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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>"
        ]
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A resposta a broncodilatadores inalat&#243;rios &#40;BD&#41; na fibrose c&#237;stica &#40;FC&#41; &#40;OMIM&#58; n&#176; 219700&#41; &#233; muito vari&#225;vel e depende do gen&#243;tipo do <span class="elsevierStyleItalic">RTFC</span> &#40;Regulador da Condut&#226;ncia Transmembrana da Fibrose C&#237;stica&#41;&#44; dos sintomas pulmonares e&#44; principalmente&#44; de variantes nos genes modificadores&#44; como o Receptor Adren&#233;rgico Beta 2 &#40;<span class="elsevierStyleItalic">ADRB2</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> At&#233; agora&#44; apenas alguns estudos investigaram essa resposta&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">As muta&#231;&#245;es no gene do <span class="elsevierStyleItalic">RTFC</span> causam FC&#44; devido a defici&#234;ncia&#44; disfun&#231;&#227;o ou aus&#234;ncia da prote&#237;na do <span class="elsevierStyleItalic">RTFC</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> A FC &#233; caracterizada por um ciclo cont&#237;nuo de inflama&#231;&#227;o cr&#244;nica das vias a&#233;reas&#44; que pode ser exacerbada pela interleucina 8 &#40;<span class="elsevierStyleItalic">IL&#8208;8</span>&#41;&#44; um importante mediador pr&#243;&#8208;inflamat&#243;rio&#46; A <span class="elsevierStyleItalic">IL&#8208;8</span> &#233; respons&#225;vel por iniciar e aumentar a resposta provocadora na presen&#231;a de pat&#243;genos espec&#237;ficos&#44; causa ativa&#231;&#227;o e migra&#231;&#227;o de neutr&#243;filos do sangue perif&#233;rico para os tecidos&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> A inflama&#231;&#227;o cr&#244;nica das vias a&#233;reas &#233; o caminho comum final de les&#227;o pulmonar&#46; Ela &#233; respons&#225;vel pelo aumento na permeabilidade vascular&#44; contribui para edema intersticial&#44; alveolar e das vias a&#233;reas&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">O tratamento da doen&#231;a pulmonar na FC inclui anti&#8208;inflamat&#243;rios&#44; corticosteroides inalat&#243;rios&#44; antibi&#243;ticos&#44; mucol&#237;tico&#44; solu&#231;&#227;o salina hipert&#244;nica e fisioterapia&#46; Dentre as poss&#237;veis terapias&#44; h&#225; pouca comprova&#231;&#227;o que corrobore um papel dos BD na FC&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;5</span></a> Contudo&#44; os BD normalmente s&#227;o prescritos por um tempo maior devido a epis&#243;dios de pieira e dispneia na FC&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Os BD reduzem a libera&#231;&#227;o de mediadores&#44; respons&#225;veis pelo recrutamento e pela ativa&#231;&#227;o de c&#233;lulas inflamat&#243;rias&#44; ativam a neurotransmiss&#227;o colin&#233;rgica&#44; e por melhorar a permeabilidade vascular&#46; Eles tamb&#233;m aumentam o transporte mucociliar&#44; levam &#224; redu&#231;&#227;o da inflama&#231;&#227;o pulmonar&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> A resposta a BD depende&#44; em parte&#44; da prote&#237;na do <span class="elsevierStyleItalic">RTFC</span>&#44; que interage com a prote&#237;na do ADRB2 para promover broncodilata&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> A espirometria &#233; o principal m&#233;todo de avaliar a fun&#231;&#227;o pulmonar&#44; a gravidade e a progress&#227;o da doen&#231;a&#44; bem como a resposta a BD&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Inflama&#231;&#227;o neutrof&#237;lica intensa e baixa hiperreactividade br&#244;nquica s&#227;o caracter&#237;sticas comumente observadas na FC&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> Ademais&#44; a resposta das variantes gen&#233;ticas aos BD &#233; pouco conhecida&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> Pode&#8208;se destacar o papel da <span class="elsevierStyleItalic">IL&#8208;8</span> no componente neutrof&#237;lico da doen&#231;a pulmonar na FC&#46; Os genes que podem estar associados &#224; gravidade da FC e possivelmente &#224; resposta a BD foram relatados aqui e na literatura cient&#237;fica de todo o mundo&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;10&#8211;12</span></a> O gene da <span class="elsevierStyleItalic">IL&#8208;8</span> deve ser destacado&#44; pois ele tem influ&#234;ncia direta sobre a inflama&#231;&#227;o pulmonar e pode ser eficaz na resposta a BD&#46; Portanto&#44; este estudo comparou as variantes gen&#233;ticas da <span class="elsevierStyleItalic">IL&#8208;8</span> rs4073&#44; rs2227306 e rs2227307 com a resposta a BD em pacientes com FC&#44; com o uso da espirometria&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Material e m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Pacientes</span><p id="par0025" class="elsevierStylePara elsevierViewall">Foi conduzido um estudo transversal com 186 pacientes com FC&#44; selecionados em dois centros universit&#225;rios de refer&#234;ncia &#40;Faculdade de Medicina de S&#227;o Jos&#233; do Rio Preto e Universidade de Campinas&#41; para tratamento de FC&#44; de 2013 a 2015&#46; O estudo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa da Universidade Estadual de Campinas&#44; S&#227;o Paulo&#44; Brasil &#40;n&#176; 528&#47;2008&#41;&#46; Todos os participantes foram informados sobre o estudo e assinaram o Documento de Consentimento Informado&#46; Para os pacientes com menos de 18 anos&#44; o Consentimento Informado foi assinado pelo pai&#47;m&#227;e ou guardi&#227;o&#46; O estudo seguiu as recomenda&#231;&#245;es da Declara&#231;&#227;o de Helsinque&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">O diagn&#243;stico de FC foi confirmado pela presen&#231;a de duas concentra&#231;&#245;es alteradas de s&#243;dio e cloreto no suor &#40;n&#237;vel de cloreto acima de 60 mEq&#47;L&#41;&#46; Al&#233;m disso&#44; nenhum paciente foi submetido a teste inicial de tripsinog&#234;nio imunorreativo &#40;IRT&#41;&#46; Em um grupo de 91 pacientes&#44; houve duas muta&#231;&#245;es no gene do <span class="elsevierStyleItalic">RTFC</span> pertencentes &#224;s classes I&#44; II e&#47;ou III &#40;associadas &#224; maior gravidade da doen&#231;a&#44; devido &#224; aus&#234;ncia ou n&#227;o funcionalidade da prote&#237;na do <span class="elsevierStyleItalic">RTFC</span>&#41;&#59;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> 60 pacientes n&#227;o apresentaram muta&#231;&#227;o identificada do gene do <span class="elsevierStyleItalic">RTFC</span> ou apresentaram duas muta&#231;&#245;es que pertencem &#224;s classes IV&#44; V ou VI&#59; e 35 pacientes apresentaram uma muta&#231;&#227;o no gene do <span class="elsevierStyleItalic">RTFC</span> que pertence &#224;s classes I&#44; II ou III e uma muta&#231;&#227;o n&#227;o identificada ou pertencente &#224;s classes IV&#44; V ou VI &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Vari&#225;veis cl&#237;nicas</span><p id="par0035" class="elsevierStylePara elsevierViewall">As seguintes vari&#225;veis foram analisadas&#58; escores cl&#237;nicos &#40;Shwachman&#8208;Kulczycki&#44; Kanga e Bhalla&#41;&#59; &#237;ndice de massa corporal &#40;IMC&#41; de pacientes com mais de 18 anos&#44; com a f&#243;rmula IMC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>peso&#47;altura&#59;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> a vers&#227;o 3&#46;0&#46;1 do programa Anthro &#40;Organiza&#231;&#227;o Mundial de Sa&#250;de &#91;OMS&#93;&#44; 2006&#41; foi usada para crian&#231;as com menos de cinco anos e a vers&#227;o 1&#46;0&#46;2 do programa Anthro Plus &#40;Organiza&#231;&#227;o Mundial de Sa&#250;de &#91;OMS&#93;&#44; 2007&#41; foi usada para crian&#231;as de cinco anos a adolescentes de 18 anos&#59; idade do paciente e idade na &#233;poca do diagn&#243;stico&#59; primeiro sintoma cl&#237;nico &#40;um sintoma geral&#44; sintomas pulmonares e digestivos&#41;&#59; per&#237;odo at&#233; a primeira coloniza&#231;&#227;o por <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> mucoide &#40;PAM&#41;&#59; microrganismos identificados na cultura de escarro de rotina &#40;<span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; <span class="elsevierStyleItalic">Achromobacter xylosoxidans</span>&#44; <span class="elsevierStyleItalic">Burkolderia cepacia</span> e <span class="elsevierStyleItalic">Staphylococcus aureus</span> mucoides e n&#227;o mucoides&#41;&#59; satura&#231;&#227;o de oxig&#234;nio no sangue arterial transcut&#226;nea &#40;SaO<span class="elsevierStyleInf">2</span>&#41;&#59; espirometria e comorbidades &#40;p&#243;lipos nasais&#44; osteoporose&#44; &#237;leo meconial&#44; <span class="elsevierStyleItalic">diabetes mellitus</span> e insufici&#234;ncia pancre&#225;tica&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A espirometria foi feita em pacientes com mais de sete anos&#44; com o espir&#244;metro CPFS&#47;D &#40;MedGraphics&#44; Saint Paul&#44; Minnesota&#44; EUA&#41;&#46; Os dados foram registrados pela vers&#227;o 3&#46;8B do <span class="elsevierStyleItalic">software</span> PF BREEZE para Windows 95&#47;98&#47;NT &#40;American Thoracic Society&#41; e avaliados em percentagem de valores preditivos para&#58; capacidade vital for&#231;ada &#40;&#37; de CVF&#41;&#44; volume expirat&#243;rio for&#231;ado no 1&#176; segundo da CVF &#40;VEF<span class="elsevierStyleInf">1</span>&#41;&#44; propor&#231;&#227;o VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#44; fluxo expirat&#243;rio for&#231;ado a 25&#37; da CVF &#40;FEF<span class="elsevierStyleInf">25&#37;</span>&#41;&#44; fluxo expirat&#243;rio for&#231;ado a 50&#37; da CVF &#40;FEF<span class="elsevierStyleInf">50&#37;</span>&#41;&#44; fluxo expirat&#243;rio for&#231;ado a 75&#37; da CVF &#40;FEF<span class="elsevierStyleInf">75&#37;</span>&#41;&#44; fluxo expirat&#243;rio for&#231;ado entre 25&#37; e 75&#37; da CVF &#40;FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#41;&#44; fluxo expirat&#243;rio for&#231;ado m&#225;ximo &#40;FEF<span class="elsevierStyleInf">max</span>&#41; e volume de reserva expirat&#243;ria &#40;VRE&#41;&#46; Os dados da espirometria s&#227;o mostrados em percentual do valor preditivo de acordo com as equa&#231;&#245;es de Polgar e Promadhat &#40;1971&#41;&#59; Pereira et al&#46; &#40;2007&#41; e Duarte et al&#46; &#40;2007&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#8211;16</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Todos os pacientes submetidos a espirometria fizeram o teste antes e 15 minutos ap&#243;s administra&#231;&#227;o dos BD &#91;albutrol&#8211;C<span class="elsevierStyleInf">13</span>H<span class="elsevierStyleInf">21</span>NO<span class="elsevierStyleInf">3</span> &#40;400 mg&#41;&#93;&#46; Os pacientes em terapia com BD foram orientados a interromper a medica&#231;&#227;o oito horas antes da espirometria&#44; caso estivessem em tratamento com BD de curta a&#231;&#227;o&#44; e 48 horas antes&#44; caso estivessem em tratamento com BD de a&#231;&#227;o prolongada&#46; A mudan&#231;a no percentual p&#243;s&#8208;BD foi usada na an&#225;lise estat&#237;stica&#46; Os crit&#233;rios de resposta a BD&#44; definidos como aumento de &#62; 12&#37; e 200 mL de VEF1 inicial&#44; foram usados como o segundo modelo para avaliar a associa&#231;&#227;o entre as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e a resposta a BD&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Extra&#231;&#227;o do DNA e genotipagem</span><p id="par0050" class="elsevierStylePara elsevierViewall">O DNA gen&#244;mico foi extra&#237;do de amostras de sangue perif&#233;rico com o m&#233;todo padr&#227;o fenol&#8208;clorof&#243;rmio e quantificado por espectrofot&#244;metro GE NanoVue&#8482; &#40;GE Healthcare Biosciences&#44; Pittsburgh&#44; EUA&#41;&#46; Neste estudo&#44; a concentra&#231;&#227;o final da amostra foi estabelecida em 50 ng&#47;&#956;L&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">As muta&#231;&#245;es do <span class="elsevierStyleItalic">RTFC</span> foram analisadas por rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#41; &#40;F508del&#41; ap&#243;s digest&#227;o enzim&#225;tica &#40;G542X&#44; R1162X&#44; R553X&#44; G551D e N1303 K&#41;&#46; Outras muta&#231;&#245;es no gene do <span class="elsevierStyleItalic">RTFC</span> podem ser identificadas por sequenciamento ou com o uso do m&#233;todo SALSA MPLA &#40;Amplifica&#231;&#227;o de M&#250;ltiplas Sondas Dependentes de Liga&#231;&#227;o&#41; Kit P091&#8208;C1 CFTR&#8208;MRC&#8208;Holland S4X&#44; 2183A &#62; G&#44; 1717&#8208;G &#62; A&#44; I618 T com MegaBace1000<span class="elsevierStyleSup">&#174;</span> &#40;GE Healthcare Biosciences&#44; Pittsburgh&#44; EUA&#41; e ABI3500 &#40;Biossistemas Aplicados &#8211; Thermo Fisher Scientific&#44; S&#227;o Paulo&#44; Brasil&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">As variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> foram analisadas por PCR ap&#243;s digest&#227;o com enzimas de restri&#231;&#227;o&#46; Para a variante rs4073&#44; foram usados os iniciadores 5&#8217;&#8208;CCA TCA TGA TAG CAT CTG TA&#8208;3&#8242; e 5&#8242;&#8208;CCA CAA TTT GGT GAA TTA TTA A&#8208;3&#8242; e a enzima de restri&#231;&#227;o <span class="elsevierStyleItalic">AseI</span>&#59; para a variante rs2227306&#44; foram usados os iniciadores 5&#8242;&#8208;CTC TAA CTC TTT ATA TAG GAA TT&#8208;3&#8242; e 5&#8242;&#8208;GAT TGA TTT TAT CAA CAG GCA&#8208;3&#8242;&#44; bem como a enzima de restri&#231;&#227;o <span class="elsevierStyleItalic">EcoRI</span>&#59; e para a variante rs2227307&#44; foram usados os iniciadores 5&#8242;&#8208;TAA AGG TTT GAT CAA TAT AGA&#8208;3&#8242; e 5&#8242;&#8208;CTT CCT TCT AAT TCCA ATA TG&#8208;3&#8242;&#44; bem como a enzima de restri&#231;&#227;o <span class="elsevierStyleItalic">ScrFI</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#44;19</span></a> Os produtos da restri&#231;&#227;o enzim&#225;tica foram submetidos a eletroforese em gel de poliacrilamida a 12&#37;&#44; ou gel de agarose a 4&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#44;19</span></a> e corados com gel Red<span class="elsevierStyleSup">&#174;</span>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">An&#225;lise estat&#237;stica</span><p id="par0065" class="elsevierStylePara elsevierViewall">Foi feita com a vers&#227;o 22&#46;0 do SPSS &#40;SPSS Inc&#46;&#44; Chicago&#44; EUA&#41;&#46; Foi usada a vers&#227;o 3&#46;1&#46;9&#46;2<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> do <span class="elsevierStyleItalic">software</span> GPower para calcular o poder da amostra&#44; considerou&#8208;se o gen&#243;tipo das variantes analisadas e adotou&#8208;se o poder para valor acima de 80&#37;&#46; As condi&#231;&#245;es a seguir foram aplicadas para calcular o poder da amostra&#58; &#40;teste de an&#225;lise da vari&#226;ncia no lugar do teste de Kruskal&#8208;Wallis&#44; considerou&#8208;se que a an&#225;lise de vari&#226;ncia &#233; um teste mais forte&#41; tamanho do efeito<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;25&#44; &#945;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#44; poder<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;80&#44; grau de liberdade do numerador<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; n&#250;mero de grupos<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; n&#176; ideal<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>158&#59; &#40;teste de Mann&#8208;Whitney&#8211;bicaudal&#41; tamanho do efeito<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;5&#44; &#945;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#44; poder<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;80&#44; propor&#231;&#227;o de atribui&#231;&#227;o N2&#47;N1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; n&#176; ideal&#8211;134&#59; &#40;teste &#967;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a>&#41; tamanho do efeito<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;3&#44; &#945;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#44; poder<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;80&#44; grau de liberdade<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; n&#176; ideal<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>108&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Os testes de Mann&#8208;Whitney e Kruskal&#8208;Wallis foram usados para compara&#231;&#227;o entre diferentes gen&#243;tipos e os grupos de variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e a resposta a BD&#46; Em caso de diferen&#231;as significativas entre os grupos do teste de Kruskal&#8208;Wallis&#44; foram feitas identifica&#231;&#227;o e avalia&#231;&#227;o adicionais das diferen&#231;as entre os gen&#243;tipos com o <span class="elsevierStyleItalic">software</span> para Windows MedCalc<span class="elsevierStyleSup">&#174;</span>&#44; vers&#227;o 16&#46;1 &#40;MedCalc<span class="elsevierStyleSup">&#174;</span> Software&#44; Ostend&#44; B&#233;lgica&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">O teste &#967;2 e o teste exato de Fisher foram usados para compara&#231;&#227;o entre os diferentes gen&#243;tipos e grupos de variantes do gene da IL&#8208;8 e a resposta a BD definidos como um aumento de &#62; 12&#37; e 200 mL de VEF1 inicial&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Para a identifica&#231;&#227;o de muta&#231;&#245;es no gene do <span class="elsevierStyleItalic">RTFC</span>&#44; os pacientes foram analisados com base em dois contextos&#58; &#40;<span class="elsevierStyleItalic">RTFC</span>&#8208;A&#41; todos os pacientes com FC&#44; independentemente das muta&#231;&#245;es do gene &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>186 pacientes&#41;&#59; &#40;<span class="elsevierStyleItalic">RTFC</span>&#8208;B&#41; pacientes com duas muta&#231;&#245;es pertencentes &#224;s classes I&#44; II e&#47;ou III &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>91 pacientes&#41;&#46; Quanto &#224;s variantes&#44; foram adotados quatro modelos de an&#225;lise&#58; &#40;i&#41; codominante &#40;teste de Kruskal&#8208;Wallis&#41;&#59; &#40;ii&#41; recessivo &#40;teste de Mann&#8208;Whitney&#41;&#59; &#40;iii&#41; dominante &#40;teste de Mann&#8208;Whitney&#41;&#59; &#40;iv&#41; superdominante &#40;teste de Mann&#8208;Whitney&#41;&#44; aplicados em associa&#231;&#227;o &#224;s vari&#225;veis cl&#237;nicas&#46; Para todas as an&#225;lises&#44; o valor alfa foi estabelecido em 0&#44;05&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Para an&#225;lise do equil&#237;brio de Hardy&#8208;Weinberg &#40;HWE&#41; foi usado o <span class="elsevierStyleItalic">software</span> Online Encyclopedia for Genetic Epidemiology Studies &#40;OEGE&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">O teste da taxa de falsa descoberta &#40;FDR&#41; foi aplicado para corrigir a compara&#231;&#227;o m&#250;ltipla de testes&#46; A FDR &#233; uma abordagem ao problema de m&#250;ltiplas compara&#231;&#245;es&#46; Em vez de controlar a chance de qualquer falso&#44; os controles da FDR controlam a propor&#231;&#227;o esperada de falsos positivos entre os resultados significativos&#46; O limite da FDR &#233; determinado a partir da distribui&#231;&#227;o do valor de p observado e&#44; assim&#44; &#233; adaptativo ao valor de sinal nos dados&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> O valor de p &#40;p&#41; e o valor de p corrigido &#40;p<span class="elsevierStyleSup">c</span>&#41; foram mostrados no manuscrito&#46; A an&#225;lise de desequil&#237;brio de liga&#231;&#227;o foi feita na vers&#227;o 4&#46;2 do <span class="elsevierStyleItalic">software</span> Haploview&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Resultados</span><p id="par0095" class="elsevierStylePara elsevierViewall">Os dados cl&#237;nicos e laboratoriais dos pacientes com FC s&#227;o descritos na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; A descri&#231;&#227;o do gen&#243;tipo e da frequ&#234;ncia de alelos das variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> encontra&#8208;se na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46; A <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a> mostra os dados com valores de p e valor de p corrigido para associa&#231;&#227;o das variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span>&#44; consideraram&#8208;se os quatros modelos de an&#225;lise propostos e o gen&#243;tipo do gene do <span class="elsevierStyleItalic">RTFC</span>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">A variante rs2227307 n&#227;o foi associada &#224; resposta a BD em nenhum dos modelos estudados&#59; ao passo que a variante rs2227306 foi associada a FEF<span class="elsevierStyleInf">50&#37;</span> para pacientes com gen&#243;tipo CC &#40;modelo dominante&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;083&#41; e gen&#243;tipo CT &#40;modelo superdominante&#59; 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; no grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>D e E&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Deve&#8208;se enfatizar de modo especial a variante rs4073&#44; associada &#224;s vari&#225;veis de espirometria&#58; FEV<span class="elsevierStyleInf">1</span>&#44; propor&#231;&#227;o VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#44; FEF<span class="elsevierStyleInf">50&#37;</span>&#44; FEF<span class="elsevierStyleInf">75&#37;</span> e FEF<span class="elsevierStyleInf">25&#8208;75&#37;&#46;</span> A menor resposta a BD foi observada para gen&#243;tipo TT &#40;modelo dominante&#41; e pacientes do grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B a VEF<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; e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a> K&#41;&#46; O mesmo foi observado para o grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;A para FEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>H&#41; e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>L&#41;&#46; Na an&#225;lise codominante&#44; o gen&#243;tipo TT apresentou menor resposta a BD para VEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>F&#41; e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a> J&#41;&#44; respectivamente para os grupos <span class="elsevierStyleItalic">RTFC</span>&#8208;A e <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#46; Para o indicador VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#44; o gen&#243;tipo AT nos pacientes do grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B mostrou menor resposta a BD &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>B&#41;&#46; Por fim&#44; nos pacientes dos grupos <span class="elsevierStyleItalic">RTFC</span>&#8208;A e <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#44; respectivamente&#44; o gen&#243;tipo AA &#40;modelo recessivo&#41; para rs4073 mostrou maior resposta a BD para FEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>I&#41; e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a> M&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">A distribui&#231;&#227;o de hapl&#243;tipos para as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> &#233; apresentada na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Para compara&#231;&#227;o entre as variantes do gene da IL&#8208;8 e a resposta a BD definida como aumento de &#62; 12&#37; e 200 mL de VEF1 inicial&#44; n&#227;o foi encontrada associa&#231;&#227;o positiva &#40;p &#62; 0&#44;05&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discuss&#227;o</span><p id="par0120" class="elsevierStylePara elsevierViewall">Mostramos anteriormente a influ&#234;ncia das diferentes variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> sobre a gravidade cl&#237;nica da FC&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> Al&#233;m disso&#44; este estudo mostra a associa&#231;&#227;o das diferentes variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e sua modula&#231;&#227;o &#224; resposta a BD&#44; avalia o impacto do medicamento sobre a fun&#231;&#227;o pulmonar&#46; A variabilidade das respostas aos BD &#233; determinada por v&#225;rios fatores&#44; como inflama&#231;&#227;o e obstru&#231;&#227;o pulmonar&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> bact&#233;rias<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> e sintomas pulmonares&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> bem como genes modificadores&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> Contudo&#44; at&#233; agora&#44; nenhum estudo investigou o papel da <span class="elsevierStyleItalic">IL&#8208;8</span> como mediador pr&#243;&#8208;inflamat&#243;rio de FC e sua rela&#231;&#227;o aos BD e se as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> podem explicar a resposta individual aos BD na FC&#46; Acredita&#8208;se que os beta&#8208;2 agonistas de curta e longa dura&#231;&#227;o podem ser ben&#233;ficos para pacientes com FC e com hiperresponsividade br&#244;nquica positiva&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Em doen&#231;as pulmonares progressivas&#44; foram avaliados diferentes marcadores e o uso dos BD parece fornecer melhor resposta ao FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#44; em compara&#231;&#227;o com outros marcadores&#44; o que indica envolvimento de vias a&#233;reas de menor calibre na FC&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> Nosso estudo&#44; em concord&#226;ncia com a literatura de refer&#234;ncia&#44; encontrou uma associa&#231;&#227;o da variante rs4073 para o marcador FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> nos modelos dominante &#40;para os grupos <span class="elsevierStyleItalic">RTFC</span>&#8208;A e <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#41;&#44; codominante &#40;grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#41; e recessivo &#40;grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#41;&#46; Houve melhoria em diversos outros marcadores de espirometria para rs4073&#44; como VEF<span class="elsevierStyleInf">1</span>&#44; VEF<span class="elsevierStyleInf">1</span>&#47;CVF e FEF<span class="elsevierStyleInf">50&#37;</span> e FEF<span class="elsevierStyleInf">75&#37;</span>&#44; o que mostra impacto sobre os padr&#245;es de respira&#231;&#227;o dos pacientes&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">O estudo de Hillian et al&#46; encontrou uma associa&#231;&#227;o das variantes rs2227307 e rs4073 do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e a gravidade da doen&#231;a pulmonar&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> Nesse estudo&#44; os pacientes foram divididos em duas coortes&#58; &#40;1&#41; pacientes homozigotos F508del&#59; &#40;2&#41; pacientes com outros gen&#243;tipos do gene do <span class="elsevierStyleItalic">RTFC</span>&#46; Na coorte 1&#44; as variantes rs4073&#44; rs2227306 e rs2227543 n&#227;o foram associadas a doen&#231;a pulmonar e a variante rs22227307 mostrou associa&#231;&#227;o&#44; independentemente do sexo&#46; Na coorte 2&#44; as variantes rs4073 e rs2227306 foram associadas a gravidade da doen&#231;a pulmonar em homens&#46; Assim&#44; o sexo do paciente&#44; o gen&#243;tipo do gene do <span class="elsevierStyleItalic">RTFC</span> e os genes modificadores podem modular a gravidade da doen&#231;a pulmonar&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> Nesse estudo&#44; o gen&#243;tipo rs2227307 n&#227;o teve impacto sobre a variabilidade da resposta a BD&#46; Isso sugere que&#44; apesar de esse gen&#243;tipo estar associado a doen&#231;a pulmonar em pacientes homozigotos F508del&#44; sua resposta a BD n&#227;o &#233; relevante&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">O alvo dos BD &#233; a prote&#237;na ADRB2&#44; expressa no m&#250;sculo liso das vias a&#233;reas&#46; As variantes de ADRB2 est&#227;o associadas &#224; resposta &#224; medica&#231;&#227;o&#46; Essa prote&#237;na foi amplamente estudada em asma e ainda muito raramente em FC&#46; A efic&#225;cia da resposta a BD e aos corticosteroides inalat&#243;rios no manejo de inflama&#231;&#227;o das vias a&#233;reas em asma est&#225; confirmada e depende das variantes Arg16Gly &#40;rs1042713&#59; c&#46;46A<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#41; e Glu27Gln &#40;rs1042714&#59; c&#46;79C<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#41; do gene <span class="elsevierStyleItalic">ADRB2</span>&#46;&#91;29&#93; A variante Gln27Glu concede resist&#234;ncia &#224; prote&#237;na ADRB2 na resposta a BD&#46; Os alelos 46&#42;G e 79&#42;G protegem contra asma&#44; reduzem o risco em 27&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> As variantes do alelo G induzem altera&#231;&#245;es na regula&#231;&#227;o do receptor&#44; devido ao aumento da susceptibilidade &#224; degrada&#231;&#227;o de prote&#237;nas&#46; Este estudo constatou que as variantes Arg16Gly e Gln27Glu do gene <span class="elsevierStyleItalic">ADRB2</span> influenciam a respostas aos BD na FC&#46; Na espirometria e em outros marcadores de gravidade&#44; a variante Arg16Gly mostrou associa&#231;&#227;o positiva&#44; ao contr&#225;rio da variante Gln27Glu&#46; O gen&#243;tipo Arg&#47;Arg da variante Arg16Gly foi associado a melhores valores de VEF<span class="elsevierStyleInf">1</span> e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#46; A resposta a BD nas an&#225;lises de hapl&#243;tipo foi positiva na aus&#234;ncia dos gen&#243;tipos Gly16Gly e Glu27Glu para a propor&#231;&#227;o VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">As variantes de ADRB2&#44; capacidade de difus&#227;o dos pulm&#245;es para&#160;mon&#243;xido de carbono&#44; condut&#226;ncia da membrana capilar alveolar&#44; volume sangu&#237;neo na capilar alveolar e SaO<span class="elsevierStyleInf">2</span>&#44; foram avaliadas na resposta a BD em 18 pacientes e 20 controles saud&#225;veis&#44; antes e depois da administra&#231;&#227;o de salbutamol &#40;30&#44; 60 e 90 minutos&#41;&#46; Os indiv&#237;duos saud&#225;veis n&#227;o apresentaram altera&#231;&#245;es nos marcadores avaliados para a variante Glu27Glu&#46; Contudo&#44; na FC&#44; essa variante influenciou a resposta a BD&#58; a melhor resposta encontrada na presen&#231;a de pelo menos um alelo 27Glu&#46; Houve uma diferen&#231;a de difus&#227;o pulmonar e SaO<span class="elsevierStyleInf">2</span> perif&#233;rica de acordo com a varia&#231;&#227;o do gene <span class="elsevierStyleItalic">ADRB2</span> na posi&#231;&#227;o 27 e a dosagem do medicamento deve ser prescrita de acordo com essa varia&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">A maior parte dos estudos foca nas variantes do gene ADRB2 na resposta a BD&#46; Contudo&#44; este estudo demonstra que&#44; mesmo indiretamente&#44; as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e possivelmente em outros genes&#44; que modulam a resposta pulmonar inflamat&#243;ria&#44; podem potencializar ou diminuir o efeito dos BD e&#44; ainda&#44; influenciar a resposta ao medicamento&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Com rela&#231;&#227;o ao HWE&#44; conforme discutido anteriormente por nosso grupo&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> duas variantes &#40;rs4073 e rs2227306&#41; n&#227;o estavam em equil&#237;brio&#46; Devemos lembrar que o HWE pressup&#245;e uma popula&#231;&#227;o ideal&#44; sem a interfer&#234;ncia de fatores evolucion&#225;rios&#46; Contudo&#44; em genes envolvidos em controle de imunidade&#44; inflama&#231;&#227;o e infec&#231;&#227;o&#44; o desequil&#237;brio do HWE parecer estar associado de forma secund&#225;ria aos mecanismos de sele&#231;&#227;o que favoreceram um alelo espec&#237;fico que pode trazer uma resposta mais efetiva&#46; O desequil&#237;brio n&#227;o invalida o estudo de associa&#231;&#227;o&#44; pois os grupos fazem parte da mesma popula&#231;&#227;o&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Limita&#231;&#245;es do estudo&#58; &#40;i&#41; banco de dados transversal &#40;a resposta a BD foi avaliada em um &#250;nico momento&#41;&#59; &#40;ii&#41; h&#225; v&#225;rios dados ausentes&#44; se levarmos em considera&#231;&#227;o os problemas para obter as informa&#231;&#245;es nos registros&#59; &#40;iii&#41; caso a resposta a BD seja diferente com base no VEF<span class="elsevierStyleInf">1</span> de base&#44; principalmente em indiv&#237;duos saud&#225;veis&#59; &#40;iv&#41; poss&#237;veis vari&#225;veis de confus&#227;o com rela&#231;&#227;o aos resultados&#44; como gravidade da doen&#231;a&#44; terapias atuais&#44; ades&#227;o &#224; medica&#231;&#227;o e esfor&#231;o adequado no teste de fun&#231;&#227;o pulmonar&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">As variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> &#40;rs2227306 e especialmente rs4073&#41; podem estar associadas &#224; resposta a BD durante a espirometria&#46; Esse medicamento pode ser uma op&#231;&#227;o para o tratamento da doen&#231;a&#44; na maior parte do tempo em pacientes com vias a&#233;reas de menor calibre&#46; Devem&#8208;se conduzir estudos que envolvam dose e combina&#231;&#245;es de medicamentos para determinar o melhor tratamento de acordo com o gen&#243;tipo do paciente com FC&#44; o gene do <span class="elsevierStyleItalic">RTFC</span>&#44; bem como os genes modificadores&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Financiamento</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;Fapesp&#41;&#44; em apoio &#224;s pesquisas n&#176; 2011&#47;12939&#8208;4&#44; n&#176; 2011&#47;18845&#8208;1&#44; n&#176; 2015&#47;12183&#8208;8 e n&#176; 2015&#47;12858&#8208;5&#59; Fundo de Apoio &#224; Pesquisa&#44; ao Ensino e &#224; Extens&#227;o da Universidade Estadual de Campinas&#44; em apoio &#224; pesquisa n&#176; 0648&#47;2015&#59; JDR&#58; Fapesp&#44; em apoio &#224;s pesquisas n&#176; 2011&#47;18845&#8208;1 e n&#176; 2015&#47;12183&#8208;8&#46; LLF&#58; Fapesp&#44; em apoio &#224; pesquisa n&#176; 2013&#47;19052&#8208;0&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflitos de interesse</span><p id="par0170" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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              "titulo" => "Vari&#225;veis cl&#237;nicas"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0085" 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="spar0090" 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&#8208;Whitney and Kruskal&#8208;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="spar0095" 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&#8208;dominant &#40;FEF<span class="elsevierStyleInf">25&#8208;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&#8208;75&#37;</span>&#41;&#44; recessive &#40;FEF<span class="elsevierStyleInf">75&#37;</span> and FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#41;&#44; and over&#8208;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="spar0100" 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>"
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        "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objetivo</span><p id="spar0105" 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="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">M&#233;todos</span><p id="spar0110" 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&#8208;Whitney e Kruskal&#8208;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="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Resultados</span><p id="spar0115" 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&#8208;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&#8208;75&#37;</span>&#41;&#44; recessivo &#40;FEF<span class="elsevierStyleInf">75&#37;</span> e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#41; e overdominante &#40;VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#41;&#46;</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conclus&#245;es</span><p id="spar0120" 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>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0030">Como citar este artigo&#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>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0035">Estudo feito na Universidade Estadual de Campinas &#40;Unicamp&#41;&#44; Campinas&#44; SP&#44; Brasil&#46;</p>"
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          "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; 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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>"
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          "leyenda" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">N&#44; tamanho da amostra&#59; <span class="elsevierStyleItalic">RTFC</span>&#44; regulador da condut&#226;ncia transmembrana da fibrose c&#237;stica&#46;</p>"
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                  <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">Gen&#243;tipo&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">N&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">Grupo de pacientes&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="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>&#47;&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29&#44;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="top">Pacientes sem muta&#231;&#227;o no gene do <span class="elsevierStyleItalic">RTFC</span> ou com uma ou duas muta&#231;&#245;es pertences &#224;s classes IV&#44; V ou VI</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">V562I&#47;&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;R668 C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&#47;TG11&#8208;5 T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#44;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="top">Pacientes com uma muta&#231;&#227;o do RTFC pertencentes &#224;s classes I&#44; II ou III e uma muta&#231;&#227;o n&#227;o identificada ou pertencentes &#224;s classes IV&#44; V ou VI</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">G542X&#47;&#8208;&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&#44;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&#8208;26A<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;R334 W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&#47;L206 W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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&#8208;2A<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#47;711<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;I618 T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#44;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="top">Pacientes com duas muta&#231;&#245;es do <span class="elsevierStyleItalic">RTFC</span> pertencentes &#224;s classes I&#44; II e&#47;ou III<br><span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>Muta&#231;&#245;es G2<br>&#40;grupo <span class="elsevierStyleItalic">CFTR&#8208;B</span>&#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="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&#44;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;N1303 K&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&#44;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="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&#44;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="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&#44;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&#8208;18672pbA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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&#8208;1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&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&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<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&#47;R1066 C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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">Duplica&#231;&#227;o do &#233;xon F508del&#47;6B a 16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;R1066 C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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&#8208;1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&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&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<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#47;2183AA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&#47;3120<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Todos os pacientes avaliados neste estudo foram inclu&#237;dos &#40;grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;A&#41;&#46;</p>"
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          "pt" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Distribui&#231;&#227;o dos pacientes com fibrose c&#237;stica para gen&#243;tipo do <span class="elsevierStyleItalic">RTFC</span> e classes de muta&#231;&#245;es identificadas&#46;<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></p>"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">CVF&#44; capacidade vital for&#231;ada&#59; FEF<span class="elsevierStyleInf">25&#37;</span>&#44; fluxo expirat&#243;rio for&#231;ado a 25&#37; da CVF&#59; FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#44; m&#233;dio do fluxo expirat&#243;rio for&#231;ado entre 25&#37; e 75&#37; da CVF&#59; FEF<span class="elsevierStyleInf">50&#37;</span>&#44; fluxo expirat&#243;rio for&#231;ado a 50&#37; da CVF&#59; FEF<span class="elsevierStyleInf">75&#37;</span>&#44; fluxo expirat&#243;rio for&#231;ado a 75&#37; da CVF&#59; FEF<span class="elsevierStyleInf">max</span>&#44; fluxo expirat&#243;rio for&#231;ado m&#225;ximo&#59; SaO<span class="elsevierStyleInf">2</span>&#44; satura&#231;&#227;o de oxig&#234;nio no sangue arterial&#59; VEF<span class="elsevierStyleInf">1</span>&#44; volume expirat&#243;rio for&#231;ado no 1&#176; segundo da CVF&#59; VRE&#44; volume de reserva expirat&#243;ria&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Os dados da espirometria s&#227;o mostrados em percentual de valor preditivo&#46; Todos os pacientes avaliados s&#227;o descritos&#46;</p>"
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                  \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">Vari&#225;veis&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">Distribui&#231;&#227;o<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">Sexo &#40;masculino&#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&#44;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">Etnia &#40;branca&#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&#44;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">Idade &#40;meses&#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&#44;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>171&#44;98&#59; 143 &#40;7 a 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">In&#237;cio dos sintomas &#40;meses&#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&#44;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>114&#44;03&#59; 3 &#40;0 a 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">Diagn&#243;stico &#40;meses&#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&#44;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>158&#44;39&#59; 20 &#40;0 a 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">In&#237;cio dos sintomas digestivos &#40;meses&#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&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>112&#44;61&#59; 3 &#40;0 a 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">In&#237;cio dos sintomas pulmonares &#40;meses&#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&#44;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>123&#44;64&#59; 6 &#40;0 a 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">&#205;ndice de massa corporal</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&#44;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;08&#59; 16&#44;28 &#40;6&#44;5 a 35&#44;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">Polipose nasal &#40;presen&#231;a&#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&#44;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">Diabetes mellitus <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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">Osteoporose &#40;presen&#231;a&#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&#44;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">Insufici&#234;ncia pancre&#225;tica &#40;presen&#231;a&#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&#44;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">&#205;leo meconial &#40;presen&#231;a&#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&#44;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">1&#170;</span> Pseudomonas aeruginosa&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&#44;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>171&#44;74&#59; 31 &#40;0 a 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">P&#46; aeruginosa mucoide <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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">P&#46; aeruginosa <span class="elsevierStyleItalic">n&#227;o mucoide &#40;presen&#231;a&#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&#44;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">Achromobacter xylosoxidans <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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">Burkolderia cepacia <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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">Staphylococcus aureus <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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&#44;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;28&#59; 96 &#40;66 a 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">Escore de Bhalla</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&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;77&#59; 8 &#40;0 a 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">Escore de Kanga</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&#44;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;82&#59; 17&#44;5 &#40;10 a 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">Escore de Shwachman&#8208;Kulczycki</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&#44;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;78&#59; 65 &#40;20 a 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">CVF</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&#44;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#44;86&#59; 77 &#40;19 a 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&#44;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#44;75&#59; 63 &#40;17 a 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">VEF</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span><span class="elsevierStyleItalic">&#47;CVF</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&#44;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;99&#59; 81 &#40;39 a 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&#44;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#44;71&#59; 60 &#40;7 a 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&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#44;25&#59; 40 &#40;3 a 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&#44;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>28&#44;77&#59; 27&#44;5 &#40;4 a 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&#8208;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&#44;16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#44;51&#59; 39 &#40;5 a 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&#44;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#44;59&#59; 73&#44;5 &#40;25 a 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">VRE</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&#44;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>52&#44;39&#59; 69 &#40;3 a 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">Resposta a broncodilatador inalat&#243;rio</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>CVF&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&#44;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;19&#59; 1 &#40;&#8722;17 a 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&#44;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;0&#59; 3 &#40;&#8722;12 a 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>VEF<span class="elsevierStyleInf">1</span>&#47;CVF&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&#44;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;43&#59; 2 &#40;&#8722;19 a 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&#44;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#44;41&#59; 5 &#40;&#8722;45 a 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&#44;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#44;06&#59; 9 &#40;&#8722;41 a 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&#44;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>46&#44;47&#59; 16 &#40;&#8722;64 a 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&#8208;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&#44;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#44;77&#59; 9&#44;5 &#40;&#8722;51 a 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&#44;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;48&#59; 3 &#40;&#8722;42 a 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>VRE&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&#44;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>101&#44;08&#59; 0 &#40;&#8722;90 a 670&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1580261.png"
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            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Os dados com distribui&#231;&#227;o categ&#243;rica s&#227;o apresentados da seguinte forma&#58; n&#176; de vari&#225;veis&#47;n&#176; total &#40;percentual&#41;&#59; os dados com distribui&#231;&#227;o num&#233;rica s&#227;o apresentados da seguinte forma&#58; tamanho da amostra&#59; m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desvio padr&#227;o&#59; mediana &#40;m&#237;nimo a m&#225;ximo&#41;&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Os valores ausentes para primeira <span class="elsevierStyleItalic">P&#46; aeruginosa</span> correspondem a pacientes com fibrose c&#237;stica que nunca apresentaram cultura positiva para <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Um paciente com fibrose c&#237;stica apresentou cultura positiva para <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; com valores negativos para IgG espec&#237;fico do ant&#237;geno <span class="elsevierStyleItalic">P&#46; aeruginosa</span> e o paciente foi exclu&#237;do para estimativa de frequ&#234;ncia&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">An&#225;lise descritiva dos marcadores cl&#237;nicos e laboratoriais de pacientes com fibrose c&#237;stica</p>"
        ]
      ]
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        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">fa&#44; frequ&#234;ncia absoluta&#59; <span class="elsevierStyleItalic">IL&#8208;8</span>&#44; interleucina 8&#59; &#37;&#44; percentual&#59; &#967;<span class="elsevierStyleSup">2</span>&#44; qui&#8208;quadrado&#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">Variantes&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">Gen&#243;tipo&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">N&#250;mero &#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">Alelo&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">N&#250;mero &#40;fa&#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">&#967;<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">Valor de p<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&#44;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&#44;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="top">3&#44;94</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">&#60; 0&#44;05</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&#44;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&#44;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&#44;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&#44;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="top">8&#44;21</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">&#60; 0&#44;05</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&#44;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&#44;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&#44;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&#44;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&#44;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="top">1&#44;48</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;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&#44;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&#44;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&#44;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>
                  """
              ]
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                0 => "xTab1580260.png"
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            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">Frequ&#234;ncia&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">Percentual &#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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;0&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&#44;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&#44;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&#44;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&#44;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&#44;0&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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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 => "xTab1580262.png"
              ]
            ]
          ]
          "notaPie" => array:1 [
            0 => array:3 [
              "identificador" => "tblfn0025"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">&#967;<span class="elsevierStyleSup">2</span> e valores de p fazem refer&#234;ncia ao c&#225;lculo de equil&#237;brio de Hardy&#8208;Weinberg&#46; Os dados significativos s&#227;o mostrados em negrito&#46; Houve uma fraca correla&#231;&#227;o entre as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> nos pacientes com fibrose c&#237;stica inscritos no estudo&#46; N&#227;o h&#225; desequil&#237;brio de liga&#231;&#227;o&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Distribui&#231;&#227;o de gen&#243;tipos&#44; alelos e hapl&#243;tipo das variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> &#40;rs4073&#44; rs2227306 e rs2227307&#41; em pacientes com fibrose c&#237;stica</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "Refer&#234;ncias"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "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"
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Cyst Fibros"
                        "fecha" => "2002"
                        "volumen" => "1"
                        "paginaInicial" => "13"
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            2 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Essential involvement of interleukin&#8208;8 &#40;IL&#8208;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 [
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                        ]
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                ]
              ]
            ]
            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"
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                          ]
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Cochrane Database Syst Rev"
                        "fecha" => "2005"
                        "volumen" => "19"
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            ]
            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&#8208;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"
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                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20425849"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
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Artigo Original
Variants in the interleukin 8 gene and the response to inhaled bronchodilators in cystic fibrosis
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,
Autor para correspondência
fernandolimamarson@hotmail.com

Autor para correspondência.
a Faculdade de Medicina de São José do Rio Preto, São José do Rio Preto, SP, Brasil
b Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Pediatria, Campinas, SP, Brasil
c Universidade Estadual de Campinas (Unicamp), Faculdade de Ciências Médicas, Departamento de Genética Médica, Campinas, SP, Brasil
d Faculdade de Medicina de São José do Rio Preto, Hospital Universitário, Departamento de Pediatria, São José do Rio Preto, SP, Brasil
e Faculdade de Medicina de São José do Rio Preto, Hospital Universitário, Departamento de Pneumologia Pediátrica, São José do Rio Preto, SP, Brasil
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, Brasil
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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>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Introdu&#231;&#227;o</span><p id="par0005" class="elsevierStylePara elsevierViewall">A resposta a broncodilatadores inalat&#243;rios &#40;BD&#41; na fibrose c&#237;stica &#40;FC&#41; &#40;OMIM&#58; n&#176; 219700&#41; &#233; muito vari&#225;vel e depende do gen&#243;tipo do <span class="elsevierStyleItalic">RTFC</span> &#40;Regulador da Condut&#226;ncia Transmembrana da Fibrose C&#237;stica&#41;&#44; dos sintomas pulmonares e&#44; principalmente&#44; de variantes nos genes modificadores&#44; como o Receptor Adren&#233;rgico Beta 2 &#40;<span class="elsevierStyleItalic">ADRB2</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> At&#233; agora&#44; apenas alguns estudos investigaram essa resposta&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">As muta&#231;&#245;es no gene do <span class="elsevierStyleItalic">RTFC</span> causam FC&#44; devido a defici&#234;ncia&#44; disfun&#231;&#227;o ou aus&#234;ncia da prote&#237;na do <span class="elsevierStyleItalic">RTFC</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> A FC &#233; caracterizada por um ciclo cont&#237;nuo de inflama&#231;&#227;o cr&#244;nica das vias a&#233;reas&#44; que pode ser exacerbada pela interleucina 8 &#40;<span class="elsevierStyleItalic">IL&#8208;8</span>&#41;&#44; um importante mediador pr&#243;&#8208;inflamat&#243;rio&#46; A <span class="elsevierStyleItalic">IL&#8208;8</span> &#233; respons&#225;vel por iniciar e aumentar a resposta provocadora na presen&#231;a de pat&#243;genos espec&#237;ficos&#44; causa ativa&#231;&#227;o e migra&#231;&#227;o de neutr&#243;filos do sangue perif&#233;rico para os tecidos&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> A inflama&#231;&#227;o cr&#244;nica das vias a&#233;reas &#233; o caminho comum final de les&#227;o pulmonar&#46; Ela &#233; respons&#225;vel pelo aumento na permeabilidade vascular&#44; contribui para edema intersticial&#44; alveolar e das vias a&#233;reas&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">O tratamento da doen&#231;a pulmonar na FC inclui anti&#8208;inflamat&#243;rios&#44; corticosteroides inalat&#243;rios&#44; antibi&#243;ticos&#44; mucol&#237;tico&#44; solu&#231;&#227;o salina hipert&#244;nica e fisioterapia&#46; Dentre as poss&#237;veis terapias&#44; h&#225; pouca comprova&#231;&#227;o que corrobore um papel dos BD na FC&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;5</span></a> Contudo&#44; os BD normalmente s&#227;o prescritos por um tempo maior devido a epis&#243;dios de pieira e dispneia na FC&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a> Os BD reduzem a libera&#231;&#227;o de mediadores&#44; respons&#225;veis pelo recrutamento e pela ativa&#231;&#227;o de c&#233;lulas inflamat&#243;rias&#44; ativam a neurotransmiss&#227;o colin&#233;rgica&#44; e por melhorar a permeabilidade vascular&#46; Eles tamb&#233;m aumentam o transporte mucociliar&#44; levam &#224; redu&#231;&#227;o da inflama&#231;&#227;o pulmonar&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a> A resposta a BD depende&#44; em parte&#44; da prote&#237;na do <span class="elsevierStyleItalic">RTFC</span>&#44; que interage com a prote&#237;na do ADRB2 para promover broncodilata&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> A espirometria &#233; o principal m&#233;todo de avaliar a fun&#231;&#227;o pulmonar&#44; a gravidade e a progress&#227;o da doen&#231;a&#44; bem como a resposta a BD&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Inflama&#231;&#227;o neutrof&#237;lica intensa e baixa hiperreactividade br&#244;nquica s&#227;o caracter&#237;sticas comumente observadas na FC&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> Ademais&#44; a resposta das variantes gen&#233;ticas aos BD &#233; pouco conhecida&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> Pode&#8208;se destacar o papel da <span class="elsevierStyleItalic">IL&#8208;8</span> no componente neutrof&#237;lico da doen&#231;a pulmonar na FC&#46; Os genes que podem estar associados &#224; gravidade da FC e possivelmente &#224; resposta a BD foram relatados aqui e na literatura cient&#237;fica de todo o mundo&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">1&#44;10&#8211;12</span></a> O gene da <span class="elsevierStyleItalic">IL&#8208;8</span> deve ser destacado&#44; pois ele tem influ&#234;ncia direta sobre a inflama&#231;&#227;o pulmonar e pode ser eficaz na resposta a BD&#46; Portanto&#44; este estudo comparou as variantes gen&#233;ticas da <span class="elsevierStyleItalic">IL&#8208;8</span> rs4073&#44; rs2227306 e rs2227307 com a resposta a BD em pacientes com FC&#44; com o uso da espirometria&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Material e m&#233;todos</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Pacientes</span><p id="par0025" class="elsevierStylePara elsevierViewall">Foi conduzido um estudo transversal com 186 pacientes com FC&#44; selecionados em dois centros universit&#225;rios de refer&#234;ncia &#40;Faculdade de Medicina de S&#227;o Jos&#233; do Rio Preto e Universidade de Campinas&#41; para tratamento de FC&#44; de 2013 a 2015&#46; O estudo foi aprovado pelo Comit&#234; de &#201;tica em Pesquisa da Universidade Estadual de Campinas&#44; S&#227;o Paulo&#44; Brasil &#40;n&#176; 528&#47;2008&#41;&#46; Todos os participantes foram informados sobre o estudo e assinaram o Documento de Consentimento Informado&#46; Para os pacientes com menos de 18 anos&#44; o Consentimento Informado foi assinado pelo pai&#47;m&#227;e ou guardi&#227;o&#46; O estudo seguiu as recomenda&#231;&#245;es da Declara&#231;&#227;o de Helsinque&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">O diagn&#243;stico de FC foi confirmado pela presen&#231;a de duas concentra&#231;&#245;es alteradas de s&#243;dio e cloreto no suor &#40;n&#237;vel de cloreto acima de 60 mEq&#47;L&#41;&#46; Al&#233;m disso&#44; nenhum paciente foi submetido a teste inicial de tripsinog&#234;nio imunorreativo &#40;IRT&#41;&#46; Em um grupo de 91 pacientes&#44; houve duas muta&#231;&#245;es no gene do <span class="elsevierStyleItalic">RTFC</span> pertencentes &#224;s classes I&#44; II e&#47;ou III &#40;associadas &#224; maior gravidade da doen&#231;a&#44; devido &#224; aus&#234;ncia ou n&#227;o funcionalidade da prote&#237;na do <span class="elsevierStyleItalic">RTFC</span>&#41;&#59;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a> 60 pacientes n&#227;o apresentaram muta&#231;&#227;o identificada do gene do <span class="elsevierStyleItalic">RTFC</span> ou apresentaram duas muta&#231;&#245;es que pertencem &#224;s classes IV&#44; V ou VI&#59; e 35 pacientes apresentaram uma muta&#231;&#227;o no gene do <span class="elsevierStyleItalic">RTFC</span> que pertence &#224;s classes I&#44; II ou III e uma muta&#231;&#227;o n&#227;o identificada ou pertencente &#224;s classes IV&#44; V ou VI &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Vari&#225;veis cl&#237;nicas</span><p id="par0035" class="elsevierStylePara elsevierViewall">As seguintes vari&#225;veis foram analisadas&#58; escores cl&#237;nicos &#40;Shwachman&#8208;Kulczycki&#44; Kanga e Bhalla&#41;&#59; &#237;ndice de massa corporal &#40;IMC&#41; de pacientes com mais de 18 anos&#44; com a f&#243;rmula IMC<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>peso&#47;altura&#59;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a> a vers&#227;o 3&#46;0&#46;1 do programa Anthro &#40;Organiza&#231;&#227;o Mundial de Sa&#250;de &#91;OMS&#93;&#44; 2006&#41; foi usada para crian&#231;as com menos de cinco anos e a vers&#227;o 1&#46;0&#46;2 do programa Anthro Plus &#40;Organiza&#231;&#227;o Mundial de Sa&#250;de &#91;OMS&#93;&#44; 2007&#41; foi usada para crian&#231;as de cinco anos a adolescentes de 18 anos&#59; idade do paciente e idade na &#233;poca do diagn&#243;stico&#59; primeiro sintoma cl&#237;nico &#40;um sintoma geral&#44; sintomas pulmonares e digestivos&#41;&#59; per&#237;odo at&#233; a primeira coloniza&#231;&#227;o por <span class="elsevierStyleItalic">Pseudomonas aeruginosa</span> mucoide &#40;PAM&#41;&#59; microrganismos identificados na cultura de escarro de rotina &#40;<span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; <span class="elsevierStyleItalic">Achromobacter xylosoxidans</span>&#44; <span class="elsevierStyleItalic">Burkolderia cepacia</span> e <span class="elsevierStyleItalic">Staphylococcus aureus</span> mucoides e n&#227;o mucoides&#41;&#59; satura&#231;&#227;o de oxig&#234;nio no sangue arterial transcut&#226;nea &#40;SaO<span class="elsevierStyleInf">2</span>&#41;&#59; espirometria e comorbidades &#40;p&#243;lipos nasais&#44; osteoporose&#44; &#237;leo meconial&#44; <span class="elsevierStyleItalic">diabetes mellitus</span> e insufici&#234;ncia pancre&#225;tica&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">A espirometria foi feita em pacientes com mais de sete anos&#44; com o espir&#244;metro CPFS&#47;D &#40;MedGraphics&#44; Saint Paul&#44; Minnesota&#44; EUA&#41;&#46; Os dados foram registrados pela vers&#227;o 3&#46;8B do <span class="elsevierStyleItalic">software</span> PF BREEZE para Windows 95&#47;98&#47;NT &#40;American Thoracic Society&#41; e avaliados em percentagem de valores preditivos para&#58; capacidade vital for&#231;ada &#40;&#37; de CVF&#41;&#44; volume expirat&#243;rio for&#231;ado no 1&#176; segundo da CVF &#40;VEF<span class="elsevierStyleInf">1</span>&#41;&#44; propor&#231;&#227;o VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#44; fluxo expirat&#243;rio for&#231;ado a 25&#37; da CVF &#40;FEF<span class="elsevierStyleInf">25&#37;</span>&#41;&#44; fluxo expirat&#243;rio for&#231;ado a 50&#37; da CVF &#40;FEF<span class="elsevierStyleInf">50&#37;</span>&#41;&#44; fluxo expirat&#243;rio for&#231;ado a 75&#37; da CVF &#40;FEF<span class="elsevierStyleInf">75&#37;</span>&#41;&#44; fluxo expirat&#243;rio for&#231;ado entre 25&#37; e 75&#37; da CVF &#40;FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#41;&#44; fluxo expirat&#243;rio for&#231;ado m&#225;ximo &#40;FEF<span class="elsevierStyleInf">max</span>&#41; e volume de reserva expirat&#243;ria &#40;VRE&#41;&#46; Os dados da espirometria s&#227;o mostrados em percentual do valor preditivo de acordo com as equa&#231;&#245;es de Polgar e Promadhat &#40;1971&#41;&#59; Pereira et al&#46; &#40;2007&#41; e Duarte et al&#46; &#40;2007&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#8211;16</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Todos os pacientes submetidos a espirometria fizeram o teste antes e 15 minutos ap&#243;s administra&#231;&#227;o dos BD &#91;albutrol&#8211;C<span class="elsevierStyleInf">13</span>H<span class="elsevierStyleInf">21</span>NO<span class="elsevierStyleInf">3</span> &#40;400 mg&#41;&#93;&#46; Os pacientes em terapia com BD foram orientados a interromper a medica&#231;&#227;o oito horas antes da espirometria&#44; caso estivessem em tratamento com BD de curta a&#231;&#227;o&#44; e 48 horas antes&#44; caso estivessem em tratamento com BD de a&#231;&#227;o prolongada&#46; A mudan&#231;a no percentual p&#243;s&#8208;BD foi usada na an&#225;lise estat&#237;stica&#46; Os crit&#233;rios de resposta a BD&#44; definidos como aumento de &#62; 12&#37; e 200 mL de VEF1 inicial&#44; foram usados como o segundo modelo para avaliar a associa&#231;&#227;o entre as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e a resposta a BD&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Extra&#231;&#227;o do DNA e genotipagem</span><p id="par0050" class="elsevierStylePara elsevierViewall">O DNA gen&#244;mico foi extra&#237;do de amostras de sangue perif&#233;rico com o m&#233;todo padr&#227;o fenol&#8208;clorof&#243;rmio e quantificado por espectrofot&#244;metro GE NanoVue&#8482; &#40;GE Healthcare Biosciences&#44; Pittsburgh&#44; EUA&#41;&#46; Neste estudo&#44; a concentra&#231;&#227;o final da amostra foi estabelecida em 50 ng&#47;&#956;L&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">As muta&#231;&#245;es do <span class="elsevierStyleItalic">RTFC</span> foram analisadas por rea&#231;&#227;o em cadeia da polimerase &#40;PCR&#41; &#40;F508del&#41; ap&#243;s digest&#227;o enzim&#225;tica &#40;G542X&#44; R1162X&#44; R553X&#44; G551D e N1303 K&#41;&#46; Outras muta&#231;&#245;es no gene do <span class="elsevierStyleItalic">RTFC</span> podem ser identificadas por sequenciamento ou com o uso do m&#233;todo SALSA MPLA &#40;Amplifica&#231;&#227;o de M&#250;ltiplas Sondas Dependentes de Liga&#231;&#227;o&#41; Kit P091&#8208;C1 CFTR&#8208;MRC&#8208;Holland S4X&#44; 2183A &#62; G&#44; 1717&#8208;G &#62; A&#44; I618 T com MegaBace1000<span class="elsevierStyleSup">&#174;</span> &#40;GE Healthcare Biosciences&#44; Pittsburgh&#44; EUA&#41; e ABI3500 &#40;Biossistemas Aplicados &#8211; Thermo Fisher Scientific&#44; S&#227;o Paulo&#44; Brasil&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">As variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> foram analisadas por PCR ap&#243;s digest&#227;o com enzimas de restri&#231;&#227;o&#46; Para a variante rs4073&#44; foram usados os iniciadores 5&#8217;&#8208;CCA TCA TGA TAG CAT CTG TA&#8208;3&#8242; e 5&#8242;&#8208;CCA CAA TTT GGT GAA TTA TTA A&#8208;3&#8242; e a enzima de restri&#231;&#227;o <span class="elsevierStyleItalic">AseI</span>&#59; para a variante rs2227306&#44; foram usados os iniciadores 5&#8242;&#8208;CTC TAA CTC TTT ATA TAG GAA TT&#8208;3&#8242; e 5&#8242;&#8208;GAT TGA TTT TAT CAA CAG GCA&#8208;3&#8242;&#44; bem como a enzima de restri&#231;&#227;o <span class="elsevierStyleItalic">EcoRI</span>&#59; e para a variante rs2227307&#44; foram usados os iniciadores 5&#8242;&#8208;TAA AGG TTT GAT CAA TAT AGA&#8208;3&#8242; e 5&#8242;&#8208;CTT CCT TCT AAT TCCA ATA TG&#8208;3&#8242;&#44; bem como a enzima de restri&#231;&#227;o <span class="elsevierStyleItalic">ScrFI</span>&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#44;19</span></a> Os produtos da restri&#231;&#227;o enzim&#225;tica foram submetidos a eletroforese em gel de poliacrilamida a 12&#37;&#44; ou gel de agarose a 4&#37;&#44;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">18&#44;19</span></a> e corados com gel Red<span class="elsevierStyleSup">&#174;</span>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">An&#225;lise estat&#237;stica</span><p id="par0065" class="elsevierStylePara elsevierViewall">Foi feita com a vers&#227;o 22&#46;0 do SPSS &#40;SPSS Inc&#46;&#44; Chicago&#44; EUA&#41;&#46; Foi usada a vers&#227;o 3&#46;1&#46;9&#46;2<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">20</span></a> do <span class="elsevierStyleItalic">software</span> GPower para calcular o poder da amostra&#44; considerou&#8208;se o gen&#243;tipo das variantes analisadas e adotou&#8208;se o poder para valor acima de 80&#37;&#46; As condi&#231;&#245;es a seguir foram aplicadas para calcular o poder da amostra&#58; &#40;teste de an&#225;lise da vari&#226;ncia no lugar do teste de Kruskal&#8208;Wallis&#44; considerou&#8208;se que a an&#225;lise de vari&#226;ncia &#233; um teste mais forte&#41; tamanho do efeito<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;25&#44; &#945;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#44; poder<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;80&#44; grau de liberdade do numerador<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; n&#250;mero de grupos<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#44; n&#176; ideal<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>158&#59; &#40;teste de Mann&#8208;Whitney&#8211;bicaudal&#41; tamanho do efeito<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;5&#44; &#945;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#44; poder<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;80&#44; propor&#231;&#227;o de atribui&#231;&#227;o N2&#47;N1<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#44; n&#176; ideal&#8211;134&#59; &#40;teste &#967;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a>&#41; tamanho do efeito<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;3&#44; &#945;<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#44; poder<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;80&#44; grau de liberdade<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>2&#44; n&#176; ideal<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>108&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Os testes de Mann&#8208;Whitney e Kruskal&#8208;Wallis foram usados para compara&#231;&#227;o entre diferentes gen&#243;tipos e os grupos de variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e a resposta a BD&#46; Em caso de diferen&#231;as significativas entre os grupos do teste de Kruskal&#8208;Wallis&#44; foram feitas identifica&#231;&#227;o e avalia&#231;&#227;o adicionais das diferen&#231;as entre os gen&#243;tipos com o <span class="elsevierStyleItalic">software</span> para Windows MedCalc<span class="elsevierStyleSup">&#174;</span>&#44; vers&#227;o 16&#46;1 &#40;MedCalc<span class="elsevierStyleSup">&#174;</span> Software&#44; Ostend&#44; B&#233;lgica&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">O teste &#967;2 e o teste exato de Fisher foram usados para compara&#231;&#227;o entre os diferentes gen&#243;tipos e grupos de variantes do gene da IL&#8208;8 e a resposta a BD definidos como um aumento de &#62; 12&#37; e 200 mL de VEF1 inicial&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Para a identifica&#231;&#227;o de muta&#231;&#245;es no gene do <span class="elsevierStyleItalic">RTFC</span>&#44; os pacientes foram analisados com base em dois contextos&#58; &#40;<span class="elsevierStyleItalic">RTFC</span>&#8208;A&#41; todos os pacientes com FC&#44; independentemente das muta&#231;&#245;es do gene &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>186 pacientes&#41;&#59; &#40;<span class="elsevierStyleItalic">RTFC</span>&#8208;B&#41; pacientes com duas muta&#231;&#245;es pertencentes &#224;s classes I&#44; II e&#47;ou III &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>91 pacientes&#41;&#46; Quanto &#224;s variantes&#44; foram adotados quatro modelos de an&#225;lise&#58; &#40;i&#41; codominante &#40;teste de Kruskal&#8208;Wallis&#41;&#59; &#40;ii&#41; recessivo &#40;teste de Mann&#8208;Whitney&#41;&#59; &#40;iii&#41; dominante &#40;teste de Mann&#8208;Whitney&#41;&#59; &#40;iv&#41; superdominante &#40;teste de Mann&#8208;Whitney&#41;&#44; aplicados em associa&#231;&#227;o &#224;s vari&#225;veis cl&#237;nicas&#46; Para todas as an&#225;lises&#44; o valor alfa foi estabelecido em 0&#44;05&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Para an&#225;lise do equil&#237;brio de Hardy&#8208;Weinberg &#40;HWE&#41; foi usado o <span class="elsevierStyleItalic">software</span> Online Encyclopedia for Genetic Epidemiology Studies &#40;OEGE&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">O teste da taxa de falsa descoberta &#40;FDR&#41; foi aplicado para corrigir a compara&#231;&#227;o m&#250;ltipla de testes&#46; A FDR &#233; uma abordagem ao problema de m&#250;ltiplas compara&#231;&#245;es&#46; Em vez de controlar a chance de qualquer falso&#44; os controles da FDR controlam a propor&#231;&#227;o esperada de falsos positivos entre os resultados significativos&#46; O limite da FDR &#233; determinado a partir da distribui&#231;&#227;o do valor de p observado e&#44; assim&#44; &#233; adaptativo ao valor de sinal nos dados&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">21</span></a> O valor de p &#40;p&#41; e o valor de p corrigido &#40;p<span class="elsevierStyleSup">c</span>&#41; foram mostrados no manuscrito&#46; A an&#225;lise de desequil&#237;brio de liga&#231;&#227;o foi feita na vers&#227;o 4&#46;2 do <span class="elsevierStyleItalic">software</span> Haploview&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Resultados</span><p id="par0095" class="elsevierStylePara elsevierViewall">Os dados cl&#237;nicos e laboratoriais dos pacientes com FC s&#227;o descritos na <a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#46; A descri&#231;&#227;o do gen&#243;tipo e da frequ&#234;ncia de alelos das variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> encontra&#8208;se na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46; A <a class="elsevierStyleCrossRef" href="#fig0005">figura 1</a> mostra os dados com valores de p e valor de p corrigido para associa&#231;&#227;o das variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span>&#44; consideraram&#8208;se os quatros modelos de an&#225;lise propostos e o gen&#243;tipo do gene do <span class="elsevierStyleItalic">RTFC</span>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">A variante rs2227307 n&#227;o foi associada &#224; resposta a BD em nenhum dos modelos estudados&#59; ao passo que a variante rs2227306 foi associada a FEF<span class="elsevierStyleInf">50&#37;</span> para pacientes com gen&#243;tipo CC &#40;modelo dominante&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;05&#59; p<span class="elsevierStyleSup">c</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;083&#41; e gen&#243;tipo CT &#40;modelo superdominante&#59; 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; no grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>D e E&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Deve&#8208;se enfatizar de modo especial a variante rs4073&#44; associada &#224;s vari&#225;veis de espirometria&#58; FEV<span class="elsevierStyleInf">1</span>&#44; propor&#231;&#227;o VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#44; FEF<span class="elsevierStyleInf">50&#37;</span>&#44; FEF<span class="elsevierStyleInf">75&#37;</span> e FEF<span class="elsevierStyleInf">25&#8208;75&#37;&#46;</span> A menor resposta a BD foi observada para gen&#243;tipo TT &#40;modelo dominante&#41; e pacientes do grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B a VEF<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; e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a> K&#41;&#46; O mesmo foi observado para o grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;A para FEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>H&#41; e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>L&#41;&#46; Na an&#225;lise codominante&#44; o gen&#243;tipo TT apresentou menor resposta a BD para VEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>F&#41; e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a> J&#41;&#44; respectivamente para os grupos <span class="elsevierStyleItalic">RTFC</span>&#8208;A e <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#46; Para o indicador VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#44; o gen&#243;tipo AT nos pacientes do grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B mostrou menor resposta a BD &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>B&#41;&#46; Por fim&#44; nos pacientes dos grupos <span class="elsevierStyleItalic">RTFC</span>&#8208;A e <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#44; respectivamente&#44; o gen&#243;tipo AA &#40;modelo recessivo&#41; para rs4073 mostrou maior resposta a BD para FEF<span class="elsevierStyleInf">75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>I&#41; e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a> M&#41;&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">A distribui&#231;&#227;o de hapl&#243;tipos para as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> &#233; apresentada na <a class="elsevierStyleCrossRef" href="#tbl0015">tabela 3</a>&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Para compara&#231;&#227;o entre as variantes do gene da IL&#8208;8 e a resposta a BD definida como aumento de &#62; 12&#37; e 200 mL de VEF1 inicial&#44; n&#227;o foi encontrada associa&#231;&#227;o positiva &#40;p &#62; 0&#44;05&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discuss&#227;o</span><p id="par0120" class="elsevierStylePara elsevierViewall">Mostramos anteriormente a influ&#234;ncia das diferentes variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> sobre a gravidade cl&#237;nica da FC&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> Al&#233;m disso&#44; este estudo mostra a associa&#231;&#227;o das diferentes variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e sua modula&#231;&#227;o &#224; resposta a BD&#44; avalia o impacto do medicamento sobre a fun&#231;&#227;o pulmonar&#46; A variabilidade das respostas aos BD &#233; determinada por v&#225;rios fatores&#44; como inflama&#231;&#227;o e obstru&#231;&#227;o pulmonar&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> bact&#233;rias<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> e sintomas pulmonares&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> bem como genes modificadores&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> Contudo&#44; at&#233; agora&#44; nenhum estudo investigou o papel da <span class="elsevierStyleItalic">IL&#8208;8</span> como mediador pr&#243;&#8208;inflamat&#243;rio de FC e sua rela&#231;&#227;o aos BD e se as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> podem explicar a resposta individual aos BD na FC&#46; Acredita&#8208;se que os beta&#8208;2 agonistas de curta e longa dura&#231;&#227;o podem ser ben&#233;ficos para pacientes com FC e com hiperresponsividade br&#244;nquica positiva&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Em doen&#231;as pulmonares progressivas&#44; foram avaliados diferentes marcadores e o uso dos BD parece fornecer melhor resposta ao FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#44; em compara&#231;&#227;o com outros marcadores&#44; o que indica envolvimento de vias a&#233;reas de menor calibre na FC&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> Nosso estudo&#44; em concord&#226;ncia com a literatura de refer&#234;ncia&#44; encontrou uma associa&#231;&#227;o da variante rs4073 para o marcador FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span> nos modelos dominante &#40;para os grupos <span class="elsevierStyleItalic">RTFC</span>&#8208;A e <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#41;&#44; codominante &#40;grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#41; e recessivo &#40;grupo <span class="elsevierStyleItalic">RTFC</span>&#8208;B&#41;&#46; Houve melhoria em diversos outros marcadores de espirometria para rs4073&#44; como VEF<span class="elsevierStyleInf">1</span>&#44; VEF<span class="elsevierStyleInf">1</span>&#47;CVF e FEF<span class="elsevierStyleInf">50&#37;</span> e FEF<span class="elsevierStyleInf">75&#37;</span>&#44; o que mostra impacto sobre os padr&#245;es de respira&#231;&#227;o dos pacientes&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">O estudo de Hillian et al&#46; encontrou uma associa&#231;&#227;o das variantes rs2227307 e rs4073 do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e a gravidade da doen&#231;a pulmonar&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> Nesse estudo&#44; os pacientes foram divididos em duas coortes&#58; &#40;1&#41; pacientes homozigotos F508del&#59; &#40;2&#41; pacientes com outros gen&#243;tipos do gene do <span class="elsevierStyleItalic">RTFC</span>&#46; Na coorte 1&#44; as variantes rs4073&#44; rs2227306 e rs2227543 n&#227;o foram associadas a doen&#231;a pulmonar e a variante rs22227307 mostrou associa&#231;&#227;o&#44; independentemente do sexo&#46; Na coorte 2&#44; as variantes rs4073 e rs2227306 foram associadas a gravidade da doen&#231;a pulmonar em homens&#46; Assim&#44; o sexo do paciente&#44; o gen&#243;tipo do gene do <span class="elsevierStyleItalic">RTFC</span> e os genes modificadores podem modular a gravidade da doen&#231;a pulmonar&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> Nesse estudo&#44; o gen&#243;tipo rs2227307 n&#227;o teve impacto sobre a variabilidade da resposta a BD&#46; Isso sugere que&#44; apesar de esse gen&#243;tipo estar associado a doen&#231;a pulmonar em pacientes homozigotos F508del&#44; sua resposta a BD n&#227;o &#233; relevante&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">O alvo dos BD &#233; a prote&#237;na ADRB2&#44; expressa no m&#250;sculo liso das vias a&#233;reas&#46; As variantes de ADRB2 est&#227;o associadas &#224; resposta &#224; medica&#231;&#227;o&#46; Essa prote&#237;na foi amplamente estudada em asma e ainda muito raramente em FC&#46; A efic&#225;cia da resposta a BD e aos corticosteroides inalat&#243;rios no manejo de inflama&#231;&#227;o das vias a&#233;reas em asma est&#225; confirmada e depende das variantes Arg16Gly &#40;rs1042713&#59; c&#46;46A<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#41; e Glu27Gln &#40;rs1042714&#59; c&#46;79C<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#41; do gene <span class="elsevierStyleItalic">ADRB2</span>&#46;&#91;29&#93; A variante Gln27Glu concede resist&#234;ncia &#224; prote&#237;na ADRB2 na resposta a BD&#46; Os alelos 46&#42;G e 79&#42;G protegem contra asma&#44; reduzem o risco em 27&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a> As variantes do alelo G induzem altera&#231;&#245;es na regula&#231;&#227;o do receptor&#44; devido ao aumento da susceptibilidade &#224; degrada&#231;&#227;o de prote&#237;nas&#46; Este estudo constatou que as variantes Arg16Gly e Gln27Glu do gene <span class="elsevierStyleItalic">ADRB2</span> influenciam a respostas aos BD na FC&#46; Na espirometria e em outros marcadores de gravidade&#44; a variante Arg16Gly mostrou associa&#231;&#227;o positiva&#44; ao contr&#225;rio da variante Gln27Glu&#46; O gen&#243;tipo Arg&#47;Arg da variante Arg16Gly foi associado a melhores valores de VEF<span class="elsevierStyleInf">1</span> e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#46; A resposta a BD nas an&#225;lises de hapl&#243;tipo foi positiva na aus&#234;ncia dos gen&#243;tipos Gly16Gly e Glu27Glu para a propor&#231;&#227;o VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">As variantes de ADRB2&#44; capacidade de difus&#227;o dos pulm&#245;es para&#160;mon&#243;xido de carbono&#44; condut&#226;ncia da membrana capilar alveolar&#44; volume sangu&#237;neo na capilar alveolar e SaO<span class="elsevierStyleInf">2</span>&#44; foram avaliadas na resposta a BD em 18 pacientes e 20 controles saud&#225;veis&#44; antes e depois da administra&#231;&#227;o de salbutamol &#40;30&#44; 60 e 90 minutos&#41;&#46; Os indiv&#237;duos saud&#225;veis n&#227;o apresentaram altera&#231;&#245;es nos marcadores avaliados para a variante Glu27Glu&#46; Contudo&#44; na FC&#44; essa variante influenciou a resposta a BD&#58; a melhor resposta encontrada na presen&#231;a de pelo menos um alelo 27Glu&#46; Houve uma diferen&#231;a de difus&#227;o pulmonar e SaO<span class="elsevierStyleInf">2</span> perif&#233;rica de acordo com a varia&#231;&#227;o do gene <span class="elsevierStyleItalic">ADRB2</span> na posi&#231;&#227;o 27 e a dosagem do medicamento deve ser prescrita de acordo com essa varia&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">A maior parte dos estudos foca nas variantes do gene ADRB2 na resposta a BD&#46; Contudo&#44; este estudo demonstra que&#44; mesmo indiretamente&#44; as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> e possivelmente em outros genes&#44; que modulam a resposta pulmonar inflamat&#243;ria&#44; podem potencializar ou diminuir o efeito dos BD e&#44; ainda&#44; influenciar a resposta ao medicamento&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Com rela&#231;&#227;o ao HWE&#44; conforme discutido anteriormente por nosso grupo&#44;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> duas variantes &#40;rs4073 e rs2227306&#41; n&#227;o estavam em equil&#237;brio&#46; Devemos lembrar que o HWE pressup&#245;e uma popula&#231;&#227;o ideal&#44; sem a interfer&#234;ncia de fatores evolucion&#225;rios&#46; Contudo&#44; em genes envolvidos em controle de imunidade&#44; inflama&#231;&#227;o e infec&#231;&#227;o&#44; o desequil&#237;brio do HWE parecer estar associado de forma secund&#225;ria aos mecanismos de sele&#231;&#227;o que favoreceram um alelo espec&#237;fico que pode trazer uma resposta mais efetiva&#46; O desequil&#237;brio n&#227;o invalida o estudo de associa&#231;&#227;o&#44; pois os grupos fazem parte da mesma popula&#231;&#227;o&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Limita&#231;&#245;es do estudo&#58; &#40;i&#41; banco de dados transversal &#40;a resposta a BD foi avaliada em um &#250;nico momento&#41;&#59; &#40;ii&#41; h&#225; v&#225;rios dados ausentes&#44; se levarmos em considera&#231;&#227;o os problemas para obter as informa&#231;&#245;es nos registros&#59; &#40;iii&#41; caso a resposta a BD seja diferente com base no VEF<span class="elsevierStyleInf">1</span> de base&#44; principalmente em indiv&#237;duos saud&#225;veis&#59; &#40;iv&#41; poss&#237;veis vari&#225;veis de confus&#227;o com rela&#231;&#227;o aos resultados&#44; como gravidade da doen&#231;a&#44; terapias atuais&#44; ades&#227;o &#224; medica&#231;&#227;o e esfor&#231;o adequado no teste de fun&#231;&#227;o pulmonar&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">As variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> &#40;rs2227306 e especialmente rs4073&#41; podem estar associadas &#224; resposta a BD durante a espirometria&#46; Esse medicamento pode ser uma op&#231;&#227;o para o tratamento da doen&#231;a&#44; na maior parte do tempo em pacientes com vias a&#233;reas de menor calibre&#46; Devem&#8208;se conduzir estudos que envolvam dose e combina&#231;&#245;es de medicamentos para determinar o melhor tratamento de acordo com o gen&#243;tipo do paciente com FC&#44; o gene do <span class="elsevierStyleItalic">RTFC</span>&#44; bem como os genes modificadores&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Financiamento</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;Fapesp&#41;&#44; em apoio &#224;s pesquisas n&#176; 2011&#47;12939&#8208;4&#44; n&#176; 2011&#47;18845&#8208;1&#44; n&#176; 2015&#47;12183&#8208;8 e n&#176; 2015&#47;12858&#8208;5&#59; Fundo de Apoio &#224; Pesquisa&#44; ao Ensino e &#224; Extens&#227;o da Universidade Estadual de Campinas&#44; em apoio &#224; pesquisa n&#176; 0648&#47;2015&#59; JDR&#58; Fapesp&#44; em apoio &#224;s pesquisas n&#176; 2011&#47;18845&#8208;1 e n&#176; 2015&#47;12183&#8208;8&#46; LLF&#58; Fapesp&#44; em apoio &#224; pesquisa n&#176; 2013&#47;19052&#8208;0&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflitos de interesse</span><p id="par0170" class="elsevierStylePara elsevierViewall">Os autores declaram n&#227;o haver conflitos de interesse&#46;</p></span></span>"
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            2 => "Interleukin 8"
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            0 => "<span class="elsevierStyleItalic">CFTR</span>"
            1 => "Gravidade da doen&#231;a"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0085" 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="spar0090" 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&#8208;Whitney and Kruskal&#8208;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="spar0095" 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&#8208;dominant &#40;FEF<span class="elsevierStyleInf">25&#8208;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&#8208;75&#37;</span>&#41;&#44; recessive &#40;FEF<span class="elsevierStyleInf">75&#37;</span> and FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#41;&#44; and over&#8208;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="spar0100" 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>"
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        "resumen" => "<span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Objetivo</span><p id="spar0105" 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="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">M&#233;todos</span><p id="spar0110" 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&#8208;Whitney e Kruskal&#8208;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="abst0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Resultados</span><p id="spar0115" 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&#8208;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&#8208;75&#37;</span>&#41;&#44; recessivo &#40;FEF<span class="elsevierStyleInf">75&#37;</span> e FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#41; e overdominante &#40;VEF<span class="elsevierStyleInf">1</span>&#47;CVF&#41;&#46;</p></span> <span id="abst0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conclus&#245;es</span><p id="spar0120" 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>"
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          "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; 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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; 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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#44;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&#8208;26A<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;R334 W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&#47;L206 W&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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&#8208;2A<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#47;711<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;&#8208;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;I618 T&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#44;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="top">Pacientes com duas muta&#231;&#245;es do <span class="elsevierStyleItalic">RTFC</span> pertencentes &#224;s classes I&#44; II e&#47;ou III<br><span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>Muta&#231;&#245;es G2<br>&#40;grupo <span class="elsevierStyleItalic">CFTR&#8208;B</span>&#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="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&#44;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;N1303 K&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&#44;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="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&#44;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="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&#44;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&#8208;18672pbA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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&#8208;1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&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&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<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&#47;R1066 C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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">Duplica&#231;&#227;o do &#233;xon F508del&#47;6B a 16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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;R1066 C&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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&#8208;1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&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&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<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&#47;2183AA<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>G&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;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<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&#47;3120<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>1G<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#44;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">CVF&#44; capacidade vital for&#231;ada&#59; FEF<span class="elsevierStyleInf">25&#37;</span>&#44; fluxo expirat&#243;rio for&#231;ado a 25&#37; da CVF&#59; FEF<span class="elsevierStyleInf">25&#8208;75&#37;</span>&#44; m&#233;dio do fluxo expirat&#243;rio for&#231;ado entre 25&#37; e 75&#37; da CVF&#59; FEF<span class="elsevierStyleInf">50&#37;</span>&#44; fluxo expirat&#243;rio for&#231;ado a 50&#37; da CVF&#59; FEF<span class="elsevierStyleInf">75&#37;</span>&#44; fluxo expirat&#243;rio for&#231;ado a 75&#37; da CVF&#59; FEF<span class="elsevierStyleInf">max</span>&#44; fluxo expirat&#243;rio for&#231;ado m&#225;ximo&#59; SaO<span class="elsevierStyleInf">2</span>&#44; satura&#231;&#227;o de oxig&#234;nio no sangue arterial&#59; VEF<span class="elsevierStyleInf">1</span>&#44; volume expirat&#243;rio for&#231;ado no 1&#176; segundo da CVF&#59; VRE&#44; volume de reserva expirat&#243;ria&#46;</p><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Os dados da espirometria s&#227;o mostrados em percentual de valor preditivo&#46; Todos os pacientes avaliados s&#227;o descritos&#46;</p>"
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                  \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">Vari&#225;veis&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">Distribui&#231;&#227;o<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">Sexo &#40;masculino&#41;</span>&nbsp;\t\t\t\t\t\t\n
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                  \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">Etnia &#40;branca&#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&#44;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">Idade &#40;meses&#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&#44;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>171&#44;98&#59; 143 &#40;7 a 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">In&#237;cio dos sintomas &#40;meses&#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&#44;23<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>114&#44;03&#59; 3 &#40;0 a 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">Diagn&#243;stico &#40;meses&#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&#44;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>158&#44;39&#59; 20 &#40;0 a 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">In&#237;cio dos sintomas digestivos &#40;meses&#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&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>112&#44;61&#59; 3 &#40;0 a 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">In&#237;cio dos sintomas pulmonares &#40;meses&#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&#44;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>123&#44;64&#59; 6 &#40;0 a 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">&#205;ndice de massa corporal</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&#44;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;08&#59; 16&#44;28 &#40;6&#44;5 a 35&#44;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">Polipose nasal &#40;presen&#231;a&#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&#44;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">Diabetes mellitus <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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">Osteoporose &#40;presen&#231;a&#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&#44;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">Insufici&#234;ncia pancre&#225;tica &#40;presen&#231;a&#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&#44;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">&#205;leo meconial &#40;presen&#231;a&#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&#44;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">1&#170;</span> Pseudomonas aeruginosa&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&#44;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>171&#44;74&#59; 31 &#40;0 a 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">P&#46; aeruginosa mucoide <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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">P&#46; aeruginosa <span class="elsevierStyleItalic">n&#227;o mucoide &#40;presen&#231;a&#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&#44;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">Achromobacter xylosoxidans <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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">Burkolderia cepacia <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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">Staphylococcus aureus <span class="elsevierStyleItalic">&#40;presen&#231;a&#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&#44;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&#44;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;28&#59; 96 &#40;66 a 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">Escore de Bhalla</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&#44;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;77&#59; 8 &#40;0 a 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">Escore de Kanga</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&#44;78<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#44;82&#59; 17&#44;5 &#40;10 a 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">Escore de Shwachman&#8208;Kulczycki</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&#44;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#44;78&#59; 65 &#40;20 a 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">CVF</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&#44;13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>23&#44;86&#59; 77 &#40;19 a 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&#44;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#44;75&#59; 63 &#40;17 a 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">VEF</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">1</span></span><span class="elsevierStyleItalic">&#47;CVF</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&#44;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;99&#59; 81 &#40;39 a 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&#44;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#44;71&#59; 60 &#40;7 a 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&#44;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>31&#44;25&#59; 40 &#40;3 a 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&#44;32<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>28&#44;77&#59; 27&#44;5 &#40;4 a 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&#8208;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&#44;16<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>32&#44;51&#59; 39 &#40;5 a 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&#44;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#44;59&#59; 73&#44;5 &#40;25 a 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">VRE</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&#44;96<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>52&#44;39&#59; 69 &#40;3 a 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">Resposta a broncodilatador inalat&#243;rio</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>CVF&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&#44;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;19&#59; 1 &#40;&#8722;17 a 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&#44;51<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#44;0&#59; 3 &#40;&#8722;12 a 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>VEF<span class="elsevierStyleInf">1</span>&#47;CVF&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&#44;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#44;43&#59; 2 &#40;&#8722;19 a 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&#44;99<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>24&#44;41&#59; 5 &#40;&#8722;45 a 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&#44;08<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#44;06&#59; 9 &#40;&#8722;41 a 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&#44;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>46&#44;47&#59; 16 &#40;&#8722;64 a 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&#8208;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&#44;28<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>27&#44;77&#59; 9&#44;5 &#40;&#8722;51 a 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&#44;63<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>14&#44;48&#59; 3 &#40;&#8722;42 a 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>VRE&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&#44;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>101&#44;08&#59; 0 &#40;&#8722;90 a 670&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1580261.png"
              ]
            ]
          ]
          "notaPie" => array:3 [
            0 => array:3 [
              "identificador" => "tblfn0010"
              "etiqueta" => "a"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Os dados com distribui&#231;&#227;o categ&#243;rica s&#227;o apresentados da seguinte forma&#58; n&#176; de vari&#225;veis&#47;n&#176; total &#40;percentual&#41;&#59; os dados com distribui&#231;&#227;o num&#233;rica s&#227;o apresentados da seguinte forma&#58; tamanho da amostra&#59; m&#233;dia<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>desvio padr&#227;o&#59; mediana &#40;m&#237;nimo a m&#225;ximo&#41;&#46;</p>"
            ]
            1 => array:3 [
              "identificador" => "tblfn0015"
              "etiqueta" => "b"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Os valores ausentes para primeira <span class="elsevierStyleItalic">P&#46; aeruginosa</span> correspondem a pacientes com fibrose c&#237;stica que nunca apresentaram cultura positiva para <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#46;</p>"
            ]
            2 => array:3 [
              "identificador" => "tblfn0020"
              "etiqueta" => "c"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Um paciente com fibrose c&#237;stica apresentou cultura positiva para <span class="elsevierStyleItalic">P&#46; aeruginosa</span>&#44; com valores negativos para IgG espec&#237;fico do ant&#237;geno <span class="elsevierStyleItalic">P&#46; aeruginosa</span> e o paciente foi exclu&#237;do para estimativa de frequ&#234;ncia&#46;</p>"
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">An&#225;lise descritiva dos marcadores cl&#237;nicos e laboratoriais de pacientes com fibrose c&#237;stica</p>"
        ]
      ]
      3 => array:8 [
        "identificador" => "tbl0015"
        "etiqueta" => "Tabela 3"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at3"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">fa&#44; frequ&#234;ncia absoluta&#59; <span class="elsevierStyleItalic">IL&#8208;8</span>&#44; interleucina 8&#59; &#37;&#44; percentual&#59; &#967;<span class="elsevierStyleSup">2</span>&#44; qui&#8208;quadrado&#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">Variantes&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">Gen&#243;tipo&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">N&#250;mero &#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">Alelo&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">N&#250;mero &#40;fa&#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">&#967;<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">Valor de p<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&#44;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&#44;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="top">3&#44;94</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">&#60; 0&#44;05</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&#44;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&#44;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&#44;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&#44;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="top">8&#44;21</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="top">&#60; 0&#44;05</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&#44;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&#44;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&#44;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&#44;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&#44;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="top">1&#44;48</td><td class="td" title="table-entry  " rowspan="3" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>0&#44;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&#44;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&#44;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&#44;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 => "xTab1580260.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">Frequ&#234;ncia&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">Percentual &#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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;0&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&#44;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&#44;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&#44;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&#44;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&#44;0&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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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&#44;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>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0025">&#967;<span class="elsevierStyleSup">2</span> e valores de p fazem refer&#234;ncia ao c&#225;lculo de equil&#237;brio de Hardy&#8208;Weinberg&#46; Os dados significativos s&#227;o mostrados em negrito&#46; Houve uma fraca correla&#231;&#227;o entre as variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> nos pacientes com fibrose c&#237;stica inscritos no estudo&#46; N&#227;o h&#225; desequil&#237;brio de liga&#231;&#227;o&#46;</p>"
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          "pt" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Distribui&#231;&#227;o de gen&#243;tipos&#44; alelos e hapl&#243;tipo das variantes do gene da <span class="elsevierStyleItalic">IL&#8208;8</span> &#40;rs4073&#44; rs2227306 e rs2227307&#41; em pacientes com fibrose c&#237;stica</p>"
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ISSN: 22555536
Idioma original: Português
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