Importance:Atopic dermatitis (AD) is the most common inflammatory disease in childhood, and children with AD are more likely to develop other allergic diseases, including food allergy, allergic rhinitis, and asthma. Objective:To determine the phenotypes of AD expression across 12 US birth cohorts and identify factors associated with phenotype and development of allergic diseases. Design, Setting, and Participants:This cohort study compiled longitudinal data from 12 observational US birth cohorts across decades (children born from April 1980 to June 2019) in the Environmental Influences on Child Health Outcomes (ECHO) Children's Respiratory and Environmental Workgroup with follow-up to September 2022. Participants were enrolled prenatally; children with 3 or more AD assessments across the first 84 months of life were included in analyses. Data were analyzed from December 2020 to April 2024. Exposures:Exposures included decade of birth, cohort type (population-based or high-risk), family history of asthma (mother, father, or sibling), birth order, gestational age at birth, delivery mode, breastfeeding, pet exposure, antibiotic use, environmental tobacco smoke exposure, allergic sensitization, peripheral blood eosinophil count, and total IgE. Main Outcomes and Measures:Primary outcomes were AD phenotype, food allergy, allergic rhinitis, asthma, and wheeze. Longitudinal latent class analysis was used to identify underlying longitudinal patterns of AD expression, and associations of AD phenotype with allergic outcomes were examined using logistic regression, multinomial logistic regression, and linear regression. Results:In 5314 children from 9 cohorts (1896 born in the 2000s [35.7%]; 2585 female [48.6%]; 1083 Black or African American [20.4%]; 3344 White [62.9%]; 350 other reported race [6.6%; including 8 American Indian or Alaska Native (0.2%); 58 Asian (1.1%); 4 Native Hawaiian or Pacific Islander (0.1%) and 280 multiracial or with any race not otherwise specified (5.3%)]), 3382 (63.6%) were from a population-based cohort, while 1932 (36.4%) were from a high-risk cohort. AD prevalence ranged from 24.1% (540 children) to 28.4% (1156 children) at each time point, and 5 phenotypes of AD were identified: transient early AD, early AD with potential reoccurrence, late-onset AD, persistent AD, and minimal or no AD. Compared with White children, Black children were at higher risk for AD (transient early AD: aOR, 3.26; 95% CI, 2.06-5.18; early AD with potential reoccurrence: aOR, 3.72; 95% CI, 2.35-5.90; persistent AD: aOR, 2.01; 95% CI, 1.54-2.63), as were children with other reported race (transient early AD: aOR, 2.31; 95% CI, 1.13-4.70; early AD with potential reoccurrence: aOR, 3.27; 95% CI, 1.73-6.18). Female children were significantly less likely to have early AD with potential reoccurrence (aOR, 0.45; 95% CI, 0.27-0.74) and persistent AD (aOR, 0.60; 95% CI, 0.49-0.74) than male children. Compared with miniml or no AD, phenotypes with early AD expression were associated with food allergy (transient early AD: adjusted odds ratio [aOR], 2.15; 95% CI, 1.48-3.08; early AD with potential reoccurrence: aOR, 2.43; 95% CI, 1.66-3.50; persistent AD: aOR, 2.26; 95% CI, 1.84-2.78), later AD expression was associated with allergic rhinitis (late-onset AD: aOR, 1.84; 95% CI, 1.38-2.43; persistent AD: aOR, 2.02; 95% CI, 1.64-2.48), and any AD disease was associated with asthma. Conclusions and Relevance:In this birth cohort study of 5314 children, timing of AD expression was associated with increased risk for atopic march pathways. Identifying risk factors for AD phenotypes may inform targeted therapeutic prevention strategies.

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.

We previously reported that asthma prevalence was higher in the United States (US) compared to Mexico (MX) (25.8% vs. 8.4%). This investigation assessed differences in microbial dust composition in relation to demographic and housing characteristics on both sides of the US-MX Border. Forty homes were recruited in the US and MX. Home visits collected floor dust and documented occupants' demographics, asthma prevalence, housing structure, and use characteristics. US households were more likely to have inhabitants who reported asthma when compared with MX households (30% vs. 5%) and had significantly different flooring types. The percentage of households on paved roads, with flushing toilets, with piped water and with air conditioning was higher in the US, while dust load was higher in MX. Significant differences exist between countries in the microbial composition of the floor dust. Dust from Mexican homes was enriched with Alishewanella , Paracoccus, Rheinheimera genera and Intrasporangiaceae family. A predictive metagenomics analysis identified 68 significantly differentially abundant functional pathways between US and MX. This study documented multiple structural, environmental, and demographic differences between homes in the US and MX that may contribute to significantly different microbial composition of dust observed in these two countries.

Rationale: Identifying the root causes of racial disparities in childhood asthma is critical for health equity. Objectives: To determine whether the racist policy of redlining in the 1930s 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 the birth address of participants from the Children's Respiratory and Environmental Workgroup birth cohort consortium into categories A, B, C, and D as defined by the Home Owners Loan Corporation, with D being the highest perceived risk. Surrogates of presentday neighborhood-level SEP were determined for each tract, including the percentage of low-income households, the CDC's Social Vulnerability Index, 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 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 Home Owners Loan Corporation grade of D. In mediation analyses, residing in Grade-D tracts (adjusted odds ratio =1.03 [95% confidence interval =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 the Social Vulnerability Index 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.

Maternal-to-fetal transmission of respiratory syncytial virus (RSV) has been shown to occur but whether late prenatal exposure to RSV season influences offspring postnatal RSV-lower respiratory illness (LRI) risk in early life or RSV immune status at birth is unclear. In this study, the duration of third trimester RSV season exposure was determined for 1,094 newborns of the Tucson Children's Respiratory Study (TCRS) and found to show an inverse relation to risk for first RSV-LRI in the first year. Cord blood anti-RSV antibody is related to third trimester RSV season exposure but not to first year RSV-LRI risk. In a separate birth cohort (the Infant Immune Study), supernatants from cord blood mononuclear cells stimulated with the recall antigen, UV-inactivated RSV, were assayed for IFN-gamma and IL-4. The frequency of detectable IFN-gamma (but not IL-4) was increased for those with at least 2 mo of third trimester RSV season exposure, suggestive of a fetal immune response to RSV. IMPORTANCE Our study found that duration of third trimester exposure to RSV season related inversely to subsequent risk of postnatal RSV-LRI in the first year, thus implicating this exposure as an important factor in reducing risk of postnatal RSV-LRIs, a risk reduction that appears to be independent of maternally transferred anti-RSV antibody level. The increase in frequency of detectable IFN-gamma and not IL-4 in response to UV-inactivated RSV in cord blood immune cells for infants with greater third trimester exposure to RSV season is suggestive of a Type-1 immune response to RSV occurring in utero.

Rationale: CC16 is an anti-inflammatory protein highly expressed in the airways. CC16 deficiency has been associated with lung function deficits, but its role in asthma has not been established conclusively. Objectives: To determine 1) the longitudinal association of circulating CC16 with the presence of active asthma from early childhood through adult life and 2) whether CC16 in early childhood predicts the clinical course of childhood asthma into adult life. Methods: We assessed the association of circulating CC16 and asthma in three population-based birth cohorts: TCRS (years 6-36; N-participants=814, N-observations=3042), BAMSE (years 8-24; Ns=2547, 3438), and MAAS (years 5-18, Ns=745, 1626). Among 233 children who had asthma at the first survey in any of the cohorts, baseline CC16 was also tested for association with persistence of symptoms. Measurements and Main Results: 1) After adjusting for covariates, CC16 deficits were associated with increased risk for the presence of asthma in all cohorts (meta-analyzed adjOR per 1-SD CC16 decrease: 1.20[95%CI 1.12-1.28];P<0.0001). The association was particularly strong for asthma with frequent symptoms (meta-analyzed adjRRR: 1.40[1.24-1.57];P<0.0001), was confirmed for both atopic and non-atopic asthma, and was independent of lung function impairment. 2) After adjustment for known predictors of persistent asthma, asthmatic children in the lowest CC16 tertile had a nearly 4-fold increased risk for having frequent symptoms persisting into adult life, compared with asthmatic children in the other two CC16 tertiles (meta-analyzed adjOR: 3.72[1.78-7.76];P<0.0001). Conclusions: Circulating CC16 deficits are associated with the presence of asthma with frequent symptoms from childhood through mid-adult life and predict the persistence of asthma symptoms into adulthood. These findings support a possible protective role of CC16 in asthma and its potential use for risk stratification.

Rationale: People with better early-life respiratory health may be more likely to work in occupations with high workplace exposures in adult life compared with people with poor respiratory health. This may manifest as a healthy worker effect bias, potentially confounding the analysis of environmental exposure studies. Objectives: To evaluate associations between lung function in adolescence and occupational exposures at initial adult employment. Methods: The TCRS (Tucson Children's Respiratory Study) is a long-term prospective study of respiratory health beginning at birth. Associations between respiratory function at age 11 years and occupational exposures at first job at age 26 years were evaluated with logistic regression. We calculated percentage predicted values for forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1:FVC ratio, and forced expiratory flow from 25% to 75% of vital capacity at age 11. At the 26-year visit, participants self-reported occupational exposures to dust, smoke, and fumes/gas at first job in a standardized interview. Results: Forced expiratory flow from 25% to 75% of vital capacity and FEV1:FVC ratio at age 11 were positively associated with dust workplace exposures at the first job. Each 10% increase in percentage predicted prebronchodilator FEV1:FVC ratio was associated with 30% higher odds of workplace dust exposure (odds ratio for a 1% increase, 1.03 [95% confidence interval, 1.00-1.06; P = 0.045]). Similar associations were observed for FEV1 and FVC with workplace smoke exposures. We also observed modification by time at job: associations were stronger for those who remained in their jobs longer than 12 months. In addition, those with better function at age 11 were more likely to stay in their jobs longer than 12 months if their first jobs involved exposure to dust. Conclusions: Childhood lung function affects initial career choice. This study supports the premise of the healthy worker effect.

Early prediction of asthma is critical to identify potential primary prevention strategies. The Pediatric Asthma Risk Score (PARS) is a continuous score to predict early-life asthma but was developed and validated in relatively homogenous populations. We compared PARS directly to the Asthma Predictive Index (API) and validated in 10 cohorts with varying race, ethnicity, sex, cohort type, missing data and birth decades, and perform a meta-analysis across all 10 cohorts. We utilized data from 5674 children participating in the Children's Respiratory and Environmental Workgroup. We applied both PARS and the API in each cohort, as well as harmonized across all cohorts, and directly compared the ability of each tool to predict asthma development at ages 5-10. The PARS area under the curve (AUC) was significantly higher than the AUC of the API in 9 cohorts (p-value range 0.01 - <0.001). The PARS AUC did not differ by cohort type (high risk or general population), decade of enrollment, race, sex, ethnicity, missing PARS factors or polysensitization definition (skin prick test vs. specific IgE). The weights of the 6 PARS factors in the meta-analysis were very similar to the original weights, validating the original PARS scoring. This multi-cohort study makes the PARS the most validated model of asthma prediction in children to date, not only with respect to the number of cohorts used but also with regards to capturing the diversity of asthma in the United States. Future studies may consider PARS the new gold standard in pediatric asthma risk prediction.

BackgroundMethods 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.MethodsWe 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).ResultsAcross 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.ConclusionsPARS 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.)

BACKGROUND:Asthma and obesity are major, interconnected public health challenges that usually have their origins in childhood, and for which the relationship is strengthened among those with insulin resistance. OBJECTIVE:To determine whether high insulin in early life confers increased longitudinal risk for asthma independent of body mass index. METHODS:The study used data from the Tucson Children's Respiratory Study (TCRS) and the Avon Longitudinal Study of Parents and Children (ALSPAC). Nonfasting insulin was measured in TCRS participants at age 6 years and fasting insulin in ALSPAC participants at age 8 years. Physician-diagnosed active asthma was determined at baseline and at subsequent assessments up to age 36 years in TCRS and 17 years in ALSPAC. RESULTS:In TCRS, high insulin (upper quartile) at age 6 years was associated with increased odds of having active asthma from ages 8 to 36 years compared with low insulin (odds ratio,1.98; 95% CI, 1.28-3.05; P = .002). Similarly, in ALSPAC, high insulin was associated with a significantly higher risk of active asthma from ages 11 to 17 years compared with low insulin (odds ratio, 1.59; 95% CI, 1.12-2.27; P = .009). These findings were independent of baseline body mass index in both cohorts, and were not related to other demographic and asthma risk factors nor other tested markers of systemic inflammation and metabolic syndrome. CONCLUSIONS:In 2 separate birth cohorts, higher blood insulin level in early childhood was associated with increased risk of active asthma through adolescence and adulthood, independent of body mass index. High insulin indicates a novel mechanism for asthma development, which may be a target for intervention.

IMPORTANCE In the United States, Black and Hispanic children have higher rates of asthma and asthma-related morbidity compared with White children and disproportionately reside in communities with economic deprivation. OBJECTIVE To determine the extent to which neighborhood-level socioeconomic indicators explain racial and ethnic disparities in childhood wheezing and asthma. DESIGN, SETTING, AND PARTICIPANTS The study population comprised children in birth cohorts located throughout the United States that are part of the Children's Respiratory and Environmental Workgroup consortium. Cox proportional hazard models were used to estimate hazard ratios (HRs} of asthma incidence, and logistic regression was used to estimate odds ratios of early and persistent wheeze prevalence accounting for mother's education, parental asthma, smoking during pregnancy, child's race and ethnicity, sex, and region and decade of birth. EXPOSURES Neighborhood-level socioeconomic indicators defined by US census tracts calculated as z scores for multiple tract-level variables relative to the US average linked to participants' birth record address and decade of birth. The parent or caregiver reported the child's race and ethnicity. MAIN OUTCOMES AND MEASURES Prevalence of early and persistent childhood wheeze and asthma incidence. RESULTS Of 5809 children, 46% reported wheezing before age 2 years, and 26% reported persistent wheeze through age 11 years. Asthma prevalence by age 11 years varied by cohort, with an overall median prevalence of 25%. Black children (HR, 1.47; 95% CI, 1.26-1.73) and Hispanic children (HR, 1.29; 95% CI, 1.09-1.53) were at significantly increased risk for asthma incidence compared with White children, with onset occurring earlier in childhood. Children born in tracts with a greater proportion of low-income households, population density, and poverty had increased asthma incidence. Results for early and persistent wheeze were similar. In effect modification analysis, census variables did not significantly modify the association between race and ethnicity and risk for asthma incidence; Black and Hispanic children remained at higher risk for asthma compared with White children across census tracts socioeconomic levels. CONCLUSIONS AND RELEVANCE Adjusting for individual-level characteristics, we observed neighborhood socioeconomic disparities in childhood wheeze and asthma. Black and Hispanic children had more asthma in neighborhoods of all income levels. Neighborhood- and individual-level characteristics and their root causes should be considered as sources of respiratory health inequities.

Background Spirometric restriction, defined as a reduced forced vital capacity (FVC) with a preserved FEV1/FVC ratio, is associated with increased respiratory and non-respiratory comorbidities and all-cause mortality in adulthood. Little is known about the early origins of this condition. We sought to identify early-life risk factors for spirometric restriction in adult life. Methods In this longitudinal, multicohort, population-based study, we used data from the Tucson Children's Respiratory Study (TCRS), which recruited 1246 healthy infants at birth between April 1980, and October 1984, in Tucson, AZ, USA. Questionnaires were answered by the primary caregiver at enrolment, immediately after the child's birth, and multiple follow-up questionnaires were completed through childhood and adulthood. At the age of 22, 26, 32, and 36 years, lung function was measured with spirometry. At each survey, three mutually exclusive spirometric patterns were defined: (1) normal (FEV1/FVC >= 10th percentile and FVC >= 10th percentile); (2) restrictive (FEV1/FVC >= 10th percentile and FVC <10th percentile); and (3) obstructive (FEV1/FVC <10th percentile, independent of FVC). Data on demographic features and parental health factors were collected from questionnaires; pregnancy and perinatal data (induding nutritional problems) and birth measurements were obtained from medical records; and weight, height, and body-mass index (BMI) during childhood (age 6-16 years) were measured by study nurses. The associations between early-life risk factors and spirometric patterns were assessed by inultivariate multinoinial logistic regression analysis, adjusted for survey year, sex, and race-ethnicity. Significant risk factors were further tested for replication in the Swedish Child (Barn), Allergy, Milieu, Stockholm, Epidemiological (BAMSE; n=1817; spirometry surveys were done at age 24 years) survey and the UK Manchester Asthma and Allergy Study (MAAS; n=411; spirometry surveys were done at age 18 years) birth cohorts, and fixed-effect ineta-analyses of relative risk ratios (RRRs) from inultinomial logistic regression models were done to generate a pooled estimate of the effect across the three cohorts. Measurements of body composition (MAAS; n=365) and total lung capacity (TCRS; n=173 and MAAS; n=407) were also available for a subset of participants. Findings Of 1246 healthy infants included in TCRS, for the present study we included data for 652 participants who had at least one set of spirometry data, contributing up to 1668 observations. In the TCRS cohort, results from the multivariate models showed that maternal nutritional problems during pregnancy (RRR 2.48 [95% CI 1.30-4.76]; p=0.0062), being born small for gestational age (birthweight <10th percentile; 3.26 [1.34-7.93]; p=0.0093), and being underweight in childhood (BMI-for-age <5th percentile; 3.54 [1.35-9-26]; p=0.010) were independent predictors of spirometric restriction in adult life. Associations between being small for gestational age (p=0.0028) and underweight in childhood (p<0.0001) with adult spirometric restriction were supported by the results of meta-analysis of data from all three cohorts. In the MAAS cohort, having a low lean BMI (ie, <10th percentile) at age 11 years predicted adult (age 18 years) spirometric restriction (RRR 3.66 [1-48-9.02]; p=0.0048). These associations of spirometric restriction with small for gestational age, childhood underweight, and low lean BMI in childhood were verified in participants with spirometric restriction who had diminished total lung capacity, indicating that these factors specifically increase the risk of lung restriction. Interpretation Poor growth and nutritional deficits in utero and throughout childhood precede and predict the development of spirometric restriction in adult life. Strategies to improve prenatal and childhood growth trajectories could help to prevent spirometric restriction and its associated morbidity and mortality burden. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

Background Asthma is the most common chronic disease in children, occurring at higher frequencies and with more severe disease in children with African ancestry. Methods We tested for association with haplotypes at the most replicated and significant childhood-onset asthma locus at 17q12-q21 and asthma in European American and African American children. Following this, we used whole-genome sequencing data from 1060 African American and 100 European American individuals to identify novel variants on a high-risk African American–specific haplotype. We characterized these variants in silico using gene expression and ATAC-seq data from airway epithelial cells, functional annotations from ENCODE, and promoter capture (pc)Hi-C maps in airway epithelial cells. Candidate causal variants were then assessed for correlation with asthma-associated phenotypes in African American children and adults. Results Our studies revealed nine novel African-specific common variants, enriched on a high-risk asthma haplotype, which regulated the expression of GSDMA in airway epithelial cells and were associated with features of severe asthma. Using ENCODE annotations, ATAC-seq, and pcHi-C, we narrowed the associations to two candidate causal variants that are associated with features of T2 low severe asthma. Conclusions Previously unknown genetic variation at the 17q12-21 childhood-onset asthma locus contributes to asthma severity in individuals with African ancestries. We suggest that many other population-specific variants that have not been discovered in GWAS contribute to the genetic risk for asthma and other common diseases.

Rationale: Birth cohort studies have identified several temporal patterns of wheezing, only some of which are associated with asthma. Whether 17q12-21 genetic variants, which are closely associated with asthma, are also associated with childhood wheezing phenotypes remains poorly explored. Objectives: To determine whether wheezing phenotypes, defined by latent class analysis (LCA), are associated with nine 17q12-21 SNPs and if so, whether these relationships differ by race/ancestry. Methods: Data from seven U.S. birth cohorts (n = 3,786) from the CREW (Children's Respiratory Research and Environment Workgroup) were harmonized to represent whether subjects wheezed in each year of life from birth until age 11 years. LCA was then performed to identify wheeze phenotypes. Genetic associations between SNPs and wheeze phenotypes were assessed separately in European American (EA) (n = 1,308) and, for the first time, in African American (AA) (n = 620) children. Measurements and Main Results: The LCA best supported four latent classes of wheeze: infrequent, transient, late-onset, and persistent. Odds of belonging to any of the three wheezing classes (vs. infrequent) increased with the risk alleles for multiple SNPs in EA children. Only one SNP, rs2305480, showed increased odds of belonging to any wheezing class in both AA and EA children. Conclusions: These results indicate that 17q12-21 is a "wheezing locus," and this association may reflect an early life susceptibility to respiratory virusescommon to all wheezing children. Which children will have their symptoms remit or reoccur during childhood may be independent of the influence of rs2305480.

Understanding place-based contributors to health requires geographically and culturally diverse study populations, but sharing location data is a significant challenge to multisite studies. Here, we describe a standardized and reproducible method to perform geospatial analyses for multisite studies. Using census tract-level information, we created software for geocoding and geospatial data linkage that was distributed to a consortium of birth cohorts located throughout the USA. Individual sites performed geospatial linkages and returned tract-level information for 8810 children to a central site for analyses. Our generalizable approach demonstrates the feasibility of geospatial analyses across study sites to promote collaborative translational research.