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Asthma is a descriptive label for an obstructive, inflammatory disease in the lower airways manifesting with symptoms including breathlessness, cough, difficulty in breathing and wheezing. From a clinician's point of view, asthma symptoms can commence at any age although most asthma patients - regardless of their age of onset - seem to have had some form of airway problems during childhood. Asthma inception and related pathophysiologic processes are therefore very likely to occur early in life, further evidenced by recent lung physiologic and mechanistic research. Herein, we present state-of-the-art updates on the role of genetics and epigenetics, early viral and bacterial infections, immune response and pathophysiology as well as lifestyle and environmental exposures in asthma across the life-course. We conclude early environmental insults in genetically vulnerable individuals to induce an abnormal, pre-asthmatic airway response as key events in asthma inception and highlight disease heterogeneity - across ages - and the potential shortness of treating all patients with asthma using the same treatments. Although there are no interventions that, at present, can modify long-term outcomes, a precision-medicine approach should be implemented to optimize treatment and tailor follow-up for all patients with asthma. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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RATIONALE: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. OBJECTIVES: To determine if the 1930's racist policy of redlining led to present-day disparities in childhood asthma by increasing community-level poverty and decreasing neighborhood socioeconomic position (SEP). METHODS: We categorized census tracts at birth of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into A, B, C, or D categories as defined by the Home Owners Loan Corporation (HOLC), with D being the highest perceived risk. Surrogates of present-day neighborhood-level SEP were determined for each tract including the percentage of low-income households, the CDC's social vulnerability index (SVI), and other tract-level variables. We performed causal mediation analysis, which, under the assumption of no unmeasured confounding, estimates the direct and mediated pathways by which redlining may cause asthma disparities through census tract-level mediators adjusting for individual-level covariates. MEASUREMENTS AND MAIN RESULTS: Of 4,849 children, the cumulative incidence of asthma through age 11 was 26.6% and 13.2% resided in census tracts with a HOLC grade of D. In mediation analyses, residing in grade D tracts (aOR = 1.03 [95%CI 1.01,1.05]) was significantly associated with childhood asthma, with 79% of this increased risk mediated by percentage of low-income households; results were similar for SVI and other tract-level variables. CONCLUSIONS: The historical structural racist policy of redlining led to present-day asthma disparities in part through decreased neighborhood SEP. Policies aimed at reversing the effects of structural racism should be considered to create more just, equitable, and healthy communities.
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The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.
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Objectives. To examine whether a previously reported association between airborne lead exposure and children's cognitive function replicates across a geographically diverse sample of the United States. Methods. Residential addresses of children (< 5 years) were spatially joined to the Risk-Screening Environmental Indicators model of relative airborne lead toxicity. Cognitive outcomes for children younger than 8 years were available for 1629 children with IQ data and 1476 with measures of executive function (EF; inhibitory control, cognitive flexibility). We used generalized linear models using generalized estimating equations to examine the associations of lead, scaled by interquartile range (IQR), accounting for individual- and area-level confounders. Results. An IQR increase in airborne lead was associated with a 0.74-point lower mean IQ score (b = -0.74; 95% confidence interval = -1.00, -0.48). The association between lead and EF was nonlinear and was modeled with a knot at the 97.5th percentile of lead in our sample. Lead was significantly associated with lower mean inhibitory control but not with cognitive flexibility. This effect was stronger among males for both IQ and inhibitory control. Conclusions. Early-life exposure to airborne lead is associated with lower cognitive functioning. (Am J Public Health. 2024;114(3):309-318. https://doi.org/10.2105/AJPH.2023.307519).
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Cognição , Chumbo , Masculino , Criança , Humanos , Estados Unidos/epidemiologia , Chumbo/toxicidade , Estudos Prospectivos , Modelos Lineares , Avaliação de Resultados em Cuidados de Saúde , Exposição Ambiental/efeitos adversosRESUMO
BACKGROUND: Adrenal steroids play important roles in early-life development. However, our understanding of the effects of perinatal adrenal steroids on the development of childhood asthma is incomplete. OBJECTIVE: To evaluate the associations between early-life adrenal steroid levels and childhood asthma. METHODS: Participants included the Infant Susceptibility to Pulmonary Infections and Asthma following Respiratory Syncytial Virus Exposure birth cohort children with untargeted urinary metabolomics data measured during early infancy (n = 264) and nasal immune mediator data measured concurrently at age 2 to 6 months (n = 76). A total of 11 adrenal steroid compounds were identified using untargeted metabolomics and 6 asthma-relevant nasal immune mediators from multiplex assays were a priori selected. Current asthma at ages 5 and 6 years was ascertained using validated questionnaires. Associations were tested using logistic and linear regression with confounders adjustment. RESULTS: Pregnenetriol disulfate (adjusted odds ratio [aOR] = 0.20, 95% CI = 0.06-0.68) and 3a,21-dihydroxy-5b-pregnane-11,20-dione-21-glucuronide (aOR = 0.34, 95% CI = 0.14-0.75) were inversely associated with childhood asthma at 5 and 6 years after multiple testing adjustment. There was a significant interaction effect of pregnanediol-3-glucuronide by biological sex assigned at birth (aOR = 0.11, 95% CI = 0.02-0.51, for those with female sex) on childhood asthma. Pregnenetriol disulfate was inversely associated with granulocyte-macrophage colony-stimulating factor (ß = -0.45, q-value = 0.05). 3a,21-dihydroxy-5b-pregnane-11,20-dione 21-glucuronide was inversely associated with interleukin [IL]-4 (ß = -0.29, q-value = 0.02), IL-5 (ß = -0.35, q-value = 0.006), IL-13 (ß = -0.26, q-value = 0.02), granulocyte-macrophage colony-stimulating factor (ß = -0.35, q-value = 0.006), and fibroblast growth factor-ß (ß = -0.24, q-value = 0.01) after multiple testing adjustment. CONCLUSION: The inverse association between adrenal steroids downstream of progesterone and 17-hydroxypregnenolone and the odds of childhood asthma and nasopharyngeal type 2 immune biomarkers suggest that increased early-life adrenal steroids may suppress type 2 inflammation and protect against the development of childhood asthma.
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Asma , Humanos , Asma/urina , Asma/epidemiologia , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Corticosteroides/urina , Corticosteroides/uso terapêutico , Infecções por Vírus Respiratório Sincicial/urina , Infecções por Vírus Respiratório Sincicial/imunologia , Fatores de RiscoRESUMO
INTRODUCTION: Health agencies have called for research evaluating e-cigarette (EC) use in supporting prenatal smoking cessation. This study aimed to describe (a) characteristics of smokers who begin using ECs during pregnancy, (b) how frequently smokers reduce or eliminate pre- and post-natal combustible cigarette (CC) use, and (c) risk for neonatal health complications among smokers who initiate ECs during pregnancy. METHODS: Pregnant women using CCs exclusively pre-pregnancy, who participated in a U.S. surveillance study, were classified by their reported late-pregnancy smoking behavior as CC-exclusive users, EC initiators, or quitters. EC initiators were further subclassified as dual users (used both ECs and CCs) or EC replacers (used ECs exclusively). RESULTS: Of 29,505 pregnant smokers, 1.5% reported using ECs during the last 3 pregnancy months. Among them, 29.7% became EC-exclusive users. EC initiators were disproportionately non-Hispanic White. Relative to quitters, EC initiators had lower income, were less likely to be married, have intended pregnancies, receive first-trimester prenatal care, and participate in a federal assistance program. Compared to CC-exclusive users, EC initiators overall, and dual users specifically, were more likely to reduce pre- and post-natal CC usage relative to pre-pregnancy levels. EC initiators' risk for neonatal health complications fell between quitters and CC-exclusive users, though differences were not statistically significant. CONCLUSIONS: Although EC initiators reduced CC use more than CC-exclusive users, only 29.7% reported complete CC cessation, and there was insufficient evidence of reduction in neonatal health complications relative to CC-exclusive users. Currently, ECs should not be considered a viable gestational smoking cessation strategy. IMPLICATIONS: Health agencies have identified a critical need for research evaluating the use of e-cigarettes in supporting prenatal smoking cessation. Using the US Pregnancy Risk Assessment Monitoring System surveillance study data, we provide real-world evidence that prenatal e-cigarette initiation as a smoking cessation tool is used infrequently among pregnant combustible cigarettes smokers. Most using e-cigarettes in the last three months of pregnancy also used combustible cigarettes.
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Childhood asthma is a common chronic disease of the airways that results from host and environment interactions. Most risk factor studies of asthma point to the first year of life as a susceptibility window of mucosal exposure that directly impacts the airway epithelium and airway epithelial cell development. The development of the airway epithelium, which forms a competent barrier resulting from coordinated interactions of different specialized cell subsets, occurs during a critical time frame in normal postnatal development in the first year of life. Understanding the normal and aberrant developmental trajectory of airway epithelial cells is important in identifying pathways that may contribute to barrier dysfunction and asthma pathogenesis. Respiratory viruses make first contact with and infect the airway mucosa. Human rhinovirus (HRV) and respiratory syncytial virus (RSV) are mucosal pathogens that are consistently identified as asthma risk factors. Respiratory viruses represent a unique early life exposure, different from passive irritant exposures which injure the developing airway epithelium. To replicate, respiratory viruses take over the host cell transcriptional and translational processes and exploit host cell energy metabolism. This takeover impacts the development and differentiation processes of airway epithelial cells. Therefore, delineating the mechanisms through which early life respiratory viral infections alter airway epithelial cell development will allow us to understand the maturation and heterogeneity of asthma and develop tools tailored to prevent disease in specific children. This review will summarize what is understood about the impact of early life respiratory viruses on the developing airway epithelium and define critical gaps in our knowledge.
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Identifying child age of RSV infection associated with increased risk of asthma is important for developing asthma prevention strategies. Our systematic review aimed to comprehensively summarize studies of the association between age of RSV infection and childhood asthma risk. The study protocol was pre-registered, and our study report adhered to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA). Inclusion criteria were prospective and retrospective cohort studies and case-control studies which assessed the association of age of RSV infection before age 2 years and risk of childhood asthma after age two years. Relevant studies were identified through MEDLINE, Embase, Cochrane and International Clinical Trials Registry Platform (ICTRP) from study inception through May 5, 2023. Studies were evaluated with the Quality In Prognosis Studies (QUIPS) tool. From 149 studies screened, five studies (two prospective cohort studies and three retrospective cohort studies) were included in our systematic review, including 47,603 participants. Available studies only assessed age of severe RSV infection and asthma risk. The included studies used different age categories and outcome definitions, and were rated as having high risk of bias. Two studies had sample sizes of less than 300 and did not provide conclusive results related to age of RSV hospitalization and asthma risk. The other three studies reported RSV hospitalization between age 6 months and 23 months compared with age 0-6 months being associated with a higher odds ratio, hazard ratio, or incidence rate ratio of asthma diagnosis/hospitalization. Due to the heterogeneous epidemiological designs, including exposures and outcome ascertainments of the included studies, we could not perform a meta-analysis, or calculate weighted averages of the effect estimates. Our systematic review highlights a major gap in our knowledge about the relationship between age of RSV infection and asthma risk.
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Asma , Infecções por Vírus Respiratório Sincicial , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Asma/complicações , Asma/epidemiologia , Hospitalização , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/complicações , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Estudos Retrospectivos , Fatores de RiscoRESUMO
Childhood asthma is among the most common chronic lung diseases in the pediatric population, having substantial consequences on the everyday life of children and their caregivers. There remains a lack of a singular, efficacious strategy for averting the inception of childhood asthma. The rate of pediatric antibiotic usage continues to be high, which makes it crucial to understand whether there exists a causal link between the use of antibiotics in infancy and the development of asthma in childhood. In this rostrum, we conduct a critical review of the literature concerning the association of infant antibiotic use and the onset of childhood asthma. Drawing on the results of 5 meta-analyses addressing this topic and of a recent randomized controlled trial, a notable association emerges between antibiotic exposure in the first year of life and the occurrence of childhood asthma that appears to be beyond potential study limitations (such as reverse causation, confounding by indication, and recall bias). Furthermore, we highlight the need for additional research in this field that could improve our understanding of important aspects of this association and lead to the design of an intervention aimed to deliver antibiotics safely during early life and reduce the burden of childhood asthma.
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Background: Currently, there are no available tools to identify infants at the highest risk of significant morbidity and mortality from respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) who would benefit most from RSV prevention products. The objective was to develop and internally validate a personalized risk prediction tool for use among all newborns that uses readily available birth/postnatal data to predict RSV LRTI requiring intensive care unit (ICU) admission. Methods: We conducted a population-based birth cohort study of infants born from 1995 to 2007, insured by the Tennessee Medicaid Program, and who did not receive RSV immunoprophylaxis during the first year of life. The primary outcome was severe RSV LRTI requiring ICU admission during the first year of life. We built a multivariable logistic regression model including demographic and clinical variables available at or shortly after birth to predict the primary outcome. Results: In a population-based sample of 429 365 infants, 713 (0.2%) had severe RSV LRTI requiring ICU admission. The median age of admission was 66 days (interquartile range, 37-120). Our tool, including 19 variables, demonstrated good predictive accuracy (area under the curve, 0.78; 95% confidence interval, 0.77-0.80) and identified infants who did not qualify for palivizumab, based on American Academy of Pediatrics guidelines, but had higher predicted risk levels than infants who qualified (27% of noneligible infants with >0.16% predicted probabilities [lower quartile for eligible infants]). Conclusions: We developed a personalized tool that identified infants at increased risk for severe RSV LRTI requiring ICU admission, expected to benefit most from immunoprophylaxis.
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Diagnosing lung infections is often challenging because of the lack of a high-quality specimen from the diseased lung. Since persons with cystic fibrosis are subject to chronic lung infection, there is frequently a need for a lung specimen. In this small, proof of principle study, we determined that PneumoniaCheckTM, a non-invasive device that captures coughed droplets from the lung on a filter, might help meet this need. We obtained 10 PneumoniaCheckTMcoughed specimens and 2 sputum specimens from adult CF patients hospitalized with an exacerbation of their illness. We detected amylase (upper respiratory tract) with an enzymatic assay, surfactant A (lower respiratory tract) with an immunoassay, pathogenic bacteria by PCR, and markers of inflammation by a Luminex multiplex immunoassay. The amylase and surfactant A levels suggested that 9/10 coughed specimens were from lower respiratory tract with minimal upper respiratory contamination. The PCR assays detected pathogenic bacteria in 7 of 9 specimens and multiplex Luminex assay detected a variety of cytokines or chemokines. These data indicate that the PneumoniaCheckTMcoughed specimens can capture good quality lower respiratory tract specimens that have the potential to help in diagnosis, management and understanding of CF exacerbations and other lung disease.
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Biomarcadores , Fibrose Cística , Humanos , Fibrose Cística/microbiologia , Fibrose Cística/diagnóstico , Biomarcadores/análise , Adulto , Masculino , Feminino , Escarro/microbiologia , Pulmão/microbiologia , Adulto JovemRESUMO
BACKGROUND: The contribution of prenatal anthropometric measures to the development of specific childhood asthma phenotypes is not known. OBJECTIVE: We aimed to evaluate associations between prepregnancy body mass index (BMI) and gestational weight gain (GWG) with allergic and nonallergic asthma phenotypes in childhood. METHODS: Our study population included term, healthy infants in the middle Tennessee region of the United States. Prepregnancy BMI and GWG were ascertained from questionnaires administered during early infancy and categorized based on World Health Organization and Institute of Medicine recommendations, respectively. Allergic asthma was defined as 5-year current asthma and a positive skin test or specific IgE to aeroallergen(s). We used multivariable logistic regression models for asthma and multinomial logistic regression models for nonasthma, allergic asthma, and nonallergic asthma. RESULTS: A total of 1266 children were included. At the 5-year follow-up, 194 (15.3%) had asthma; among them, 102 (52.6%) had allergic asthma. Both inadequate and excessive GWG, compared with adequate GWG, were associated with increased odds of asthma (inadequate: adjusted odds ratio [aOR]: 1.76 [95% confidence interval (CI): 1.03-2.98]; excessive: aOR: 1.70 [95% CI: 1.12-2.57]) and increased odds of allergic asthma compared with no asthma (inadequate: aOR: 3.49 [95% CI: 1.66-7.32]; excessive: aOR: 2.55 [95% CI: 1.34-4.85]). Prepregnancy BMI was not associated with asthma nor with asthma phenotypes. CONCLUSIONS: Both inadequate and excessive GWG were associated with allergic asthma risk. These results support the benefits of optimal GWG during pregnancy on child health outcomes.
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Background: Recruitment for research studies is a challenging endeavor that was further complicated by the coronavirus disease 2019 pandemic. We launched a new multicenter birth cohort, Childhood Allergy and the NeOnatal Environment (CANOE), supported by the National Institutes of Health in January 2020 across 4 sites. Although the pandemic temporarily halted clinical research, we restructured the study and instituted novel recruitment methods that we hypothesized would enable brisk enrollment when research activities resumed. Objective: We sought to develop protocol modifications and recruitment methods that promote successful recruitment of diverse populations in clinical research despite a global pandemic. Methods: Even though study activities were suspended, we modified recruitment strategies to limit in-person contact, shifting toward alternative HIPAA-compliant methods such as clinician referrals, institutional social media, and telemedicine screening and consent procedures. Protocol changes included reducing the frequency of in-person visits, leveraging clinical care visits to collect biospecimens, expanded self-collection of samples at home, and making study materials available online. Results: Remote methods, including targeted social media posts, mailed letters, and email, combined with in-clinic recruitment with modifications for social distancing led to successful recruitment at all sites. Rates of consent have been similar across recruitment sites, with the highest rates of enrollment of mother-infant dyads realized by sites that implemented multiple recruitment strategies. Conclusions: Study procedures that prioritize health and safety measures such as social distancing, study participant convenience, and use diverse recruitment strategies enable successful enrollment of pregnant women and their newborns into clinical research while adhering to public health restrictions during a global pandemic.
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Although childhood asthma is in part an airway epithelial disorder, the development of the airway epithelium in asthma is not understood. We sought to characterize airway epithelial developmental phenotypes in those with and without recurrent wheeze and the impact of infant infection with respiratory syncytial virus (RSV). Nasal airway epithelial cells (NAECs) were collected at age 2-3 years from an a priori designed nested birth cohort of children from four mutually exclusive groups of wheezers/non-wheezers and RSV-infected/uninfected in the first year of life. NAECs were cultured in air-liquid interface differentiation conditions followed by a combined analysis of single cell RNA sequencing (scRNA-seq) and in vitro infection with respiratory syncytial virus (RSV). NAECs from children with a wheeze phenotype were characterized by abnormal differentiation and basal cell activation of developmental pathways, plasticity in precursor differentiation and a delayed onset of maturation. NAECs from children with wheeze also had increased diversity of currently known RSV receptors and blunted anti-viral immune responses to in vitro infection. The most dramatic changes in differentiation of cultured epithelium were observed in NAECs derived from children that had both wheeze and RSV in the first year of life. Together this suggests that airway epithelium in children with wheeze is developmentally reprogrammed and characterized by increased barrier permeability, decreased antiviral response, and increased RSV receptors, which may predispose to and amplify the effects of RSV infection in infancy and susceptibility to other asthma risk factors that interact with the airway mucosa. SUMMARY: Nasal airway epithelial cells from children with wheeze are characterized by altered development and increased susceptibility to RSV infection.
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Background: Electronic health records (EHR) are increasingly used for studying multimorbidities. However, concerns about accuracy, completeness, and EHRs being primarily designed for billing and administrative purposes raise questions about the consistency and reproducibility of EHR-based multimorbidity research. Methods: Utilizing phecodes to represent the disease phenome, we analyzed pairwise comorbidity strengths using a dual logistic regression approach and constructed multimorbidity as an undirected weighted graph. We assessed the consistency of the multimorbidity networks within and between two major EHR systems at local (nodes and edges), meso (neighboring patterns), and global (network statistics) scales. We present case studies to identify disease clusters and uncover clinically interpretable disease relationships. We provide an interactive web tool and a knowledge base combining data from multiple sources for online multimorbidity analysis. Findings: Analyzing data from 500,000 patients across Vanderbilt University Medical Center and Mass General Brigham health systems, we observed a strong correlation in disease frequencies (Kendall's τ = 0.643) and comorbidity strengths (Pearson ρ = 0.79). Consistent network statistics across EHRs suggest similar structures of multimorbidity networks at various scales. Comorbidity strengths and similarities of multimorbidity connection patterns align with the disease genetic correlations. Graph-theoretic analyses revealed a consistent core-periphery structure, implying efficient network clustering through threshold graph construction. Using hydronephrosis as a case study, we demonstrated the network's ability to uncover clinically relevant disease relationships and provide novel insights. Interpretation: Our findings demonstrate the robustness of large-scale EHR data for studying phenome-wide multimorbidities. The alignment of multimorbidity patterns with genetic data suggests the potential utility for uncovering shared biology of diseases. The consistent core-periphery structure offers analytical insights to discover complex disease interactions. This work also sets the stage for advanced disease modeling, with implications for precision medicine. Funding: VUMC Biostatistics Development Award, the National Institutes of Health, and the VA CSRD.
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A large body of research has established a relation between maternal education and children's neurocognitive functions, such as executive function and language. However, most studies have focused on early childhood and relatively few studies have examined associations with changes in maternal education over time. Consequently, it remains unclear if early maternal education is longitudinally related to neurocognitive functions in children, adolescents, and young adults. In addition, the associations between changes in maternal education across development and more broadly defined neurocognitive outcomes remain relatively untested. The current study leveraged a large multicohort sample to examine the longitudinal relations between perinatal maternal education and changes in maternal education during development with children's, adolescents', and young adults' neurocognitive functions (N = 2,688; Mage = 10.32 years; SDage = 4.26; range = 3-20 years). Moreover, we examined the differential effects of perinatal maternal education and changes in maternal education across development on executive function and language performance. Perinatal maternal education was positively associated with children's later overall neurocognitive function. This longitudinal relation was stronger for language than executive function. In addition, increases in maternal education were related to improved language performance but were not associated with executive functioning performance. Our findings support perinatal maternal education as an important predictor of neurocognitive outcomes later in development. Moreover, our results suggest that examining how maternal education changes across development can provide important insights that can help inform policies and interventions designed to foster neurocognitive development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Desenvolvimento Infantil , Escolaridade , Função Executiva , Mães , Humanos , Feminino , Criança , Função Executiva/fisiologia , Masculino , Pré-Escolar , Adolescente , Estudos Longitudinais , Desenvolvimento Infantil/fisiologia , Adulto Jovem , Mães/psicologia , Adulto , Cognição/fisiologia , Desenvolvimento da LinguagemRESUMO
Importance: Exposure to outdoor air pollution contributes to childhood asthma development, but many studies lack the geographic, racial and ethnic, and socioeconomic diversity to evaluate susceptibility by individual-level and community-level contextual factors. Objective: To examine early life exposure to fine particulate matter (PM2.5) and nitrogen oxide (NO2) air pollution and asthma risk by early and middle childhood, and whether individual and community-level characteristics modify associations between air pollution exposure and asthma. Design, Setting, and Participants: This cohort study included children enrolled in cohorts participating in the Children's Respiratory and Environmental Workgroup consortium. The birth cohorts were located throughout the US, recruited between 1987 and 2007, and followed up through age 11 years. The survival analysis was adjusted for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, neighborhood characteristics, and cohort. Statistical analysis was performed from February 2022 to December 2023. Exposure: Early-life exposures to PM2.5 and NO2 according to participants' birth address. Main Outcomes and Measures: Caregiver report of physician-diagnosed asthma through early (age 4 years) and middle (age 11 years) childhood. Results: Among 5279 children included, 1659 (31.4%) were Black, 835 (15.8%) were Hispanic, 2555 (48.4%) where White, and 229 (4.3%) were other race or ethnicity; 2721 (51.5%) were male and 2596 (49.2%) were female; 1305 children (24.7%) had asthma by 11 years of age and 954 (18.1%) had asthma by 4 years of age. Mean values of pollutants over the first 3 years of life were associated with asthma incidence. A 1 IQR increase in NO2 (6.1 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.25 [95% CI, 1.03-1.52]) and children younger than 11 years (HR, 1.22 [95% CI, 1.04-1.44]). A 1 IQR increase in PM2.5 (3.4 µg/m3) was associated with increased asthma incidence among children younger than 5 years (HR, 1.31 [95% CI, 1.04-1.66]) and children younger than 11 years (OR, 1.23 [95% CI, 1.01-1.50]). Associations of PM2.5 or NO2 with asthma were increased when mothers had less than a high school diploma, among Black children, in communities with fewer child opportunities, and in census tracts with higher percentage Black population and population density; for example, there was a significantly higher association between PM2.5 and asthma incidence by younger than 5 years of age in Black children (HR, 1.60 [95% CI, 1.15-2.22]) compared with White children (HR, 1.17 [95% CI, 0.90-1.52]). Conclusions and Relevance: In this cohort study, early life air pollution was associated with increased asthma incidence by early and middle childhood, with higher risk among minoritized families living in urban communities characterized by fewer opportunities and resources and multiple environmental coexposures. Reducing asthma risk in the US requires air pollution regulation and reduction combined with greater environmental, educational, and health equity at the community level.
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Poluição do Ar , Asma , Criança , Gravidez , Feminino , Masculino , Humanos , Pré-Escolar , Incidência , Estudos de Coortes , Dióxido de Nitrogênio , Asma/epidemiologia , Asma/etiologia , Poluição do Ar/efeitos adversos , Material Particulado/efeitos adversosRESUMO
BACKGROUND: Methods to determine whether a toddler is likely to develop asthma are of value to parents and clinical trialists testing primary prevention strategies. The Pediatric Asthma Risk Score (PARS) is a 14-point score of six factors designed to predict asthma in early life. PARS was developed and validated in relatively homogenous populations, so its generalizability is unknown. METHODS: We computed PARS using the six factors of self-declared race (parent-reported as "Black" or "not Black"), parental asthma, eczema, any wheezing, wheezing without a cold, and polysensitization in 5634 children from birth to 3 years of age. The primary outcome of our analysis was the ability of PARS to predict asthma development at 5 to 10 years of age using the area under the receiver operating curve in each cohort and across all cohorts with varying ethnicity, sex, cohort type, birth decades, missing PARS factors, and polysensitization definition. We also performed a meta-analysis across all the cohorts. Finally, we compared PARS predictive ability with the binary Asthma Predictive Index (API). RESULTS: Across 10 cohorts, the area under the receiver operating curve for PARS was 0.76. PARS performance did not differ by ethnicity, sex, cohort type, enrollment decade, missing PARS factors, or polysensitization definition (all P>0.05). The weights of each factor in the meta-analysis were similar to the original PARS weights. PARS and API equally identified children at high risk for developing asthma or not; API missed 31% of children at moderate asthma risk. CONCLUSIONS: PARS provided robust estimates of asthma risk in children from a wide range of ethnicities, backgrounds, and susceptibility. (Funded by the National Institute of Allergy and Infectious Diseases and others.)