Adverse early-life environmental exposures and their repercussions on adult respiratory health

array:22 ["pii" => "S0021755721001650" "issn" => "00217557" "doi" => "10.1016/j.jped.2021.11.005" "estado" => "S300" "fechaPublicacion" => "2022-03-01" "aid" => "1048" "copyrightAnyo" => "2021" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "J Pediatr (Rio J). 2022;98 Supl 1:S86-S95" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "itemAnterior" => array:18 [ "pii" => "S0021755721001637" "issn" => "00217557" "doi" => "10.1016/j.jped.2021.11.003" "estado" => "S300" "fechaPublicacion" => "2022-03-01" "aid" => "1045" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "J Pediatr (Rio J). 2022;98 Supl 1:S73-S85" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "New insights on the effects of endocrine-disrupting chemicals on children" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S73" "paginaFinal" => "S85" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0002" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2564 "Ancho" => 2917 "Tamanyo" => 353365 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0005" "detalle" => "Fig. " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "PRISMA flow diagram. (From: Moher D, Liberati A, Tetzlaff J, Altman DG; The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097. For more information, visit www.prisma-statement.org)." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Barbara Predieri, Crésio A.D. Alves, Lorenzo Iughetti" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Barbara" "apellidos" => "Predieri" ] 1 => array:2 [ "nombre" => "Crésio A.D." "apellidos" => "Alves" ] 2 => array:2 [ "nombre" => "Lorenzo" "apellidos" => "Iughetti" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755721001637?idApp=UINPBA000049" "url" => "/00217557/00000098000000S1/v1_202203240549/S0021755721001637/v1_202203240549/en/main.assets" ] "en" => array:17 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Adverse early-life environmental exposures and their repercussions on adult respiratory health" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "S86" "paginaFinal" => "S95" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Helena Teresinha Mocelin, Gilberto Bueno Fischer, Andrew Bush" "autores" => array:3 [ 0 => array:4 [ "nombre" => "Helena Teresinha" "apellidos" => "Mocelin" "email" => array:1 [ 0 => "helenatm@ufcspa.edu.br" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0002" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0001" ] ] ] 1 => array:3 [ "nombre" => "Gilberto Bueno" "apellidos" => "Fischer" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "b" "identificador" => "aff0002" ] 2 => array:2 [ "etiqueta" => "c" "identificador" => "aff0003" ] ] ] 2 => array:3 [ "nombre" => "Andrew" "apellidos" => "Bush" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0004" ] 1 => array:2 [ "etiqueta" => "e" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Departamento de Pediatria, Porto Alegre, RS, Brazil" "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "Hospital da Criança Santo Antônio, Seção de Pneumologia Pediátrica, Porto Alegre, RS, Brazil" "etiqueta" => "b" "identificador" => "aff0002" ] 2 => array:3 [ "entidad" => "Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pós-Graduação em Pediatria, Porto Alegre, RS, Brazil" "etiqueta" => "c" "identificador" => "aff0003" ] 3 => array:3 [ "entidad" => "Imperial College London, Faculty of Medicine, National Heart and Lung Institute, Section of Paediatrics, London, United Kingdom" "etiqueta" => "d" "identificador" => "aff0004" ] 4 => array:3 [ "entidad" => "Royal Brompton Hospital, Department of Paediatric Respiratory Medicine, London, United Kingdom" "etiqueta" => "e" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "textoCompleto" => "IntroductionEnvironmental pollution is recognized as a global health emergency affecting high- and low-income countries. Exposure to environmental risk factors contributes to the onset and progression of respiratory diseases.<a class="elsevierStyleCrossRef" href="#bib0001">1</a>Data from the World Health Organization (WHO) show that 4.2 million deaths annually are attributed to exposure to environmental pollution.<a class="elsevierStyleCrossRef" href="#bib0002">2</a>The environmental conditions in utero and in early childhood are critical for the individual to achieve potential growth and lung function and will determine a child's future. Children exposed to pollutants from the prenatal period are particularly vulnerable to certain risks.<a class="elsevierStyleCrossRef" href="#bib0003">3</a> The exposure occurs through the interaction with the environment during the natural process of growth and development. Adverse environmental exposure in this critical period of life will determine structural and functional changes in the respiratory system. The association of environmental exposure, prenatal or perinatal, with adverse birth outcomes, such as preterm delivery, lower birth weight, and lung development defects, is well documented.<a class="elsevierStyleCrossRef" href="#bib0004">4</a>Epidemiological studies demonstrate that respiratory diseases that manifest in adults most often have prenatal and early life origins.<a class="elsevierStyleCrossRefs" href="#bib0005">5-7</a>Adverse childhood exposures affect adult respiratory health resulting in an increased risk of non-communicable chronic respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma; pulmonary aging with an accelerated or premature decline in lung function; and reduced life expectancy.<a class="elsevierStyleCrossRef" href="#bib0003">3</a>,<a class="elsevierStyleCrossRef" href="#bib0008">8</a>,<a class="elsevierStyleCrossRef" href="#bib0009">9</a>Environmental pollution, indoor pollutants (especially tobacco exposure), traffic-related pollution can cause neonatal problems and respiratory diseases that will have repercussions in adulthood. There are many studies showing associations between exposure to environmental tobacco in the fetal period causing a higher risk of prematurity and early decline in lung function in adults.<a class="elsevierStyleCrossRefs" href="#bib0010">10-13</a>In this review, the authors will address how exposure to environmental hazards early in life can have an impact on adult respiratory health. The effects resulting from respiratory infections and late exposure and into adulthood will not be addressed.EpidemiologyIn the pediatric age group, exposure tends to be daily, persistent, and in most cases cannot be avoided. In 2021, 91% of the world population will live in places with pollution levels above the limits recommended by the WHO guidelines. The intensity of exposure to air pollutants varies depending on geographic regions and household conditions. Low- and middle-income countries have higher exposures. Half of the world's population is exposed to indoor smoke from fires and wood stoves, responsible for up to 1.5 million premature deaths annually.<a class="elsevierStyleCrossRef" href="#bib0014">14</a> In Africa, 80% of children live in homes with dirty energy sources. About 12.9 million women are potentially exposed to toxic electronic waste that puts them and their children at risk.<a class="elsevierStyleCrossRef" href="#bib0002">2</a>,<a class="elsevierStyleCrossRef" href="#bib0015">15</a>,<a class="elsevierStyleCrossRef" href="#bib0016">16</a>In 2017, 42% of the world population was exposed to fine particulate matter (PM2.5) above that recommended by the WHO, and 43% were exposed to ozone. In Europe, in 2021, 84% of the population was exposed to PM2.5 and 9% to Nitrogen dioxide above the limits of this guideline.<a class="elsevierStyleCrossRef" href="#bib0008">8</a>It is estimated that 24% of deaths are associated with environmental conditions.<a class="elsevierStyleCrossRef" href="#bib0001">1</a> In Europe, there are 400,000 premature deaths/year caused by air pollution. It is estimated that the average life expectancy of a European is reduced by one year due to air pollution. A considerable proportion of premature deaths in European cities could be avoided annually by reducing air pollution concentrations. It must be considered that any death and loss of years of healthy life are not acceptable as both are preventable. Furthermore, there is no safe exposure limit below which air pollution is not harmful to human health.<a class="elsevierStyleCrossRef" href="#bib0008">8</a>The child and the environmentPollutants come from air pollution; inadequate water, sanitation, and hygiene; hazardous chemicals and waste; radiation; as well as emerging threats such as electronic waste.<a class="elsevierStyleCrossRef" href="#bib0016">16</a>Children are particularly vulnerable to environmental pollution as they receive a proportionally higher dose than an adult exposed to the same environment and often the adverse effect is greater due to their lower capacity to metabolize and excrete the toxic substance.<a class="elsevierStyleCrossRef" href="#bib0004">4</a> Newborns and young children have a higher respiratory rate and proportionally inhale a higher dose of pollutants than older children and adults in the same environment. When exercising outdoors, children are more exposed to air pollutants as they have a relatively larger lung surface compared to body size.<a class="elsevierStyleCrossRef" href="#bib0003">3</a>,<a class="elsevierStyleCrossRef" href="#bib0004">4</a>Pathways of exposure to environmental insultsTransplacentalThe placental barrier has a protective function for the fetus, but it is not complete. Toxic substances inhaled by the mother or absorbed by the maternal oral mucosa that pass directly into the maternal bloodstream reaching the fetal circulation.<a class="elsevierStyleCrossRef" href="#bib0003">3</a>,<a class="elsevierStyleCrossRef" href="#bib0004">4</a>Breast milkIt is the ideal food for babies, but it can contain harmful substances. Water-soluble chemical compounds and lipids can be transferred into breast milk, such as organochlorine pesticides, metals, solvents, etc.<a class="elsevierStyleCrossRef" href="#bib0003">3</a>,<a class="elsevierStyleCrossRef" href="#bib0004">4</a>Ingestion of contaminated water and food and non-nutritive ingestionIt is part of a child's normal development to take objects and hands to the mouth, which can favor the ingestion of household dust, soil, and chemical contaminants present in the objects.<a class="elsevierStyleCrossRef" href="#bib0003">3</a>,<a class="elsevierStyleCrossRef" href="#bib0004">4</a>CutaneousInfants and young children have a proportionally larger body surface area than adults and older children, with a larger area of exposure per kilogram of weight, and have immaturity in the protective functions of the skin and subcutaneous tissue. Also, they may have more uncovered areas of the skin surface and are in greater contact with particulate matter from household dust, soil, chemicals such as pesticides, and cleaning products.<a class="elsevierStyleCrossRef" href="#bib0003">3</a>,<a class="elsevierStyleCrossRef" href="#bib0004">4</a>InhaledAir pollutants can accumulate in the airways or pass through lung tissues, depending on the size and chemical nature of the pollutants. Ultrafine particles can pass into the bloodstream and reach distal organs.<a class="elsevierStyleCrossRef" href="#bib0003">3</a>,<a class="elsevierStyleCrossRef" href="#bib0004">4</a>The respiratory systemPulmonary morphogenesis begins in the embryonic period of fetal development, 3-4 weeks post-conception, while growth and maturation continue until the age of 18-20 years. Lung development is subdivided into five different periods of morphogenesis based on morphological characteristics: Pseudoglandular stage (6-17 weeks gestation) - Bronchi, bronchioles, and acinar tubules; Canalicular (16-26 weeks gestation) - acinar structures; Saccular (26-36 weeks gestation) - saccules and alveoli and cell differentiation and; Alveolar after 36 weeks post-conception and continues during somatic growth.<a class="elsevierStyleCrossRef" href="#bib0004">4</a>,<a class="elsevierStyleCrossRef" href="#bib0017">17</a>From the 36th week after conception, there is greater growth and expansion of pulmonary acini and development of the distal capillary network. In this phase, the lung grows mainly due to septation, proliferation, and thinning of the alveolar walls, as well as the elongation and luminal enlargement of the conducting airways.<a class="elsevierStyleCrossRef" href="#bib0004">4</a> The respiratory system is not fully developed at birth, and lung growth occurs mainly in the postnatal period. Adverse environmental exposure in the pseudoglandular phase interferes with the structural development of the airways, and later exposures can cause bronchial thickening and hyperresponsiveness after birth.<a class="elsevierStyleCrossRef" href="#bib0004">4</a>How does damage to the respiratory system occur?The respiratory system is vulnerable to environmental exposure, which occurs both prenatally and postnatally, especially in the first 18-24 months of life.<a class="elsevierStyleCrossRef" href="#bib0004">4</a>,<a class="elsevierStyleCrossRef" href="#bib0018">18</a>The degree of impact caused by adverse exposure varies and depends on the period of exposure. Sly et al. call this period the “window of susceptibility”.<a class="elsevierStyleCrossRef" href="#bib0003">3</a> It would be the period in which a certain environmental exposure can cause structural or functional abnormality, resulting in impaired respiratory health. Occurring outside this period, the pollutant would have much less of an effect.<a class="elsevierStyleCrossRef" href="#bib0003">3</a>Individual vulnerability to a given exposure can be influenced by the child's stage of development (prenatal, infant, child); type and route of exposure; genetic and epigenetic factors; comorbidities; nutritional status; and sociodemographic conditions. Transgenerational factors and preconceptions also have deleterious effects on lung development. Lung health can be affected by several mechanisms such as interruption of lung growth potential, modulation of function, modification of gene expression, and alteration of the pathophysiological mechanisms of the airways.<a class="elsevierStyleCrossRef" href="#bib0003">3</a> Furthermore, the respiratory system does not work in isolation. Factors that cause dysfunction of the immune system, the central nervous system, may also have consequences for respiratory problems and diseases.<a class="elsevierStyleCrossRef" href="#bib0003">3</a>,<a class="elsevierStyleCrossRef" href="#bib0004">4</a>What is the impact of environmental problems on respiratory health?The main consequences of environmental damage on adult respiratory health are associated with loss of lung function and diseases such as COPD and asthma.Impairments to pulmonary functionThe assessment of lung function by spirometry, commonly presented as Forced Expiratory Volume in First Second (FEV1) and Forced Vital Capacity (FVC), allows indirect measurement of lung growth. Lung volumes increase from childhood to young adult with maximum values reached at 20-25 years of age, remaining on a plateau for around five years and then gradually decreasing with aging. This process is called the trajectory of lung function. This decrease of lung function varies between individuals and is impacted by genetic and environmental factors that, in turn, influence both the development and progression of COPD.Lung function early in life (at birth and at age 4-6) can predict the maximum lung volume a person will reach when they reach the plateau.<a class="elsevierStyleCrossRef" href="#bib0019">19</a> In adults, low FEV1 is associated with greater morbidity and mortality.<a class="elsevierStyleCrossRef" href="#bib0020">20</a> Low lung function early in life usually does not recover and is a risk factor for airflow obstruction into adulthood.<a class="elsevierStyleCrossRef" href="#bib0021">21</a> In rare circumstances, there is potential for recovery. Harmful environmental exposures in early life may cause a reduction in the expected increase of lung function in early childhood and are associated with an increased risk of respiratory diseases in adulthood.COPDCOPD is the main cause of chronic morbidity and is among the three leading causes of death worldwide. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines COPD as persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities, caused by exposure to harmful particles or gases and influenced by individual, genetic and environmental factors.<a class="elsevierStyleCrossRef" href="#bib0022">22</a> Results from different trajectories or their combinations (assessed in young adults): abnormal at birth; failure to reach a normal spirometric plateau or accelerated decline in lung function.<a class="elsevierStyleCrossRef" href="#bib0007">7</a>,<a class="elsevierStyleCrossRef" href="#bib0021">21</a>,<a class="elsevierStyleCrossRef" href="#bib0023">23</a> Exposure to tobacco is a risk factor for COPD, but there is evidence that non-smokers also develop the disease. Harmful events that occur in pregnancy or childhood have the potential to alter lung growth and increase the risk of developing the disease.<a class="elsevierStyleCrossRef" href="#bib0006">6</a>AsthmaAsthma is a heterogeneous disease characterized by chronic airway inflammation. It manifests as wheezing, ventilatory difficulty and chest tightness, which vary over time and in intensity, associated with variable obstruction of the expiratory airflow. The obstruction can become permanent.<a class="elsevierStyleCrossRef" href="#bib0024">24</a>Environmental exposures and adult respiratory healthThe main environmental pollutants, their characteristics, and the result of exposure on respiratory health are presented below.Tobacco exposureTobacco exposure affects not just individual smokers, but those around them, including casual contacts in bars, and potentially especially but not exclusively in women, transgenerational adverse effects. Since tobacco contains many chemicals in addition to nicotine, it is only in the context of animal experiments that the authors can be certain which compound(s) is the causative agent. However, from animal data (below), it is clear that many adverse effects on the fetus are caused by nicotine. The role of e-cigarettes must also be considered in this context; they have some toxicities which overlap with tobacco, some effects which are unique to these devices, and many deliver high concentrations of nicotine. Thus the assumption must be that e-cigarettes are as harmful if not more so than conventional tobacco, unless and until proven otherwise – and it is for the vaping industry to prove they are safe, not for pediatricians to prove they are unsafe, just as Pharma have to prove the safety of a novel inhaled medication.<a class="elsevierStyleCrossRef" href="#bib0025">25</a>Transgenerational effectsThe earliest exposure is from grand maternal smoking, presumably by an epigenetic effect on the germline, although this is controversial. Her own offspring will be more likely to smoke and more likely to have asthma in consequence. However, if she has a daughter, even if that daughter does not smoke, her children are more likely to have asthma. If she does smoke, and they also smoke, the effects on the children's lung function are much greater.<a class="elsevierStyleCrossRef" href="#bib0026">26</a>,<a class="elsevierStyleCrossRef" href="#bib0027">27</a> Whether the same effect is seen in great-grand-children is unknown.Antenatal effectsKnown effects of nicotine from animal workThe experimental administration of nicotine to different pregnant animal models has established the following:<ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001">•There is increased collagen type 1 and 3 mRNA and immunostaining in the developing airway and lung parenchyma; there was increased elastin mRNA but not protein.<a class="elsevierStyleCrossRef" href="#bib0028">28</a></li><li class="elsevierStyleListItem" id="celistitem0002">•MUC5AC is over-expressed; this is of particular interest in terms of later mucus hypersecretion, a chronic obstructive pulmonary disease trait that is increasingly recognized as important.<a class="elsevierStyleCrossRef" href="#bib0029">29</a></li><li class="elsevierStyleListItem" id="celistitem0003">•There is dysanaptic airway growth, the airways are abnormally long, and there is airway hyper-responsiveness (AHR) in the newborn period, independent of infection or allergen exposure.<a class="elsevierStyleCrossRef" href="#bib0030">30</a> This is particularly important in that AHR in the newborn period is strongly predictive of later asthma and impaired lung function in human studies, and dysanaptic airway growth is associated with worse asthma outcomes in childhood and adult life.<a class="elsevierStyleCrossRef" href="#bib0031">31</a></li><li class="elsevierStyleListItem" id="celistitem0004">•There is a failure of secondary septation leading to early-onset emphysema.<a class="elsevierStyleCrossRef" href="#bib0032">32</a> As yet unpublished studies measuring alveolar size using hyperpolarized Helium suggest that teenage offspring of mothers who smoked in pregnancy have abnormally large alveoli.</li><li class="elsevierStyleListItem" id="celistitem0005">•There is the increased airway wall thickness and loss of alveolar attachments to the airway. These attachments stabilize airways by interdependence. This finding has been confirmed in early infant deaths of offspring of mothers who smoked in pregnancy.<a class="elsevierStyleCrossRef" href="#bib0033">33</a></li></ul>Human studies on cigarette exposure<ul class="elsevierStyleList" id="celist0001a"><li class="elsevierStyleListItem" id="celistitem0006">•(The exact components of cigarettes causing these abnormalities is not known)</li><li class="elsevierStyleListItem" id="celistitem0007">•There is increased cord blood mononuclear cell reactivity to allergens in the offspring of smoking mothers.<a class="elsevierStyleCrossRef" href="#bib0034">34</a></li><li class="elsevierStyleListItem" id="celistitem0008">•There is reduced cytokine and Toll-like receptor function associated with antenatal tobacco exposure.<a class="elsevierStyleCrossRef" href="#bib0035">35</a> Children who subsequently develop wheeze in the first year of life with either rhinovirus, respiratory syncytial virus, or other viral infection have reduced cord gamma interferon responses.<a class="elsevierStyleCrossRef" href="#bib0036">36</a></li></ul>Longer-term implications of antenatal tobacco exposureIn summary, the readout of tobacco exposure antenatally is:<a class="elsevierStyleCrossRef" href="#bib0010">10</a><ul class="elsevierStyleList" id="celist0002"><li class="elsevierStyleListItem" id="celistitem0009">•Low birth weight, itself an independent risk factor for impaired lung function and subsequent asthma.</li><li class="elsevierStyleListItem" id="celistitem0010">•Prematurity and small for gestational age birth. The effects of these two factors could be the subject of a whole review, and not all their effects are the same, but these patients have persistent airflow obstruction without evidence of Type 2 inflammation (unless there is coincidentally an atopic background). Interestingly, and relevant to data discussed below, there is more than associated respiratory morbidity associated with prematurity; early ischemic heart disease and cardiac failure are associations of bronchopulmonary dysplasia.</li><li class="elsevierStyleListItem" id="celistitem0011">•Airflow obstruction at birth, also predictive of the later development of asthma.</li><li class="elsevierStyleListItem" id="celistitem0012">•Altered immunological function at birth (and discussed in more detail below).</li><li class="elsevierStyleListItem" id="celistitem0013">•Sensitization to the effects of later adverse stimuli such as occupational exposures.</li><li class="elsevierStyleListItem" id="celistitem0014">•Increased likelihood of impaired lung growth and later accelerated decline in lung function.</li><li class="elsevierStyleListItem" id="celistitem0015">•Premature cardiovascular and all-cause morbidity and mortality.</li></ul>These implications may extend beyond mothers who smoke to non-smoking mothers who are passively exposed to tobacco. For example, Belgium's data showed very clearly that, as passive smoke exposure was reduced by a series of new laws, the rate of preterm delivery fell.<a class="elsevierStyleCrossRef" href="#bib0011">11</a> This is a really important message; these and other data emphasize that smoking does not merely affect the smoker but also the innocent bystander. Pediatricians must be advocates to prevent these exposures.Effects of smoke exposure in childhoodThe effects of smoke exposure on childhood respiratory morbidity are very well known and have been summarized elsewhere; pediatricians are fully familiar with these and know that smoke exposure must be minimized.<a class="elsevierStyleCrossRef" href="#bib0035">35</a> Indeed, smoke-free legislation dramatically reduces asthma attacks in children. Recently, it has been shown conclusively that three environmental factors are associated with impaired lung growth and progression of preschool wheeze to school-age asthma; these are aeroallergen sensitization, attacks of severe wheeze, and exposure to tobacco smoke, of which only the last is readily modifiable.<a class="elsevierStyleCrossRef" href="#bib0037">37</a> What is far less appreciated is the long-term consequences, both respiratory and systemic, of childhood smoke exposure, discussed in more detail below.Lung growth and developmentA major recent advance in the field has been the use of mathematical tools to delineate the different growth trajectories objectively, letting the data speak for itself rather than imposing investigator bias. These have typically identified 4-6 trajectories, although it should be noted that at least some individuals appear to change trajectory in childhood. Thus combining the Manchester and Avon longitudinal studies, nearly 2,500 children, the four classes were persistently high, normal, below average, and persistently low, of which the persistently high group were least likely to have been exposed to tobacco.<a class="elsevierStyleCrossRef" href="#bib0037">37</a> The Tasmanian cohort, extending from the first to the sixth decade of life, delineated six: persistently high, average, below average, persistently low, early below average with accelerated decline, and early low with accelerated growth and normal decline.<a class="elsevierStyleCrossRef" href="#bib0038">38</a> The likelihood of chronic obstructive pulmonary disease (COPD, 46%) was highest in the below-average, fast decline group, and childhood tobacco exposure was one factor in this trajectory.How adult respiratory morbidity is determined by early life events<ul class="elsevierStyleList" id="celist0003"><li class="elsevierStyleListItem" id="celistitem0016">•Occupational asthma: although this is considered to be a pure adult disease, in fact this is not the case. An important study hypothesized that early life disadvantage sensitizes to occupational lung disease. The investigators used the RHINE III questionnaire on occupational cleaning in 13,499 subjects and found that early life disadvantage (which included maternal smoking) was associated with an increased risk of wheeze, ‘adult onset’ asthma (discussed below), and self-reported COPD in 2138 cleaners. The strongest effect was early life disadvantage.<a class="elsevierStyleCrossRef" href="#bib0013">13</a></li><li class="elsevierStyleListItem" id="celistitem0017">•“Late-onset” asthma: this is a condition much talked about by adult physicians, but it actually does not exist. In the Tucson study, the prevalence of Physician diagnosed asthma and airway function was determined at age 22 years; and 25% of active asthma were newly diagnosed at that age (71% women).<a class="elsevierStyleCrossRef" href="#bib0039">39</a> However, when the prospectively obtained data were examined, AHR and low airway function at age 6, wheeze onset age 3-6 years, and persistent wheeze through first six years of life all predicted “newly diagnosed” asthma at age 22; and most of these factors are unequivocally associated with early tobacco exposure. It is very clear that this is not ‘late-onset asthma” but “late recrudescent airway disease”, and the roots need to be sought in early life.</li></ul>Why do adults get COPD?The two routes to COPD are accelerated decline in lung function having reached a normal plateau age 20-25 years (7% risk of COPD), and normal rate of decline from a reduced plateau (26% risk).<a class="elsevierStyleCrossRef" href="#bib0040">40</a> The latter is clearly the result of early life factors, of which tobacco exposure is an important factor. In the classic Fletcher and Peto paper, accelerated decline was attributed to current smoking, which could be halted if the patient abstained from tobacco.<a class="elsevierStyleCrossRef" href="#bib0007">7</a> Although, of course, smoking is a “BAD THING”, in many but not all COPD cohort studies, there is no effect of current smoking on decline in spirometry. In an illuminating study in the SPALDIA and ECRHS cohorts, early disadvantage (including maternal smoking) was associated with a more rapid decline in spirometry; as with the Tucson study, personal smoking effects were potentiated by maternal smoking.<a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0041">41</a> Similar findings were reported by the ECFS study, wherein accelerated decline in lung function was associated with (amongst other exposures) early tobacco exposure. Importantly, the idea that was just stopping adults smoking, beneficial though that would be, will prevent COPD is simply not true. In many cohorts, there is no signal for current smoking, causing an accelerated decline in spirometry.<a class="elsevierStyleCrossRef" href="#bib0042">42</a>More than just lungs: is reduced lung function the “canary in the mine”?Early low lung function, for which tobacco exposure is probably the main cause, is unsurprisingly associated with bad long-term respiratory outcomes (above). But it is also very clear that a reduction in the first second forced expired volume (FEV1) means more than just a bad respiratory outlook. It is associated with early and increased cardiovascular and all cause morbidity and mortality, and this is unsurprising when the multi-organ adverse effects of nicotine are considered.<a class="elsevierStyleCrossRef" href="#bib0012">12</a> Also, the same study reported a transgenerational effect on spirometry – low parental FEV1 was strongly predictive of offspring FEV1 (r2 = 0.28), another example of how the smokers poison not merely themselves, but those around them and future unborn generations.<a class="elsevierStyleCrossRef" href="#bib0012">12</a>Air pollutionAir pollution is the presence of one or more contaminants in the atmosphere, such as dust, gas, mist, odor, smoke, or vapor, in an amount and duration that can be harmful to human health. Pollutants produce inflammation, oxidative stress, immunosuppression, and mutagenicity in cells, which can affect other organs, causing diseases.<a class="elsevierStyleCrossRef" href="#bib0015">15</a> The pollutants present in the atmospheric air originate mainly from human activity in urban areas, originating from automotive vehicles, and, in non-urban areas, biomass burning. Sources of natural environmental exposures are derived from accidental fires, sandstorms, and electrical lightning that can generate nitrogen oxides (NOx).<a class="elsevierStyleCrossRef" href="#bib0015">15</a> Pollutants have different physical and chemical characteristics depending on the type of pollution source. The so-called primary ones are those emitted directly into the atmosphere and produced mainly by industries, thermoelectric plants, and automotive vehicles. The most frequent are sulfur dioxide (SO2), nitrogen oxides (NOx, NO, and NO2), metals, carbon monoxide (CO), volatile organic compounds (VOC), and particulate matter (PM). Secondary calls are those originating from chemical reactions between vehicular and industrial emission pollutants, such as NOx, which react with volatile organic compounds (VOCs) emitted by vehicles, solvents, and industry. The process takes place in the presence of ultraviolet rays from sunlight, thus giving rise to ozone.<a class="elsevierStyleCrossRef" href="#bib0015">15</a> Nitrogen dioxide (NO2), a toxic gas that causes significant inflammation of the airways, originates from combustion processes (heating, power generation, and engines in vehicles and ships). Sulfur dioxide (SO2) is a gas produced by burning fossil fuels (coal and oil) for domestic heating, power generation, and vehicles.Prenatal and early life exposure to pollutants, including nicotine and air pollution, leads to impaired lung function, which remains largely altered until the sixth decade of life. Maternal exposure to air pollutants is associated with decreased lung function during childhood that may be further reduced in adults and consequently lead to COPD.<a class="elsevierStyleCrossRef" href="#bib0038">38</a> Both outdoor and indoor pollution increase the chance of COPD.Fetuses born to mothers exposed to environmental pollutants are at increased risk for adverse birth outcomes such as intrauterine growth restriction, prematurity, low birth weight, and fetal lung development defects.<a class="elsevierStyleCrossRef" href="#bib0043">43</a>,<a class="elsevierStyleCrossRef" href="#bib0044">44</a> These adverse outcomes are associated with the development of late-onset respiratory diseases and reduced lung function, in addition to increasing the susceptibility to the harmful effects of other pollutants. Maternal exposure to Benzene and NO2 in the third trimester of pregnancy determine decreased lung function at school age.<a class="elsevierStyleCrossRef" href="#bib0045">45</a>Babies who grow up breathing polluted air, even at levels below EU regulations, have lower lung function from infancy through adolescence, and the results are worse in children with asthma. Part of the risk of exposure to pollution can be reduced if babies are breastfed for at least 12 weeks.<a class="elsevierStyleCrossRef" href="#bib0046">46</a>The reduction in the increase in lung function is also linked to NO2 exposure.<a class="elsevierStyleCrossRef" href="#bib0047">47</a> Children exposed to higher levels of NO2 and PM2.5 are five times more likely to have reduced lung function than children living in areas with lower levels.<a class="elsevierStyleCrossRef" href="#bib0048">48</a> Another study demonstrated that decreasing environmental NO2 and PM2.5 significantly decreases the risk of reduced lung growth.<a class="elsevierStyleCrossRef" href="#bib0049">49</a>Particulate matter (PM)Mixture of droplets or particles suspended in the air, composed of hundreds of organic or chemical substances such as ozone, nitrogen oxides, SO2, dust, soot or smoke, from coal and natural gas plants, cars, fires, unpaved roads and construction sites. Particles with an aerodynamic diameter less than 10 µm (MP10), such as sand, dust, and pollen, usually deposit in the nasopharynx and are less toxic. Fine particles, smaller than 2.5 µm (PM2.5), originating from combustion and ultra-fine particles (less than 0.1 mm), emitted by diesel engines, can penetrate tissues and organs, causing greater risk to health. Prenatal exposure to PM10 is associated with reduced lung function.<a class="elsevierStyleCrossRef" href="#bib0050">50</a> The effects may be even greater in children born prematurely.<a class="elsevierStyleCrossRef" href="#bib0051">51</a>External pollutantsOriginating from emissions from agricultural industries and activities, vehicles and air traffic, products used in agriculture, war, accidents, and fires, or from natural events such as volcanic eruption, forest fires, manufacturing, and distribution of chemical materials. Individuals exposed in the first year of life or during pregnancy to the Great Smog of London in 1952 were more likely to have asthma (9.53%) in adulthood.<a class="elsevierStyleCrossRef" href="#bib0052">52</a> Another study showed that a higher incidence of asthma at age 20 years was associated with greater exposure to all pollutants at birth, including PM10 and NO2.<a class="elsevierStyleCrossRef" href="#bib0053">53</a>Household pollutantsThe main source is cigarette smoke (above). Other sources are wood-burning, charcoal, crop residues, animal manure, and kerosene used as a fuel source for cooking and heating. Burning these materials combined with inefficient stoves leads to the emission of high concentrations of gaseous and particulate pollutants, methane, carbon monoxide, polyaromatic hydrocarbons (PAH), and VOCs. Other factors include products eliminated by air conditioning, cleaning products or flavorings from environments with oils, use of sprays and aerosols, and windows and doors open, allowing ingress of external pollution and the effects of pollution. Household pollutants are more problematic for infants and young children as they stay longer within the home. The quality of indoor air, including exposure to fungi, is associated with the onset of asthma. Individuals who were exposed to indoor pollutants during the first three years of life with early specific sensitization (mites, cat or dog) are at increased risk of developing asthma at 20 years of age. The effect is greatest if associated with pre-and postnatal exposure to tobacco smoke.<a class="elsevierStyleCrossRef" href="#bib0054">54</a> Individuals with early mite sensitization progress with worsening lung function that is lower at school age than at age five years and remains low until age 26.<a class="elsevierStyleCrossRef" href="#bib0055">55</a> Data from developing countries show that in individuals with COPD, 35% were early exposed to cigarette smoke and indoor biomass combustion. Childhood exposure to indoor coal pollution increases all-cause mortality, with a greater impact on respiratory causes, and the risk is greatest when associated with exposure to fuel.<a class="elsevierStyleCrossRef" href="#bib0056">56</a>Air pollution associated with traffic (TRAP)Automobile exhaust releases pollutants into the environment. There is an increased risk of asthma in children exposed to external pollutants such as ozone, sulfur dioxide, particulates, and nitrogen oxide. The highest incidence of asthma also occurred in adults who had been exposed to traffic pollution during the fetal period. Children living near major highways in contact with external pollutants (PM, O3 and SO2 from vehicular traffic) have a lower FEV1 than those living further away.<a class="elsevierStyleCrossRef" href="#bib0057">57</a> This reduction in FEV1 is associated with the development of COPD. Children who spent more time outdoors in areas with high levels of ozone had reduced lung function, while those who grew up in environments with low levels of pollution had greater lung function. Traffic-based pollution is associated with many childhood morbidities and an increased risk of adult COPD and lung cancer. A meta-analysis showed that childhood exposure to TRAP (Black Carbon, NO2, PM2.5, PM10) contributes to the development of asthma.<a class="elsevierStyleCrossRef" href="#bib0058">58</a> Another study demonstrated that improvements in air quality were associated with statistically and clinically significant positive effects on lung function growth in children.<a class="elsevierStyleCrossRef" href="#bib0049">49</a>Asthma and allergiesThe immune system is not yet fully developed, so there is an increased risk of respiratory infections and asthma. In asthmatic patients, exposure to air pollutants can cause oxidative damage to the airway, leading to inflammation, remodeling, and an increased risk of sensitization. In adults, the accumulated effect of exposure to environmental pollutants can contribute to new-onset asthma.<a class="elsevierStyleCrossRef" href="#bib0059">59</a>Household and outdoor pollutants, including O3, CO, NO2, SO2, PM10, PM2.5, dust mites, pollen, pet dander, and smoke, contribute to more severe allergic responses. One study showed that 11% of asthmatic children with abnormal lung function had pulmonary function with fixed obstruction in adulthood compatible with COPD.<a class="elsevierStyleCrossRef" href="#bib0060">60</a> Exposure to traffic pollution contributes to 13% of the global incidence of asthma in children.<a class="elsevierStyleCrossRef" href="#bib0061">61</a>Patients with COPD have more asthma-like symptoms in the early years of life, as demonstrated in three cohorts over several decades.<a class="elsevierStyleCrossRef" href="#bib0037">37</a> Having severe childhood asthma was the strongest predictor of COPD at age 50.<a class="elsevierStyleCrossRef" href="#bib0062">62</a> In a study of 3290 mother-infant pairs, 23% had asthma-like symptoms in childhood, and these individuals had more admissions and use of COPD medication in adulthood compared to those without asthma-like symptoms.<a class="elsevierStyleCrossRef" href="#bib0063">63</a> Another study in adults aged 50 years showed that those with symptoms of severe asthma at 6-7 years were 32 times more likely to have COPD than those without symptoms. In this group, only 40% were smokers suggesting that other harmful exposures may have contributed to the disease.<a class="elsevierStyleCrossRef" href="#bib0064">64</a>Persistently low or rapidly declining lung function and development of COPD are associated with risk factors present in childhood (maternal and paternal asthma, maternal smoking, childhood asthma, and respiratory infections).<a class="elsevierStyleCrossRef" href="#bib0038">38</a>,<a class="elsevierStyleCrossRef" href="#bib0065">65</a> In addition, preterm (< 35 s) and underweight (< 2,000 x < 2,100 g) girls are at higher risk of COPD and asthma than preterm boys.<a class="elsevierStyleCrossRef" href="#bib0066">66</a>Belgrave et al. studied the trajectory of lung function from childhood to adulthood in 2436 individuals and identified four trajectories: persistently high, normal, below average, and persistently low. Children with a persistently low trajectory were more likely to recurrent wheezing, including severe exacerbations of wheezing, early allergic sensitization, and exposure to tobacco smoke.<a class="elsevierStyleCrossRef" href="#bib0037">37</a> Avoiding these exposures could decrease the chance of lower lung function in adulthood.<a class="elsevierStyleCrossRef" href="#bib0037">37</a>A study of 69,365 individuals identified that exposure to prenatal and early life smoking is a risk factor for COPD. Low birth weight, lower respiratory tract infections, recurrent wheezing, and childhood asthma also appear to be important determinants of the development of COPD.<a class="elsevierStyleCrossRef" href="#bib0067">67</a> Parental asthma and smoking, preterm birth may be risk factors for the development of COPD.Exposure to smoking and e-cigarette during pregnancy possibly impair the maturation of the immune system.<a class="elsevierStyleCrossRef" href="#bib0068">68</a>,<a class="elsevierStyleCrossRef" href="#bib0069">69</a> Severe respiratory infections in childhood are associated with decreased lung function and increased respiratory symptoms in adults.<a class="elsevierStyleCrossRef" href="#bib0060">60</a>Adverse childhood experiencesAdverse Childhood Experiences (ACEs) have a prevalence of around 10% and are currently a global public health and social welfare concern. EAIs include harm that affects children directly (neglect, physical, sexual, or emotional abuse) and indirectly through their living environments (conflict with parents, substance abuse or mental illness) and are powerful predictors of harmful behavior to health in adults. A systematic review and meta-analysis of studies measuring the associations between various (ACEs) and health in over 18s found that individuals who had at least four adverse experiences during childhood or adolescence were twice as likely to be smokers and to have respiratory diseases than those who did not have ACEs.<a class="elsevierStyleCrossRef" href="#bib0070">70</a> Another meta-analysis has shown an association between ACEs and the occurrence of cancer in adults, including lung cancer.<a class="elsevierStyleCrossRef" href="#bib0071">71</a> One hypothesis about the mechanism linking ACEs and cancer development in adults would be the possible association with risk behaviors such as smoking, physical inactivity, poor diet, and use of psychoactive substances.<a class="elsevierStyleCrossRef" href="#bib0071">71</a>Socioeconomic factorsThere is a complex interrelationship between socioeconomic, ethnic/racial factors and health outcomes. Poverty and nutritional disorders (malnutrition and obesity) can increase the adverse effects of exposure and the risk of diseases attributed to a pollutant. Socioeconomic factors can influence the ’child's birth weight (which impacts lung growth and development) which increases susceptibility to the disease.<a class="elsevierStyleCrossRef" href="#bib0004">4</a> Lange et al. demonstrated that 50% of individuals with COPD had abnormal lung growth and development (failure to reach the normal plateau, above), with the functional decline being within normal limits.<a class="elsevierStyleCrossRef" href="#bib0040">40</a> Another study demonstrated synergism between overcrowding at home, smoking, and respiratory infection resulting in worse lung function at 43 years of age.<a class="elsevierStyleCrossRef" href="#bib0049">49</a> However, it is not well defined to what extent the socioeconomic situation may reflect exposure to indoor and environmental pollutants, overcrowding, or other factors related to social conditions.“Childhood disadvantage factors”They appear to be as important or more important than heavy smoking in predicting lung function in adulthood. Svanes et al. showed that children with a score indicating greater handicap had a more accelerated decline in lung function.<a class="elsevierStyleCrossRef" href="#bib0042">42</a> The effect on more vulnerable individuals, such as preterm infants, may have even greater repercussions.<a class="elsevierStyleCrossRef" href="#bib0042">42</a> Reduced lung function at birth and less-than-expected increased lung function in early childhood are associated with an increased risk of respiratory disease. Children of mothers exposed to CO have lower lung function at 30 days of life, and the effect is greater in girls.<a class="elsevierStyleCrossRef" href="#bib0072">72</a> Dratva et al. studied 12862 adults aged 28 to 73 years and demonstrated that early exposure to certain factors (born during the winter season, mothers >31 years at delivery, with ≥ 2 younger siblings or exposed to maternal smoking) can predict a further decline in lung function and that the effect on decline in FEV1 was as significant as the effect of smoking.<a class="elsevierStyleCrossRef" href="#bib0005">5</a> The greatest decline in FEV1 was in winter-born individuals with older mothers and mothers who smoked or had younger siblings. These same authors noted that if the mothers were older or smokers, there was a potentiation of the effects of smoking on the decline in lung function.<a class="elsevierStyleCrossRef" href="#bib0005">5</a>In summary, in this review, the authors present evidence that early lung exposure to environmental pollutants (tobacco smoke, particulate matter, air pollution associated with traffic) and adverse childhood experiences and socioeconomic status cause an increased incidence of Chronic Obstructive Pulmonary Disease (COPD), asthma and allergies; and decline in lung function. There is evidence demonstrating that adult respiratory diseases can almost always have their origins in early life. It is emphasized that health professionals must know, diagnose, monitor, and prevent toxic exposure among children and women. By recognizing these risk factors, early interventions should be implemented to reduce the progression of lung disease throughout life and into adulthood.How to prevent respiratory problems resulting from environmental exposure?In <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>,<a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0016">16</a>,<a class="elsevierStyleCrossRef" href="#bib0024">24</a>,<a class="elsevierStyleCrossRef" href="#bib0070">70</a>,<a class="elsevierStyleCrossRef" href="#bib0073">73</a>,<a class="elsevierStyleCrossRef" href="#bib0074">74</a> interventions that the pediatrician can perform are listed below.<elsevierMultimedia ident="tbl0001"></elsevierMultimedia>For the prevention of childhood-onset adult lung disease, political and social measures are needed with the aim of<ul class="elsevierStyleList" id="celist0004"><li class="elsevierStyleListItem" id="celistitem0018">•Reducing the emission of pollutants, including air pollution and tobacco, is the best way to avoid damage to the respiratory system. In Europe, reducing air pollution by PM2.5 and NO2 could prevent 6 and 4% premature deaths annually, respectively.<a class="elsevierStyleCrossRef" href="#bib0008">8</a></li><li class="elsevierStyleListItem" id="celistitem0019">•Create alternatives for transport, industries, and energy sources with a reduction in the emission of smoke and toxic gases, and particulate matter.</li><li class="elsevierStyleListItem" id="celistitem0020">•Afforest urban areas with minimally allergenic trees.</li><li class="elsevierStyleListItem" id="celistitem0021">•Properly dispose of electronic waste.</li><li class="elsevierStyleListItem" id="celistitem0022">•Implement local and international measures such as the WHO Global Strategy on Health, Environment and Climate Change.</li></ul>ConclusionMost children are exposed to some pollutants, and the home is the place where exposure is more intense and frequent, especially exposure to tobacco smoke. Exposure to environmental hazards early in life increases the risk of acute and chronic respiratory diseases. Future longitudinal studies are needed to assess the effect of specific exposures early in life, individual and collective prevention measures, behavioral and pharmacological interventions, and the impact on adult respiratory health. Pediatricians and the whole society must work together to identify risk factors, reduce avoidable exposures, protect the developing respiratory tract to reduce lifelong worsening or onset of disease and lung problems." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1683792" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Sources" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Summary of the findings" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1493456" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0002" "titulo" => "Epidemiology" ] 4 => array:3 [ "identificador" => "sec0003" "titulo" => "The child and the environment" "secciones" => array:7 [ 0 => array:3 [ "identificador" => "sec0004" "titulo" => "Pathways of exposure to environmental insults" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Transplacental" ] 1 => array:2 [ "identificador" => "sec0006" "titulo" => "Breast milk" ] 2 => array:2 [ "identificador" => "sec0007" "titulo" => "Ingestion of contaminated water and food and non-nutritive ingestion" ] 3 => array:2 [ "identificador" => "sec0008" "titulo" => "Cutaneous" ] 4 => array:2 [ "identificador" => "sec0009" "titulo" => "Inhaled" ] ] ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "The respiratory system" ] 2 => array:2 [ "identificador" => "sec0011" "titulo" => "How does damage to the respiratory system occur?" ] 3 => array:2 [ "identificador" => "sec0012" "titulo" => "What is the impact of environmental problems on respiratory health?" ] 4 => array:2 [ "identificador" => "sec0013" "titulo" => "Impairments to pulmonary function" ] 5 => array:2 [ "identificador" => "sec0014" "titulo" => "COPD" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Asthma" ] ] ] 5 => array:3 [ "identificador" => "sec0016" "titulo" => "Environmental exposures and adult respiratory health" "secciones" => array:16 [ 0 => array:2 [ "identificador" => "sec0017" "titulo" => "Tobacco exposure" ] 1 => array:2 [ "identificador" => "sec0018" "titulo" => "Transgenerational effects" ] 2 => array:3 [ "identificador" => "sec0019" "titulo" => "Antenatal effects" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Known effects of nicotine from animal work" ] 1 => array:2 [ "identificador" => "sec0020a" "titulo" => "Human studies on cigarette exposure" ] 2 => array:2 [ "identificador" => "sec0021" "titulo" => "Longer-term implications of antenatal tobacco exposure" ] ] ] 3 => array:2 [ "identificador" => "sec0022" "titulo" => "Effects of smoke exposure in childhood" ] 4 => array:2 [ "identificador" => "sec0023" "titulo" => "Lung growth and development" ] 5 => array:2 [ "identificador" => "sec0024" "titulo" => "How adult respiratory morbidity is determined by early life events" ] 6 => array:2 [ "identificador" => "sec0025" "titulo" => "Why do adults get COPD?" ] 7 => array:2 [ "identificador" => "sec0026" "titulo" => "More than just lungs: is reduced lung function the “canary in the mine”?" ] 8 => array:3 [ "identificador" => "sec0027" "titulo" => "Air pollution" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0028" "titulo" => "Particulate matter (PM)" ] 1 => array:2 [ "identificador" => "sec0029" "titulo" => "External pollutants" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Household pollutants" ] ] ] 9 => array:2 [ "identificador" => "sec0031" "titulo" => "Air pollution associated with traffic (TRAP)" ] 10 => array:2 [ "identificador" => "sec0032" "titulo" => "Asthma and allergies" ] 11 => array:2 [ "identificador" => "sec0033" "titulo" => "Adverse childhood experiences" ] 12 => array:2 [ "identificador" => "sec0034" "titulo" => "Socioeconomic factors" ] 13 => array:2 [ "identificador" => "sec0035" "titulo" => "“Childhood disadvantage factors”" ] 14 => array:2 [ "identificador" => "sec0036" "titulo" => "How to prevent respiratory problems resulting from environmental exposure?" ] 15 => array:2 [ "identificador" => "sec0037" "titulo" => "For the prevention of childhood-onset adult lung disease, political and social measures are needed with the aim of" ] ] ] 6 => array:2 [ "identificador" => "sec0038" "titulo" => "Conclusion" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-11-10" "fechaAceptado" => "2021-11-11" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1493456" "palabras" => array:6 [ 0 => "Environmental exposures" 1 => "Early childhood exposures" 2 => "Early disease origin" 3 => "Air pollution" 4 => "Respiratory diseases" 5 => "Lung function" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo review in the literature the environmental problems in early life that impact the respiratory health of adults. SourcesNon-systematic review including articles in English. Search filters were not used in relation to the publication date, but the authors selected mainly publications from the last five years. Summary of the findingsIn this review, the authors present the exposure pathways and how the damage occurs depending on the child's stage of development; the authors describe the main environmental pollutants - tobacco smoke, particulate matter, air pollution associated with traffic, adverse childhood experiences and socioeconomic status; the authors present studies that evaluated the repercussions on the respiratory system of adults resulting from exposure to adverse environmental factors in childhood, such as increased incidence of Chronic Obstructive Pulmonary Disease (COPD), asthma and allergies; and, a decline in lung function. The authors emphasize that evidence demonstrates that adult respiratory diseases almost always have their origins in early life. Finally, the authors emphasize that health professionals must know, diagnose, monitor, and prevent toxic exposure among children and women. ConclusionThe authors conclude that it is necessary to recognize risk factors and intervene in the period of greatest vulnerability to the occurrence of harmful effects of environmental exposures, to prevent, delay the onset or modify the progression of lung disease throughout life and into adulthood." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Sources" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Summary of the findings" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><a name="en0001"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top"><ul class="elsevierStyleList" id="celist0005"><li class="elsevierStyleListItem" id="celistitem0023">•Recognize risk factors and intervene when the child is most vulnerable.<a class="elsevierStyleCrossRef" href="#bib0005">5</a></li><li class="elsevierStyleListItem" id="celistitem0024">•To identify, diagnose, monitor, and prevent toxic exposure among children and women.<a class="elsevierStyleCrossRef" href="#bib0016">16</a></li><li class="elsevierStyleListItem" id="celistitem0025">•Guide to avoid smoking, including electronic cigarettes and alcohol.<a class="elsevierStyleCrossRef" href="#bib0073">73</a></li><li class="elsevierStyleListItem" id="celistitem0027">•Improve the quality of prenatal care by reducing factors associated with prematurity.<a class="elsevierStyleCrossRef" href="#bib0005">5</a></li><li class="elsevierStyleListItem" id="celistitem0028">•Acting in the diagnosis and prevention of asthma with an emphasis on modifiable factors (environment, lifestyle and comorbidities).<a class="elsevierStyleCrossRef" href="#bib0024">24</a>,<a class="elsevierStyleCrossRef" href="#bib0074">74</a></li><li class="elsevierStyleListItem" id="celistitem0029">•Act to prevent nutritional disorders and infections (immunization) that contribute to lung problems and COPD risk.<a class="elsevierStyleCrossRef" href="#bib0074">74</a></li><li class="elsevierStyleListItem" id="celistitem0030">•Prevent adverse childhood experiences.<a class="elsevierStyleCrossRef" href="#bib0070">70</a></li><li class="elsevierStyleListItem" id="celistitem0031">•Identify and monitor individuals at increased risk for rapid decline in lung function.</li></ul> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2864110.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Pediatric intervention." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:74 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Air Pollution" "autores" => array:1 [ 0 => array:2 [ "colaboracion" => "World Health Organization (WHO)" "etal" => false ] ] ] ] "host" => array:2 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2021" ] ] 1 => array:1 [ "WWW" => array:1 [ "link" => "https://www.who.int/health-topics/air-pollution" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0002" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization (WHO). Mortality from environmental pollution [Internet]. SDG Target 3.9 Mortality from environmental pollution; 2021 [cited 2021 Nov 1]. Available from:<a target="_blank" href="https://www.who.int/data/gho/data/themes/topics/sdg-target-3_9-mortality-from-environmental-pollution">https://www.who.int/data/gho/data/themes/topics/sdg-target-3_9-mortality-from-environmental-pollution</a>" ] ] ] 2 => array:3 [ "identificador" => "bib0003" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of prenatal and early life environmental exposures on normal human development" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "P Sly" 1 => "T Blake" 2 => "Z. Islam" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.prrv.2021.05.007" "Revista" => array:6 [ "tituloSerie" => "Paediatr Respir Rev" "fecha" => "2021" "volumen" => "40" "paginaInicial" => "10" "paginaFinal" => "14" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34148806" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0004" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Environmental contributions to respiratory disease in children" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P Sly" 1 => "A. Bush" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:3 [ "editores" => "RWilmott, RDeterding, ALi, FRatjen, PSly, HJZar" "titulo" => "Kendig's Disorders of the Respiratory Tract in Children" "serieFecha" => "2019" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0005" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early life origins of lung ageing: early life exposures and lung function decline in adulthood in two European cohorts aged 28-73 years" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J Dratva" 1 => "E Zemp" 2 => "SC Dharmage" 3 => "S Accordini" 4 => "L Burdet" 5 => "T Gislason" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0166947" "Revista" => array:4 [ "tituloSerie" => "PLoS One" "fecha" => "2016" "volumen" => "11" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28002457" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0006" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "DJ Barker" 1 => "KM Godfrey" 2 => "C Fall" 3 => "C Osmond" 4 => "PD Winter" 5 => "SO Shaheen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.303.6804.671" "Revista" => array:6 [ "tituloSerie" => "BMJ" "fecha" => "1991" "volumen" => "303" "paginaInicial" => "671" "paginaFinal" => "675" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1912913" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0007" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The natural history of chronic airflow obstruction" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C Fletcher" 1 => "R. Peto" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Br Med J" "fecha" => "1977" "volumen" => "1" "paginaInicial" => "1645" "paginaFinal" => "1648" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20792867" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0008" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Premature mortality due to air pollution in European cities: a health impact assessment" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S Khomenko" 1 => "M Cirach" 2 => "E Pereira-Barboza" 3 => "N Mueller" 4 => "J Barrera-Gómez" 5 => "D Rojas-Rueda" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Lancet Planet Health" "fecha" => "2021" "volumen" => "5" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0009" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung consequences in adults born prematurely" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "CE Bolton" 1 => "A Bush" 2 => "JR Hurst" 3 => "S Kotecha" 4 => "L. McGarvey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2014-206590" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2015" "volumen" => "70" "paginaInicial" => "574" "paginaFinal" => "580" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25825005" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0010" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of early life exposures on respiratory disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Bush" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.prrv.2021.05.006" "Revista" => array:6 [ "tituloSerie" => "Paediatr Respir Rev" "fecha" => "2021" "volumen" => "40" "paginaInicial" => "24" "paginaFinal" => "32" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34144911" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0011" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of a stepwise introduction of smoke-free legislation on the rate of preterm births: analysis of routinely collected birth data" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "B Cox" 1 => "E Martens" 2 => "B Nemery" 3 => "J Vangronsveld" 4 => "TS. Nawrot" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.f441" "Revista" => array:5 [ "tituloSerie" => "BMJ" "fecha" => "2013" "volumen" => "346" "paginaInicial" => "f441" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23412829" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0012" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung function in early adulthood and health in later life: a transgenerational cohort analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A Agustí" 1 => "G Noell" 2 => "J Brugada" 3 => "R. Faner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(17)30434-4" "Revista" => array:6 [ "tituloSerie" => "Lancet Respir Med" "fecha" => "2017" "volumen" => "5" "paginaInicial" => "935" "paginaFinal" => "945" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29150410" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0013" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Respiratory health in cleaners in northern Europe: is susceptibility established in early life?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Ø Svanes" 1 => "TD Skorge" 2 => "A Johannessen" 3 => "RJ Bertelsen" 4 => "M Bråtveit" 5 => "B Forsberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0141892" "Revista" => array:4 [ "tituloSerie" => "PLoS One" "fecha" => "2015" "volumen" => "10" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26720074" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0014" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "European Respiratory Society. Environment and health. 2020 [cited 2021 Nov 1]. Available from: <a target="_blank" href="https://www.ersnet.org/advocacy/environment-and-health/">https://www.ersnet.org/advocacy/environment-and-health/</a>" ] ] ] 14 => array:3 [ "identificador" => "bib0015" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization (WHO). Air quality and health. 2021 [cited 2021 Nov 1]. Available from:<a target="_blank" href="http://www.who.int/teams/environment-climate-change-and-health/air-quality-and-health/health-impacts">www.who.int/teams/environment-climate-change-and-health/air-quality-and-health/health-impacts</a>" ] ] ] 15 => array:3 [ "identificador" => "bib0016" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization (WHO). Health topics. Soaring e-waste affects the health of millions of children, WHO warns. 2021 [cited 2021 Nov 1]. Available from:<a target="_blank" href="http://www.who.int/news/item/15-06-2021-soaring-e-waste-affects-the-health-of-millions-of-children-who-warns">www.who.int/news/item/15-06-2021-soaring-e-waste-affects-the-health-of-millions-of-children-who-warns</a>" ] ] ] 16 => array:3 [ "identificador" => "bib0017" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Alveolarization continues during childhood and adolescence: new evidence from helium-3 magnetic resonance" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M Narayanan" 1 => "J Owers-Bradley" 2 => "CS Beardsmore" 3 => "M Mada" 4 => "I Ball" 5 => "R Garipov" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201107-1348OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2012" "volumen" => "185" "paginaInicial" => "186" "paginaFinal" => "191" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22071328" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0018" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Susceptibility of children to environmental pollutants" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "PD Sly" 1 => "F. Flack" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Ann N Y Acad Sci" "fecha" => "2008" "volumen" => "1140" "paginaInicial" => "163" "paginaFinal" => "183" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0019" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "WJ Morgan" 1 => "DA Stern" 2 => "DL Sherrill" 3 => "S Guerra" 4 => "CJ Holberg" 5 => "TW Guilbert" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.200504-525OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2005" "volumen" => "172" "paginaInicial" => "1253" "paginaFinal" => "1258" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16109980" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0020" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Low lung function in young adult life is associated with early mortality" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "MM Vasquez" 1 => "M Zhou" 2 => "C Hu" 3 => "FD Martinez" 4 => "S. Guerra" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201608-1561LE" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2017" "volumen" => "195" "paginaInicial" => "1399" "paginaFinal" => "1401" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28504596" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0021" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Poor airway function in early infancy and lung function by age 22 years: a non-selective longitudinal cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "DA Stern" 1 => "WJ Morgan" 2 => "AL Wright" 3 => "S Guerra" 4 => "FD. Martinez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(07)61379-8" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2007" "volumen" => "370" "paginaInicial" => "758" "paginaFinal" => "764" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17765525" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0022" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Global initiative for chronic obstructive lung disease (GOLD). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease (2021 report). [cited 2021 Nov 1st]. <a target="_blank" href="https://goldcopd.org">https://goldcopd.org</a>" ] ] ] 22 => array:3 [ "identificador" => "bib0023" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The relationship of acute respiratory illness history to the prevalence and incidence of obstructive lung disorders" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "MD Lebowitz" 1 => "B. Burrows" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/oxfordjournals.aje.a112418" "Revista" => array:6 [ "tituloSerie" => "Am J Epidemiol" "fecha" => "1977" "volumen" => "105" "paginaInicial" => "544" "paginaFinal" => "554" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/868858" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0024" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Global Initiative for Asthma. 2021 GINA report, global strategy for asthma management and prevention. 2021. [cited 2021 Nov 1]. Available from: <a target="_blank" href="https://ginasthma.org/gina-reports/">https://ginasthma.org/gina-reports/</a>" ] ] ] 24 => array:3 [ "identificador" => "bib0025" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "E-Cigarettes as a growing threat for children and adolescents: position statement from the European Academy of Paediatrics" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A Bush" 1 => "A Lintowska" 2 => "A Mazur" 3 => "A Hadjipanayis" 4 => "Z Grossman" 5 => "S Del Torso" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fped.2021.569594" "Revista" => array:4 [ "tituloSerie" => "Front Pediatr." "fecha" => "2021" "volumen" => "9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33748036" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0026" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Grandmother's smoking when pregnant with the mother and asthma in the grandchild: the Norwegian Mother and Child Cohort Study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "MC Magnus" 1 => "SE Haberg" 2 => "O Karlstad" 3 => "P Nafstad" 4 => "SJ London" 5 => "W. Nystad" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2014-206438" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2015" "volumen" => "70" "paginaInicial" => "237" "paginaFinal" => "243" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25572596" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0027" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Maternal and grandmaternal smoking patterns are associated with early childhood asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Y-F Li" 1 => "B Langholz" 2 => "MT Salam" 3 => "FD. Gilliland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1378/chest.127.4.1232" "Revista" => array:6 [ "tituloSerie" => "Chest" "fecha" => "2005" "volumen" => "127" "paginaInicial" => "1232" "paginaFinal" => "1241" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15821200" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0028" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Maternal nicotine exposure upregulates collagen gene expression in fetal monkey lung. Association with alpha7 nicotinic acetylcholine receptors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "HS Sekhon" 1 => "JA Keller" 2 => "BJ Proskocil" 3 => "EL Martin" 4 => "ER. Spindel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/ajrcmb.26.1.4170" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "2002" "volumen" => "26" "paginaInicial" => "31" "paginaFinal" => "41" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11751201" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0029" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prenatal nicotine exposure increases GABA signaling and mucin expression in airway epithelium" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "XW Fu" 1 => "K Wood" 2 => "ER. Spindel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/rcmb.2010-0109OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "2011" "volumen" => "44" "paginaInicial" => "222" "paginaFinal" => "229" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20448051" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0030" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prenatal nicotine exposure alters lung function and airway geometry through α7 nicotinic receptors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C Wongtrakool" 1 => "N Wang" 2 => "DM Hyde" 3 => "J Roman" 4 => "ER. Spindel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/rcmb.2011-0028OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "2012" "volumen" => "46" "paginaInicial" => "695" "paginaFinal" => "702" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22246862" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0031" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interaction between asthma and lung function growth in early life" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "H Bisgaard" 1 => "SM Jensen" 2 => "K. Bønnelykke" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201110-1922OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2012" "volumen" => "185" "paginaInicial" => "1183" "paginaFinal" => "1189" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22461370" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0032" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prenatal nicotine increases pulmonary α7 nicotinic receptor expression and alters fetal lung development in monkeys" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "HS Sekhon" 1 => "Y Jia" 2 => "R Raab" 3 => "A Kuryatov" 4 => "JF Pankow" 5 => "JA Whitsett" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI5232" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "1999" "volumen" => "103" "paginaInicial" => "637" "paginaFinal" => "647" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10074480" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0033" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Maternal cigarette smoking is associated with increased inner airway wall thickness in children who die from sudden infant death syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J Elliot" 1 => "P Vullermin" 2 => "P. Robinson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1998" "volumen" => "158" "paginaInicial" => "802" "paginaFinal" => "806" ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0034" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Antenatal determinants of neonatal immune responses to allergens" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G Devereux" 1 => "RN Barker" 2 => "A. Seaton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1046/j.0022-0477.2001.01267.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2002" "volumen" => "32" "paginaInicial" => "43" "paginaFinal" => "50" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12002736" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0035" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "PS Noakes" 1 => "J Hale" 2 => "R Thomas" 3 => "C Lane" 4 => "SG Devadason" 5 => "SL. Prescott" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1183/09031936.06.00050206" "Revista" => array:6 [ "tituloSerie" => "Eur Respir J" "fecha" => "2006" "volumen" => "28" "paginaInicial" => "721" "paginaFinal" => "729" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16870663" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0036" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Bush A. Health effects of passive smoking in children. In Loddenkemper R, Kreuter M, eds. The Tobacco Epidemic. 2nd ed., Volume 42. Progress in Respiratory Research. Basel, Switzerland: Karger; 2015. p. 97-109" ] ] ] 36 => array:3 [ "identificador" => "bib0037" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung function trajectories from pre-school age to adulthood and their associations with early life factors: a retrospective analysis of three population-based birth cohort studies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "DC Belgrave" 1 => "R Granell" 2 => "SW Turner" 3 => "JA Curtin" 4 => "IE Buchan" 5 => "PN Le Souëf" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(18)30099-7" "Revista" => array:6 [ "tituloSerie" => "Lancet Respir Med" "fecha" => "2018" "volumen" => "6" "paginaInicial" => "526" "paginaFinal" => "534" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29628377" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0038" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "DS Bui" 1 => "CJ Lodge" 2 => "JA Burgess" 3 => "AJ Lowe" 4 => "J Perret" 5 => "MQ Bui" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-2600(18)30100-0" "Revista" => array:6 [ "tituloSerie" => "Lancet Respir Med" "fecha" => "2018" "volumen" => "6" "paginaInicial" => "535" "paginaFinal" => "544" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29628376" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0039" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "DA Stern" 1 => "WJ Morgan" 2 => "M Halonen" 3 => "AL Wright" 4 => "FD. Martinez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(08)61447-6" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2008" "volumen" => "372" "paginaInicial" => "1058" "paginaFinal" => "1064" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18805334" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib0040" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lung-function trajectories leading to chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P Lange" 1 => "B Celli" 2 => "A Agustí" 3 => "G Boje Jensen" 4 => "M Divo" 5 => "R Faner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1411532" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2015" "volumen" => "373" "paginaInicial" => "111" "paginaFinal" => "122" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26154786" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib0041" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined effects of parental and active smoking on early lung function deficits: a prospective study from birth to age 26 years" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:7 [ 0 => "S Guerra" 1 => "DA Stern" 2 => "M Zhou" 3 => "DL Sherrill" 4 => "AL Wright" 5 => "WJ Morgan" 6 => "FD. Martinez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2013-203538" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2013" "volumen" => "68" "paginaInicial" => "1021" "paginaFinal" => "1028" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23847259" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0042" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early life origins of chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C Svanes" 1 => "J Sunyer" 2 => "E Plana" 3 => "S Dharmage" 4 => "J Heinrich" 5 => "D Jarvis" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2008.112136" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2010" "volumen" => "65" "paginaInicial" => "14" "paginaFinal" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19729360" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0043" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Impact of ””” ’London's road traffic air and noise pollution on birth weight: retrospective population based cohort study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "RB Smith" 1 => "D Fecht" 2 => "J Gulliver" 3 => "SD Beevers" 4 => "D Dajnak" 5 => "M Blangiardo" 6 => "RE Ghosh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.j5299" "Revista" => array:5 [ "tituloSerie" => "BMJ" "fecha" => "2017" "volumen" => "359" "paginaInicial" => "j5299" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29208602" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib0044" "etiqueta" => "44" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver, Canada" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S Liu" 1 => "D Krewski" 2 => "Y Shi" 3 => "Y Chen" 4 => "RT. Burnett" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1289/ehp.6251" "Revista" => array:6 [ "tituloSerie" => "Environ Health Perspect." "fecha" => "2003" "volumen" => "111" "paginaInicial" => "1773" "paginaFinal" => "1778" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14594630" "web" => "Medline" ] ] ] ] ] ] ] ] 44 => array:3 [ "identificador" => "bib0045" "etiqueta" => "45" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E Morales" 1 => "R Garcia-Esteban" 2 => "OA de la Cruz" 3 => "M Basterrechea" 4 => "A Lertxundi" 5 => "MD de Dicastillo" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2014-205413" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2015" "volumen" => "70" "paginaInicial" => "64" "paginaFinal" => "73" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25331281" "web" => "Medline" ] ] ] ] ] ] ] ] 45 => array:3 [ "identificador" => "bib0046" "etiqueta" => "46" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "European Respiratory Society. Exposure to air pollution within EU limits linked to impaired breathing in children and asthma in adults. 2020 [cited 2021 Nov 1]. Available from:<a target="_blank" href="https://www.ersnet.org/news-and-features/news/exposure-to-air-pollution-within-eu-limits-linked-to-impaired-breathing-in-children-and-asthma-in-adults/">https://www.ersnet.org/news-and-features/news/exposure-to-air-pollution-within-eu-limits-linked-to-impaired-breathing-in-children-and-asthma-in-adults/</a>" ] ] ] 46 => array:3 [ "identificador" => "bib0047" "etiqueta" => "47" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization (WHO). Ambient (outdoor) air pollution [Internet]. Health-topics. 2021 [cited 2021 Nov 1]. Available from: <a target="_blank" href="https://www.who.int/news-room/fact-sheets/detail/ambient-(outdoor)-air-quality-and-health">https://www.who.int/news-room/fact-sheets/detail/ambient-(outdoor)-air-quality-and-health</a>" ] ] ] 47 => array:3 [ "identificador" => "bib0048" "etiqueta" => "48" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of air pollution on lung development from 10 to 18 years of age" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "WJ Gauderman" 1 => "E Avol" 2 => "F Gilliland" 3 => "H Vora" 4 => "D Thomas" 5 => "K Berhane" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa040610" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2004" "volumen" => "351" "paginaInicial" => "1057" "paginaFinal" => "1067" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15356303" "web" => "Medline" ] ] ] ] ] ] ] ] 48 => array:3 [ "identificador" => "bib0049" "etiqueta" => "49" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of improved air quality with lung development in children" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "WJ Gauderman" 1 => "R Urman" 2 => "E Avol" 3 => "K Berhane" 4 => "R McConnell" 5 => "E Rappaport" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1414123" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2015" "volumen" => "372" "paginaInicial" => "905" "paginaFinal" => "913" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25738666" "web" => "Medline" ] ] ] ] ] ] ] ] 49 => array:3 [ "identificador" => "bib0050" "etiqueta" => "50" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Associations between pre- and postnatal exposure to air pollution and lung health in children and assessment of CC16 as a potential mediator" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A Stapleton" 1 => "M Casas" 2 => "J García" 3 => "R García" 4 => "J Sunyer" 5 => "S Guerra" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Environ Res" "fecha" => "2021" "volumen" => "204" ] ] ] ] ] ] 50 => array:3 [ "identificador" => "bib0051" "etiqueta" => "51" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Influences of environmental exposures on preterm lung disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "JM Collaco" 1 => "BC Aoyama" 2 => "JL Rice" 3 => "SA. McGrath-Morrow" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1080/17476348.2021.1941886" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Respir Med" "fecha" => "2021" "volumen" => "15" "paginaInicial" => "1271" "paginaFinal" => "1279" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34114906" "web" => "Medline" ] ] ] ] ] ] ] ] 51 => array:3 [ "identificador" => "bib0052" "etiqueta" => "52" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early-life exposure to the great smog of 1952 and the development of asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P Bharadwaj" 1 => "JG Zivin" 2 => "JT Mullins" 3 => "M. Neidell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201603-0451OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2016" "volumen" => "194" "paginaInicial" => "1475" "paginaFinal" => "1482" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27392261" "web" => "Medline" ] ] ] ] ] ] ] ] 52 => array:3 [ "identificador" => "bib0053" "etiqueta" => "53" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Air pollution and the development of asthma from birth until young adulthood" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "U Gehring" 1 => "AH Wijga" 2 => "GH Koppelman" 3 => "JM Vonk" 4 => "HA Smit" 5 => "B. Brunekreef" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Eur Respir J" "fecha" => "2020" "volumen" => "56" ] ] ] ] ] ] 53 => array:3 [ "identificador" => "bib0054" "etiqueta" => "54" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Allergy and atopy from infancy to adulthood: messages from the German birth cohort MAS" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S Lau" 1 => "PM Matricardi" 2 => "U Wahn" 3 => "YA Lee" 4 => "T. Keil" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.anai.2018.05.012" "Revista" => array:6 [ "tituloSerie" => "Ann Allergy Asthma Immunol" "fecha" => "2019" "volumen" => "122" "paginaInicial" => "25" "paginaFinal" => "32" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29803707" "web" => "Medline" ] ] ] ] ] ] ] ] 54 => array:3 [ "identificador" => "bib0055" "etiqueta" => "55" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A longitudinal, population-based, cohort study of childhood asthma followed to adulthood" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "MR Sears" 1 => "JM Greene" 2 => "AR Willan" 3 => "EM Wiecek" 4 => "DR Taylor" 5 => "EM Flannery" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa022363" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2003" "volumen" => "349" "paginaInicial" => "1414" "paginaFinal" => "1422" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14534334" "web" => "Medline" ] ] ] ] ] ] ] ] 55 => array:3 [ "identificador" => "bib0056" "etiqueta" => "56" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluating the long-term consequences of air pollution in early life: geographical correlations between coal consumption in 1951/1952 and current mortality in England and Wales" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "DI Phillips" 1 => "C Osmond" 2 => "H Southall" 3 => "P Aucott" 4 => "A Jones" 5 => "ST. Holgate" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmjopen-2018-022991" "Revista" => array:4 [ "tituloSerie" => "BMJ Open" "fecha" => "2018" "volumen" => "8" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30598485" "web" => "Medline" ] ] ] ] ] ] ] ] 56 => array:3 [ "identificador" => "bib0057" "etiqueta" => "57" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Particulate air pollution and fetal health: a systematic review of the epidemiologic evidence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "SV Glinianaia" 1 => "J Rankin" 2 => "R Bell" 3 => "T Pless-Mulloli" 4 => "D. Howel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/01.ede.0000101023.41844.ac" "Revista" => array:6 [ "tituloSerie" => "Epidemiology" "fecha" => "2004" "volumen" => "15" "paginaInicial" => "36" "paginaFinal" => "45" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14712145" "web" => "Medline" ] ] ] ] ] ] ] ] 57 => array:3 [ "identificador" => "bib0058" "etiqueta" => "58" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Exposure to traffic-related air pollution and risk of development of childhood asthma: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "H Khreis" 1 => "C Kelly" 2 => "J Tate" 3 => "R Parslow" 4 => "K Lucas" 5 => "M. Nieuwenhuijsen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.envint.2016.11.012" "Revista" => array:6 [ "tituloSerie" => "Environ Int" "fecha" => "2017" "volumen" => "100" "paginaInicial" => "1" "paginaFinal" => "31" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27881237" "web" => "Medline" ] ] ] ] ] ] ] ] 58 => array:3 [ "identificador" => "bib0059" "etiqueta" => "59" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outdoor air pollution and asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M Guarnieri" 1 => "JR. Balmes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(14)60617-6" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2014" "volumen" => "383" "paginaInicial" => "1581" "paginaFinal" => "1592" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24792855" "web" => "Medline" ] ] ] ] ] ] ] ] 59 => array:3 [ "identificador" => "bib0060" "etiqueta" => "60" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Patterns of growth and decline in lung function in persistent childhood asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "MJ McGeachie" 1 => "KP Yates" 2 => "X Zhou" 3 => "F Guo" 4 => "AL Sternberg" 5 => "ML Van Natta" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1513737" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2016" "volumen" => "374" "paginaInicial" => "1842" "paginaFinal" => "1852" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27168434" "web" => "Medline" ] ] ] ] ] ] ] ] 60 => array:3 [ "identificador" => "bib0061" "etiqueta" => "61" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global, national, and urban burdens of paediatric asthma incidence attributable to ambient NO pollution: estimates from global datasets" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P Achakulwisut" 1 => "M Brauer" 2 => "P Hystad" 3 => "SC. Anenberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2542-5196(19)30046-4" "Revista" => array:6 [ "tituloSerie" => "Lancet Planet Health" "fecha" => "2019" "volumen" => "3" "paginaInicial" => "e166" "paginaFinal" => "e178" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30981709" "web" => "Medline" ] ] ] ] ] ] ] ] 61 => array:3 [ "identificador" => "bib0062" "etiqueta" => "62" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Outcomes of childhood asthma to the age of 50 years" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A Tai" 1 => "H Tran" 2 => "M Roberts" 3 => "N Clarke" 4 => "A-M Gibson" 5 => "S Vidmar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaci.2013.09.002" "Revista" => array:4 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2014" "volumen" => "133" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24139497" "web" => "Medline" ] ] ] ] ] ] ] ] 62 => array:3 [ "identificador" => "bib0063" "etiqueta" => "63" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Asthma-like symptoms in young children increase the risk of COPD" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H Bisgaard" 1 => "S Nørgaard" 2 => "A Sevelsted" 3 => "BL Chawes" 4 => "J Stokholm" 5 => "EL Mortensen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "2021" "volumen" => "147" ] ] ] ] ] ] 63 => array:3 [ "identificador" => "bib0064" "etiqueta" => "64" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The association between childhood asthma and adult chronic obstructive pulmonary disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "A Tai" 1 => "H Tran" 2 => "M Roberts" 3 => "N Clarke" 4 => "J Wilson" 5 => "CF. Robertson" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thoraxjnl-2013-204815" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2014" "volumen" => "69" "paginaInicial" => "805" "paginaFinal" => "810" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24646659" "web" => "Medline" ] ] ] ] ] ] ] ] 64 => array:3 [ "identificador" => "bib0065" "etiqueta" => "65" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for chronic obstructive pulmonary disease in a European cohort of young adults" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R de Marco" 1 => "S Accordini" 2 => "A Marcon" 3 => "I Cerveri" 4 => "JM Antó" 5 => "T Gislason" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201007-1125OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2011" "volumen" => "183" "paginaInicial" => "891" "paginaFinal" => "897" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20935112" "web" => "Medline" ] ] ] ] ] ] ] ] 65 => array:3 [ "identificador" => "bib0066" "etiqueta" => "66" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Obstructive pulmonary disease in old age among individuals born preterm" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "EB Broström" 1 => "O Akre" 2 => "M Katz-Salamon" 3 => "D Jaraj" 4 => "M Kaijser" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10654-013-9761-7" "Revista" => array:6 [ "tituloSerie" => "Eur J Epidemiol" "fecha" => "2013" "volumen" => "28" "paginaInicial" => "79" "paginaFinal" => "85" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23341027" "web" => "Medline" ] ] ] ] ] ] ] ] 66 => array:3 [ "identificador" => "bib0067" "etiqueta" => "67" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Early life insults as determinants of chronic obstructive pulmonary disease in adult life" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "O Savran" 1 => "CS. Ulrik" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/COPD.S153555" "Revista" => array:6 [ "tituloSerie" => "Int J Chron Obstruct Pulmon Dis" "fecha" => "2018" "volumen" => "13" "paginaInicial" => "683" "paginaFinal" => "693" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29520136" "web" => "Medline" ] ] ] ] ] ] ] ] 67 => array:3 [ "identificador" => "bib0068" "etiqueta" => "68" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Maternal smoking during pregnancy. Effects on lung function during the first 18 months of life" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "IB Tager" 1 => "L Ngo" 2 => "JP. Hanrahan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.152.3.7663813" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1995" "volumen" => "152" "paginaInicial" => "977" "paginaFinal" => "983" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7663813" "web" => "Medline" ] ] ] ] ] ] ] ] 68 => array:3 [ "identificador" => "bib0069" "etiqueta" => "69" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of nicotine in the effects of maternal smoking during pregnancy on lung development and childhood respiratory disease. implications for dangers of E-Cigarettes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "ER Spindel" 1 => "CT McEvoy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201510-2013PP" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2016" "volumen" => "193" "paginaInicial" => "486" "paginaFinal" => "494" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26756937" "web" => "Medline" ] ] ] ] ] ] ] ] 69 => array:3 [ "identificador" => "bib0070" "etiqueta" => "70" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K Hughes" 1 => "MA Bellis" 2 => "KA Hardcastle" 3 => "D Sethi" 4 => "A Butchart" 5 => "C Mikton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2468-2667(17)30118-4" "Revista" => array:6 [ "tituloSerie" => "Lancet Public Health" "fecha" => "2017" "volumen" => "2" "paginaInicial" => "e356" "paginaFinal" => "e366" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29253477" "web" => "Medline" ] ] ] ] ] ] ] ] 70 => array:3 [ "identificador" => "bib0071" "etiqueta" => "71" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Adverse childhood experiences and risk of cancer during adulthood: A systematic review and meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Z Hu" 1 => "AC Kaminga" 2 => "J Yang" 3 => "J Liu" 4 => "H. Xu" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:3 [ "tituloSerie" => "Child Abuse Negl" "fecha" => "2021" "volumen" => "117" ] ] ] ] ] ] 71 => array:3 [ "identificador" => "bib0072" "etiqueta" => "72" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prenatal household air pollution is associated with impaired infant lung function with sex-specific effects. Evidence from GRAPHS, a cluster randomized cookstove intervention trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "AG Lee" 1 => "S Kaali" 2 => "A Quinn" 3 => "R Delimini" 4 => "K Burkart" 5 => "J Opoku-Mensah" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/rccm.201804-0694OC" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "2019" "volumen" => "199" "paginaInicial" => "738" "paginaFinal" => "776" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30256656" "web" => "Medline" ] ] ] ] ] ] ] ] 72 => array:3 [ "identificador" => "bib0073" "etiqueta" => "73" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Sociedade Brasileira de Pediatria (SBP). Documentos científicos toxicologia e Saúde Ambiental [cited 2021 Nov 1]. Available from: <a target="_blank" href="https://www.sbp.com.br/departamentos-cientificos/toxicologia-e-saude-ambiental/documentos-cientificos/">https://www.sbp.com.br/departamentos-cientificos/toxicologia-e-saude-ambiental/documentos-cientificos/</a>" ] ] ] 73 => array:3 [ "identificador" => "bib0074" "etiqueta" => "74" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improving lung health in low-income and middle-income countries: from challenges to solutions" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J Meghji" 1 => "K Mortimer" 2 => "A Agusti" 3 => "BW Allwood" 4 => "I Asher" 5 => "ED Bateman" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(21)00458-X" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2021" "volumen" => "397" "paginaInicial" => "928" "paginaFinal" => "940" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33631128" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/00217557/00000098000000S1/v1_202203240549/S0021755721001650/v1_202203240549/en/main.assets" "Apartado" => array:4 [ "identificador" => "10176" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Review articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/00217557/00000098000000S1/v1_202203240549/S0021755721001650/v1_202203240549/en/main.pdf?idApp=UINPBA000049&text.app=https://jped.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755721001650?idApp=UINPBA000049"]

Statistics

Review article

Helena Teresinha Mocelina,b,

Corresponding author

helenatm@ufcspa.edu.br

Corresponding author.

, Gilberto Bueno Fischera,b,c, Andrew Bushd,e

a Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Departamento de Pediatria, Porto Alegre, RS, Brazil

b Hospital da Criança Santo Antônio, Seção de Pneumologia Pediátrica, Porto Alegre, RS, Brazil

c Universidade Federal de Ciências da Saúde de Porto Alegre (UFCSPA), Programa de Pós-Graduação em Pediatria, Porto Alegre, RS, Brazil

d Imperial College London, Faculty of Medicine, National Heart and Lung Institute, Section of Paediatrics, London, United Kingdom

e Royal Brompton Hospital, Department of Paediatric Respiratory Medicine, London, United Kingdom

Read

3094

Times
was read the article

1156

Total PDF

1938

Total HTML

Share statistics

 array:22 [
  "pii" => "S0021755721001650"
  "issn" => "00217557"
  "doi" => "10.1016/j.jped.2021.11.005"
  "estado" => "S300"
  "fechaPublicacion" => "2022-03-01"
  "aid" => "1048"
  "copyrightAnyo" => "2021"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "rev"
  "cita" => "J Pediatr &#40;Rio J&#41;. 2022;98 Supl 1:S86-S95"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:1 [
    "total" => 0
  ]
  "itemAnterior" => array:18 [
    "pii" => "S0021755721001637"
    "issn" => "00217557"
    "doi" => "10.1016/j.jped.2021.11.003"
    "estado" => "S300"
    "fechaPublicacion" => "2022-03-01"
    "aid" => "1045"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "rev"
    "cita" => "J Pediatr &#40;Rio J&#41;. 2022;98 Supl 1:S73-S85"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>"
      "titulo" => "New insights on the effects of endocrine-disrupting chemicals on children"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "S73"
          "paginaFinal" => "S85"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:8 [
          "identificador" => "fig0002"
          "etiqueta" => "Figure 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 2564
              "Ancho" => 2917
              "Tamanyo" => 353365
            ]
          ]
          "detalles" => array:1 [
            0 => array:3 [
              "identificador" => "alt0005"
              "detalle" => "Fig&#46; "
              "rol" => "short"
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">PRISMA flow diagram&#46; &#40;From&#58; Moher D&#44; Liberati A&#44; Tetzlaff J&#44; Altman DG&#59; The PRISMA Group&#46; Preferred reporting items for systematic reviews and meta-analyses&#58; the PRISMA statement&#46; PLoS Med&#46; 2009&#59;6&#58;e1000097&#46; For more information&#44; visit <span class="elsevierStyleInterRef" id="interref0001" href="http://www.prisma-statement.org">www&#46;prisma-statement&#46;org</span>&#41;&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Barbara Predieri, Cr&#233;sio A&#46;D&#46; Alves, Lorenzo Iughetti"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Barbara"
              "apellidos" => "Predieri"
            ]
            1 => array:2 [
              "nombre" => "Cr&#233;sio A&#46;D&#46;"
              "apellidos" => "Alves"
            ]
            2 => array:2 [
              "nombre" => "Lorenzo"
              "apellidos" => "Iughetti"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755721001637?idApp=UINPBA000049"
    "url" => "/00217557/00000098000000S1/v1_202203240549/S0021755721001637/v1_202203240549/en/main.assets"
  ]
  "en" => array:17 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Review article</span>"
    "titulo" => "Adverse early-life environmental exposures and their repercussions on adult respiratory health"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "S86"
        "paginaFinal" => "S95"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Helena Teresinha Mocelin, Gilberto Bueno Fischer, Andrew Bush"
        "autores" => array:3 [
          0 => array:4 [
            "nombre" => "Helena Teresinha"
            "apellidos" => "Mocelin"
            "email" => array:1 [
              0 => "helenatm@ufcspa.edu.br"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0001"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0002"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0001"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Gilberto Bueno"
            "apellidos" => "Fischer"
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0001"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0002"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0003"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Andrew"
            "apellidos" => "Bush"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0004"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:5 [
          0 => array:3 [
            "entidad" => "Universidade Federal de Ci&#234;ncias da Sa&#250;de de Porto Alegre &#40;UFCSPA&#41;&#44; Departamento de Pediatria&#44; Porto Alegre&#44; RS&#44; Brazil"
            "etiqueta" => "a"
            "identificador" => "aff0001"
          ]
          1 => array:3 [
            "entidad" => "Hospital da Crian&#231;a Santo Ant&#244;nio&#44; Se&#231;&#227;o de Pneumologia Pedi&#225;trica&#44; Porto Alegre&#44; RS&#44; Brazil"
            "etiqueta" => "b"
            "identificador" => "aff0002"
          ]
          2 => array:3 [
            "entidad" => "Universidade Federal de Ci&#234;ncias da Sa&#250;de de Porto Alegre &#40;UFCSPA&#41;&#44; Programa de P&#243;s-Gradua&#231;&#227;o em Pediatria&#44; Porto Alegre&#44; RS&#44; Brazil"
            "etiqueta" => "c"
            "identificador" => "aff0003"
          ]
          3 => array:3 [
            "entidad" => "Imperial College London&#44; Faculty of Medicine&#44; National Heart and Lung Institute&#44; Section of Paediatrics&#44; London&#44; United Kingdom"
            "etiqueta" => "d"
            "identificador" => "aff0004"
          ]
          4 => array:3 [
            "entidad" => "Royal Brompton Hospital&#44; Department of Paediatric Respiratory Medicine&#44; London&#44; United Kingdom"
            "etiqueta" => "e"
            "identificador" => "aff0005"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0001"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Introduction</span><p id="para0005" class="elsevierStylePara elsevierViewall">Environmental pollution is recognized as a global health emergency affecting high- and low-income countries&#46; Exposure to environmental risk factors contributes to the onset and progression of respiratory diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a></p><p id="para0006" class="elsevierStylePara elsevierViewall">Data from the World Health Organization &#40;WHO&#41; show that 4&#46;2 million deaths annually are attributed to exposure to environmental pollution&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a></p><p id="para0007" class="elsevierStylePara elsevierViewall">The environmental conditions <span class="elsevierStyleItalic">in utero</span> and in early childhood are critical for the individual to achieve potential growth and lung function and will determine a child&#39;s future&#46; Children exposed to pollutants from the prenatal period are particularly vulnerable to certain risks&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> The exposure occurs through the interaction with the environment during the natural process of growth and development&#46; Adverse environmental exposure in this critical period of life will determine structural and functional changes in the respiratory system&#46; The association of environmental exposure&#44; prenatal or perinatal&#44; with adverse birth outcomes&#44; such as preterm delivery&#44; lower birth weight&#44; and lung development defects&#44; is well documented&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p><p id="para0008" class="elsevierStylePara elsevierViewall">Epidemiological studies demonstrate that respiratory diseases that manifest in adults most often have prenatal and early life origins&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">5-7</span></a></p><p id="para0009" class="elsevierStylePara elsevierViewall">Adverse childhood exposures affect adult respiratory health resulting in an increased risk of non-communicable chronic respiratory diseases such as chronic obstructive pulmonary disease &#40;COPD&#41; and asthma&#59; pulmonary aging with an accelerated or premature decline in lung function&#59; and reduced life expectancy&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a></p><p id="para0010" class="elsevierStylePara elsevierViewall">Environmental pollution&#44; indoor pollutants &#40;especially tobacco exposure&#41;&#44; traffic-related pollution can cause neonatal problems and respiratory diseases that will have repercussions in adulthood&#46; There are many studies showing associations between exposure to environmental tobacco in the fetal period causing a higher risk of prematurity and early decline in lung function in adults&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">10-13</span></a></p><p id="para0011" class="elsevierStylePara elsevierViewall">In this review&#44; the authors will address how exposure to environmental hazards early in life can have an impact on adult respiratory health&#46; The effects resulting from respiratory infections and late exposure and into adulthood will not be addressed&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Epidemiology</span><p id="para0012" class="elsevierStylePara elsevierViewall">In the pediatric age group&#44; exposure tends to be daily&#44; persistent&#44; and in most cases cannot be avoided&#46; In 2021&#44; 91&#37; of the world population will live in places with pollution levels above the limits recommended by the WHO guidelines&#46; The intensity of exposure to air pollutants varies depending on geographic regions and household conditions&#46; Low- and middle-income countries have higher exposures&#46; Half of the world&#39;s population is exposed to indoor smoke from fires and wood stoves&#44; responsible for up to 1&#46;5 million premature deaths annually&#46;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> In Africa&#44; 80&#37; of children live in homes with dirty energy sources&#46; About 12&#46;9 million women are potentially exposed to toxic electronic waste that puts them and their children at risk&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a></p><p id="para0013" class="elsevierStylePara elsevierViewall">In 2017&#44; 42&#37; of the world population was exposed to fine particulate matter &#40;PM2&#46;5&#41; above that recommended by the WHO&#44; and 43&#37; were exposed to ozone&#46; In Europe&#44; in 2021&#44; 84&#37; of the population was exposed to PM2&#46;5 and 9&#37; to Nitrogen dioxide above the limits of this guideline&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a></p><p id="para0014" class="elsevierStylePara elsevierViewall">It is estimated that 24&#37; of deaths are associated with environmental conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> In Europe&#44; there are 400&#44;000 premature deaths&#47;year caused by air pollution&#46; It is estimated that the average life expectancy of a European is reduced by one year due to air pollution&#46; A considerable proportion of premature deaths in European cities could be avoided annually by reducing air pollution concentrations&#46; It must be considered that any death and loss of years of healthy life are not acceptable as both are preventable&#46; Furthermore&#44; there is no safe exposure limit below which air pollution is not harmful to human health&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">The child and the environment</span><p id="para0015" class="elsevierStylePara elsevierViewall">Pollutants come from air pollution&#59; inadequate water&#44; sanitation&#44; and hygiene&#59; hazardous chemicals and waste&#59; radiation&#59; as well as emerging threats such as electronic waste&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a></p><p id="para0016" class="elsevierStylePara elsevierViewall">Children are particularly vulnerable to environmental pollution as they receive a proportionally higher dose than an adult exposed to the same environment and often the adverse effect is greater due to their lower capacity to metabolize and excrete the toxic substance&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> Newborns and young children have a higher respiratory rate and proportionally inhale a higher dose of pollutants than older children and adults in the same environment&#46; When exercising outdoors&#44; children are more exposed to air pollutants as they have a relatively larger lung surface compared to body size&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Pathways of exposure to environmental insults</span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Transplacental</span><p id="para0017" class="elsevierStylePara elsevierViewall">The placental barrier has a protective function for the fetus&#44; but it is not complete&#46; Toxic substances inhaled by the mother or absorbed by the maternal oral mucosa that pass directly into the maternal bloodstream reaching the fetal circulation&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Breast milk</span><p id="para0018" class="elsevierStylePara elsevierViewall">It is the ideal food for babies&#44; but it can contain harmful substances&#46; Water-soluble chemical compounds and lipids can be transferred into breast milk&#44; such as organochlorine pesticides&#44; metals&#44; solvents&#44; etc&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Ingestion of contaminated water and food and non-nutritive ingestion</span><p id="para0019" class="elsevierStylePara elsevierViewall">It is part of a child&#39;s normal development to take objects and hands to the mouth&#44; which can favor the ingestion of household dust&#44; soil&#44; and chemical contaminants present in the objects&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Cutaneous</span><p id="para0020" class="elsevierStylePara elsevierViewall">Infants and young children have a proportionally larger body surface area than adults and older children&#44; with a larger area of &#8203;&#8203;exposure per kilogram of weight&#44; and have immaturity in the protective functions of the skin and subcutaneous tissue&#46; Also&#44; they may have more uncovered areas of the skin surface and are in greater contact with particulate matter from household dust&#44; soil&#44; chemicals such as pesticides&#44; and cleaning products&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0009" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0015">Inhaled</span><p id="para0021" class="elsevierStylePara elsevierViewall">Air pollutants can accumulate in the airways or pass through lung tissues&#44; depending on the size and chemical nature of the pollutants&#46; Ultrafine particles can pass into the bloodstream and reach distal organs&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p></span></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0016">The respiratory system</span><p id="para0022" class="elsevierStylePara elsevierViewall">Pulmonary morphogenesis begins in the embryonic period of fetal development&#44; 3-4 weeks post-conception&#44; while growth and maturation continue until the age of 18-20 years&#46; Lung development is subdivided into five different periods of morphogenesis based on morphological characteristics&#58; Pseudoglandular stage &#40;6-17 weeks gestation&#41; - Bronchi&#44; bronchioles&#44; and acinar tubules&#59; Canalicular &#40;16-26 weeks gestation&#41; - acinar structures&#59; Saccular &#40;26-36 weeks gestation&#41; - saccules and alveoli and cell differentiation and&#59; Alveolar after 36 weeks post-conception and continues during somatic growth&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a></p><p id="para0023" class="elsevierStylePara elsevierViewall">From the 36th week after conception&#44; there is greater growth and expansion of pulmonary acini and development of the distal capillary network&#46; In this phase&#44; the lung grows mainly due to septation&#44; proliferation&#44; and thinning of the alveolar walls&#44; as well as the elongation and luminal enlargement of the conducting airways&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> The respiratory system is not fully developed at birth&#44; and lung growth occurs mainly in the postnatal period&#46; Adverse environmental exposure in the pseudoglandular phase interferes with the structural development of the airways&#44; and later exposures can cause bronchial thickening and hyperresponsiveness after birth&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0011" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0017">How does damage to the respiratory system occur&#63;</span><p id="para0024" class="elsevierStylePara elsevierViewall">The respiratory system is vulnerable to environmental exposure&#44; which occurs both prenatally and postnatally&#44; especially in the first 18-24 months of life&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a></p><p id="para0025" class="elsevierStylePara elsevierViewall">The degree of impact caused by adverse exposure varies and depends on the period of exposure&#46; Sly et al&#46; call this period the <span class="elsevierStyleItalic">&#8220;window of susceptibility</span>&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> It would be the period in which a certain environmental exposure can cause structural or functional abnormality&#44; resulting in impaired respiratory health&#46; Occurring outside this period&#44; the pollutant would have much less of an effect&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a></p><p id="para0026" class="elsevierStylePara elsevierViewall">Individual vulnerability to a given exposure can be influenced by the child&#39;s stage of development &#40;prenatal&#44; infant&#44; child&#41;&#59; type and route of exposure&#59; genetic and epigenetic factors&#59; comorbidities&#59; nutritional status&#59; and sociodemographic conditions&#46; Transgenerational factors and preconceptions also have deleterious effects on lung development&#46; Lung health can be affected by several mechanisms such as interruption of lung growth potential&#44; modulation of function&#44; modification of gene expression&#44; and alteration of the pathophysiological mechanisms of the airways&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> Furthermore&#44; the respiratory system does not work in isolation&#46; Factors that cause dysfunction of the immune system&#44; the central nervous system&#44; may also have consequences for respiratory problems and diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0012" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0018">What is the impact of environmental problems on respiratory health&#63;</span><p id="para0027" class="elsevierStylePara elsevierViewall">The main consequences of environmental damage on adult respiratory health are associated with loss of lung function and diseases such as COPD and asthma&#46;</p></span><span id="sec0013" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0019"><span class="elsevierStyleItalic">Impairments to pulmonary function</span></span><p id="para0028" class="elsevierStylePara elsevierViewall">The assessment of lung function by spirometry&#44; commonly presented as Forced Expiratory Volume in First Second &#40;FEV1&#41; and Forced Vital Capacity &#40;FVC&#41;&#44; allows indirect measurement of lung growth&#46; Lung volumes increase from childhood to young adult with maximum values reached at 20-25 years of age&#44; remaining on a plateau for around five years and then gradually decreasing with aging&#46; This process is called the trajectory of lung function&#46; This decrease of lung function varies between individuals and is impacted by genetic and environmental factors that&#44; in turn&#44; influence both the development and progression of COPD&#46;</p><p id="para0029" class="elsevierStylePara elsevierViewall">Lung function early in life &#40;at birth and at age 4-6&#41; can predict the maximum lung volume a person will reach when they reach the plateau&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> In adults&#44; low FEV1 is associated with greater morbidity and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a> Low lung function early in life usually does not recover and is a risk factor for airflow obstruction into adulthood&#46;<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> In rare circumstances&#44; there is potential for recovery&#46; Harmful environmental exposures in early life may cause a reduction in the expected increase of lung function in early childhood and are associated with an increased risk of respiratory diseases in adulthood&#46;</p></span><span id="sec0014" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0020"><span class="elsevierStyleItalic">COPD</span></span><p id="para0030" class="elsevierStylePara elsevierViewall">COPD is the main cause of chronic morbidity and is among the three leading causes of death worldwide&#46; The Global Initiative for Chronic Obstructive Lung Disease &#40;GOLD&#41; defines COPD as persistent respiratory symptoms and airflow limitation due to airway and&#47;or alveolar abnormalities&#44; caused by exposure to harmful particles or gases and influenced by individual&#44; genetic and environmental factors&#46;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> Results from different trajectories or their combinations &#40;assessed in young adults&#41;&#58; abnormal at birth&#59; failure to reach a normal spirometric plateau or accelerated decline in lung function&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> Exposure to tobacco is a risk factor for COPD&#44; but there is evidence that non-smokers also develop the disease&#46; Harmful events that occur in pregnancy or childhood have the potential to alter lung growth and increase the risk of developing the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0021"><span class="elsevierStyleItalic">Asthma</span></span><p id="para0031" class="elsevierStylePara elsevierViewall">Asthma is a heterogeneous disease characterized by chronic airway inflammation&#46; It manifests as wheezing&#44; ventilatory difficulty and chest tightness&#44; which vary over time and in intensity&#44; associated with variable obstruction of the expiratory airflow&#46; The obstruction can become permanent&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a></p></span></span><span id="sec0016" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0022">Environmental exposures and adult respiratory health</span><p id="para0032" class="elsevierStylePara elsevierViewall">The main environmental pollutants&#44; their characteristics&#44; and the result of exposure on respiratory health are presented below&#46;</p><span id="sec0017" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0023">Tobacco exposure</span><p id="para0033" class="elsevierStylePara elsevierViewall">Tobacco exposure affects not just individual smokers&#44; but those around them&#44; including casual contacts in bars&#44; and potentially especially but not exclusively in women&#44; transgenerational adverse effects&#46; Since tobacco contains many chemicals in addition to nicotine&#44; it is only in the context of animal experiments that the authors can be certain which compound&#40;s&#41; is the causative agent&#46; However&#44; from animal data &#40;below&#41;&#44; it is clear that many adverse effects on the fetus are caused by nicotine&#46; The role of e-cigarettes must also be considered in this context&#59; they have some toxicities which overlap with tobacco&#44; some effects which are unique to these devices&#44; and many deliver high concentrations of nicotine&#46; Thus the assumption must be that e-cigarettes are as harmful if not more so than conventional tobacco&#44; unless and until proven otherwise &#8211; and it is for the vaping industry to prove they are safe&#44; not for pediatricians to prove they are unsafe&#44; just as Pharma have to prove the safety of a novel inhaled medication&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0018" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0024">Transgenerational effects</span><p id="para0034" class="elsevierStylePara elsevierViewall">The earliest exposure is from grand maternal smoking&#44; presumably by an epigenetic effect on the germline&#44; although this is controversial&#46; Her own offspring will be more likely to smoke and more likely to have asthma in consequence&#46; However&#44; if she has a daughter&#44; even if that daughter does not smoke&#44; her children are more likely to have asthma&#46; If she does smoke&#44; and they also smoke&#44; the effects on the children&#39;s lung function are much greater&#46;<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a> Whether the same effect is seen in great-grand-children is unknown&#46;</p></span><span id="sec0019" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0025">Antenatal effects</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0026">Known effects of nicotine from animal work</span><p id="para0035" class="elsevierStylePara elsevierViewall">The experimental administration of nicotine to different pregnant animal models has established the following&#58;<ul class="elsevierStyleList" id="celist0001"><li class="elsevierStyleListItem" id="celistitem0001"><span class="elsevierStyleLabel">&#8226;</span><p id="para0036" class="elsevierStylePara elsevierViewall">There is increased collagen type 1 and 3 mRNA and immunostaining in the developing airway and lung parenchyma&#59; there was increased elastin mRNA but not protein&#46;<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0002"><span class="elsevierStyleLabel">&#8226;</span><p id="para0037" class="elsevierStylePara elsevierViewall">MUC5AC is over-expressed&#59; this is of particular interest in terms of later mucus hypersecretion&#44; a chronic obstructive pulmonary disease trait that is increasingly recognized as important&#46;<a class="elsevierStyleCrossRef" href="#bib0029"><span class="elsevierStyleSup">29</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0003"><span class="elsevierStyleLabel">&#8226;</span><p id="para0038" class="elsevierStylePara elsevierViewall">There is dysanaptic airway growth&#44; the airways are abnormally long&#44; and there is airway hyper-responsiveness &#40;AHR&#41; in the newborn period&#44; independent of infection or allergen exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">30</span></a> This is particularly important in that AHR in the newborn period is strongly predictive of later asthma and impaired lung function in human studies&#44; and dysanaptic airway growth is associated with worse asthma outcomes in childhood and adult life&#46;<a class="elsevierStyleCrossRef" href="#bib0031"><span class="elsevierStyleSup">31</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0004"><span class="elsevierStyleLabel">&#8226;</span><p id="para0039" class="elsevierStylePara elsevierViewall">There is a failure of secondary septation leading to early-onset emphysema&#46;<a class="elsevierStyleCrossRef" href="#bib0032"><span class="elsevierStyleSup">32</span></a> As yet unpublished studies measuring alveolar size using hyperpolarized Helium suggest that teenage offspring of mothers who smoked in pregnancy have abnormally large alveoli&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0005"><span class="elsevierStyleLabel">&#8226;</span><p id="para0040" class="elsevierStylePara elsevierViewall">There is the increased airway wall thickness and loss of alveolar attachments to the airway&#46; These attachments stabilize airways by interdependence&#46; This finding has been confirmed in early infant deaths of offspring of mothers who smoked in pregnancy&#46;<a class="elsevierStyleCrossRef" href="#bib0033"><span class="elsevierStyleSup">33</span></a></p></li></ul></p></span><span id="sec0020a" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0026a">Human studies on cigarette exposure</span><p id="para0035a" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="celist0001a"><li class="elsevierStyleListItem" id="celistitem0006"><span class="elsevierStyleLabel">&#8226;</span><p id="para0041" class="elsevierStylePara elsevierViewall">&#40;The exact components of cigarettes causing these abnormalities is not known&#41;</p></li><li class="elsevierStyleListItem" id="celistitem0007"><span class="elsevierStyleLabel">&#8226;</span><p id="para0042" class="elsevierStylePara elsevierViewall">There is increased cord blood mononuclear cell reactivity to allergens in the offspring of smoking mothers&#46;<a class="elsevierStyleCrossRef" href="#bib0034"><span class="elsevierStyleSup">34</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0008"><span class="elsevierStyleLabel">&#8226;</span><p id="para0043" class="elsevierStylePara elsevierViewall">There is reduced cytokine and Toll-like receptor function associated with antenatal tobacco exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">35</span></a> Children who subsequently develop wheeze in the first year of life with either rhinovirus&#44; respiratory syncytial virus&#44; or other viral infection have reduced cord gamma interferon responses&#46;<a class="elsevierStyleCrossRef" href="#bib0036"><span class="elsevierStyleSup">36</span></a></p></li></ul></p></span><span id="sec0021" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0027">Longer-term implications of antenatal tobacco exposure</span><p id="para0044" class="elsevierStylePara elsevierViewall">In summary&#44; the readout of tobacco exposure antenatally is&#58;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a><ul class="elsevierStyleList" id="celist0002"><li class="elsevierStyleListItem" id="celistitem0009"><span class="elsevierStyleLabel">&#8226;</span><p id="para0045" class="elsevierStylePara elsevierViewall">Low birth weight&#44; itself an independent risk factor for impaired lung function and subsequent asthma&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0010"><span class="elsevierStyleLabel">&#8226;</span><p id="para0046" class="elsevierStylePara elsevierViewall">Prematurity and small for gestational age birth&#46; The effects of these two factors could be the subject of a whole review&#44; and not all their effects are the same&#44; but these patients have persistent airflow obstruction without evidence of Type 2 inflammation &#40;unless there is coincidentally an atopic background&#41;&#46; Interestingly&#44; and relevant to data discussed below&#44; there is more than associated respiratory morbidity associated with prematurity&#59; early ischemic heart disease and cardiac failure are associations of bronchopulmonary dysplasia&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0011"><span class="elsevierStyleLabel">&#8226;</span><p id="para0047" class="elsevierStylePara elsevierViewall">Airflow obstruction at birth&#44; also predictive of the later development of asthma&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0012"><span class="elsevierStyleLabel">&#8226;</span><p id="para0048" class="elsevierStylePara elsevierViewall">Altered immunological function at birth &#40;and discussed in more detail below&#41;&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0013"><span class="elsevierStyleLabel">&#8226;</span><p id="para0049" class="elsevierStylePara elsevierViewall">Sensitization to the effects of later adverse stimuli such as occupational exposures&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0014"><span class="elsevierStyleLabel">&#8226;</span><p id="para0050" class="elsevierStylePara elsevierViewall">Increased likelihood of impaired lung growth and later accelerated decline in lung function&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0015"><span class="elsevierStyleLabel">&#8226;</span><p id="para0051" class="elsevierStylePara elsevierViewall">Premature cardiovascular and all-cause morbidity and mortality&#46;</p></li></ul></p><p id="para0052" class="elsevierStylePara elsevierViewall">These implications may extend beyond mothers who smoke to non-smoking mothers who are passively exposed to tobacco&#46; For example&#44; Belgium&#39;s data showed very clearly that&#44; as passive smoke exposure was reduced by a series of new laws&#44; the rate of preterm delivery fell&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> This is a really important message&#59; these and other data emphasize that smoking does not merely affect the smoker but also the innocent bystander&#46; Pediatricians must be advocates to prevent these exposures&#46;</p></span></span><span id="sec0022" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0028"><span class="elsevierStyleItalic">Effects of smoke exposure in childhood</span></span><p id="para0053" class="elsevierStylePara elsevierViewall">The effects of smoke exposure on childhood respiratory morbidity are very well known and have been summarized elsewhere&#59; pediatricians are fully familiar with these and know that smoke exposure must be minimized&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">35</span></a> Indeed&#44; smoke-free legislation dramatically reduces asthma attacks in children&#46; Recently&#44; it has been shown conclusively that three environmental factors are associated with impaired lung growth and progression of preschool wheeze to school-age asthma&#59; these are aeroallergen sensitization&#44; attacks of severe wheeze&#44; and exposure to tobacco smoke&#44; of which only the last is readily modifiable&#46;<a class="elsevierStyleCrossRef" href="#bib0037"><span class="elsevierStyleSup">37</span></a> What is far less appreciated is the long-term consequences&#44; both respiratory and systemic&#44; of childhood smoke exposure&#44; discussed in more detail below&#46;</p></span><span id="sec0023" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0029"><span class="elsevierStyleItalic">Lung growth and development</span></span><p id="para0054" class="elsevierStylePara elsevierViewall">A major recent advance in the field has been the use of mathematical tools to delineate the different growth trajectories objectively&#44; letting the data speak for itself rather than imposing investigator bias&#46; These have typically identified 4-6 trajectories&#44; although it should be noted that at least some individuals appear to change trajectory in childhood&#46; Thus combining the Manchester and Avon longitudinal studies&#44; nearly 2&#44;500 children&#44; the four classes were persistently high&#44; normal&#44; below average&#44; and persistently low&#44; of which the persistently high group were least likely to have been exposed to tobacco&#46;<a class="elsevierStyleCrossRef" href="#bib0037"><span class="elsevierStyleSup">37</span></a> The Tasmanian cohort&#44; extending from the first to the sixth decade of life&#44; delineated six&#58; persistently high&#44; average&#44; below average&#44; persistently low&#44; early below average with accelerated decline&#44; and early low with accelerated growth and normal decline&#46;<a class="elsevierStyleCrossRef" href="#bib0038"><span class="elsevierStyleSup">38</span></a> The likelihood of chronic obstructive pulmonary disease &#40;COPD&#44; 46&#37;&#41; was highest in the below-average&#44; fast decline group&#44; and childhood tobacco exposure was one factor in this trajectory&#46;</p></span><span id="sec0024" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0030">How adult respiratory morbidity is determined by early life events</span><p id="para0055" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleHsp" style=""></span><ul class="elsevierStyleList" id="celist0003"><li class="elsevierStyleListItem" id="celistitem0016"><span class="elsevierStyleLabel">&#8226;</span><p id="para0056" class="elsevierStylePara elsevierViewall">Occupational asthma&#58; although this is considered to be a pure adult disease&#44; in fact this is not the case&#46; An important study hypothesized that early life disadvantage sensitizes to occupational lung disease&#46; The investigators used the RHINE III questionnaire on occupational cleaning in 13&#44;499 subjects and found that early life disadvantage &#40;which included maternal smoking&#41; was associated with an increased risk of wheeze&#44; &#8216;adult onset&#8217; asthma &#40;discussed below&#41;&#44; and self-reported COPD in 2138 cleaners&#46; The strongest effect was early life disadvantage&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0017"><span class="elsevierStyleLabel">&#8226;</span><p id="para0057" class="elsevierStylePara elsevierViewall">&#8220;Late-onset&#8221; asthma&#58; this is a condition much talked about by adult physicians&#44; but it actually does not exist&#46; In the Tucson study&#44; the prevalence of Physician diagnosed asthma and airway function was determined at age 22 years&#59; and 25&#37; of active asthma were newly diagnosed at that age &#40;71&#37; women&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0039"><span class="elsevierStyleSup">39</span></a> However&#44; when the prospectively obtained data were examined&#44; AHR and low airway function at age 6&#44; wheeze onset age 3-6 years&#44; and persistent wheeze through first six years of life all predicted &#8220;newly diagnosed&#8221; asthma at age 22&#59; and most of these factors are unequivocally associated with early tobacco exposure&#46; It is very clear that this is not &#8216;late-onset asthma&#8221; but &#8220;late recrudescent airway disease&#8221;&#44; and the roots need to be sought in early life&#46;</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0031">Why do adults get COPD&#63;</span><p id="para0058" class="elsevierStylePara elsevierViewall">The two routes to COPD are accelerated decline in lung function having reached a normal plateau age 20-25 years &#40;7&#37; risk of COPD&#41;&#44; and normal rate of decline from a reduced plateau &#40;26&#37; risk&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">40</span></a> The latter is clearly the result of early life factors&#44; of which tobacco exposure is an important factor&#46; In the classic Fletcher and Peto paper&#44; accelerated decline was attributed to current smoking&#44; which could be halted if the patient abstained from tobacco&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> Although&#44; of course&#44; smoking is a &#8220;BAD THING&#8221;&#44; in many but not all COPD cohort studies&#44; there is no effect of current smoking on decline in spirometry&#46; In an illuminating study in the SPALDIA and ECRHS cohorts&#44; early disadvantage &#40;including maternal smoking&#41; was associated with a more rapid decline in spirometry&#59; as with the Tucson study&#44; personal smoking effects were potentiated by maternal smoking&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0041"><span class="elsevierStyleSup">41</span></a> Similar findings were reported by the ECFS study&#44; wherein accelerated decline in lung function was associated with &#40;amongst other exposures&#41; early tobacco exposure&#46; Importantly&#44; the idea that was just stopping adults smoking&#44; beneficial though that would be&#44; will prevent COPD is simply not true&#46; In many cohorts&#44; there is no signal for current smoking&#44; causing an accelerated decline in spirometry&#46;<a class="elsevierStyleCrossRef" href="#bib0042"><span class="elsevierStyleSup">42</span></a></p></span><span id="sec0026" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0032">More than just lungs&#58; is reduced lung function the &#8220;canary in the mine&#8221;&#63;</span><p id="para0059" class="elsevierStylePara elsevierViewall">Early low lung function&#44; for which tobacco exposure is probably the main cause&#44; is unsurprisingly associated with bad long-term respiratory outcomes &#40;above&#41;&#46; But it is also very clear that a reduction in the first second forced expired volume &#40;FEV<span class="elsevierStyleInf">1</span>&#41; means more than just a bad respiratory outlook&#46; It is associated with early and increased cardiovascular and all cause morbidity and mortality&#44; and this is unsurprising when the multi-organ adverse effects of nicotine are considered&#46;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> Also&#44; the same study reported a transgenerational effect on spirometry &#8211; low parental FEV<span class="elsevierStyleInf">1</span> was strongly predictive of offspring FEV<span class="elsevierStyleInf">1</span> &#40;r2&#160;&#61;&#160;0&#46;28&#41;&#44; another example of how the smokers poison not merely themselves&#44; but those around them and future unborn generations&#46;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0027" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0033">Air pollution</span><p id="para0060" class="elsevierStylePara elsevierViewall">Air pollution is the presence of one or more contaminants in the atmosphere&#44; such as dust&#44; gas&#44; mist&#44; odor&#44; smoke&#44; or vapor&#44; in an amount and duration that can be harmful to human health&#46; Pollutants produce inflammation&#44; oxidative stress&#44; immunosuppression&#44; and mutagenicity in cells&#44; which can affect other organs&#44; causing diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> The pollutants present in the atmospheric air originate mainly from human activity in urban areas&#44; originating from automotive vehicles&#44; and&#44; in non-urban areas&#44; biomass burning&#46; Sources of natural environmental exposures are derived from accidental fires&#44; sandstorms&#44; and electrical lightning that can generate nitrogen oxides &#40;NOx&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> Pollutants have different physical and chemical characteristics depending on the type of pollution source&#46; The so-called primary ones are those emitted directly into the atmosphere and produced mainly by industries&#44; thermoelectric plants&#44; and automotive vehicles&#46; The most frequent are sulfur dioxide &#40;SO<span class="elsevierStyleInf">2</span>&#41;&#44; nitrogen oxides &#40;NOx&#44; NO&#44; and NO<span class="elsevierStyleInf">2</span>&#41;&#44; metals&#44; carbon monoxide &#40;CO&#41;&#44; volatile organic compounds &#40;VOC&#41;&#44; and particulate matter &#40;PM&#41;&#46; Secondary calls are those originating from chemical reactions between vehicular and industrial emission pollutants&#44; such as NOx&#44; which react with volatile organic compounds &#40;VOCs&#41; emitted by vehicles&#44; solvents&#44; and industry&#46; The process takes place in the presence of ultraviolet rays from sunlight&#44; thus giving rise to ozone&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a> Nitrogen dioxide &#40;NO<span class="elsevierStyleInf">2</span>&#41;&#44; a toxic gas that causes significant inflammation of the airways&#44; originates from combustion processes &#40;heating&#44; power generation&#44; and engines in vehicles and ships&#41;&#46; Sulfur dioxide &#40;SO<span class="elsevierStyleInf">2</span>&#41; is a gas produced by burning fossil fuels &#40;coal and oil&#41; for domestic heating&#44; power generation&#44; and vehicles&#46;</p><p id="para0061" class="elsevierStylePara elsevierViewall">Prenatal and early life exposure to pollutants&#44; including nicotine and air pollution&#44; leads to impaired lung function&#44; which remains largely altered until the sixth decade of life&#46; Maternal exposure to air pollutants is associated with decreased lung function during childhood that may be further reduced in adults and consequently lead to COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0038"><span class="elsevierStyleSup">38</span></a> Both outdoor and indoor pollution increase the chance of COPD&#46;</p><p id="para0062" class="elsevierStylePara elsevierViewall">Fetuses born to mothers exposed to environmental pollutants are at increased risk for adverse birth outcomes such as intrauterine growth restriction&#44; prematurity&#44; low birth weight&#44; and fetal lung development defects&#46;<a class="elsevierStyleCrossRef" href="#bib0043"><span class="elsevierStyleSup">43</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0044"><span class="elsevierStyleSup">44</span></a> These adverse outcomes are associated with the development of late-onset respiratory diseases and reduced lung function&#44; in addition to increasing the susceptibility to the harmful effects of other pollutants&#46; Maternal exposure to Benzene and NO2 in the third trimester of pregnancy determine decreased lung function at school age&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">45</span></a></p><p id="para0063" class="elsevierStylePara elsevierViewall">Babies who grow up breathing polluted air&#44; even at levels below EU regulations&#44; have lower lung function from infancy through adolescence&#44; and the results are worse in children with asthma&#46; Part of the risk of exposure to pollution can be reduced if babies are breastfed for at least 12 weeks&#46;<a class="elsevierStyleCrossRef" href="#bib0046"><span class="elsevierStyleSup">46</span></a></p><p id="para0064" class="elsevierStylePara elsevierViewall">The reduction in the increase in lung function is also linked to NO2 exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0047"><span class="elsevierStyleSup">47</span></a> Children exposed to higher levels of NO2 and PM2&#46;5 are five times more likely to have reduced lung function than children living in areas with lower levels&#46;<a class="elsevierStyleCrossRef" href="#bib0048"><span class="elsevierStyleSup">48</span></a> Another study demonstrated that decreasing environmental NO2 and PM2&#46;5 significantly decreases the risk of reduced lung growth&#46;<a class="elsevierStyleCrossRef" href="#bib0049"><span class="elsevierStyleSup">49</span></a></p><span id="sec0028" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0034">Particulate matter &#40;PM&#41;</span><p id="para0065" class="elsevierStylePara elsevierViewall">Mixture of droplets or particles suspended in the air&#44; composed of hundreds of organic or chemical substances such as ozone&#44; nitrogen oxides&#44; SO2&#44; dust&#44; soot or smoke&#44; from coal and natural gas plants&#44; cars&#44; fires&#44; unpaved roads and construction sites&#46; Particles with an aerodynamic diameter less than 10 &#181;m &#40;MP10&#41;&#44; such as sand&#44; dust&#44; and pollen&#44; usually deposit in the nasopharynx and are less toxic&#46; Fine particles&#44; smaller than 2&#46;5 &#181;m &#40;PM2&#46;5&#41;&#44; originating from combustion and ultra-fine particles &#40;less than 0&#46;1 mm&#41;&#44; emitted by diesel engines&#44; can penetrate tissues and organs&#44; causing greater risk to health&#46; Prenatal exposure to PM10 is associated with reduced lung function&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">50</span></a> The effects may be even greater in children born prematurely&#46;<a class="elsevierStyleCrossRef" href="#bib0051"><span class="elsevierStyleSup">51</span></a></p></span><span id="sec0029" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0035">External pollutants</span><p id="para0066" class="elsevierStylePara elsevierViewall">Originating from emissions from agricultural industries and activities&#44; vehicles and air traffic&#44; products used in agriculture&#44; war&#44; accidents&#44; and fires&#44; or from natural events such as volcanic eruption&#44; forest fires&#44; manufacturing&#44; and distribution of chemical materials&#46; Individuals exposed in the first year of life or during pregnancy to the Great Smog of London in 1952 were more likely to have asthma &#40;9&#46;53&#37;&#41; in adulthood&#46;<a class="elsevierStyleCrossRef" href="#bib0052"><span class="elsevierStyleSup">52</span></a> Another study showed that a higher incidence of asthma at age 20 years was associated with greater exposure to all pollutants at birth&#44; including PM10 and NO<span class="elsevierStyleInf">2</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0053"><span class="elsevierStyleSup">53</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0036">Household pollutants</span><p id="para0067" class="elsevierStylePara elsevierViewall">The main source is cigarette smoke &#40;above&#41;&#46; Other sources are wood-burning&#44; charcoal&#44; crop residues&#44; animal manure&#44; and kerosene used as a fuel source for cooking and heating&#46; Burning these materials combined with inefficient stoves leads to the emission of high concentrations of gaseous and particulate pollutants&#44; methane&#44; carbon monoxide&#44; polyaromatic hydrocarbons &#40;PAH&#41;&#44; and VOCs&#46; Other factors include products eliminated by air conditioning&#44; cleaning products or flavorings from environments with oils&#44; use of sprays and aerosols&#44; and windows and doors open&#44; allowing ingress of external pollution and the effects of pollution&#46; Household pollutants are more problematic for infants and young children as they stay longer within the home&#46; The quality of indoor air&#44; including exposure to fungi&#44; is associated with the onset of asthma&#46; Individuals who were exposed to indoor pollutants during the first three years of life with early specific sensitization &#40;mites&#44; cat or dog&#41; are at increased risk of developing asthma at 20 years of age&#46; The effect is greatest if associated with pre-and postnatal exposure to tobacco smoke&#46;<a class="elsevierStyleCrossRef" href="#bib0054"><span class="elsevierStyleSup">54</span></a> Individuals with early mite sensitization progress with worsening lung function that is lower at school age than at age five years and remains low until age 26&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">55</span></a> Data from developing countries show that in individuals with COPD&#44; 35&#37; were early exposed to cigarette smoke and indoor biomass combustion&#46; Childhood exposure to indoor coal pollution increases all-cause mortality&#44; with a greater impact on respiratory causes&#44; and the risk is greatest when associated with exposure to fuel&#46;<a class="elsevierStyleCrossRef" href="#bib0056"><span class="elsevierStyleSup">56</span></a></p></span></span><span id="sec0031" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0037">Air pollution associated with traffic &#40;TRAP&#41;</span><p id="para0068" class="elsevierStylePara elsevierViewall">Automobile exhaust releases pollutants into the environment&#46; There is an increased risk of asthma in children exposed to external pollutants such as ozone&#44; sulfur dioxide&#44; particulates&#44; and nitrogen oxide&#46; The highest incidence of asthma also occurred in adults who had been exposed to traffic pollution during the fetal period&#46; Children living near major highways in contact with external pollutants &#40;PM&#44; O<span class="elsevierStyleInf">3</span> and SO<span class="elsevierStyleInf">2</span> from vehicular traffic&#41; have a lower FEV1 than those living further away&#46;<a class="elsevierStyleCrossRef" href="#bib0057"><span class="elsevierStyleSup">57</span></a> This reduction in FEV1 is associated with the development of COPD&#46; Children who spent more time outdoors in areas with high levels of ozone had reduced lung function&#44; while those who grew up in environments with low levels of pollution had greater lung function&#46; Traffic-based pollution is associated with many childhood morbidities and an increased risk of adult COPD and lung cancer&#46; A meta-analysis showed that childhood exposure to TRAP &#40;Black Carbon&#44; NO<span class="elsevierStyleInf">2</span>&#44; PM2&#46;5&#44; PM10&#41; contributes to the development of asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0058"><span class="elsevierStyleSup">58</span></a> Another study demonstrated that improvements in air quality were associated with statistically and clinically significant positive effects on lung function growth in children&#46;<a class="elsevierStyleCrossRef" href="#bib0049"><span class="elsevierStyleSup">49</span></a></p></span><span id="sec0032" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0038">Asthma and allergies</span><p id="para0069" class="elsevierStylePara elsevierViewall">The immune system is not yet fully developed&#44; so there is an increased risk of respiratory infections and asthma&#46; In asthmatic patients&#44; exposure to air pollutants can cause oxidative damage to the airway&#44; leading to inflammation&#44; remodeling&#44; and an increased risk of sensitization&#46; In adults&#44; the accumulated effect of exposure to environmental pollutants can contribute to new-onset asthma&#46;<a class="elsevierStyleCrossRef" href="#bib0059"><span class="elsevierStyleSup">59</span></a></p><p id="para0070" class="elsevierStylePara elsevierViewall">Household and outdoor pollutants&#44; including O3&#44; CO&#44; NO2&#44; SO2&#44; PM10&#44; PM2&#46;5&#44; dust mites&#44; pollen&#44; pet dander&#44; and smoke&#44; contribute to more severe allergic responses&#46; One study showed that 11&#37; of asthmatic children with abnormal lung function had pulmonary function with fixed obstruction in adulthood compatible with COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">60</span></a> Exposure to traffic pollution contributes to 13&#37; of the global incidence of asthma in children&#46;<a class="elsevierStyleCrossRef" href="#bib0061"><span class="elsevierStyleSup">61</span></a></p><p id="para0071" class="elsevierStylePara elsevierViewall">Patients with COPD have more asthma-like symptoms in the early years of life&#44; as demonstrated in three cohorts over several decades&#46;<a class="elsevierStyleCrossRef" href="#bib0037"><span class="elsevierStyleSup">37</span></a> Having severe childhood asthma was the strongest predictor of COPD at age 50&#46;<a class="elsevierStyleCrossRef" href="#bib0062"><span class="elsevierStyleSup">62</span></a> In a study of 3290 mother-infant pairs&#44; 23&#37; had asthma-like symptoms in childhood&#44; and these individuals had more admissions and use of COPD medication in adulthood compared to those without asthma-like symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0063"><span class="elsevierStyleSup">63</span></a> Another study in adults aged 50 years showed that those with symptoms of severe asthma at 6-7 years were 32 times more likely to have COPD than those without symptoms&#46; In this group&#44; only 40&#37; were smokers suggesting that other harmful exposures may have contributed to the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0064"><span class="elsevierStyleSup">64</span></a></p><p id="para0072" class="elsevierStylePara elsevierViewall">Persistently low or rapidly declining lung function and development of COPD are associated with risk factors present in childhood &#40;maternal and paternal asthma&#44; maternal smoking&#44; childhood asthma&#44; and respiratory infections&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0038"><span class="elsevierStyleSup">38</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">65</span></a> In addition&#44; preterm &#40;&#60; 35 s&#41; and underweight &#40;&#60; 2&#44;000 <span class="elsevierStyleItalic">x</span> &#60; 2&#44;100 g&#41; girls are at higher risk of COPD and asthma than preterm boys&#46;<a class="elsevierStyleCrossRef" href="#bib0066"><span class="elsevierStyleSup">66</span></a></p><p id="para0073" class="elsevierStylePara elsevierViewall">Belgrave et al&#46; studied the trajectory of lung function from childhood to adulthood in 2436 individuals and identified four trajectories&#58; persistently high&#44; normal&#44; below average&#44; and persistently low&#46; Children with a persistently low trajectory were more likely to recurrent wheezing&#44; including severe exacerbations of wheezing&#44; early allergic sensitization&#44; and exposure to tobacco smoke&#46;<a class="elsevierStyleCrossRef" href="#bib0037"><span class="elsevierStyleSup">37</span></a> Avoiding these exposures could decrease the chance of lower lung function in adulthood&#46;<a class="elsevierStyleCrossRef" href="#bib0037"><span class="elsevierStyleSup">37</span></a></p><p id="para0074" class="elsevierStylePara elsevierViewall">A study of 69&#44;365 individuals identified that exposure to prenatal and early life smoking is a risk factor for COPD&#46; Low birth weight&#44; lower respiratory tract infections&#44; recurrent wheezing&#44; and childhood asthma also appear to be important determinants of the development of COPD&#46;<a class="elsevierStyleCrossRef" href="#bib0067"><span class="elsevierStyleSup">67</span></a> Parental asthma and smoking&#44; preterm birth may be risk factors for the development of COPD&#46;</p><p id="para0075" class="elsevierStylePara elsevierViewall">Exposure to smoking and e-cigarette during pregnancy possibly impair the maturation of the immune system&#46;<a class="elsevierStyleCrossRef" href="#bib0068"><span class="elsevierStyleSup">68</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0069"><span class="elsevierStyleSup">69</span></a> Severe respiratory infections in childhood are associated with decreased lung function and increased respiratory symptoms in adults&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">60</span></a></p></span><span id="sec0033" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0039">Adverse childhood experiences</span><p id="para0076" class="elsevierStylePara elsevierViewall">Adverse Childhood Experiences &#40;ACEs&#41; have a prevalence of around 10&#37; and are currently a global public health and social welfare concern&#46; EAIs include harm that affects children directly &#40;neglect&#44; physical&#44; sexual&#44; or emotional abuse&#41; and indirectly through their living environments &#40;conflict with parents&#44; substance abuse or mental illness&#41; and are powerful predictors of harmful behavior to health in adults&#46; A systematic review and meta-analysis of studies measuring the associations between various &#40;ACEs&#41; and health in over 18s found that individuals who had at least four adverse experiences during childhood or adolescence were twice as likely to be smokers and to have respiratory diseases than those who did not have ACEs&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">70</span></a> Another meta-analysis has shown an association between ACEs and the occurrence of cancer in adults&#44; including lung cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0071"><span class="elsevierStyleSup">71</span></a> One hypothesis about the mechanism linking ACEs and cancer development in adults would be the possible association with risk behaviors such as smoking&#44; physical inactivity&#44; poor diet&#44; and use of psychoactive substances&#46;<a class="elsevierStyleCrossRef" href="#bib0071"><span class="elsevierStyleSup">71</span></a></p></span><span id="sec0034" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0040">Socioeconomic factors</span><p id="para0077" class="elsevierStylePara elsevierViewall">There is a complex interrelationship between socioeconomic&#44; ethnic&#47;racial factors and health outcomes&#46; Poverty and nutritional disorders &#40;malnutrition and obesity&#41; can increase the adverse effects of exposure and the risk of diseases attributed to a pollutant&#46; Socioeconomic factors can influence the &#8217;child&#39;s birth weight &#40;which impacts lung growth and development&#41; which increases susceptibility to the disease&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> Lange et al&#46; demonstrated that 50&#37; of individuals with COPD had abnormal lung growth and development &#40;failure to reach the normal plateau&#44; above&#41;&#44; with the functional decline being within normal limits&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">40</span></a> Another study demonstrated synergism between overcrowding at home&#44; smoking&#44; and respiratory infection resulting in worse lung function at 43 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0049"><span class="elsevierStyleSup">49</span></a> However&#44; it is not well defined to what extent the socioeconomic situation may reflect exposure to indoor and environmental pollutants&#44; overcrowding&#44; or other factors related to social conditions&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0041">&#8220;Childhood disadvantage factors&#8221;</span><p id="para0078" class="elsevierStylePara elsevierViewall">They appear to be as important or more important than heavy smoking in predicting lung function in adulthood&#46; Svanes et al&#46; showed that children with a score indicating greater handicap had a more accelerated decline in lung function&#46;<a class="elsevierStyleCrossRef" href="#bib0042"><span class="elsevierStyleSup">42</span></a> The effect on more vulnerable individuals&#44; such as preterm infants&#44; may have even greater repercussions&#46;<a class="elsevierStyleCrossRef" href="#bib0042"><span class="elsevierStyleSup">42</span></a> Reduced lung function at birth and less-than-expected increased lung function in early childhood are associated with an increased risk of respiratory disease&#46; Children of mothers exposed to CO have lower lung function at 30 days of life&#44; and the effect is greater in girls&#46;<a class="elsevierStyleCrossRef" href="#bib0072"><span class="elsevierStyleSup">72</span></a> Dratva et al&#46; studied 12862 adults aged 28 to 73 years and demonstrated that early exposure to certain factors &#40;born during the winter season&#44; mothers &#62;31 years at delivery&#44; with &#8805; 2 younger siblings or exposed to maternal smoking&#41; can predict a further decline in lung function and that the effect on decline in FEV1 was as significant as the effect of smoking&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> The greatest decline in FEV1 was in winter-born individuals with older mothers and mothers who smoked or had younger siblings&#46; These same authors noted that if the mothers were older or smokers&#44; there was a potentiation of the effects of smoking on the decline in lung function&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a></p><p id="para0079" class="elsevierStylePara elsevierViewall">In summary&#44; in this review&#44; the authors present evidence that early lung exposure to environmental pollutants &#40;tobacco smoke&#44; particulate matter&#44; air pollution associated with traffic&#41; and adverse childhood experiences and socioeconomic status cause an increased incidence of Chronic Obstructive Pulmonary Disease &#40;COPD&#41;&#44; asthma and allergies&#59; and decline in lung function&#46; There is evidence demonstrating that adult respiratory diseases can almost always have their origins in early life&#46; It is emphasized that health professionals must know&#44; diagnose&#44; monitor&#44; and prevent toxic exposure among children and women&#46; By recognizing these risk factors&#44; early interventions should be implemented to reduce the progression of lung disease throughout life and into adulthood&#46;</p></span><span id="sec0036" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0042">How to prevent respiratory problems resulting from environmental exposure&#63;</span><p id="para0080" class="elsevierStylePara elsevierViewall">In <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">70</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0073"><span class="elsevierStyleSup">73</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0074"><span class="elsevierStyleSup">74</span></a> interventions that the pediatrician can perform are listed below&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia></span><span id="sec0037" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0043">For the prevention of childhood-onset adult lung disease&#44; political and social measures are needed with the aim of</span><p id="para0081" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleHsp" style=""></span><ul class="elsevierStyleList" id="celist0004"><li class="elsevierStyleListItem" id="celistitem0018"><span class="elsevierStyleLabel">&#8226;</span><p id="para0082" class="elsevierStylePara elsevierViewall">Reducing the emission of pollutants&#44; including air pollution and tobacco&#44; is the best way to avoid damage to the respiratory system&#46; In Europe&#44; reducing air pollution by PM2&#46;5 and NO2 could prevent 6 and 4&#37; premature deaths annually&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0019"><span class="elsevierStyleLabel">&#8226;</span><p id="para0083" class="elsevierStylePara elsevierViewall">Create alternatives for transport&#44; industries&#44; and energy sources with a reduction in the emission of smoke and toxic gases&#44; and particulate matter&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0020"><span class="elsevierStyleLabel">&#8226;</span><p id="para0084" class="elsevierStylePara elsevierViewall">Afforest urban areas with minimally allergenic trees&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0021"><span class="elsevierStyleLabel">&#8226;</span><p id="para0085" class="elsevierStylePara elsevierViewall">Properly dispose of electronic waste&#46;</p></li><li class="elsevierStyleListItem" id="celistitem0022"><span class="elsevierStyleLabel">&#8226;</span><p id="para0086" class="elsevierStylePara elsevierViewall">Implement local and international measures such as the WHO Global Strategy on Health&#44; Environment and Climate Change&#46;</p></li></ul></p></span></span><span id="sec0038" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0044">Conclusion</span><p id="para0087" class="elsevierStylePara elsevierViewall">Most children are exposed to some pollutants&#44; and the home is the place where exposure is more intense and frequent&#44; especially exposure to tobacco smoke&#46; Exposure to environmental hazards early in life increases the risk of acute and chronic respiratory diseases&#46; Future longitudinal studies are needed to assess the effect of specific exposures early in life&#44; individual and collective prevention measures&#44; behavioral and pharmacological interventions&#44; and the impact on adult respiratory health&#46; Pediatricians and the whole society must work together to identify risk factors&#44; reduce avoidable exposures&#44; protect the developing respiratory tract to reduce lifelong worsening or onset of disease and lung problems&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:8 [
        0 => array:3 [
          "identificador" => "xres1683792"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abss0001"
              "titulo" => "Objective"
            ]
            1 => array:2 [
              "identificador" => "abss0002"
              "titulo" => "Sources"
            ]
            2 => array:2 [
              "identificador" => "abss0003"
              "titulo" => "Summary of the findings"
            ]
            3 => array:2 [
              "identificador" => "abss0004"
              "titulo" => "Conclusion"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1493456"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "sec0001"
          "titulo" => "Introduction"
        ]
        3 => array:2 [
          "identificador" => "sec0002"
          "titulo" => "Epidemiology"
        ]
        4 => array:3 [
          "identificador" => "sec0003"
          "titulo" => "The child and the environment"
          "secciones" => array:7 [
            0 => array:3 [
              "identificador" => "sec0004"
              "titulo" => "Pathways of exposure to environmental insults"
              "secciones" => array:5 [
                0 => array:2 [
                  "identificador" => "sec0005"
                  "titulo" => "Transplacental"
                ]
                1 => array:2 [
                  "identificador" => "sec0006"
                  "titulo" => "Breast milk"
                ]
                2 => array:2 [
                  "identificador" => "sec0007"
                  "titulo" => "Ingestion of contaminated water and food and non-nutritive ingestion"
                ]
                3 => array:2 [
                  "identificador" => "sec0008"
                  "titulo" => "Cutaneous"
                ]
                4 => array:2 [
                  "identificador" => "sec0009"
                  "titulo" => "Inhaled"
                ]
              ]
            ]
            1 => array:2 [
              "identificador" => "sec0010"
              "titulo" => "The respiratory system"
            ]
            2 => array:2 [
              "identificador" => "sec0011"
              "titulo" => "How does damage to the respiratory system occur&#63;"
            ]
            3 => array:2 [
              "identificador" => "sec0012"
              "titulo" => "What is the impact of environmental problems on respiratory health&#63;"
            ]
            4 => array:2 [
              "identificador" => "sec0013"
              "titulo" => "Impairments to pulmonary function"
            ]
            5 => array:2 [
              "identificador" => "sec0014"
              "titulo" => "COPD"
            ]
            6 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Asthma"
            ]
          ]
        ]
        5 => array:3 [
          "identificador" => "sec0016"
          "titulo" => "Environmental exposures and adult respiratory health"
          "secciones" => array:16 [
            0 => array:2 [
              "identificador" => "sec0017"
              "titulo" => "Tobacco exposure"
            ]
            1 => array:2 [
              "identificador" => "sec0018"
              "titulo" => "Transgenerational effects"
            ]
            2 => array:3 [
              "identificador" => "sec0019"
              "titulo" => "Antenatal effects"
              "secciones" => array:3 [
                0 => array:2 [
                  "identificador" => "sec0020"
                  "titulo" => "Known effects of nicotine from animal work"
                ]
                1 => array:2 [
                  "identificador" => "sec0020a"
                  "titulo" => "Human studies on cigarette exposure"
                ]
                2 => array:2 [
                  "identificador" => "sec0021"
                  "titulo" => "Longer-term implications of antenatal tobacco exposure"
                ]
              ]
            ]
            3 => array:2 [
              "identificador" => "sec0022"
              "titulo" => "Effects of smoke exposure in childhood"
            ]
            4 => array:2 [
              "identificador" => "sec0023"
              "titulo" => "Lung growth and development"
            ]
            5 => array:2 [
              "identificador" => "sec0024"
              "titulo" => "How adult respiratory morbidity is determined by early life events"
            ]
            6 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Why do adults get COPD&#63;"
            ]
            7 => array:2 [
              "identificador" => "sec0026"
              "titulo" => "More than just lungs&#58; is reduced lung function the &#8220;canary in the mine&#8221;&#63;"
            ]
            8 => array:3 [
              "identificador" => "sec0027"
              "titulo" => "Air pollution"
              "secciones" => array:3 [
                0 => array:2 [
                  "identificador" => "sec0028"
                  "titulo" => "Particulate matter &#40;PM&#41;"
                ]
                1 => array:2 [
                  "identificador" => "sec0029"
                  "titulo" => "External pollutants"
                ]
                2 => array:2 [
                  "identificador" => "sec0030"
                  "titulo" => "Household pollutants"
                ]
              ]
            ]
            9 => array:2 [
              "identificador" => "sec0031"
              "titulo" => "Air pollution associated with traffic &#40;TRAP&#41;"
            ]
            10 => array:2 [
              "identificador" => "sec0032"
              "titulo" => "Asthma and allergies"
            ]
            11 => array:2 [
              "identificador" => "sec0033"
              "titulo" => "Adverse childhood experiences"
            ]
            12 => array:2 [
              "identificador" => "sec0034"
              "titulo" => "Socioeconomic factors"
            ]
            13 => array:2 [
              "identificador" => "sec0035"
              "titulo" => "&#8220;Childhood disadvantage factors&#8221;"
            ]
            14 => array:2 [
              "identificador" => "sec0036"
              "titulo" => "How to prevent respiratory problems resulting from environmental exposure&#63;"
            ]
            15 => array:2 [
              "identificador" => "sec0037"
              "titulo" => "For the prevention of childhood-onset adult lung disease&#44; political and social measures are needed with the aim of"
            ]
          ]
        ]
        6 => array:2 [
          "identificador" => "sec0038"
          "titulo" => "Conclusion"
        ]
        7 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2021-11-10"
    "fechaAceptado" => "2021-11-11"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1493456"
          "palabras" => array:6 [
            0 => "Environmental exposures"
            1 => "Early childhood exposures"
            2 => "Early disease origin"
            3 => "Air pollution"
            4 => "Respiratory diseases"
            5 => "Lung function"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Objective</span><p id="spara002" class="elsevierStyleSimplePara elsevierViewall">To review in the literature the environmental problems in early life that impact the respiratory health of adults&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Sources</span><p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Non-systematic review including articles in English&#46; Search filters were not used in relation to the publication date&#44; but the authors selected mainly publications from the last five years&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Summary of the findings</span><p id="spara004" class="elsevierStyleSimplePara elsevierViewall">In this review&#44; the authors present the exposure pathways and how the damage occurs depending on the child&#39;s stage of development&#59; the authors describe the main environmental pollutants - tobacco smoke&#44; particulate matter&#44; air pollution associated with traffic&#44; adverse childhood experiences and socioeconomic status&#59; the authors present studies that evaluated the repercussions on the respiratory system of adults resulting from exposure to adverse environmental factors in childhood&#44; such as increased incidence of Chronic Obstructive Pulmonary Disease &#40;COPD&#41;&#44; asthma and allergies&#59; and&#44; a decline in lung function&#46; The authors emphasize that evidence demonstrates that adult respiratory diseases almost always have their origins in early life&#46; Finally&#44; the authors emphasize that health professionals must know&#44; diagnose&#44; monitor&#44; and prevent toxic exposure among children and women&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusion</span><p id="spara005" class="elsevierStyleSimplePara elsevierViewall">The authors conclude that it is necessary to recognize risk factors and intervene in the period of greatest vulnerability to the occurrence of harmful effects of environmental exposures&#44; to prevent&#44; delay the onset or modify the progression of lung disease throughout life and into adulthood&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abss0001"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abss0002"
            "titulo" => "Sources"
          ]
          2 => array:2 [
            "identificador" => "abss0003"
            "titulo" => "Summary of the findings"
          ]
          3 => array:2 [
            "identificador" => "abss0004"
            "titulo" => "Conclusion"
          ]
        ]
      ]
    ]
    "multimedia" => array:1 [
      0 => array:8 [
        "identificador" => "tbl0001"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0001"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><a name="en0001"></a><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="" valign="top"><ul class="elsevierStyleList" id="celist0005"><li class="elsevierStyleListItem" id="celistitem0023"><span class="elsevierStyleLabel">&#8226;</span><p id="para0089" class="elsevierStylePara elsevierViewall">Recognize risk factors and intervene when the child is most vulnerable&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0024"><span class="elsevierStyleLabel">&#8226;</span><p id="para0090" class="elsevierStylePara elsevierViewall">To identify&#44; diagnose&#44; monitor&#44; and prevent toxic exposure among children and women&#46;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0025"><span class="elsevierStyleLabel">&#8226;</span><p id="para0091" class="elsevierStylePara elsevierViewall">Guide to avoid smoking&#44; including electronic cigarettes and alcohol&#46;<a class="elsevierStyleCrossRef" href="#bib0073"><span class="elsevierStyleSup">73</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0027"><span class="elsevierStyleLabel">&#8226;</span><p id="para0093" class="elsevierStylePara elsevierViewall">Improve the quality of prenatal care by reducing factors associated with prematurity&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0028"><span class="elsevierStyleLabel">&#8226;</span><p id="para0094" class="elsevierStylePara elsevierViewall">Acting in the diagnosis and prevention of asthma with an emphasis on modifiable factors &#40;environment&#44; lifestyle and comorbidities&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0074"><span class="elsevierStyleSup">74</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0029"><span class="elsevierStyleLabel">&#8226;</span><p id="para0095" class="elsevierStylePara elsevierViewall">Act to prevent nutritional disorders and infections &#40;immunization&#41; that contribute to lung problems and COPD risk&#46;<a class="elsevierStyleCrossRef" href="#bib0074"><span class="elsevierStyleSup">74</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0030"><span class="elsevierStyleLabel">&#8226;</span><p id="para0096" class="elsevierStylePara elsevierViewall">Prevent adverse childhood experiences&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">70</span></a></p></li><li class="elsevierStyleListItem" id="celistitem0031"><span class="elsevierStyleLabel">&#8226;</span><p id="para0097" class="elsevierStylePara elsevierViewall">Identify and monitor individuals at increased risk for rapid decline in lung function&#46;</p></li></ul>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2864110.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Pediatric intervention&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec1"
          "bibliografiaReferencia" => array:74 [
            0 => array:3 [
              "identificador" => "bib0001"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Air Pollution"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "World Health Organization &#40;WHO&#41;"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2021"
                      ]
                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;www&#46;who&#46;int&#47;health-topics&#47;air-pollution"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0002"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization &#40;WHO&#41;&#46; Mortality from environmental pollution &#91;Internet&#93;&#46; SDG Target 3&#46;9 Mortality from environmental pollution&#59; 2021 &#91;cited 2021 Nov 1&#93;&#46; Available from&#58;<a target="_blank" href="https://www.who.int/data/gho/data/themes/topics/sdg-target-3_9-mortality-from-environmental-pollution">https&#58;&#47;&#47;www&#46;who&#46;int&#47;data&#47;gho&#47;data&#47;themes&#47;topics&#47;sdg-target-3&#95;9-mortality-from-environmental-pollution</a>"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0003"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of prenatal and early life environmental exposures on normal human development"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "P Sly"
                            1 => "T Blake"
                            2 => "Z&#46; Islam"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.prrv.2021.05.007"
                      "Revista" => array:6 [
                        "tituloSerie" => "Paediatr Respir Rev"
                        "fecha" => "2021"
                        "volumen" => "40"
                        "paginaInicial" => "10"
                        "paginaFinal" => "14"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34148806"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0004"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Environmental contributions to respiratory disease in children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "P Sly"
                            1 => "A&#46; Bush"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "LibroEditado" => array:3 [
                        "editores" => "RWilmott, RDeterding, ALi, FRatjen, PSly, HJZar"
                        "titulo" => "Kendig&#39;s Disorders of the Respiratory Tract in Children"
                        "serieFecha" => "2019"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early life origins of lung ageing&#58; early life exposures and lung function decline in adulthood in two European cohorts aged 28-73 years"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J Dratva"
                            1 => "E Zemp"
                            2 => "SC Dharmage"
                            3 => "S Accordini"
                            4 => "L Burdet"
                            5 => "T Gislason"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0166947"
                      "Revista" => array:4 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2016"
                        "volumen" => "11"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28002457"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0006"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "DJ Barker"
                            1 => "KM Godfrey"
                            2 => "C Fall"
                            3 => "C Osmond"
                            4 => "PD Winter"
                            5 => "SO Shaheen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmj.303.6804.671"
                      "Revista" => array:6 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "1991"
                        "volumen" => "303"
                        "paginaInicial" => "671"
                        "paginaFinal" => "675"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/1912913"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0007"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The natural history of chronic airflow obstruction"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "C Fletcher"
                            1 => "R&#46; Peto"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Br Med J"
                        "fecha" => "1977"
                        "volumen" => "1"
                        "paginaInicial" => "1645"
                        "paginaFinal" => "1648"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20792867"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0008"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Premature mortality due to air pollution in European cities&#58; a health impact assessment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S Khomenko"
                            1 => "M Cirach"
                            2 => "E Pereira-Barboza"
                            3 => "N Mueller"
                            4 => "J Barrera-G&#243;mez"
                            5 => "D Rojas-Rueda"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Lancet Planet Health"
                        "fecha" => "2021"
                        "volumen" => "5"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0009"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung consequences in adults born prematurely"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "CE Bolton"
                            1 => "A Bush"
                            2 => "JR Hurst"
                            3 => "S Kotecha"
                            4 => "L&#46; McGarvey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thoraxjnl-2014-206590"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2015"
                        "volumen" => "70"
                        "paginaInicial" => "574"
                        "paginaFinal" => "580"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25825005"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of early life exposures on respiratory disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "A&#46; Bush"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.prrv.2021.05.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "Paediatr Respir Rev"
                        "fecha" => "2021"
                        "volumen" => "40"
                        "paginaInicial" => "24"
                        "paginaFinal" => "32"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34144911"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0011"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of a stepwise introduction of smoke-free legislation on the rate of preterm births&#58; analysis of routinely collected birth data"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "B Cox"
                            1 => "E Martens"
                            2 => "B Nemery"
                            3 => "J Vangronsveld"
                            4 => "TS&#46; Nawrot"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmj.f441"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "2013"
                        "volumen" => "346"
                        "paginaInicial" => "f441"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23412829"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0012"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung function in early adulthood and health in later life&#58; a transgenerational cohort analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A Agust&#237;"
                            1 => "G Noell"
                            2 => "J Brugada"
                            3 => "R&#46; Faner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(17)30434-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2017"
                        "volumen" => "5"
                        "paginaInicial" => "935"
                        "paginaFinal" => "945"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29150410"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0013"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Respiratory health in cleaners in northern Europe&#58; is susceptibility established in early life&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "&#216; Svanes"
                            1 => "TD Skorge"
                            2 => "A Johannessen"
                            3 => "RJ Bertelsen"
                            4 => "M Br&#229;tveit"
                            5 => "B Forsberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0141892"
                      "Revista" => array:4 [
                        "tituloSerie" => "PLoS One"
                        "fecha" => "2015"
                        "volumen" => "10"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26720074"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0014"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "European Respiratory Society&#46; Environment and health&#46; 2020 &#91;cited 2021 Nov 1&#93;&#46; Available from&#58; <a target="_blank" href="https://www.ersnet.org/advocacy/environment-and-health/">https&#58;&#47;&#47;www&#46;ersnet&#46;org&#47;advocacy&#47;environment-and-health&#47;</a>"
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization &#40;WHO&#41;&#46; Air quality and health&#46; 2021 &#91;cited 2021 Nov 1&#93;&#46; Available from&#58;<a target="_blank" href="http://www.who.int/teams/environment-climate-change-and-health/air-quality-and-health/health-impacts">www&#46;who&#46;int&#47;teams&#47;environment-climate-change-and-health&#47;air-quality-and-health&#47;health-impacts</a>"
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0016"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization &#40;WHO&#41;&#46; Health topics&#46; Soaring e-waste affects the health of millions of children&#44; WHO warns&#46; 2021 &#91;cited 2021 Nov 1&#93;&#46; Available from&#58;<a target="_blank" href="http://www.who.int/news/item/15-06-2021-soaring-e-waste-affects-the-health-of-millions-of-children-who-warns">www&#46;who&#46;int&#47;news&#47;item&#47;15-06-2021-soaring-e-waste-affects-the-health-of-millions-of-children-who-warns</a>"
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0017"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Alveolarization continues during childhood and adolescence&#58; new evidence from helium-3 magnetic resonance"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M Narayanan"
                            1 => "J Owers-Bradley"
                            2 => "CS Beardsmore"
                            3 => "M Mada"
                            4 => "I Ball"
                            5 => "R Garipov"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201107-1348OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2012"
                        "volumen" => "185"
                        "paginaInicial" => "186"
                        "paginaFinal" => "191"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22071328"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0018"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Susceptibility of children to environmental pollutants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "PD Sly"
                            1 => "F&#46; Flack"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann N Y Acad Sci"
                        "fecha" => "2008"
                        "volumen" => "1140"
                        "paginaInicial" => "163"
                        "paginaFinal" => "183"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0019"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcome of asthma and wheezing in the first 6 years of life&#58; follow-up through adolescence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "WJ Morgan"
                            1 => "DA Stern"
                            2 => "DL Sherrill"
                            3 => "S Guerra"
                            4 => "CJ Holberg"
                            5 => "TW Guilbert"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.200504-525OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2005"
                        "volumen" => "172"
                        "paginaInicial" => "1253"
                        "paginaFinal" => "1258"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16109980"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low lung function in young adult life is associated with early mortality"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "MM Vasquez"
                            1 => "M Zhou"
                            2 => "C Hu"
                            3 => "FD Martinez"
                            4 => "S&#46; Guerra"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201608-1561LE"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2017"
                        "volumen" => "195"
                        "paginaInicial" => "1399"
                        "paginaFinal" => "1401"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28504596"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0021"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Poor airway function in early infancy and lung function by age 22 years&#58; a non-selective longitudinal cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "DA Stern"
                            1 => "WJ Morgan"
                            2 => "AL Wright"
                            3 => "S Guerra"
                            4 => "FD&#46; Martinez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(07)61379-8"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2007"
                        "volumen" => "370"
                        "paginaInicial" => "758"
                        "paginaFinal" => "764"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17765525"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0022"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Global initiative for chronic obstructive lung disease &#40;GOLD&#41;&#46; Global strategy for the diagnosis&#44; management&#44; and prevention of chronic obstructive pulmonary disease &#40;2021 report&#41;&#46; &#91;cited 2021 Nov 1st&#93;&#46; <a target="_blank" href="https://goldcopd.org">https&#58;&#47;&#47;goldcopd&#46;org</a>"
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0023"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The relationship of acute respiratory illness history to the prevalence and incidence of obstructive lung disorders"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "MD Lebowitz"
                            1 => "B&#46; Burrows"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/oxfordjournals.aje.a112418"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Epidemiol"
                        "fecha" => "1977"
                        "volumen" => "105"
                        "paginaInicial" => "544"
                        "paginaFinal" => "554"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/868858"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0024"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Global Initiative for Asthma&#46; 2021 GINA report&#44; global strategy for asthma management and prevention&#46; 2021&#46; &#91;cited 2021 Nov 1&#93;&#46; Available from&#58; <a target="_blank" href="https://ginasthma.org/gina-reports/">https&#58;&#47;&#47;ginasthma&#46;org&#47;gina-reports&#47;</a>"
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "E-Cigarettes as a growing threat for children and adolescents&#58; position statement from the European Academy of Paediatrics"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A Bush"
                            1 => "A Lintowska"
                            2 => "A Mazur"
                            3 => "A Hadjipanayis"
                            4 => "Z Grossman"
                            5 => "S Del Torso"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3389/fped.2021.569594"
                      "Revista" => array:4 [
                        "tituloSerie" => "Front Pediatr&#46;"
                        "fecha" => "2021"
                        "volumen" => "9"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33748036"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0026"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Grandmother&#39;s smoking when pregnant with the mother and asthma in the grandchild&#58; the Norwegian Mother and Child Cohort Study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "MC Magnus"
                            1 => "SE Haberg"
                            2 => "O Karlstad"
                            3 => "P Nafstad"
                            4 => "SJ London"
                            5 => "W&#46; Nystad"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thoraxjnl-2014-206438"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2015"
                        "volumen" => "70"
                        "paginaInicial" => "237"
                        "paginaFinal" => "243"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25572596"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0027"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maternal and grandmaternal smoking patterns are associated with early childhood asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "Y-F Li"
                            1 => "B Langholz"
                            2 => "MT Salam"
                            3 => "FD&#46; Gilliland"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1378/chest.127.4.1232"
                      "Revista" => array:6 [
                        "tituloSerie" => "Chest"
                        "fecha" => "2005"
                        "volumen" => "127"
                        "paginaInicial" => "1232"
                        "paginaFinal" => "1241"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15821200"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0028"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maternal nicotine exposure upregulates collagen gene expression in fetal monkey lung&#46; Association with alpha7 nicotinic acetylcholine receptors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "HS Sekhon"
                            1 => "JA Keller"
                            2 => "BJ Proskocil"
                            3 => "EL Martin"
                            4 => "ER&#46; Spindel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/ajrcmb.26.1.4170"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2002"
                        "volumen" => "26"
                        "paginaInicial" => "31"
                        "paginaFinal" => "41"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11751201"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0029"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prenatal nicotine exposure increases GABA signaling and mucin expression in airway epithelium"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "XW Fu"
                            1 => "K Wood"
                            2 => "ER&#46; Spindel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/rcmb.2010-0109OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2011"
                        "volumen" => "44"
                        "paginaInicial" => "222"
                        "paginaFinal" => "229"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20448051"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prenatal nicotine exposure alters lung function and airway geometry through &#945;7 nicotinic receptors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C Wongtrakool"
                            1 => "N Wang"
                            2 => "DM Hyde"
                            3 => "J Roman"
                            4 => "ER&#46; Spindel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/rcmb.2011-0028OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "2012"
                        "volumen" => "46"
                        "paginaInicial" => "695"
                        "paginaFinal" => "702"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22246862"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0031"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interaction between asthma and lung function growth in early life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "H Bisgaard"
                            1 => "SM Jensen"
                            2 => "K&#46; B&#248;nnelykke"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201110-1922OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2012"
                        "volumen" => "185"
                        "paginaInicial" => "1183"
                        "paginaFinal" => "1189"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22461370"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0032"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prenatal nicotine increases pulmonary &#945;7 nicotinic receptor expression and alters fetal lung development in monkeys"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "HS Sekhon"
                            1 => "Y Jia"
                            2 => "R Raab"
                            3 => "A Kuryatov"
                            4 => "JF Pankow"
                            5 => "JA Whitsett"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI5232"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "1999"
                        "volumen" => "103"
                        "paginaInicial" => "637"
                        "paginaFinal" => "647"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10074480"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0033"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maternal cigarette smoking is associated with increased inner airway wall thickness in children who die from sudden infant death syndrome"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "J Elliot"
                            1 => "P Vullermin"
                            2 => "P&#46; Robinson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1998"
                        "volumen" => "158"
                        "paginaInicial" => "802"
                        "paginaFinal" => "806"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0034"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antenatal determinants of neonatal immune responses to allergens"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G Devereux"
                            1 => "RN Barker"
                            2 => "A&#46; Seaton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.0022-0477.2001.01267.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Allergy"
                        "fecha" => "2002"
                        "volumen" => "32"
                        "paginaInicial" => "43"
                        "paginaFinal" => "50"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12002736"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maternal smoking is associated with impaired neonatal toll-like-receptor-mediated immune responses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "PS Noakes"
                            1 => "J Hale"
                            2 => "R Thomas"
                            3 => "C Lane"
                            4 => "SG Devadason"
                            5 => "SL&#46; Prescott"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1183/09031936.06.00050206"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2006"
                        "volumen" => "28"
                        "paginaInicial" => "721"
                        "paginaFinal" => "729"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16870663"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            35 => array:3 [
              "identificador" => "bib0036"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Bush A&#46; Health effects of passive smoking in children&#46; In Loddenkemper R&#44; Kreuter M&#44; eds&#46; The Tobacco Epidemic&#46; 2nd ed&#46;&#44; Volume 42&#46; Progress in Respiratory Research&#46; Basel&#44; Switzerland&#58; Karger&#59; 2015&#46; p&#46; 97-109"
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0037"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung function trajectories from pre-school age to adulthood and their associations with early life factors&#58; a retrospective analysis of three population-based birth cohort studies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "DC Belgrave"
                            1 => "R Granell"
                            2 => "SW Turner"
                            3 => "JA Curtin"
                            4 => "IE Buchan"
                            5 => "PN Le Sou&#235;f"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(18)30099-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2018"
                        "volumen" => "6"
                        "paginaInicial" => "526"
                        "paginaFinal" => "534"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29628377"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            37 => array:3 [
              "identificador" => "bib0038"
              "etiqueta" => "38"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Childhood predictors of lung function trajectories and future COPD risk&#58; a prospective cohort study from the first to the sixth decade of life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "DS Bui"
                            1 => "CJ Lodge"
                            2 => "JA Burgess"
                            3 => "AJ Lowe"
                            4 => "J Perret"
                            5 => "MQ Bui"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-2600(18)30100-0"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Respir Med"
                        "fecha" => "2018"
                        "volumen" => "6"
                        "paginaInicial" => "535"
                        "paginaFinal" => "544"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29628376"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            38 => array:3 [
              "identificador" => "bib0039"
              "etiqueta" => "39"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood&#58; a longitudinal birth-cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "DA Stern"
                            1 => "WJ Morgan"
                            2 => "M Halonen"
                            3 => "AL Wright"
                            4 => "FD&#46; Martinez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(08)61447-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2008"
                        "volumen" => "372"
                        "paginaInicial" => "1058"
                        "paginaFinal" => "1064"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18805334"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            39 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "40"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Lung-function trajectories leading to chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P Lange"
                            1 => "B Celli"
                            2 => "A Agust&#237;"
                            3 => "G Boje Jensen"
                            4 => "M Divo"
                            5 => "R Faner"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1411532"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2015"
                        "volumen" => "373"
                        "paginaInicial" => "111"
                        "paginaFinal" => "122"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26154786"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            40 => array:3 [
              "identificador" => "bib0041"
              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Combined effects of parental and active smoking on early lung function deficits&#58; a prospective study from birth to age 26 years"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:7 [
                            0 => "S Guerra"
                            1 => "DA Stern"
                            2 => "M Zhou"
                            3 => "DL Sherrill"
                            4 => "AL Wright"
                            5 => "WJ Morgan"
                            6 => "FD&#46; Martinez"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thoraxjnl-2013-203538"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2013"
                        "volumen" => "68"
                        "paginaInicial" => "1021"
                        "paginaFinal" => "1028"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23847259"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            41 => array:3 [
              "identificador" => "bib0042"
              "etiqueta" => "42"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early life origins of chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C Svanes"
                            1 => "J Sunyer"
                            2 => "E Plana"
                            3 => "S Dharmage"
                            4 => "J Heinrich"
                            5 => "D Jarvis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.2008.112136"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2010"
                        "volumen" => "65"
                        "paginaInicial" => "14"
                        "paginaFinal" => "20"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19729360"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            42 => array:3 [
              "identificador" => "bib0043"
              "etiqueta" => "43"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Impact of &#8221;&#8221;&#8221; &#8217;London&#39;s road traffic air and noise pollution on birth weight&#58; retrospective population based cohort study"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:7 [
                            0 => "RB Smith"
                            1 => "D Fecht"
                            2 => "J Gulliver"
                            3 => "SD Beevers"
                            4 => "D Dajnak"
                            5 => "M Blangiardo"
                            6 => "RE Ghosh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmj.j5299"
                      "Revista" => array:5 [
                        "tituloSerie" => "BMJ"
                        "fecha" => "2017"
                        "volumen" => "359"
                        "paginaInicial" => "j5299"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29208602"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            43 => array:3 [
              "identificador" => "bib0044"
              "etiqueta" => "44"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association between gaseous ambient air pollutants and adverse pregnancy outcomes in Vancouver&#44; Canada"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S Liu"
                            1 => "D Krewski"
                            2 => "Y Shi"
                            3 => "Y Chen"
                            4 => "RT&#46; Burnett"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1289/ehp.6251"
                      "Revista" => array:6 [
                        "tituloSerie" => "Environ Health Perspect&#46;"
                        "fecha" => "2003"
                        "volumen" => "111"
                        "paginaInicial" => "1773"
                        "paginaFinal" => "1778"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14594630"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            44 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "45"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Intrauterine and early postnatal exposure to outdoor air pollution and lung function at preschool age"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E Morales"
                            1 => "R Garcia-Esteban"
                            2 => "OA de la Cruz"
                            3 => "M Basterrechea"
                            4 => "A Lertxundi"
                            5 => "MD de Dicastillo"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thoraxjnl-2014-205413"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2015"
                        "volumen" => "70"
                        "paginaInicial" => "64"
                        "paginaFinal" => "73"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25331281"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            45 => array:3 [
              "identificador" => "bib0046"
              "etiqueta" => "46"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "European Respiratory Society&#46; Exposure to air pollution within EU limits linked to impaired breathing in children and asthma in adults&#46; 2020 &#91;cited 2021 Nov 1&#93;&#46; Available from&#58;<a target="_blank" href="https://www.ersnet.org/news-and-features/news/exposure-to-air-pollution-within-eu-limits-linked-to-impaired-breathing-in-children-and-asthma-in-adults/">https&#58;&#47;&#47;www&#46;ersnet&#46;org&#47;news-and-features&#47;news&#47;exposure-to-air-pollution-within-eu-limits-linked-to-impaired-breathing-in-children-and-asthma-in-adults&#47;</a>"
                ]
              ]
            ]
            46 => array:3 [
              "identificador" => "bib0047"
              "etiqueta" => "47"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization &#40;WHO&#41;&#46; Ambient &#40;outdoor&#41; air pollution &#91;Internet&#93;&#46; Health-topics&#46; 2021 &#91;cited 2021 Nov 1&#93;&#46; Available from&#58; <a target="_blank" href="https://www.who.int/news-room/fact-sheets/detail/ambient-(outdoor)-air-quality-and-health">https&#58;&#47;&#47;www&#46;who&#46;int&#47;news-room&#47;fact-sheets&#47;detail&#47;ambient-&#40;outdoor&#41;-air-quality-and-health</a>"
                ]
              ]
            ]
            47 => array:3 [
              "identificador" => "bib0048"
              "etiqueta" => "48"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of air pollution on lung development from 10 to 18 years of age"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "WJ Gauderman"
                            1 => "E Avol"
                            2 => "F Gilliland"
                            3 => "H Vora"
                            4 => "D Thomas"
                            5 => "K Berhane"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa040610"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "351"
                        "paginaInicial" => "1057"
                        "paginaFinal" => "1067"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15356303"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            48 => array:3 [
              "identificador" => "bib0049"
              "etiqueta" => "49"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Association of improved air quality with lung development in children"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "WJ Gauderman"
                            1 => "R Urman"
                            2 => "E Avol"
                            3 => "K Berhane"
                            4 => "R McConnell"
                            5 => "E Rappaport"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1414123"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2015"
                        "volumen" => "372"
                        "paginaInicial" => "905"
                        "paginaFinal" => "913"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25738666"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            49 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "50"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Associations between pre- and postnatal exposure to air pollution and lung health in children and assessment of CC16 as a potential mediator"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A Stapleton"
                            1 => "M Casas"
                            2 => "J Garc&#237;a"
                            3 => "R Garc&#237;a"
                            4 => "J Sunyer"
                            5 => "S Guerra"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Environ Res"
                        "fecha" => "2021"
                        "volumen" => "204"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            50 => array:3 [
              "identificador" => "bib0051"
              "etiqueta" => "51"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Influences of environmental exposures on preterm lung disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "JM Collaco"
                            1 => "BC Aoyama"
                            2 => "JL Rice"
                            3 => "SA&#46; McGrath-Morrow"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1080/17476348.2021.1941886"
                      "Revista" => array:6 [
                        "tituloSerie" => "Expert Rev Respir Med"
                        "fecha" => "2021"
                        "volumen" => "15"
                        "paginaInicial" => "1271"
                        "paginaFinal" => "1279"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/34114906"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            51 => array:3 [
              "identificador" => "bib0052"
              "etiqueta" => "52"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early-life exposure to the great smog of 1952 and the development of asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "P Bharadwaj"
                            1 => "JG Zivin"
                            2 => "JT Mullins"
                            3 => "M&#46; Neidell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201603-0451OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2016"
                        "volumen" => "194"
                        "paginaInicial" => "1475"
                        "paginaFinal" => "1482"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27392261"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            52 => array:3 [
              "identificador" => "bib0053"
              "etiqueta" => "53"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Air pollution and the development of asthma from birth until young adulthood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "U Gehring"
                            1 => "AH Wijga"
                            2 => "GH Koppelman"
                            3 => "JM Vonk"
                            4 => "HA Smit"
                            5 => "B&#46; Brunekreef"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Eur Respir J"
                        "fecha" => "2020"
                        "volumen" => "56"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            53 => array:3 [
              "identificador" => "bib0054"
              "etiqueta" => "54"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Allergy and atopy from infancy to adulthood&#58; messages from the German birth cohort MAS"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "S Lau"
                            1 => "PM Matricardi"
                            2 => "U Wahn"
                            3 => "YA Lee"
                            4 => "T&#46; Keil"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.anai.2018.05.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Allergy Asthma Immunol"
                        "fecha" => "2019"
                        "volumen" => "122"
                        "paginaInicial" => "25"
                        "paginaFinal" => "32"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29803707"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            54 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "55"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A longitudinal&#44; population-based&#44; cohort study of childhood asthma followed to adulthood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "MR Sears"
                            1 => "JM Greene"
                            2 => "AR Willan"
                            3 => "EM Wiecek"
                            4 => "DR Taylor"
                            5 => "EM Flannery"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa022363"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2003"
                        "volumen" => "349"
                        "paginaInicial" => "1414"
                        "paginaFinal" => "1422"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14534334"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            55 => array:3 [
              "identificador" => "bib0056"
              "etiqueta" => "56"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluating the long-term consequences of air pollution in early life&#58; geographical correlations between coal consumption in 1951&#47;1952 and current mortality in England and Wales"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "DI Phillips"
                            1 => "C Osmond"
                            2 => "H Southall"
                            3 => "P Aucott"
                            4 => "A Jones"
                            5 => "ST&#46; Holgate"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/bmjopen-2018-022991"
                      "Revista" => array:4 [
                        "tituloSerie" => "BMJ Open"
                        "fecha" => "2018"
                        "volumen" => "8"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30598485"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            56 => array:3 [
              "identificador" => "bib0057"
              "etiqueta" => "57"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Particulate air pollution and fetal health&#58; a systematic review of the epidemiologic evidence"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "SV Glinianaia"
                            1 => "J Rankin"
                            2 => "R Bell"
                            3 => "T Pless-Mulloli"
                            4 => "D&#46; Howel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/01.ede.0000101023.41844.ac"
                      "Revista" => array:6 [
                        "tituloSerie" => "Epidemiology"
                        "fecha" => "2004"
                        "volumen" => "15"
                        "paginaInicial" => "36"
                        "paginaFinal" => "45"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14712145"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            57 => array:3 [
              "identificador" => "bib0058"
              "etiqueta" => "58"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Exposure to traffic-related air pollution and risk of development of childhood asthma&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H Khreis"
                            1 => "C Kelly"
                            2 => "J Tate"
                            3 => "R Parslow"
                            4 => "K Lucas"
                            5 => "M&#46; Nieuwenhuijsen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.envint.2016.11.012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Environ Int"
                        "fecha" => "2017"
                        "volumen" => "100"
                        "paginaInicial" => "1"
                        "paginaFinal" => "31"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27881237"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            58 => array:3 [
              "identificador" => "bib0059"
              "etiqueta" => "59"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outdoor air pollution and asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "M Guarnieri"
                            1 => "JR&#46; Balmes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(14)60617-6"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2014"
                        "volumen" => "383"
                        "paginaInicial" => "1581"
                        "paginaFinal" => "1592"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24792855"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            59 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "60"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Patterns of growth and decline in lung function in persistent childhood asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "MJ McGeachie"
                            1 => "KP Yates"
                            2 => "X Zhou"
                            3 => "F Guo"
                            4 => "AL Sternberg"
                            5 => "ML Van Natta"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1513737"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2016"
                        "volumen" => "374"
                        "paginaInicial" => "1842"
                        "paginaFinal" => "1852"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27168434"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            60 => array:3 [
              "identificador" => "bib0061"
              "etiqueta" => "61"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global&#44; national&#44; and urban burdens of paediatric asthma incidence attributable to ambient NO pollution&#58; estimates from global datasets"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "P Achakulwisut"
                            1 => "M Brauer"
                            2 => "P Hystad"
                            3 => "SC&#46; Anenberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2542-5196(19)30046-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Planet Health"
                        "fecha" => "2019"
                        "volumen" => "3"
                        "paginaInicial" => "e166"
                        "paginaFinal" => "e178"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30981709"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            61 => array:3 [
              "identificador" => "bib0062"
              "etiqueta" => "62"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Outcomes of childhood asthma to the age of 50 years"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A Tai"
                            1 => "H Tran"
                            2 => "M Roberts"
                            3 => "N Clarke"
                            4 => "A-M Gibson"
                            5 => "S Vidmar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jaci.2013.09.002"
                      "Revista" => array:4 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2014"
                        "volumen" => "133"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24139497"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            62 => array:3 [
              "identificador" => "bib0063"
              "etiqueta" => "63"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Asthma-like symptoms in young children increase the risk of COPD"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H Bisgaard"
                            1 => "S N&#248;rgaard"
                            2 => "A Sevelsted"
                            3 => "BL Chawes"
                            4 => "J Stokholm"
                            5 => "EL Mortensen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "2021"
                        "volumen" => "147"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            63 => array:3 [
              "identificador" => "bib0064"
              "etiqueta" => "64"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The association between childhood asthma and adult chronic obstructive pulmonary disease"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "A Tai"
                            1 => "H Tran"
                            2 => "M Roberts"
                            3 => "N Clarke"
                            4 => "J Wilson"
                            5 => "CF&#46; Robertson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thoraxjnl-2013-204815"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2014"
                        "volumen" => "69"
                        "paginaInicial" => "805"
                        "paginaFinal" => "810"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24646659"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            64 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "65"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors for chronic obstructive pulmonary disease in a European cohort of young adults"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R de Marco"
                            1 => "S Accordini"
                            2 => "A Marcon"
                            3 => "I Cerveri"
                            4 => "JM Ant&#243;"
                            5 => "T Gislason"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201007-1125OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2011"
                        "volumen" => "183"
                        "paginaInicial" => "891"
                        "paginaFinal" => "897"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20935112"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            65 => array:3 [
              "identificador" => "bib0066"
              "etiqueta" => "66"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Obstructive pulmonary disease in old age among individuals born preterm"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "EB Brostr&#246;m"
                            1 => "O Akre"
                            2 => "M Katz-Salamon"
                            3 => "D Jaraj"
                            4 => "M Kaijser"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s10654-013-9761-7"
                      "Revista" => array:6 [
                        "tituloSerie" => "Eur J Epidemiol"
                        "fecha" => "2013"
                        "volumen" => "28"
                        "paginaInicial" => "79"
                        "paginaFinal" => "85"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23341027"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            66 => array:3 [
              "identificador" => "bib0067"
              "etiqueta" => "67"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Early life insults as determinants of chronic obstructive pulmonary disease in adult life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "O Savran"
                            1 => "CS&#46; Ulrik"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2147/COPD.S153555"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J Chron Obstruct Pulmon Dis"
                        "fecha" => "2018"
                        "volumen" => "13"
                        "paginaInicial" => "683"
                        "paginaFinal" => "693"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29520136"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            67 => array:3 [
              "identificador" => "bib0068"
              "etiqueta" => "68"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Maternal smoking during pregnancy&#46; Effects on lung function during the first 18 months of life"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "IB Tager"
                            1 => "L Ngo"
                            2 => "JP&#46; Hanrahan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.152.3.7663813"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1995"
                        "volumen" => "152"
                        "paginaInicial" => "977"
                        "paginaFinal" => "983"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7663813"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            68 => array:3 [
              "identificador" => "bib0069"
              "etiqueta" => "69"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The role of nicotine in the effects of maternal smoking during pregnancy on lung development and childhood respiratory disease&#46; implications for dangers of E-Cigarettes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "ER Spindel"
                            1 => "CT McEvoy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201510-2013PP"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2016"
                        "volumen" => "193"
                        "paginaInicial" => "486"
                        "paginaFinal" => "494"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26756937"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            69 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "70"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The effect of multiple adverse childhood experiences on health&#58; a systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K Hughes"
                            1 => "MA Bellis"
                            2 => "KA Hardcastle"
                            3 => "D Sethi"
                            4 => "A Butchart"
                            5 => "C Mikton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2468-2667(17)30118-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Public Health"
                        "fecha" => "2017"
                        "volumen" => "2"
                        "paginaInicial" => "e356"
                        "paginaFinal" => "e366"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29253477"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            70 => array:3 [
              "identificador" => "bib0071"
              "etiqueta" => "71"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Adverse childhood experiences and risk of cancer during adulthood&#58; A systematic review and meta-analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "Z Hu"
                            1 => "AC Kaminga"
                            2 => "J Yang"
                            3 => "J Liu"
                            4 => "H&#46; Xu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Child Abuse Negl"
                        "fecha" => "2021"
                        "volumen" => "117"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            71 => array:3 [
              "identificador" => "bib0072"
              "etiqueta" => "72"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prenatal household air pollution is associated with impaired infant lung function with sex-specific effects&#46; Evidence from GRAPHS&#44; a cluster randomized cookstove intervention trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "AG Lee"
                            1 => "S Kaali"
                            2 => "A Quinn"
                            3 => "R Delimini"
                            4 => "K Burkart"
                            5 => "J Opoku-Mensah"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/rccm.201804-0694OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "2019"
                        "volumen" => "199"
                        "paginaInicial" => "738"
                        "paginaFinal" => "776"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30256656"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            72 => array:3 [
              "identificador" => "bib0073"
              "etiqueta" => "73"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Sociedade Brasileira de Pediatria &#40;SBP&#41;&#46; Documentos cient&#237;ficos toxicologia e Sa&#250;de Ambiental &#91;cited 2021 Nov 1&#93;&#46; Available from&#58; <a target="_blank" href="https://www.sbp.com.br/departamentos-cientificos/toxicologia-e-saude-ambiental/documentos-cientificos/">https&#58;&#47;&#47;www&#46;sbp&#46;com&#46;br&#47;departamentos-cientificos&#47;toxicologia-e-saude-ambiental&#47;documentos-cientificos&#47;</a>"
                ]
              ]
            ]
            73 => array:3 [
              "identificador" => "bib0074"
              "etiqueta" => "74"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Improving lung health in low-income and middle-income countries&#58; from challenges to solutions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J Meghji"
                            1 => "K Mortimer"
                            2 => "A Agusti"
                            3 => "BW Allwood"
                            4 => "I Asher"
                            5 => "ED Bateman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(21)00458-X"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2021"
                        "volumen" => "397"
                        "paginaInicial" => "928"
                        "paginaFinal" => "940"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/33631128"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/00217557/00000098000000S1/v1_202203240549/S0021755721001650/v1_202203240549/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "10176"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Review articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/00217557/00000098000000S1/v1_202203240549/S0021755721001650/v1_202203240549/en/main.pdf?idApp=UINPBA000049&text.app=https://jped.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755721001650?idApp=UINPBA000049"
]

Article information

ISSN: 00217557
Original language: English

DOI:10.1016/j.jped.2021.11.005

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	10	9	19
2024 October	54	52	106
2024 September	47	42	89
2024 August	51	43	94
2024 July	50	44	94
2024 June	55	37	92
2024 May	33	25	58
2024 April	37	22	59
2024 March	32	26	58
2024 February	112	34	146
2024 January	25	30	55
2023 December	20	30	50
2023 November	44	41	85
2023 October	47	40	87
2023 September	39	44	83
2023 August	74	53	127
2023 July	83	17	100
2023 June	94	25	119
2023 May	64	16	80
2023 April	26	14	40
2023 March	36	22	58
2023 February	29	16	45
2023 January	30	23	53
2022 December	53	25	78
2022 November	40	32	72
2022 October	44	32	76
2022 September	52	43	95
2022 August	35	44	79
2022 July	98	54	152
2022 June	33	33	66
2022 May	99	24	123
2022 April	223	68	291
2022 March	97	47	144
2022 February	40	20	60
2022 January	32	29	61

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter