59; m&#233;dia de 1&#44;47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#44;22&#59; mediana de 0 &#40;varia&#231;&#227;o de &#8722;20 a 29&#41;&#46; &#40;CT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#59; m&#233;dia de 15&#44;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#44;04&#59; mediana de 10&#44;50 &#40;varia&#231;&#227;o de &#8722;28 a 89&#41;&#46; E&#46; Associa&#231;&#227;o do FEF<span class="elsevierStyleInf">50&#37;</span> &#224; variante rs2227306&#44; modelo superdominante e grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;033&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;083&#41;&#46; &#40;CC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#59; m&#233;dia de 6&#44;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#44;27&#59; mediana de 4 &#40;varia&#231;&#227;o de &#8722;20 a 55&#41;&#46; &#40;CT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#59; m&#233;dia de 19&#44;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#44;43&#59; mediana de 19 &#40;varia&#231;&#227;o de &#8722;28 a 89&#41;&#46; F&#46; Associa&#231;&#227;o do fluxo expirat&#243;rio for&#231;ado de 75&#37; &#40;FEF<span class="elsevierStyleInf">75&#37;</span>&#41; da CVF &#224; variante rs4073&#44; modelo codominante independentemente das muta&#231;&#245;es identificadas no gene do <span class="elsevierStyleItalic">RTFC</span> &#40;grupo RTFC&#8208;A&#41; &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;044&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;058&#41;&#46; 1 &#8800; 3&#46; &#40;AA&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; m&#233;dia de 29&#44;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#44;98&#59; mediana de 30 &#40;varia&#231;&#227;o de &#8722;47 a 142&#41;&#46; &#40;AT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#59; m&#233;dia de 24&#44;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>53&#44;57&#59; mediana de 14 &#40;varia&#231;&#227;o de &#8722;58 a 235&#41;&#46; &#40;TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; m&#233;dia de 9&#44;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#44;95&#59; mediana de 2&#44;5 &#40;varia&#231;&#227;o de &#8722;35 a 119&#41;&#46; G&#46; Associa&#231;&#227;o do FEF<span class="elsevierStyleInf">75&#37;</span> &#224; variante rs4073&#44; modelo dominante e grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;096&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#59; m&#233;dia de 33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>55&#44;23&#59; mediana de &#40;varia&#231;&#227;o de &#8722;27 a 235&#41;&#46; &#40;TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; m&#233;dia de 5&#44;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#44;93&#59; mediana de 2 &#40;varia&#231;&#227;o de &#8722;35 a 119&#41;&#46; H&#46; Associa&#231;&#227;o do FEF<span class="elsevierStyleInf">75&#37;</span> &#224; variante rs4073&#44; modelo dominante e grupo <span class="elsevierStyleItalic">RTFC&#8208;A</span> &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;034&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;058&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#59; m&#233;dia de 26&#44;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>48&#44;34&#59; mediana de 18 &#40;varia&#231;&#227;o de &#8722;58 a 235&#41;&#46; &#40;TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; m&#233;dia de 9&#44;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#44;95&#59; mediana de 2&#44;5 &#40;varia&#231;&#227;o de &#8722;35 a 119&#41;&#46; I&#46; Associa&#231;&#227;o do FEF<span class="elsevierStyleInf">75&#37;</span> &#224; variante rs4073&#44; modelo recessivo e grupo <span class="elsevierStyleItalic">RTFC&#8208;A</span> &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;040&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;058&#41;&#46; &#40;AA&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; m&#233;dia de 29&#44;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#44;98&#59; mediana de 30 &#40;varia&#231;&#227;o de &#8722;47 a 142&#41;&#46; &#40;AT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#59; m&#233;dia de 18&#44;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>47&#44;95&#59; mediana de 10 &#40;varia&#231;&#227;o de &#8722;58 a 235&#41;&#46; J&#46; Associa&#231;&#227;o do FEF entre 25 e 75&#37; &#40;FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#41; da CVF &#224; variante rs4073&#44; modelo codominante e grupo <span class="elsevierStyleItalic">RTFC&#8208;B</span> &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;012&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024&#41;&#46; TT &#8800; AA e AT&#46; &#40;AA&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#59; m&#233;dia de 25&#44;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#44;14&#59; mediana de 30 &#40;varia&#231;&#227;o de &#8722;21 a 57&#41;&#46; &#40;AT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#59; m&#233;dia de 18&#44;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29&#44;04&#59; mediana de 14 &#40;varia&#231;&#227;o de &#8722;33 a 117&#41;&#46; &#40;TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; m&#233;dia de 2&#44;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#44;74&#59; mediana de 0 &#40;varia&#231;&#227;o de &#8722;51 a 65&#41;&#46; K&#46; Associa&#231;&#227;o do FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#224; variante rs4073&#44; modelo dominante e grupo <span class="elsevierStyleItalic">RTFC&#8208;B</span> &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;007&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;024&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ATT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#59; m&#233;dia de 20&#44;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#44;64&#59; mediana de 18&#44;50 &#40;varia&#231;&#227;o de &#8722;33 a 117&#41;&#46; &#40;TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#59; m&#233;dia de 2&#44;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#44;74&#59; mediana de 0 &#40;varia&#231;&#227;o de &#8722;51 a 65&#41;&#46; L&#46; Associa&#231;&#227;o do FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#224; variante rs4073&#44; modelo dominante e grupo <span class="elsevierStyleItalic">RTFC&#8208;A</span> &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;029&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;100&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>82&#59; m&#233;dia de 15&#44;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#44;20&#59; mediana de 15 &#40;varia&#231;&#227;o de &#8722;40 a 117&#41;&#46; &#40;TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#59; m&#233;dia de 5&#44;94<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#44;33&#59; mediana de 0 &#40;varia&#231;&#227;o de &#8722;51 a 76&#41;&#46; M&#46; Associa&#231;&#227;o do FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#224; variante rs4073&#44; modelo recessivo e grupo <span class="elsevierStyleItalic">RTFC&#8208;B</span> &#40;p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;047&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;063&#41;&#46; &#40;AA&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#59; m&#233;dia de 25&#44;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#44;14&#59; mediana de 30 &#40;varia&#231;&#227;o de &#8722;21 a 57&#41;&#46; &#40;AT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#59; m&#233;dia de 11&#44;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#44;89&#59; mediana de 8 &#40;varia&#231;&#227;o de &#8722;51 a 117&#41;&#46; O ponto corresponde aos valores medianos e a barra corresponde a intervalo de confian&#231;a de 95&#37;&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Larissa Lazzarini Furlan, Jos&#233; Dirceu Ribeiro, Carmen S&#237;lvia Bertuzzo, Jo&#227;o Batista Salom&#227;o Junior, Dorot&#233;ia Rossi Silva Souza, Fernando Augusto Lima Marson"
            "autores" => array:6 [
              0 => array:2 [
                "nombre" => "Larissa Lazzarini"
                "apellidos" => "Furlan"
              ]
              1 => array:2 [
                "nombre" => "Jos&#233; Dirceu"
                "apellidos" => "Ribeiro"
              ]
              2 => array:2 [
                "nombre" => "Carmen S&#237;lvia"
                "apellidos" => "Bertuzzo"
              ]
              3 => array:2 [
                "nombre" => "Jo&#227;o Batista"
                "apellidos" => "Salom&#227;o Junior"
              ]
              4 => array:2 [
                "nombre" => "Dorot&#233;ia Rossi Silva"
                "apellidos" => "Souza"
              ]
              5 => array:2 [
                "nombre" => "Fernando Augusto Lima"
                "apellidos" => "Marson"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "pt"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S0021755717306344"
          "doi" => "10.1016/j.jped.2017.03.005"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => true
            "ES2" => true
            "LATM" => true
          ]
          "gratuito" => true
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755717306344?idApp=UINPBA000049"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255553617300794?idApp=UINPBA000049"
      "url" => "/22555536/0000009300000006/v1_201711030110/S2255553617300794/v1_201711030110/pt/main.assets"
    ]
  ]
  "itemSiguiente" => array:20 [
    "pii" => "S002175571630170X"
    "issn" => "00217557"
    "doi" => "10.1016/j.jped.2017.05.003"
    "estado" => "S300"
    "fechaPublicacion" => "2017-11-01"
    "aid" => "515"
    "copyright" => "Sociedade Brasileira de Pediatria"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "J Pediatr &#40;Rio J&#41;. 2017;93:649-54"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 1150
      "formatos" => array:3 [
        "EPUB" => 76
        "HTML" => 762
        "PDF" => 312
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Neonatal screening&#58; 9&#37; of children with filter paper thyroid-stimulating hormone levels between 5 and 10<span class="elsevierStyleHsp" style=""></span>&#956;IU&#47;mL have congenital hypothyroidism"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "pt"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "649"
          "paginaFinal" => "654"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "pt" => array:1 [
          "titulo" => "Triagem neonatal&#58; 9&#37; das crian&#231;as com TSH em papel filtro entre 5 e 10 &#956;UI&#47;mL t&#234;m hipotireoidismo cong&#234;nito"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1162
              "Ancho" => 1628
              "Tamanyo" => 89204
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Flowchart of the screening for congenital hypothyroidism from April 2003 to September 2009&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Fl&#225;via C&#46; Christensen-Adad, Carolina T&#46; Mendes-dos-Santos, Maura M&#46;F&#46; Goto, Let&#237;cia E&#46; Sewaybricker, L&#237;lia F&#46;R&#46; D&#39;Souza-Li, Gil Guerra-Junior, Andr&#233; M&#46; Morcillo, Sofia Helena V&#46; Lemos-Marini"
          "autores" => array:8 [
            0 => array:2 [
              "nombre" => "Fl&#225;via C&#46;"
              "apellidos" => "Christensen-Adad"
            ]
            1 => array:2 [
              "nombre" => "Carolina T&#46;"
              "apellidos" => "Mendes-dos-Santos"
            ]
            2 => array:2 [
              "nombre" => "Maura M&#46;F&#46;"
              "apellidos" => "Goto"
            ]
            3 => array:2 [
              "nombre" => "Let&#237;cia E&#46;"
              "apellidos" => "Sewaybricker"
            ]
            4 => array:2 [
              "nombre" => "L&#237;lia F&#46;R&#46;"
              "apellidos" => "D&#39;Souza-Li"
            ]
            5 => array:2 [
              "nombre" => "Gil"
              "apellidos" => "Guerra-Junior"
            ]
            6 => array:2 [
              "nombre" => "Andr&#233; M&#46;"
              "apellidos" => "Morcillo"
            ]
            7 => array:2 [
              "nombre" => "Sofia Helena V&#46;"
              "apellidos" => "Lemos-Marini"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "pt" => array:9 [
        "pii" => "S2255553617300824"
        "doi" => "10.1016/j.jpedp.2017.08.001"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "pt"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255553617300824?idApp=UINPBA000049"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S002175571630170X?idApp=UINPBA000049"
    "url" => "/00217557/0000009300000006/v1_201711050042/S002175571630170X/v1_201711050042/en/main.assets"
  ]
  "itemAnterior" => array:20 [
    "pii" => "S0021755717305247"
    "issn" => "00217557"
    "doi" => "10.1016/j.jped.2017.01.006"
    "estado" => "S300"
    "fechaPublicacion" => "2017-11-01"
    "aid" => "509"
    "copyright" => "Sociedade Brasileira de Pediatria"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "J Pediatr &#40;Rio J&#41;. 2017;93:632-8"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 862
      "formatos" => array:3 [
        "EPUB" => 85
        "HTML" => 516
        "PDF" => 261
      ]
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Do infants with cow&#39;s milk protein allergy have inadequate levels of vitamin D&#63;"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "pt"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "632"
          "paginaFinal" => "638"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "pt" => array:1 [
          "titulo" => "Lactentes com alergia &#224; prote&#237;na do leite de vaca apresentam n&#237;veis inadequados de vitamina D&#63;"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "pt" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Figure 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1546
              "Ancho" => 2076
              "Tamanyo" => 80368
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Frequencies of vitamin D sufficiency levels in infants with cow&#39;s milk protein allergy and in the control group&#44; treated at an outpatient clinic in a university hospital&#44; Recife&#44; PE&#44; Brazil &#40;2013&#8211;2015&#41;&#46;</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span> Fisher&#39;s exact test&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Cristiane M&#46; Silva, Silvia A&#46; da Silva, Margarida M&#46; de C&#46; Antunes, Gis&#233;lia Alves Pontes da Silva, Emanuel S&#225;vio Cavalcanti Sarinho, Katia G&#46; Brandt"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Cristiane M&#46;"
              "apellidos" => "Silva"
            ]
            1 => array:2 [
              "nombre" => "Silvia A&#46; da"
              "apellidos" => "Silva"
            ]
            2 => array:2 [
              "nombre" => "Margarida M&#46; de C&#46;"
              "apellidos" => "Antunes"
            ]
            3 => array:2 [
              "nombre" => "Gis&#233;lia Alves Pontes da"
              "apellidos" => "Silva"
            ]
            4 => array:2 [
              "nombre" => "Emanuel S&#225;vio Cavalcanti"
              "apellidos" => "Sarinho"
            ]
            5 => array:2 [
              "nombre" => "Katia G&#46;"
              "apellidos" => "Brandt"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "pt" => array:9 [
        "pii" => "S2255553617300678"
        "doi" => "10.1016/j.jpedp.2017.06.006"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => true
          "ES2" => true
          "LATM" => true
        ]
        "gratuito" => true
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "pt"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2255553617300678?idApp=UINPBA000049"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755717305247?idApp=UINPBA000049"
    "url" => "/00217557/0000009300000006/v1_201711050042/S0021755717305247/v1_201711050042/en/main.assets"
  ]
  "en" => array:21 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "639"
        "paginaFinal" => "648"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Larissa Lazzarini Furlan, Jos&#233; Dirceu Ribeiro, Carmen S&#237;lvia Bertuzzo, Jo&#227;o Batista Salom&#227;o Junior, Dorot&#233;ia Rossi Silva Souza, Fernando Augusto Lima Marson"
        "autores" => array:6 [
          0 => array:3 [
            "nombre" => "Larissa Lazzarini"
            "apellidos" => "Furlan"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Jos&#233; Dirceu"
            "apellidos" => "Ribeiro"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Carmen S&#237;lvia"
            "apellidos" => "Bertuzzo"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Jo&#227;o Batista"
            "apellidos" => "Salom&#227;o Junior"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Dorot&#233;ia Rossi Silva"
            "apellidos" => "Souza"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">f</span>"
                "identificador" => "aff0030"
              ]
            ]
          ]
          5 => array:4 [
            "nombre" => "Fernando Augusto Lima"
            "apellidos" => "Marson"
            "email" => array:1 [
              0 => "fernandolimamarson&#64;hotmail&#46;com"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:6 [
          0 => array:3 [
            "entidad" => "Faculdade de Medicina de S&#227;o Jos&#233; do Rio Preto&#44; S&#227;o Jos&#233; do Rio Preto&#44; SP&#44; Brazil"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Universidade Estadual de Campinas &#40;Unicamp&#41;&#44; Faculdade de Ci&#234;ncias M&#233;dicas&#44; Departamento de Pediatria&#44; Campinas&#44; SP&#44; Brazil"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Universidade Estadual de Campinas &#40;Unicamp&#41;&#44; Faculdade de Ci&#234;ncias M&#233;dicas&#44; Departamento de Gen&#233;tica M&#233;dica&#44; Campinas&#44; SP&#44; Brazil"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Faculdade de Medicina de S&#227;o Jos&#233; do Rio Preto&#44; Hospital Universit&#225;rio&#44; Departamento de Pediatria&#44; S&#227;o Jos&#233; do Rio Preto&#44; SP&#44; Brazil"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Faculdade de Medicina de S&#227;o Jos&#233; do Rio Preto&#44; Hospital Universit&#225;rio&#44; Departamento de Pneumologia Pedi&#225;trica&#44; S&#227;o Jos&#233; do Rio Preto&#44; SP&#44; Brazil"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
          5 => array:3 [
            "entidad" => "Faculdade de Medicina de S&#227;o Jos&#233; do Rio Preto&#44; Centro de Pesquisa de Bioqu&#237;mica e Biologia Molecular&#44; Departamento de Biologia Molecular&#44; S&#227;o Jos&#233; do Rio Preto&#44; SP&#44; Brazil"
            "etiqueta" => "f"
            "identificador" => "aff0030"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "pt" => array:1 [
        "titulo" => "Variantes no gene da interleucina 8 e a resposta a broncodilatadores inalat&#243;rios na fibrose c&#237;stica"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 4239
            "Ancho" => 3284
            "Tamanyo" => 641459
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Association of rs4073 and rs2227306 variants of <span class="elsevierStyleItalic">IL-8</span> &#40;interleukin-8&#41; with the response to inhaled bronchodilators in cystic fibrosis patients&#46; &#40;A&#41; Association between forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s &#40;FEV<span class="elsevierStyleInf">1</span>&#41; of forced vital capacity &#40;FVC&#41; and rs4073&#44; dominant model and two identified mutations in the <span class="elsevierStyleItalic">CFTR</span> gene &#40;cystic fibrosis transmembrane regulator&#41; belonging to classes I&#44; II&#44; and&#47;or III &#40;<span class="elsevierStyleItalic">CFTR-B</span> group&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;028&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;112&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#59; mean of 4&#46;77<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;95&#59; median of 4 &#40;ranging from &#8722;9 to 48&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; mean of &#8722;0&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;42&#59; median of &#8722;1 &#40;ranging from &#8722;6 to 15&#41;&#46; &#40;B&#41; Association of FEV<span class="elsevierStyleInf">1</span>&#47;FVC ratio with rs4073&#44; over-dominant model and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;029&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;116&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#59; mean of 1&#46;17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;36&#59; median of 0 &#40;ranging from &#8722;12 to 23&#41;&#46; &#40;AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#59; mean of 4&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;58&#59; median of 4 &#40;ranging from &#8722;9 to 32&#41;&#46; &#40;C&#41; Association of forced expiratory flow of 50&#37; &#40;FEF<span class="elsevierStyleInf">50&#37;</span>&#41; of FVC with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;046&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;184&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&#59; mean of 17&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;18&#59; median of 16 &#40;ranging from &#8722;20 to 89&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; mean of 4&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;8&#59; median of &#8722;2 &#40;ranging from &#8722;19 to 55&#41;&#46; &#40;D&#41; Association of FEF<span class="elsevierStyleInf">50&#37;</span> with rs2227306&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;083&#41;&#46; &#40;CC&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#59; mean of 1&#46;47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;22&#59; median of 0 &#40;ranging from &#8722;20 to 29&#41;&#46; &#40;CT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#59; mean of 15&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;04&#59; median of 10&#46;5 &#40;ranging from &#8722;28 to 89&#41;&#46; &#40;E&#41; Association of FEF<span class="elsevierStyleInf">50&#37;</span> with rs2227306&#44; over-dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;033&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;083&#41;&#46; &#40;CC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#59; mean of 6&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;27&#59; median of 4 &#40;ranging from &#8722;20 to 55&#41;&#46; &#40;CT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#59; mean of 19&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#46;43&#59; median of 19 &#40;ranging from &#8722;28 to 89&#41;&#46; &#40;F&#41; Association of forced expiratory flow of 75&#37; &#40;FEF<span class="elsevierStyleInf">75&#37;</span>&#41; of FVC with rs4073&#44; co-dominant model regardless of identified mutations in the <span class="elsevierStyleItalic">CFTR</span> gene &#40;<span class="elsevierStyleItalic">CFTR-A</span> group&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;044&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41;&#46; 1<span class="elsevierStyleHsp" style=""></span>&#8800;<span class="elsevierStyleHsp" style=""></span>3&#46; &#40;AA&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; mean of 29&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#46;98&#59; median of 30 &#40;ranging from &#8722;47 to 142&#41;&#46; &#40;AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#59; mean of 24&#46;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>53&#46;57&#59; median of 14 &#40;ranging from &#8722;58 to 235&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; mean of 9&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;95&#59; median of 2&#46;5 &#40;ranging from &#8722;35 to 119&#41;&#46; &#40;G&#41; Association of FEF<span class="elsevierStyleInf">75&#37;</span> with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;096&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#59; mean of 33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>55&#46;23&#59; median of 16 &#40;ranging from &#8722;27 to 235&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; mean of 5&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#46;93&#59; median of 2 &#40;ranging from &#8722;35 to 119&#41;&#46; &#40;H&#41; Association of FEF<span class="elsevierStyleInf">75&#37;</span> with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-A</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#59; mean of 26&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>48&#46;34&#59; median of 18 &#40;ranging from &#8722;58 to 235&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; mean of 9&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;95&#59; median of 2&#46;5 &#40;ranging from &#8722;35 to 119&#41;&#46; &#40;I&#41; Association of FEF<span class="elsevierStyleInf">75&#37;</span> with rs4073&#44; recessive model&#44; and <span class="elsevierStyleItalic">CFTR-A</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41;&#46; &#40;AA&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; mean of 29&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#46;98&#59; median of 30 &#40;ranging from &#8722;47 to 142&#41;&#46; &#40;AT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#59; mean of 18&#46;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>47&#46;95&#59; median of 10 &#40;ranging from &#8722;58 to 235&#41;&#46; &#40;J&#41; Association of FEF between 25&#37; and 75&#37; &#40;FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&#41; of FVC with rs4073&#44; co-dominant model and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41;&#46; TT<span class="elsevierStyleHsp" style=""></span>&#8800;<span class="elsevierStyleHsp" style=""></span>AA and AT&#46; &#40;AA&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#59; mean of 25&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;14&#59; median of 30 &#40;ranging from &#8722;21 to 57&#41;&#46; &#40;AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#59; mean of 18&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29&#46;04&#59; median of 14 &#40;ranging from &#8722;33 to 117&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; mean of 2&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;74&#59; median of 0 &#40;ranging from &#8722;51 to 65&#41;&#46; &#40;K&#41; Association of FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ATT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#59; mean of 20&#46;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;64&#59; median of 18&#46;5 &#40;ranging from &#8722;33 to 117&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#59; mean of 2&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;74&#59; median of 0 &#40;ranging from &#8722;51 to 65&#41;&#46; &#40;L&#41; Association of FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-A</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;029&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>82&#59; mean of 15&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;2&#59; median of 15 &#40;ranging from &#8722;40 to 117&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#59; mean of 5&#46;94<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;33&#59; median of 0 &#40;ranging from &#8722;51 to 76&#41;&#46; &#40;M&#41; Association of FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> with rs4073&#44; recessive model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;047&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;063&#41;&#46; &#40;AA&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#59; mean of 25&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;14&#59; median of 30 &#40;ranging from &#8722;21 to 57&#41;&#46; &#40;AT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#59; mean of 11&#46;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;89&#59; median of 8 &#40;ranging from &#8722;51 to 117&#41;&#46; The dot corresponds to median values and the bar corresponds to the 95&#37; confidence interval&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The response to inhaled bronchodilators &#40;BD&#41; in cystic fibrosis &#40;CF&#41; &#40;OMIM&#58; n&#46; 219700&#41; is quite variable and depends on the cystic fibrosis transmembrane regulator &#40;<span class="elsevierStyleItalic">CFTR</span>&#41; genotype&#44; pulmonary symptoms&#44; and mainly&#44; on variants in the modifier genes&#44; such as the beta-2-adrenergic receptor &#40;<span class="elsevierStyleItalic">ADRB2</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> So far&#44; only a few studies have investigated such response&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Mutations in the <span class="elsevierStyleItalic">CFTR</span> gene cause CF&#44; due to deficiency&#44; dysfunction&#44; or absence of the CFTR protein&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> CF is characterized by a continuous cycle of chronic airway inflammation&#44; which can be exacerbated by interleukin-8 &#40;IL-8&#41;&#44; a key pro-inflammatory mediator&#46; IL-8 is responsible for initiating and increasing the inflammatory response in the presence of specific pathogens&#44; causing activation and migration of neutrophils from peripheral blood to tissues&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Chronic airway inflammation is the final common pathway of lung injury&#46; It is responsible for increased vascular permeability&#44; contributing to interstitial&#44; alveolar&#44; and airway edema&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">The treatment of CF lung disease includes anti-inflammatory drugs&#44; inhaled corticosteroids&#44; antibiotics&#44; mucolytic&#44; hypertonic saline&#44; and physiotherapy&#46; Among the possible therapies&#44; there is little evidence supporting the role of BD in CF&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;5</span></a> However&#44; BD is often prescribed for a longer period due to wheezing and dyspnea episodes in CF&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> BD reduces the liberation of mediators&#44; which are responsible for recruiting and activating inflammatory cells&#44; activating cholinergic neurotransmission and improving vascular permeability&#46; It also increases mucociliary clearance&#44; leading to reduced lung inflammation&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> The response to BD depends&#44; in part&#44; on the CFTR protein&#44; which interacts with the ADRB2 protein to promote broncodilatation&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> Spirometry is the primary method to assess lung function&#44; severity and progression of the disease&#44; as well as response to BD&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Intense neutrophil inflammation and low bronchial hyperresponsiveness are commonly observed characteristics in CF&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> Moreover&#44; the response of genetic variants to BD is little known&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> The role of IL-8 in the neutrophilic component of CF lung disease can be pointed out&#46; Genes that might be associated with the severity of CF and possibly with the response to BD have been reported in the present study and in the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;10&#8211;12</span></a> The <span class="elsevierStyleItalic">IL-8</span> gene should be highlighted&#44; as it has a direct influence on lung inflammation and can be effective in the response to BD&#46; Therefore&#44; this study compared the rs4073&#44; rs2227306&#44; and rs2227307 <span class="elsevierStyleItalic">IL-8</span> gene variants with the response to BD in CF patients&#44; using spirometry&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0025" class="elsevierStylePara elsevierViewall">A cross-sectional study was conducted in 186 CF patients&#44; selected in two university referral centers &#40;Medical School of S&#227;o Jos&#233; do Rio Preto and Universidade Estadual de Campinas&#41; for CF treatment&#44; from 2013 to 2015&#46; The study was approved by the Research Ethics Committee of the Universidade Estadual de Campinas&#44; Brazil &#40;under No&#46; 528&#47;2008&#41;&#46; All participants were informed of the study and signed an informed consent form&#46; For patients under the age of 18&#44; the informed consent form was signed by the parents or guardians&#46; The study followed the recommendations of the Declaration of Helsinki&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">The diagnosis of CF was confirmed by the presence of two altered concentrations of sodium and chloride in sweat &#40;chloride level higher than 60<span class="elsevierStyleHsp" style=""></span>mEq&#47;L&#41;&#46; Furthermore&#44; no patient underwent initial immunoreactive trypsinogen &#40;IRT&#41; measurement&#46; In a group of 91 patients&#44; there were two mutations in the <span class="elsevierStyleItalic">CFTR</span> gene belonging to classes I&#44; II&#44; and&#47;or III &#40;associated with greater disease severity&#44; due to the absence or non-functionality of the CFTR protein&#41;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a>&#59; 60 patients did not present an identified mutation of the <span class="elsevierStyleItalic">CFTR</span> gene&#44; or had two mutations belonging to classes IV&#44; V&#44; or VI&#59; and 35 patients had a mutation in the <span class="elsevierStyleItalic">CFTR</span> gene belonging to classes I&#44; II&#44; or III&#44; and a non-identified mutation&#44; or belonging to classes IV&#44; V&#44; or VI &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinical variables</span><p id="par0035" class="elsevierStylePara elsevierViewall">The following variables were analyzed&#58; clinical scores &#40;Shwachman-Kulczycki&#44; Kanga&#44; and Bhalla&#41;&#59; body mass index &#40;BMI&#41; for patients older than 18 years&#44; using the formula BMI<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>weight&#47;&#40;height&#41;<span class="elsevierStyleSup">2</span>&#44; the Anthro program version 3&#46;0&#46;1 &#40;World Health Organization &#91;WHO&#93;&#44; 2006&#41; was used for children under five years of age and the Anthro Plus version 1&#46;0&#46;2 &#40;World Health Organization &#91;WHO&#93;&#44; 2007&#41; was used for patients aged between five and 18 years&#59; patient&#39;s age and age at diagnosis&#59; first clinical symptom &#40;one general symptom&#44; pulmonary and digestive symptoms&#41;&#59; period until the first colonization with <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span>&#59; microorganisms identified in the routine sputum culture &#40;mucoid and non-mucoid <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; <span class="elsevierStyleItalic">Achromobacter xylosoxidans</span>&#44; <span class="elsevierStyleItalic">Burkolderia cepacia</span>&#44; and <span class="elsevierStyleItalic">Staphylococcus aureus</span>&#41;&#59; transcutaneous arterial hemoglobin oxygen-saturation &#40;SaO<span class="elsevierStyleInf">2</span>&#41;&#59; spirometry&#59; and comorbidities &#40;nasal polyps&#44; osteoporosis&#44; meconium ileus&#44; diabetes mellitus&#44; and pancreatic insufficiency&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Spirometry was performed in patients over seven years of age&#44; using the CPFS&#47;D spirometer &#40;MedGraphics &#8211; Saint Paul&#44; Minnesota&#44; USA&#41;&#46; Data were recorded in the PF BREEZE software version 3&#46;8B for Windows 95&#47;98&#47;NT &#40;American Thoracic Society&#41;&#44; and assessed in percentage predicted values for&#58; forced vital capacity &#40;FVC&#41;&#44; forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s &#40;FEV<span class="elsevierStyleInf">1</span>&#41;&#44; FEV<span class="elsevierStyleInf">1</span>&#47;FVC ratio&#44; forced expiratory flow at 25&#37; of FVC &#40;FEF<span class="elsevierStyleInf">25&#37;</span>&#41;&#44; forced expiratory flow at 50&#37; of FVC &#40;FEF<span class="elsevierStyleInf">50&#37;</span>&#41;&#44; forced expiratory flow at 75&#37; of FVC &#40;FEF<span class="elsevierStyleInf">75&#37;</span>&#41;&#44; forced expiratory flow between 25&#37; and 75&#37; of FVC &#40;FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&#41;&#44; maximum forced expiratory flow &#40;FEF<span class="elsevierStyleInf">max</span>&#41;&#44; and expiratory reserve volume &#40;ERV&#41;&#46; Spirometry data were shown in percentage of the predicted value according to the Polgar and Promadhat &#40;1971&#41;&#44; Pereira et al&#46; &#40;2007&#41;&#44; and Duarte et al&#46; &#40;2007&#41; equations&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#8211;16</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">In all patients undergoing spirometry&#44; the test was performed before and 15<span class="elsevierStyleHsp" style=""></span>min after administration of BD &#40;albuterol &#8211; C<span class="elsevierStyleInf">13</span>H<span class="elsevierStyleInf">21</span>NO<span class="elsevierStyleInf">3</span> &#91;400<span class="elsevierStyleHsp" style=""></span>mg&#93;&#41;&#46; Patients under BD therapy were instructed to interrupt the medication eight hours prior to spirometry&#44; if they were under short-acting BD treatment&#59; and 48<span class="elsevierStyleHsp" style=""></span>hours&#44; if they were under long-acting BD treatment&#46; The post-BD percentage change was used for the statistical analysis&#46; The BD response criteria&#44; defined as an increase of &#62;12&#37; and 200<span class="elsevierStyleHsp" style=""></span>mL of initial FEV<span class="elsevierStyleInf">1</span>&#44; was used as a second model to evaluate the association between the <span class="elsevierStyleItalic">IL-8</span> gene variants and BD response&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">DNA extraction and genotyping</span><p id="par0050" class="elsevierStylePara elsevierViewall">Genomic DNA was extracted from peripheral blood samples using standard phenol-chloroform method and quantified by GE NanoVue&#8482; spectrophotometer &#40;GE Healthcare Biosciences &#8211; Pittsburgh&#44; USA&#41;&#46; In this study&#44; the final sample concentration was set at 50<span class="elsevierStyleHsp" style=""></span>ng&#47;&#956;L&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Mutations of the <span class="elsevierStyleItalic">CFTR</span> gene were analyzed by polymerase chain reaction &#40;PCR&#59; F508del&#41; followed by enzymatic digestion &#40;G542X&#44; R1162X&#44; R553X&#44; G551D&#44; and N1303K&#41;&#46; Other mutations in the <span class="elsevierStyleItalic">CFTR</span> gene were identified by sequencing or with the use of the SALSA Multiplex Ligation-dependent Probe Amplification &#40;MPLA method&#41; Kit P091-C1 CFTR-MRC-Holland S4X&#44; 2183A&#62;G&#44; 1717-G&#62;A&#44; I618T with MegaBace1000<span class="elsevierStyleSup">&#174;</span> &#40;GE Healthcare Biosciences &#8211; Pittsburgh&#44; USA&#41;&#44; and ABI3500 &#40;Applied Biosystems &#8211; Thermo Fisher Scientific &#8211; S&#227;o Paulo&#44; Brazil&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">IL-8</span> gene variants were analyzed by PCR followed by restriction enzyme digestion&#46; For the rs4073 variant&#44; the primers 5&#8242;-CCA TCA TGA TAG CAT CTG TA-3&#8242; and 5&#8242;-CCA CAA TTT GGT GAA TTA TTA A-3&#8242;&#44; and the <span class="elsevierStyleItalic">Ase</span>I restriction enzyme were used&#59; for the rs2227306 variant&#44; primers 5&#8242;-CTC TAA CTC TTT ATA TAG GAA TT-3&#8242; and 5&#8242;-GAT TGA TTT TAT CAA CAG GCA-3&#8242;&#44; as well as the <span class="elsevierStyleItalic">Eco</span>RI restriction enzyme&#59; and for the rs2227307 variant&#44; primers 5&#8242;-TAA AGG TTT GAT CAA TAT AGA-3&#8242; and 5&#8242;-CTT CCT TCT AAT TCCA ATA TG-3&#8242;&#44; as well as the <span class="elsevierStyleItalic">Scr</span>FI restriction enzyme&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#44;19</span></a> The products of the enzymatic restriction were submitted to electrophoresis on a 12&#37; polyacrylamide gel&#44; or 4&#37; agarose gel&#44;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#44;19</span></a> and stained with Red<span class="elsevierStyleSup">&#174;</span> gel&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical analysis</span><p id="par0065" class="elsevierStylePara elsevierViewall">Statistical analyses were performed using Statistical Package for the Social Sciences version 22&#46;0 &#40;SPSS Inc&#46; &#8211; Chicago&#44; USA&#41;&#46; The GPower software version 3&#46;1&#46;9&#46;2<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> was used to calculate the sample power&#44; considering the genotype of the analyzed variants and adopting power for value above 80&#37;&#46; The following conditions were applied to calculate the sample power&#58; analysis of variance test&#44; in place of Kruskal&#8211;Wallis test considering that analysis of variance is a stronger test &#40;effect size<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;25&#44; <span class="elsevierStyleItalic">&#945;</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#44; power<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;80&#44; numerator degree of freedom<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; number of groups<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; ideal <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>158&#41;&#59; two-tailed Mann&#8211;Whitney test &#40;effect size<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;5&#44; <span class="elsevierStyleItalic">&#945;</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#44; power<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;80&#44; allocation ratio N2&#47;N1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; ideal <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>134&#41;&#59; chi-squared test &#40;effect size<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;3&#44; <span class="elsevierStyleItalic">&#945;</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#44; power<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;80&#44; degree of freedom<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; ideal <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>108&#41;&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The Mann&#8211;Whitney and Kruskal&#8211;Wallis tests were used for the comparison between different genotypes and groups of <span class="elsevierStyleItalic">IL-8</span> gene variants and the response to BD&#46; In case of significant differences between the groups for the Kruskal&#8211;Wallis test&#44; further identification and evaluation of the differences between genotypes were performed with MedCalc<span class="elsevierStyleSup">&#174;</span> software for Windows&#44; version 16&#46;1 &#40;MedCalc<span class="elsevierStyleSup">&#174;</span> Software &#8211; Ostend&#44; Belgium&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The chi-squared test and Fisher&#39;s exact test were used for the comparison between different genotypes and groups of <span class="elsevierStyleItalic">IL-8</span> gene variants&#44; as well as the response to BD&#44; defined as an increase of &#62;12&#37; and 200<span class="elsevierStyleHsp" style=""></span>mL of initial FEV<span class="elsevierStyleInf">1</span>&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">For the identification of mutations in the <span class="elsevierStyleItalic">CFTR</span> gene&#44; patients were analyzed based on two contexts&#58; <span class="elsevierStyleItalic">CFTR</span>-A&#44; all CF patients&#44; regardless of gene mutations &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>186 patients&#41;&#59; and <span class="elsevierStyleItalic">CFTR</span>-B&#44; patients with two mutations belonging to classes I&#44; II&#44; and&#47;or III &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>91 patients&#41;&#46; As for the variants&#44; four analysis models were adopted&#58; &#40;i&#41; co-dominant &#40;Kruskal&#8211;Wallis test&#41;&#59; &#40;ii&#41; recessive &#40;Mann&#8211;Whitney test&#41;&#59; &#40;iii&#41; dominant &#40;Mann&#8211;Whitney test&#41;&#59; &#40;iv&#41; over-dominant &#40;Mann&#8211;Whitney test&#41;&#44; applied in association with clinical variables&#46; For all analyses&#44; the alpha value was set at 0&#46;05&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">For analysis of the Hardy&#8211;Weinberg equilibrium &#40;HWE&#41;&#44; the Online Encyclopedia software for Genetic Epidemiology Studies &#40;OEGE&#41; was used&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The false discovery rate &#40;FDR&#41; test was applied to correct the multiple test comparison&#46; FDR is an approach to the multiple comparisons problem&#46; Instead of controlling the chance of any false&#44; FDR controls the expected proportion of false positives among supra threshold voxels&#46; A FDR threshold is determined from the observed <span class="elsevierStyleItalic">p</span>-value distribution&#44; and hence is adaptive to the amount of signal in the data&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> The <span class="elsevierStyleItalic">p</span>-value and corrected <span class="elsevierStyleItalic">p</span>-value &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span>&#41; were shown in the manuscript&#46; The linkage disequilibrium analysis was performed in Haploview software version 4&#46;2&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0095" class="elsevierStylePara elsevierViewall">Clinical and laboratory data of CF patients are described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> describes the genotype and allele frequency of <span class="elsevierStyleItalic">IL-8</span> gene variants&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the data with <span class="elsevierStyleItalic">p</span>-values and corrected <span class="elsevierStyleItalic">p</span>-values for association of the three <span class="elsevierStyleItalic">IL-8</span> gene variants&#44; considering the four models of analysis proposed and the genotype of the <span class="elsevierStyleItalic">CFTR</span> gene&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">The rs2227307 variant was not associated with response to BD in any of the studied models&#59; in turn&#44; rs2227306 was associated with FEF<span class="elsevierStyleInf">50&#37;</span> for patients with CC genotype &#40;dominant model&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;083&#41; and CT genotype &#40;over-dominant model&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;033&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;083&#41; in the <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>D and E&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Special emphasis should be given to the rs4073 variant&#44; which was associated with the following spirometry variables&#58; FEV<span class="elsevierStyleInf">1</span>&#44; FEV<span class="elsevierStyleInf">1</span>&#47;FVC ratio&#44; FEF<span class="elsevierStyleInf">50&#37;</span> FEF<span class="elsevierStyleInf">75&#37;</span>&#44; and FEF<span class="elsevierStyleInf">25&#8211;75&#37;&#46;</span> The lowest response to BD was observed for the TT genotype &#40;dominant model&#41; and patients of the <span class="elsevierStyleItalic">CFTR</span>-B group to FEV<span class="elsevierStyleInf">1</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>A&#41;&#44; FEF<span class="elsevierStyleInf">50&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>C&#41;&#44; FEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>G&#41;&#44; and FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>K&#41;&#46; The same was observed for the <span class="elsevierStyleItalic">CFTR-A</span> group for FEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>H&#41; and FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>L&#41;&#46; In the co-dominant analysis&#44; the TT genotype presented a lower response to BD for FEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>F&#41; and FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>J&#41;&#44; respectively&#44; in the <span class="elsevierStyleItalic">CFTR-A</span> and <span class="elsevierStyleItalic">CFTR-B</span> groups&#46; For the marker FEV<span class="elsevierStyleInf">1</span>&#47;FVC&#44; the AT genotype in patients from the <span class="elsevierStyleItalic">CFTR</span>-B group showed lower response to BD &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>B&#41;&#46; Finally&#44; in patients from the <span class="elsevierStyleItalic">CFTR-A</span> and <span class="elsevierStyleItalic">CFTR-B</span> groups the AA genotype &#40;recessive model&#41; for rs4073 showed higher response to BD for FEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>I&#41; and FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&#44; respectively &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>M&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The haplotype distribution for the <span class="elsevierStyleItalic">IL-8</span> gene variants is presented in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">For the comparison between <span class="elsevierStyleItalic">IL-8</span> gene variants and the response to BD&#44; defined as an increase of &#62;12&#37; and 200<span class="elsevierStyleHsp" style=""></span>mL of initial FEV<span class="elsevierStyleInf">1</span>&#44; no positive association was found &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">The influence of different <span class="elsevierStyleItalic">IL-8</span> gene variants in the clinical severity of CF has been previously demonstrated&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> This study showed the association of different <span class="elsevierStyleItalic">IL-8</span> gene variants and their modulation to BD response&#44; assessing the impact of the drug on pulmonary function&#46; The variability of responses to BD is determined by multiple factors&#44; such as inflammation and pulmonary obstruction&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> bacteria&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> and lung symptoms&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> as well as modifier genes&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> However&#44; no studies so far have investigated the role of IL-8 as a pro-inflammatory mediator of CF and its relationship to BD&#44; and whether the <span class="elsevierStyleItalic">IL-8</span> gene variants may explain the individual response to BD in CF&#46; It is believed that the short-acting and long-acting beta-2-agonists may be beneficial for CF patients with positive bronchial hyperresponsiveness&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In progressive lung diseases&#44; different markers have been assessed&#59; the use of BD appears to provide better response to FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&#44; when compared with other markers&#44; which indicates involvement of smaller caliber airways in CF&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> In the present study&#44; in agreement with the reference literature&#44; an association was observed between the rs4073 variant and the FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> marker in the dominant &#40;for both <span class="elsevierStyleItalic">CFTR</span>-A and <span class="elsevierStyleItalic">CFTR</span>-B groups&#41;&#44; co-dominant &#40;<span class="elsevierStyleItalic">CFTR</span>-B group&#41;&#44; and recessive models &#40;<span class="elsevierStyleItalic">CFTR</span>-B group&#41;&#46; There was improvement in several other markers of spirometry for rs4073&#44; such as FEV<span class="elsevierStyleInf">1</span>&#44; FEV<span class="elsevierStyleInf">1</span>&#47;FVC&#44; FEF<span class="elsevierStyleInf">50&#37;</span>&#44; and FEF<span class="elsevierStyleInf">75&#37;</span>&#44; which shows impact on breathing patterns of patients&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The study by Hillian et al&#46; &#40;2008&#41; found an association of rs2227307 and rs4073 <span class="elsevierStyleItalic">IL-8</span> gene variants and severity of pulmonary disease&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> In that study&#44; patients were divided into two cohorts&#58; &#40;1&#41; homozygous F508del patients&#59; &#40;2&#41; patients with other genotypes of the <span class="elsevierStyleItalic">CFTR</span> gene&#46; In cohort 1&#44; the rs4073&#44; rs2227306&#44; and rs2227543 variants were not associated with lung disease&#44; and an association was observed for rs22227307&#44; regardless of gender&#46; In cohort 2&#44; the rs4073 and rs2227306 variants were associated with lung disease severity in males&#46; Thus&#44; the gender of the patient&#44; genotype of the <span class="elsevierStyleItalic">CFTR</span> gene&#44; and modifier genes may modulate the severity of the lung disease&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> In this study&#44; the rs2227307 genotype did not have an impact on the variability of the response to BD&#46; This suggests that although this genotype is associated with lung disease in homozygous F508del patients&#44; its response to BD is not relevant&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The target of BD is the ADRB2 protein&#44; which is expressed in the airway smooth muscle&#46; Variants of <span class="elsevierStyleItalic">ADRB2</span> are associated with response to the medication&#46; Although this protein has been widely studied in asthma&#44; it was very seldom studied in CF&#46; The effectiveness of the response to BD and inhaled corticosteroids to manage airway inflammation in asthma has been confirmed&#44; and depends on the Arg16Gly &#40;rs1042713&#59; c&#46;46A&#62;G&#41; and Glu27Gln &#40;rs1042714&#59; c&#46;79C&#62;G&#41; <span class="elsevierStyleItalic">ADRB2</span> gene variants&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> The Gln27Glu variant confers resistance to the ADRB2 protein in BD response&#46; The 46&#42;G and 79&#42;G alleles are protective against asthma&#44; reducing the risk by 27&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> Both variants of the G allele induce changes in the regulation of the receptor due to increased susceptibility to protein degradation&#46; This study found that the Arg16Gly and Gln27Glu <span class="elsevierStyleItalic">ADRB2</span> gene variants influence the response to BD in CF&#46; In spirometry and in other markers of severity&#44; the Arg16Gly variant showed a positive association&#44; unlike Gln27Glu&#46; The Arg&#47;Arg genotype for the Arg16Gly variant was associated with better values of FEV<span class="elsevierStyleInf">1</span> and FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&#46; The response to BD in the analyses of haplotype was positive in the absence of Gly16Gly and Glu27Glu genotypes for FEV<span class="elsevierStyleInf">1</span>&#47;FVC ratio&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Variants of <span class="elsevierStyleItalic">ADRB2</span>&#44; diffusing capacity of the lungs for carbon monoxide&#44; alveolar capillary membrane conductance&#44; volume of blood in the alveolar capillary&#44; and SaO<span class="elsevierStyleInf">2</span> were evaluated in the response to BD in 18 patients and 20 healthy controls&#44; before and after the administration of salbutamol &#40;30&#44; 60&#44; and 90<span class="elsevierStyleHsp" style=""></span>min&#41;&#46; Healthy subjects showed no changes in markers assessed for the Glu27Glu variant&#46; However&#44; in CF&#44; this variant influenced the response to BD&#58; the best response was found in the presence of at least one allele 27Glu&#46; There was a difference in pulmonary diffusion and peripheral SaO<span class="elsevierStyleInf">2</span> according to the variation of the <span class="elsevierStyleItalic">ADRB2</span> gene at position 27&#44; and the dosage of the drug should be prescribed according to this variation&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Most studies focus on the <span class="elsevierStyleItalic">ADRB2</span> gene variants in the response to BD&#46; However&#44; this study demonstrated that&#44; even indirectly&#44; the <span class="elsevierStyleItalic">IL-8</span> gene variants &#40;and possibly in other genes&#44; which modulate the inflammatory lung response&#41; may potentiate or minimize the effect of BD and also influence the response to the medication&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Regarding the HWE&#44; as previously discussed by this group&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> two variants &#40;rs4073 and rs2227306&#41; were not in balance&#46; It is important to remember that the HWE assumes an ideal population&#44; without the interference of evolutionary factors&#46; However&#44; in genes as those involved in immunity&#44; inflammation&#44; and infection control&#44; the HWE imbalance may appear secondarily associated with the selection mechanisms that favored a particular allele that can bring a more effective response&#46; The disequilibrium does not invalidate the association study since the groups are part of the same population&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The limitations of the present study include &#40;i&#41; cross-sectional dataset &#40;BD response was evaluated at a single time&#41;&#59; &#40;ii&#41; numerous missing data considering the problems to achieve information in the records&#59; &#40;iii&#41; whether BD response differs based on baseline FEV<span class="elsevierStyleInf">1</span>&#44; mainly in health subjects&#59; &#40;iv&#41; potential confounders to the results&#44; such as disease severity&#44; current therapies&#44; medication adherence&#44; and adequate pulmonary function test effort&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">In conclusion&#44; <span class="elsevierStyleItalic">IL-8</span> gene variants &#40;rs2227306 and specially rs4073&#41; can be associated with the response to BD during spirometry&#46; This drug may be an alternative for the treatment of the disease&#44; mostly among patients with airways of smaller caliber&#46; Studies involving dosage and combinations of drugs should be further conducted&#44; in order determine the best treatment according to CF patient genotype&#44; the <span class="elsevierStyleItalic">CFTR</span> gene&#44; as well as modifier genes&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0165" class="elsevierStylePara elsevierViewall">FALM&#58; Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo &#40;<span class="elsevierStyleGrantSponsor" id="gs1">FAPESP</span>&#41; for supporting the researches <span class="elsevierStyleGrantNumber" refid="gs1">&#35;2011&#47;12939-4</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs1">&#35;2011&#47;18845-1</span>&#44; <span class="elsevierStyleGrantNumber" refid="gs1">&#35;2015&#47;12183-8</span>&#44; and <span class="elsevierStyleGrantNumber" refid="gs1">&#35;2015&#47;12858-5</span>&#59; <span class="elsevierStyleGrantSponsor" id="gs2">Fundo de Apoio &#224; Pesquisa&#44; ao Ensino e &#224; Extens&#227;o da Universidade Estadual de Campinas</span> for supporting the research <span class="elsevierStyleGrantNumber" refid="gs2">&#35;0648&#47;2015</span>&#59; JDR&#58; FAPESP for supporting the research <span class="elsevierStyleGrantNumber" refid="gs1">&#35;2011&#47;18845-1</span> and <span class="elsevierStyleGrantNumber" refid="gs1">&#35;2015&#47;12183-8</span>&#46; LLF&#58; FAPESP for supporting the research <span class="elsevierStyleGrantNumber" refid="gs1">&#35;2013&#47;19052-0</span>&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:12 [
        0 => array:3 [
          "identificador" => "xres935732"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Objective"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusions"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec909678"
          "titulo" => "Keywords"
        ]
        2 => array:3 [
          "identificador" => "xres935733"
          "titulo" => "Resumo"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0025"
              "titulo" => "Objetivo"
            ]
            1 => array:2 [
              "identificador" => "abst0030"
              "titulo" => "M&#233;todos"
            ]
            2 => array:2 [
              "identificador" => "abst0035"
              "titulo" => "Resultados"
            ]
            3 => array:2 [
              "identificador" => "abst0040"
              "titulo" => "Conclus&#245;es"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "xpalclavsec909677"
          "titulo" => "Palavras-chave"
        ]
        4 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        5 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Methods"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Patients"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Clinical variables"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "DNA extraction and genotyping"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Results"
        ]
        7 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Discussion"
        ]
        8 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Funding"
        ]
        9 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Conflicts of interest"
        ]
        10 => array:2 [
          "identificador" => "xack315964"
          "titulo" => "Acknowledgements"
        ]
        11 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2016-08-02"
    "fechaAceptado" => "2017-01-09"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec909678"
          "palabras" => array:4 [
            0 => "<span class="elsevierStyleItalic">CFTR</span>"
            1 => "Disease severity"
            2 => "Interleukin 8"
            3 => "Lung function"
          ]
        ]
      ]
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec909677"
          "palabras" => array:4 [
            0 => "<span class="elsevierStyleItalic">CFTR</span>"
            1 => "Gravidade da doen&#231;a"
            2 => "Interleucina 8"
            3 => "Fun&#231;&#227;o pulmonar"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Interleukin 8 protein promotes inflammatory responses&#44; even in airways&#46; The presence of interleukin 8 gene variants causes altered inflammatory responses and possibly varied responses to inhaled bronchodilators&#46; Thus&#44; this study analyzed the interleukin 8 variants &#40;rs4073&#44; rs2227306&#44; and rs2227307&#41; and their association with the response to inhaled bronchodilators in cystic fibrosis patients&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Analysis of interleukin 8 gene variants was performed by restriction fragment length polymorphism of polymerase chain reaction&#46; The association between spirometry markers and the response to inhaled bronchodilators was evaluated by Mann&#8211;Whitney and Kruskal&#8211;Wallis tests&#46; The analysis included all cystic fibrosis patients&#44; and subsequently patients with two mutations in the cystic fibrosis transmembrane conductance regulator gene belonging to classes I to III&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This study included 186 cystic fibrosis patients&#46; There was no association of the rs2227307 variant with the response to inhaled bronchodilators&#46; The rs2227306 variant was associated with FEF<span class="elsevierStyleInf">50&#37;</span> in the dominant group and in the group with two identified mutations in the cystic fibrosis transmembrane conductance regulator gene&#46; The rs4073 variant was associated with spirometry markers in four genetic models&#58; co-dominant &#40;FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> and FEF<span class="elsevierStyleInf">75&#37;</span>&#41;&#44; dominant &#40;FEV<span class="elsevierStyleInf">1</span>&#44; FEF<span class="elsevierStyleInf">50&#37;</span>&#44; FEF<span class="elsevierStyleInf">75&#37;</span>&#44; and FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&#41;&#44; recessive &#40;FEF<span class="elsevierStyleInf">75&#37;</span> and FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&#41;&#44; and over-dominant &#40;FEV<span class="elsevierStyleInf">1</span>&#47;FVC&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This study highlighted the importance of the rs4073 variant of the interleukin 8 gene&#44; regarding response to inhaled bronchodilators&#44; and of the assessment of mutations in the cystic fibrosis transmembrane conductance regulator gene&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "pt" => array:3 [
        "titulo" => "Resumo"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">A prote&#237;na interleucina 8 promove respostas inflamat&#243;rias&#44; o que inclui sua atua&#231;&#227;o nas vias a&#233;reas&#46; A presen&#231;a de variantes no gene da interleucina 8 causa respostas inflamat&#243;rias alteradas e possivelmente respostas variadas ao uso de broncodilatadores inalat&#243;rios&#46; Assim&#44; este estudo analisou as variantes da interleucina 8 &#40;rs4073&#44; rs2227306&#44; rs2227307&#41; e sua associa&#231;&#227;o &#224; resposta a broncodilatadores inalat&#243;rios em pacientes com fibrose c&#237;stica&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Foi feita an&#225;lise das variantes gen&#233;ticas da interleucina 8 por <span class="elsevierStyleItalic">restriction fragment length polymorphism</span> da rea&#231;&#227;o em cadeia da polimerase&#46; A associa&#231;&#227;o entre os marcadores da espirometria e a resposta a broncodilatadores inalat&#243;rios foi feita pelos testes de Mann-Whitney e Kruskal-Wallis&#46; A an&#225;lise incluiu todos os pacientes com fibrose c&#237;stica e posteriormente pacientes com duas muta&#231;&#245;es no gene <span class="elsevierStyleItalic">cystic fibrosis transmembrane conductance regulator</span> pertencentes &#224;s Classes I a II&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Este estudo incluiu 186 pacientes com fibrose c&#237;stica&#46; N&#227;o houve associa&#231;&#227;o da variante rs2227307 &#224; resposta a broncodilatadores inalat&#243;rios&#46; A variante rs2227306 foi associada a FEF<span class="elsevierStyleInf">50&#37;</span> no grupo dominante e no grupo com duas muta&#231;&#245;es identificadas no gene <span class="elsevierStyleItalic">cystic fibrosis transmembrane conductance regulator</span>&#46; A variante rs4073 foi associada a marcadores da espirometria em quatro modelos gen&#233;ticos&#58; codominante &#40;FEF<span class="elsevierStyleInf">25-75&#37;</span> e FEF<span class="elsevierStyleInf">75&#37;</span>&#41;&#44; dominante &#40;VEF<span class="elsevierStyleInf">1</span>&#44; FEF<span class="elsevierStyleInf">50&#37;</span>&#44; FEF<span class="elsevierStyleInf">75&#37;</span> e FEF<span class="elsevierStyleInf">25-75&#37;</span>&#41;&#44; recessivo &#40;FEF<span class="elsevierStyleInf">75&#37;</span> e FEF<span class="elsevierStyleInf">25-75&#37;</span>&#41; e overdominante &#40;VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este estudo destaca&#44; principalmente&#44; a import&#226;ncia da variante rs4073 do gene da interleucina 8&#44; na resposta a broncodilatadores inalat&#243;rios&#44; concomitantemente ao gen&#243;tipo das muta&#231;&#245;es no gene <span class="elsevierStyleItalic">cystic fibrosis transmembrane conductance regulator</span>&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "M&#233;todos"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Resultados"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclus&#245;es"
          ]
        ]
      ]
    ]
    "NotaPie" => array:2 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Please cite this article as&#58; Furlan LL&#44; Ribeiro JD&#44; Bertuzzo CS&#44; Salom&#227;o Junior JB&#44; Souza DR&#44; Marson FA&#46; Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis&#46; J Pediatr &#40;Rio J&#41;&#46; 2017&#59;93&#58;639&#8211;48&#46;</p>"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Study conducted at Universidade Estadual de Campinas &#40;Unicamp&#41;&#44; Campinas&#44; SP&#44; Brazil&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 4239
            "Ancho" => 3284
            "Tamanyo" => 641459
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Association of rs4073 and rs2227306 variants of <span class="elsevierStyleItalic">IL-8</span> &#40;interleukin-8&#41; with the response to inhaled bronchodilators in cystic fibrosis patients&#46; &#40;A&#41; Association between forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s &#40;FEV<span class="elsevierStyleInf">1</span>&#41; of forced vital capacity &#40;FVC&#41; and rs4073&#44; dominant model and two identified mutations in the <span class="elsevierStyleItalic">CFTR</span> gene &#40;cystic fibrosis transmembrane regulator&#41; belonging to classes I&#44; II&#44; and&#47;or III &#40;<span class="elsevierStyleItalic">CFTR-B</span> group&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;028&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;112&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>39&#59; mean of 4&#46;77<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;95&#59; median of 4 &#40;ranging from &#8722;9 to 48&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; mean of &#8722;0&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;42&#59; median of &#8722;1 &#40;ranging from &#8722;6 to 15&#41;&#46; &#40;B&#41; Association of FEV<span class="elsevierStyleInf">1</span>&#47;FVC ratio with rs4073&#44; over-dominant model and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;029&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;116&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>30&#59; mean of 1&#46;17<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;36&#59; median of 0 &#40;ranging from &#8722;12 to 23&#41;&#46; &#40;AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#59; mean of 4&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;58&#59; median of 4 &#40;ranging from &#8722;9 to 32&#41;&#46; &#40;C&#41; Association of forced expiratory flow of 50&#37; &#40;FEF<span class="elsevierStyleInf">50&#37;</span>&#41; of FVC with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;046&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;184&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>37&#59; mean of 17&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;18&#59; median of 16 &#40;ranging from &#8722;20 to 89&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; mean of 4&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;8&#59; median of &#8722;2 &#40;ranging from &#8722;19 to 55&#41;&#46; &#40;D&#41; Association of FEF<span class="elsevierStyleInf">50&#37;</span> with rs2227306&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;083&#41;&#46; &#40;CC&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>15&#59; mean of 1&#46;47<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;22&#59; median of 0 &#40;ranging from &#8722;20 to 29&#41;&#46; &#40;CT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#59; mean of 15&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;04&#59; median of 10&#46;5 &#40;ranging from &#8722;28 to 89&#41;&#46; &#40;E&#41; Association of FEF<span class="elsevierStyleInf">50&#37;</span> with rs2227306&#44; over-dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;033&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;083&#41;&#46; &#40;CC<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#59; mean of 6&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>20&#46;27&#59; median of 4 &#40;ranging from &#8722;20 to 55&#41;&#46; &#40;CT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#59; mean of 19&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#46;43&#59; median of 19 &#40;ranging from &#8722;28 to 89&#41;&#46; &#40;F&#41; Association of forced expiratory flow of 75&#37; &#40;FEF<span class="elsevierStyleInf">75&#37;</span>&#41; of FVC with rs4073&#44; co-dominant model regardless of identified mutations in the <span class="elsevierStyleItalic">CFTR</span> gene &#40;<span class="elsevierStyleItalic">CFTR-A</span> group&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;044&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41;&#46; 1<span class="elsevierStyleHsp" style=""></span>&#8800;<span class="elsevierStyleHsp" style=""></span>3&#46; &#40;AA&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; mean of 29&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#46;98&#59; median of 30 &#40;ranging from &#8722;47 to 142&#41;&#46; &#40;AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>42&#59; mean of 24&#46;81<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>53&#46;57&#59; median of 14 &#40;ranging from &#8722;58 to 235&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; mean of 9&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;95&#59; median of 2&#46;5 &#40;ranging from &#8722;35 to 119&#41;&#46; &#40;G&#41; Association of FEF<span class="elsevierStyleInf">75&#37;</span> with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;096&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#59; mean of 33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>55&#46;23&#59; median of 16 &#40;ranging from &#8722;27 to 235&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; mean of 5&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>35&#46;93&#59; median of 2 &#40;ranging from &#8722;35 to 119&#41;&#46; &#40;H&#41; Association of FEF<span class="elsevierStyleInf">75&#37;</span> with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-A</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;034&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#59; mean of 26&#46;86<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>48&#46;34&#59; median of 18 &#40;ranging from &#8722;58 to 235&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; mean of 9&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>36&#46;95&#59; median of 2&#46;5 &#40;ranging from &#8722;35 to 119&#41;&#46; &#40;I&#41; Association of FEF<span class="elsevierStyleInf">75&#37;</span> with rs4073&#44; recessive model&#44; and <span class="elsevierStyleItalic">CFTR-A</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;04&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;058&#41;&#46; &#40;AA&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#59; mean of 29&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>39&#46;98&#59; median of 30 &#40;ranging from &#8722;47 to 142&#41;&#46; &#40;AT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>70&#59; mean of 18&#46;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>47&#46;95&#59; median of 10 &#40;ranging from &#8722;58 to 235&#41;&#46; &#40;J&#41; Association of FEF between 25&#37; and 75&#37; &#40;FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&#41; of FVC with rs4073&#44; co-dominant model and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;012&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41;&#46; TT<span class="elsevierStyleHsp" style=""></span>&#8800;<span class="elsevierStyleHsp" style=""></span>AA and AT&#46; &#40;AA&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#59; mean of 25&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;14&#59; median of 30 &#40;ranging from &#8722;21 to 57&#41;&#46; &#40;AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>29&#59; mean of 18&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>29&#46;04&#59; median of 14 &#40;ranging from &#8722;33 to 117&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&#59; mean of 2&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;74&#59; median of 0 &#40;ranging from &#8722;51 to 65&#41;&#46; &#40;K&#41; Association of FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>ATT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>38&#59; mean of 20&#46;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;64&#59; median of 18&#46;5 &#40;ranging from &#8722;33 to 117&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>23&#59; mean of 2&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;74&#59; median of 0 &#40;ranging from &#8722;51 to 65&#41;&#46; &#40;L&#41; Association of FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> with rs4073&#44; dominant model&#44; and <span class="elsevierStyleItalic">CFTR-A</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;029&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;1&#41;&#46; &#40;AA<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>AT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>82&#59; mean of 15&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;2&#59; median of 15 &#40;ranging from &#8722;40 to 117&#41;&#46; &#40;TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#59; mean of 5&#46;94<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;33&#59; median of 0 &#40;ranging from &#8722;51 to 76&#41;&#46; &#40;M&#41; Association of FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span> with rs4073&#44; recessive model&#44; and <span class="elsevierStyleItalic">CFTR-B</span> group &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;047&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;063&#41;&#46; &#40;AA&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>9&#59; mean of 25&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;14&#59; median of 30 &#40;ranging from &#8722;21 to 57&#41;&#46; &#40;AT<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>TT&#41; <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#59; mean of 11&#46;56<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;89&#59; median of 8 &#40;ranging from &#8722;51 to 117&#41;&#46; The dot corresponds to median values and the bar corresponds to the 95&#37; confidence interval&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">n</span>&#44; sample size&#59; <span class="elsevierStyleItalic">CFTR</span>&#44; cystic fibrosis transmembrane regulator&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">n</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#8211;&#47;&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">29&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="6" align="left" valign="middle">Patients without known mutation in the <span class="elsevierStyleItalic">CFTR</span> gene&#44; or with one or two classes IV&#44; V or VI <span class="elsevierStyleItalic">CFTR</span> mutations</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">V562I&#47;&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I507V&#47;&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D110H&#47;V232H&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G576A&#47;R668C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">p&#46;Glu528G&#62;A&#47;TG11-5T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="10" align="left" valign="middle">Patients with one classes I&#44; II or III <span class="elsevierStyleItalic">CFTR</span> mutation&#44; and one non-identified mutation or IV&#44; V or VI <span class="elsevierStyleItalic">CFTR</span> mutation</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X&#47;&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;3272-26A&#62;G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;P205S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X&#47;P205S&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X&#47;R334W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3120&#43;1G&#62;A&#47;L206W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">622-2A&#62;G&#47;711&#43;1G&#62;T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">R1162X&#47;-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X&#47;I618T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="4" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;F508del&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="22" align="left" valign="middle">Patients with two classes I&#44; II&#44; and&#47;or III <span class="elsevierStyleItalic">CFTR</span> mutations<br>&#40;<span class="elsevierStyleItalic">CFTR-B</span> group&#41;</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;G542X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;N1303K&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;R1162X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;R553X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;1584-18672pbA&#62;G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;c&#46;1717-1G&#62;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3120&#43;1G&#62;A&#47;R1066C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;2183AA&#62;G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;2184insA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;6B to 16 exon duplication&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;G85E&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;S549R &#40;T&#62;G&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;S4X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X&#47;2183AA&#62;G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X&#47;R1162X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">A561E&#47;A561E&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;R1066C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">R1070Q&#59; S466X&#47;G542X&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">F508del&#47;1812-1G&#62;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">2183AA&#62;G&#47;2183AA&#62;G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">3120&#43;1G&#62;A&#47;3120&#43;1G&#62;A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1581575.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">All patients assessed in this study have been included &#40;<span class="elsevierStyleItalic">CFTR-A</span> group&#41;&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Distribution of cystic fibrosis patients for the <span class="elsevierStyleItalic">CFTR</span> genotype and classes of identified mutations&#46;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">SaO<span class="elsevierStyleInf">2</span>&#44; transcutaneous arterial hemoglobin oxygen-saturation&#59; FVC&#44; forced vital capacity&#59; FEV<span class="elsevierStyleInf">1</span>&#44; forced expiratory volume in 1<span class="elsevierStyleHsp" style=""></span>s of FVC&#59; FEF<span class="elsevierStyleInf">25&#37;</span>&#44; forced expiratory flow at 25&#37; of FVC&#59; FEF<span class="elsevierStyleInf">50&#37;</span>&#44; forced expiratory flow at 50&#37; of FVC&#59; FEF<span class="elsevierStyleInf">75&#37;</span>&#44; forced expiratory flow at 75&#37; of FVC&#59; FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&#44; average forced expiratory flow between 25&#37; and 75&#37; of FVC&#59; FEF<span class="elsevierStyleInf">max</span>&#44; maximum forced expiratory flow&#59; ERV&#44; expiratory reserve volume&#46; Spirometry data are shown in percentage of the predicted value&#46; All evaluated patients are described&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Distribution<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Gender &#40;male&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">92&#47;186 &#40;49&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Ethnicity &#40;White&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">169&#47;180 &#40;93&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Age &#40;months&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">169&#59; 201&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>171&#46;98&#59; 143 &#40;7 to 932&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Onset of symptoms &#40;months&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">159&#59; 38&#46;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>114&#46;03&#59; 3 &#40;0 to 720&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Diagnosis &#40;months&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">171&#59; 87&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>158&#46;39&#59; 20 &#40;0 to 833&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Onset of digestive symptoms &#40;months&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">140&#59; 41&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>112&#46;61&#59; 3 &#40;0 to 720&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Onset of pulmonary symptoms &#40;months&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">156&#59; 46&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>123&#46;64&#59; 6 &#40;0 to 720&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Body mass index &#40;Kg&#47;m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">178&#59; 17&#46;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;08&#59; 16&#46;28 &#40;6&#46;5 to 35&#46;67&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Nasal polyposis &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&#47;162 &#40;17&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Diabetes mellitus &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">32&#47;164 &#40;19&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Osteoporosis &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#47;162 &#40;15&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Pancreatic insufficiency &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">130&#47;162 &#40;80&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Meconium ileus &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#47;162 &#40;14&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">1st Pseudomonas aeruginosa</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">121&#59; 103&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>171&#46;74&#59; 31 &#40;0 to 872&#41;<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Mucoid P&#46; aeruginosa &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&#47;173 &#40;42&#46;8&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Non-mucoid P&#46; aeruginosa &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">99&#47;173 &#40;57&#46;2&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Achromobacter xylosoxidans &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17&#47;174 &#40;9&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Burkolderia cepacia &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#47;174 &#40;14&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Staphylococcus aureus &#40;presence&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">131&#47;174 &#40;75&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">SaO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">159&#59; 94&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;28&#59; 96 &#40;66 to 99&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Bhalla score</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113&#59; 8&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;77&#59; 8 &#40;0 to 25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Kanga score</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">118&#59; 18&#46;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;82&#59; 17&#46;5 &#40;10 to 40&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Shwachman-Kulczycki score</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">143&#59; 65&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;78&#59; 65 &#40;20 to 95&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FVC</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">142&#59; 72&#46;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#46;86&#59; 77 &#40;19 to 126&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FEV</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">141&#59; 60&#46;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;75&#59; 63 &#40;17 to 116&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FEV</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span><span class="elsevierStyleItalic">&#47;FVC</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">144&#59; 79&#46;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;99&#59; 81 &#40;39 to 113&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FEF</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">25&#37;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">119&#59; 61&#46;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#46;71&#59; 60 &#40;7 to 138&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FEF</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">50&#37;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">119&#59; 46&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#46;25&#59; 40 &#40;3 to 126&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FEF</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">75&#37;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">116&#59; 36&#46;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>28&#46;77&#59; 27&#46;5 &#40;4 to 142&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FEF</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">25&#8211;75&#37;</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">140&#59; 47&#46;16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#46;51&#59; 39 &#40;5 to 150&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">FEF</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">Max</span></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">114&#59; 75&#46;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;59&#59; 73&#46;5 &#40;25 to 137&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">ERV</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">112&#59; 80&#46;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>52&#46;39&#59; 69 &#40;3 to 248&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Response to inhaled bronchodilator</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FVC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">117&#59; 1&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;19&#59; 1 &#40;&#8722;17 to 32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">117&#59; 3&#46;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;0&#59; 3 &#40;&#8722;12 to 48&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEV<span class="elsevierStyleInf">1</span>&#47;FVC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">111&#59; 2&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;43&#59; 2 &#40;&#8722;19 to 32&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEF<span class="elsevierStyleInf">25&#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">99&#59; 9&#46;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#46;41&#59; 5 &#40;&#8722;45 to 110&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEF<span class="elsevierStyleInf">50&#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">99&#59; 13&#46;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#46;06&#59; 9 &#40;&#8722;41 to 114&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEF<span class="elsevierStyleInf">75&#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">99&#59; 20&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>46&#46;47&#59; 16 &#40;&#8722;64 to 235&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEF<span class="elsevierStyleInf">25&#8211;75&#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">99&#59; 12&#46;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#46;77&#59; 9&#46;5 &#40;&#8722;51 to 117&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>FEF<span class="elsevierStyleInf">Max</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">116&#59; 2&#46;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#46;48&#59; 3 &#40;&#8722;42 to 69&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>ERV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&#59; 23&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>101&#46;08&#59; 0 &#40;&#8722;90 to 670&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1581577.png"
              ]
            ]
          ]
          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">The data with categorical distribution are presented as follows&#58; <span class="elsevierStyleItalic">n</span> of variable&#47;<span class="elsevierStyleItalic">n</span> total &#40;percentage&#41;&#59; data with numeric distribution are presented as follows&#58; sample size&#59; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#59; median &#40;minimum to maximum&#41;&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Missing values for first <span class="elsevierStyleItalic">P&#46; aeruginosa</span> correspond to cystic fibrosis patients that never presented a <span class="elsevierStyleItalic">P&#46; aeruginosa</span> positive culture&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">One cystic fibrosis patient showed a positive culture for <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; with negative values for <span class="elsevierStyleItalic">P&#46; aeruginosa</span> antigen specific IgG and the patient was excluded for the frequency estimation&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Descriptive analysis of clinical and laboratory markers of cystic fibrosis patients&#46;</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Table 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar1045" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleItalic">IL-8</span>&#44; interleukin 8&#59; &#37;&#44; percentage&#59; <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&#44; chi-square&#59; af&#44; absolute frequency&#46;</p>"
          "tablatextoimagen" => array:2 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Genotype&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Allele&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number &#40;af&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-Value<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">rs4073</td><td class="td" title="table-entry  " align="left" valign="top">AA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">54 &#40;29&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">187 &#40;0&#46;51&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="middle">3&#46;94</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="middle"><span class="elsevierStyleBold">&#60;0&#46;05</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">79 &#40;42&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">183 &#40;0&#46;49&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">52 &#40;28&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">370&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">185&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">rs2227306</td><td class="td" title="table-entry  " align="left" valign="top">CC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70 &#40;38&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">211 &#40;0&#46;57&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="middle">8&#46;21</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="middle"><span class="elsevierStyleBold">&#60;0&#46;05</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">71 &#40;38&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">157 &#40;0&#46;43&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43 &#40;23&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">368&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">184&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="7" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="4" align="left" valign="top">rs2227307</td><td class="td" title="table-entry  " align="left" valign="top">GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31 &#40;17&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">139 &#40;0&#46;39&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="middle">1&#46;48</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="middle">&#62;0&#46;05</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77 &#40;43&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">217 &#40;0&#46;61&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70 &#40;39&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">356&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">178&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1581574.png"
              ]
            ]
            1 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">rs4073&#47;rs2227306&#47;rs2227307&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Frequency&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Percentage &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CC GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CC GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CC TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CT GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CT GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA CT TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA TT GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA TT GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AA TT TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT CC GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT CC TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT CT GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT CT TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT TT GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT TT GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">AT TT TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CC GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CC GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CC TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CT GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CT GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT CT TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT TT GG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT TT GT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TT TT TT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">177&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1581576.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025"><span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> and <span class="elsevierStyleItalic">p</span>-values refer to the calculation of Hardy&#8211;Weinberg equilibrium&#46; Significant data are shown in bold type&#46; There was weak correlation among the <span class="elsevierStyleItalic">IL-8</span> gene variants in the cystic fibrosis patients enrolled in the study&#46; There is no linkage disequilibrium&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Distribution of genotypes&#44; alleles and haplotype of <span class="elsevierStyleItalic">IL-8</span> gene variants &#40;rs4073&#44; rs2227306 and rs2227307&#41; in cystic fibrosis patients&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polymorphisms in ADRB2 gene can modulate the response to bronchodilators and the severity of cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46;A&#46;L&#46; Marson"
                            1 => "C&#46;S&#46; Bertuzzo"
                            2 => "A&#46;F&#46; Ribeiro"
                            3 => "J&#46;D&#46; Ribeiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2466-12-50"
                      "Revista" => array:6 [
                        "tituloSerie" => "BMC Pulm Med"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "50"
                        "paginaFinal" => "59"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22950544"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The cystic fibrosis transmembrane conductance regulator&#58; an intriguing protein with pleiotropic functions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46; Vankeerberghen"
                            1 => "H&#46; Cuppens"
                            2 => "J&#46;J&#46; Cassiman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cyst Fibros"
                        "fecha" => "2002"
                        "volumen" => "1"
                        "paginaInicial" => "13"
                        "paginaFinal" => "29"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15463806"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Essential involvement of interleukin-8 &#40;IL-8&#41; in acute inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A&#46; Harada"
                            1 => "N&#46; Sekido"
                            2 => "T&#46; Akahoshi"
                            3 => "T&#46; Wada"
                            4 => "N&#46; Mukaida"
                            5 => "K&#46; Matsushima"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Leukoc Biol"
                        "fecha" => "1994"
                        "volumen" => "56"
                        "paginaInicial" => "559"
                        "paginaFinal" => "564"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7964163"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Inhaled bronchodilators for cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46; Halfhide"
                            1 => "H&#46;J&#46; Evans"
                            2 => "J&#46; Couriel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2005"
                        "volumen" => "19"
                        "paginaInicial" => "CD003428"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung function testing in preschool-aged children with cystic fibrosis in the clinical setting"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46;L&#46; Gangell"
                            1 => "G&#46;L&#46; Hall"
                            2 => "S&#46;M&#46; Stick"
                            3 => "P&#46;D&#46; Sly"
                            4 => "C&#46;F&#46; Arest"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/ppul.21192"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pediatr Pulmonol"
                        "fecha" => "2010"
                        "volumen" => "45"
                        "paginaInicial" => "419"
                        "paginaFinal" => "433"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20425849"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "WITHDRAWN&#58; inhaled bronchodilators for cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46; Halfhide"
                            1 => "H&#46;J&#46; Evans"
                            2 => "J&#46; Couriel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/14651858.CD003428.pub3"
                      "Revista" => array:5 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2016"
                        "volumen" => "2"
                        "paginaInicial" => "CD003428"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26866910"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biochemical basis of asthma therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "P&#46;J&#46; Barnes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1074/jbc.R110.206466"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Biol Chem"
                        "fecha" => "2011"
                        "volumen" => "286"
                        "paginaInicial" => "32899"
                        "paginaFinal" => "32905"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21799015"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association of CFTR gene mutation with bronchial asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "N&#46; Maurya"
                            1 => "S&#46; Awasthi"
                            2 => "P&#46; Dixit"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Indian J Med Res"
                        "fecha" => "2012"
                        "volumen" => "135"
                        "paginaInicial" => "469"
                        "paginaFinal" => "478"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22664493"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Distinct patterns of inflammation in the airway lumen and bronchial mucosa of children with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Regamey"
                            1 => "L&#46; Tsartsali"
                            2 => "T&#46;N&#46; Hilliard"
                            3 => "O&#46; Fuchs"
                            4 => "H&#46;L&#46; Tan"
                            5 => "J&#46; Zhu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thoraxjnl-2011-200585"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2012"
                        "volumen" => "67"
                        "paginaInicial" => "164"
                        "paginaFinal" => "170"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22008188"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CFTR mutations and GSTM1 and GSTT1 deletions in Brazilian cystic fibrosis patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C&#46;S&#46; Lima"
                            1 => "M&#46;M&#46; Ortega"
                            2 => "F&#46;A&#46;L&#46; Marson"
                            3 => "R&#46; Zulli"
                            4 => "A&#46;F&#46; Ribeiro"
                            5 => "C&#46;S&#46; Bertuzzo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bras Pneumol"
                        "fecha" => "2012"
                        "volumen" => "38"
                        "paginaInicial" => "50"
                        "paginaFinal" => "56"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22407040"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The ACE gene D&#47;I polymorphism as a modulator of severity of cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "F&#46;A&#46; Marson"
                            1 => "C&#46;S&#46; Bertuzzo"
                            2 => "T&#46;D&#46; Hortencio"
                            3 => "J&#46;D&#46; Ribeiro"
                            4 => "L&#46;C&#46; Bonadia"
                            5 => "A&#46;F&#46; Ribeiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2466-12-41"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Pulm Med"
                        "fecha" => "2012"
                        "volumen" => "12"
                        "paginaInicial" => "41"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22874010"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polymorphisms in the glutathione pathway modulate cystic fibrosis severity&#58; a cross-sectional study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46;A&#46; Marson"
                            1 => "C&#46;S&#46; Bertuzzo"
                            2 => "A&#46;F&#46; Ribeiro"
                            3 => "J&#46;D&#46; Ribeiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/1471-2350-15-27"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMC Med Genet"
                        "fecha" => "2014"
                        "volumen" => "15"
                        "paginaInicial" => "27"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24593045"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Personalized drug therapy in cystic fibrosis&#58; from fiction to reality"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "F&#46;A&#46; Marson"
                            1 => "C&#46;S&#46; Bertuzzo"
                            2 => "J&#46;D&#46; Ribeiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Drug Targets"
                        "fecha" => "2015"
                        "volumen" => "16"
                        "paginaInicial" => "1007"
                        "paginaFinal" => "1017"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25438972"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0220"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pulmonary function testing in children&#58; techniques and standards"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "G&#46; Polgar"
                            1 => "V&#46; Promadhat"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "1971"
                        "editorial" => "WB Saunders Company"
                        "editorialLocalizacion" => "Philadelphia &#40;PA&#41;"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0225"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "New reference values for forced spirometry in white adults in Brazil"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "C&#46;A&#46; Pereira"
                            1 => "T&#46; Sato"
                            2 => "S&#46;C&#46; Rodrigues"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bras Pneumol"
                        "fecha" => "2007"
                        "volumen" => "33"
                        "paginaInicial" => "397"
                        "paginaFinal" => "406"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17982531"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Validation of new Brazilian predicted values for forced spirometry in Caucasians and comparison with predicted values obtained using other reference equations"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;A&#46; Duarte"
                            1 => "C&#46;A&#46; Pereira"
                            2 => "S&#46;C&#46; Rodrigues"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bras Pneumol"
                        "fecha" => "2007"
                        "volumen" => "33"
                        "paginaInicial" => "527"
                        "paginaFinal" => "535"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18026650"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "CFTR genotype and clinical outcomes of adult patients carried as cystic fibrosis disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;C&#46; Bonadia"
                            1 => "F&#46;A&#46; Marson"
                            2 => "J&#46;D&#46; Ribeiro"
                            3 => "I&#46;A&#46; Paschoal"
                            4 => "M&#46;C&#46; Pereira"
                            5 => "A&#46;F&#46; Ribeiro"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.gene.2014.02.040"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gene"
                        "fecha" => "2014"
                        "volumen" => "540"
                        "paginaInicial" => "183"
                        "paginaFinal" => "190"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24583165"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association study suggests opposite effects of polymorphisms within IL-8 on bronchial asthma and respiratory syncytial virus bronchiolitis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "A&#46; Heinzmann"
                            1 => "I&#46; Ahlert"
                            2 => "T&#46; Kurz"
                            3 => "R&#46; Berner"
                            4 => "K&#46;A&#46; Deichmann"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2004.06.038"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2004"
                        "volumen" => "114"
                        "paginaInicial" => "671"
                        "paginaFinal" => "676"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15356575"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Haplotypes in the interleukin 8 gene and their association with chronic periodontitis susceptibility"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;M&#46; Scarel-Caminaga"
                            1 => "Y&#46;J&#46; Kim"
                            2 => "A&#46;C&#46; Viana"
                            3 => "K&#46;M&#46; Curtis"
                            4 => "S&#46;C&#46; Corbi"
                            5 => "P&#46;M&#46; Sogumo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10528-010-9407-3"
                      "Revista" => array:6 [
                        "tituloSerie" => "Biochem Genet"
                        "fecha" => "2011"
                        "volumen" => "49"
                        "paginaInicial" => "292"
                        "paginaFinal" => "302"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21188496"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "GPower 3&#58; a flexible statistical power analysis program for the social&#44; behavioral&#44; and biomedical sciences"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46; Faul"
                            1 => "E&#46; Erdfelde"
                            2 => "A&#46;G&#46; Lang"
                            3 => "A&#46; Buchner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Behav Res Methods"
                        "fecha" => "2007"
                        "volumen" => "39"
                        "paginaInicial" => "175"
                        "paginaFinal" => "191"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17695343"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Discovering the false discovery rate"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Y&#46; Benjamini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J R Stat Soc Ser B &#40;Stat Method&#41;"
                        "fecha" => "2010"
                        "volumen" => "72"
                        "paginaInicial" => "405"
                        "paginaFinal" => "416"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "IL8 gene as modifier of cystic fibrosis&#58; unraveling the factors which influence clinical variability"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "L&#46;L&#46; Furlan"
                            1 => "F&#46;A&#46; Marson"
                            2 => "J&#46;D&#46; Ribeiro"
                            3 => "C&#46;S&#46; Bertuzzo"
                            4 => "J&#46;B&#46; Salom&#227;o Junior"
                            5 => "D&#46;R&#46; Souza"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00439-016-1684-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Hum Genet"
                        "fecha" => "2016"
                        "volumen" => "135"
                        "paginaInicial" => "881"
                        "paginaFinal" => "894"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27209008"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association of blood eosinophils and plasma periostin with FEV1 response after 3-month inhaled corticosteroid and long-acting beta2-agonist treatment in stable COPD patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H&#46;Y&#46; Park"
                            1 => "H&#46; Lee"
                            2 => "W&#46; Koh"
                            3 => "S&#46; Kim"
                            4 => "I&#46; Jeong"
                            5 => "H&#46;K&#46; Koo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Int J Chronic Obstruct Pulm Dis"
                        "fecha" => "2016"
                        "volumen" => "11"
                        "paginaInicial" => "23"
                        "paginaFinal" => "30"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0270"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Biomarkers of progression of chronic obstructive pulmonary disease &#40;COPD&#41;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;G&#46; Shaw"
                            1 => "A&#46; Vaughan"
                            2 => "A&#46;G&#46; Dent"
                            3 => "P&#46;E&#46; O&#8217;Hare"
                            4 => "F&#46; Goh"
                            5 => "R&#46;V&#46; Bowman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3978/j.issn.2072-1439.2014.11.33"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Thorac Dis"
                        "fecha" => "2014"
                        "volumen" => "6"
                        "paginaInicial" => "1532"
                        "paginaFinal" => "1547"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25478195"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of age and sex on response to asthma therapy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;M&#46; Dunn"
                            1 => "E&#46; Lehman"
                            2 => "V&#46;M&#46; Chinchilli"
                            3 => "R&#46;J&#46; Martin"
                            4 => "H&#46;A&#46; Boushey"
                            5 => "E&#46; Israel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201503-0426OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2015"
                        "volumen" => "192"
                        "paginaInicial" => "551"
                        "paginaFinal" => "558"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26068329"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A genome-wide association study of bronchodilator response in asthmatics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Q&#46;L&#46; Duan"
                            1 => "J&#46; Lasky-Su"
                            2 => "B&#46;E&#46; Himes"
                            3 => "W&#46; Qiu"
                            4 => "A&#46;A&#46; Litonjua"
                            5 => "A&#46; Damask"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/tpj.2013.5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pharmacogenomics J"
                        "fecha" => "2014"
                        "volumen" => "14"
                        "paginaInicial" => "41"
                        "paginaFinal" => "47"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23508266"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pulmonary function parameters and use of bronchodilators in patients with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "L&#46;H&#46; Muramatu"
                            1 => "R&#46; Stirbulov"
                            2 => "W&#46;C&#46; Forte"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bras Pneumol"
                        "fecha" => "2013"
                        "volumen" => "39"
                        "paginaInicial" => "48"
                        "paginaFinal" => "55"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23503485"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0290"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Modulation of cystic fibrosis lung disease by variants in interleukin-8"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;D&#46; Hillian"
                            1 => "D&#46; Londono"
                            2 => "J&#46;M&#46; Dunn"
                            3 => "K&#46;A&#46; Goddard"
                            4 => "R&#46;G&#46; Pace"
                            5 => "M&#46;R&#46; Knowles"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/gene.2008.42"
                      "Revista" => array:6 [
                        "tituloSerie" => "Genes Immun"
                        "fecha" => "2008"
                        "volumen" => "9"
                        "paginaInicial" => "501"
                        "paginaFinal" => "508"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18563170"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0295"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Systematic review and meta-analysis of the association between &#946;2-adrenoceptor polymorphisms and asthma&#58; a HuGE review"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Thakkinstian"
                            1 => "M&#46; McEvoy"
                            2 => "C&#46; Minelli"
                            3 => "P&#46; Gibson"
                            4 => "B&#46; Hancox"
                            5 => "D&#46; Duffy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "J Epidemiol"
                        "fecha" => "2005"
                        "volumen" => "162"
                        "paginaInicial" => "201"
                        "paginaFinal" => "211"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0300"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Influence of genetic variation of the &#946;2-adrenergic receptor on lung diffusion in patients with cystic fibrosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46;R&#46; Traylor"
                            1 => "C&#46;M&#46; Wheatley"
                            2 => "T&#46;T&#46; Skrentny Jr&#46;"
                            3 => "W&#46;T&#46; Foxx-Lupo"
                            4 => "H&#46; Phan"
                            5 => "A&#46;E&#46; Patanwala"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.pupt.2011.06.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Pulm Pharmacol Ther"
                        "fecha" => "2011"
                        "volumen" => "24"
                        "paginaInicial" => "610"
                        "paginaFinal" => "616"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21703359"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack315964"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0175" class="elsevierStylePara elsevierViewall">To Luciana Montes Rezende&#44; Luciana Cardoso Bonadia&#44; and Stephanie Villa-Nova for their technical support during DNA extraction and identification of mutations of the <span class="elsevierStyleItalic">CFTR</span> gene&#46; To Marcela Augusta de Souza Pinhel&#44; Michele Lima Greg&#243;rio&#44; Rafael Fernandes Ferreira&#44; Graciele Domitila Tenani&#44; and Heloisa Cristina Caldas for their technical support during standardization of <span class="elsevierStyleItalic">IL</span>-8 genotyping&#46; To Maria &#194;ngela Gon&#231;alves de Oliveira Ribeiro for conducting pulmonary function tests &#40;LAFIP&#47;Ciped&#47;Unicamp&#41;&#46; To Rafaella Maionchi Pereira Martins for her technical support to determine clinical scores&#46; To Maria de F&#225;tima Corr&#234;a Pimenta Servidoni for promoting a link between both Universities&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/00217557/0000009300000006/v1_201711050042/S0021755717306344/v1_201711050042/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "10179"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/00217557/0000009300000006/v1_201711050042/S0021755717306344/v1_201711050042/en/main.pdf?idApp=UINPBA000049&text.app=https://jped.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755717306344?idApp=UINPBA000049"
]

Article information

ISSN: 00217557
Original language: English

DOI:10.1016/j.jped.2017.03.005

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	1	0	1
2024 October	15	27	42
2024 September	21	32	53
2024 August	39	30	69
2024 July	39	27	66
2024 June	19	16	35
2024 May	23	10	33
2024 April	28	16	44
2024 March	30	13	43
2024 February	26	23	49
2024 January	25	24	49
2023 December	17	22	39
2023 November	17	24	41
2023 October	17	22	39
2023 September	18	30	48
2023 August	13	14	27
2023 July	13	12	25
2023 June	14	13	27
2023 May	16	12	28
2023 April	16	8	24
2023 March	34	15	49
2023 February	15	12	27
2023 January	15	24	39
2022 December	36	23	59
2022 November	31	32	63
2022 October	25	34	59
2022 September	23	27	50
2022 August	17	35	52
2022 July	18	29	47
2022 June	22	30	52
2022 May	27	24	51
2022 April	37	36	73
2022 March	28	35	63
2022 February	19	22	41
2022 January	14	16	30
2021 December	10	19	29
2021 November	13	20	33
2021 October	9	25	34
2021 September	7	6	13
2021 August	7	12	19
2021 July	4	7	11
2021 June	12	7	19
2021 May	12	16	28
2021 April	22	8	30
2021 March	10	8	18
2021 February	10	4	14
2021 January	6	13	19
2020 December	12	6	18
2020 November	9	13	22
2020 October	10	15	25
2020 September	8	8	16
2020 August	3	5	8
2020 July	4	6	10
2020 June	9	5	14
2020 May	8	2	10
2020 April	7	9	16
2020 March	4	3	7
2020 February	12	13	25
2020 January	8	14	22
2019 December	7	4	11
2019 November	4	3	7
2019 October	10	10	20
2019 September	7	11	18
2019 August	8	11	19
2019 July	6	8	14
2019 June	10	8	18
2019 May	4	5	9
2019 April	18	8	26
2019 March	8	6	14
2019 February	6	3	9
2019 January	7	3	10
2018 December	6	8	14
2018 November	20	5	25
2018 October	18	10	28
2018 September	10	8	18
2018 August	15	2	17
2018 July	6	11	17
2018 June	15	31	46
2018 May	38	29	67
2018 April	10	2	12
2018 March	20	3	23
2018 February	8	5	13
2018 January	20	8	28
2017 December	21	19	40
2017 November	25	15	40
2017 October	3	7	10
2017 September	0	5	5
2017 August	0	6	6

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter