BACKGROUND:Early childhood wheeze is characterized by heterogeneous trajectories having differential associations with later-life asthma development. OBJECTIVE:We sought to determine how early-life wheeze trajectories impact later life asthma gene expression. METHODS:The Children's Respiratory Environmental Workgroup is a collective of 12 birth cohorts, 7 of which conducted an additional visit with a nasal lavage collected and subjected to bulk RNA-sequencing. Early-life wheeze trajectories were defined using latent class analysis of longitudinal early-life wheezing data. Weighted gene correlation network analysis was used to associate gene expression patterns and current asthma with early-life wheeze trajectories. RESULTS:We investigated 743 children (mean age, 17 ± 5.1 years; 360 [48.5%] male). Four patterns of early-life wheeze were identified: infrequent, transient, late-onset, and persistent. Early-life transient wheeze was associated with gene expression patterns related to increased antiviral response, and late-onset wheeze was associated with decreased insulin signaling and glucose metabolism. Early-life persistent wheeze was associated with gene expression modules of type 2 inflammation and epithelial development, but these modules did not distinguish those with current asthma. Children who had persistent wheeze in early life and current asthma displayed a unique increase in expression of genes enriched for neuronal processes and ciliated epithelial function compared with those without asthma. CONCLUSIONS:Early-life longitudinal wheeze trajectories are associated with specific asthma transcriptomes later in life. These data suggest that early-life asthma prevention strategies may be most beneficial when tailored to the specific wheeze pattern.

Rationale: Race-based estimates of pulmonary function in children could influence the evaluation of asthma in children from racial and ethnic minoritized backgrounds. Objectives: To determine if race-neutral (Global Lung Function Initiative [GLI]-Global) versus race-specific (GLI-Race-Specific) reference equations differentially impact spirometry evaluation of childhood asthma. Methods: The analysis included 8,719 children aged 5 to <12 years from 27 cohorts across the United States grouped by parent-reported race and ethnicity. We analyzed how the equations affected FEV1, FVC, and FEV1/FVC z-scores. We used multivariable logistic models to evaluate associations between z-scores calculated with different equations and asthma diagnosis, emergency department visits, and hospitalization. Measurements and Main Results: For Black children, the GLI-Global versus GLI-Race-Specific equations estimated significantly lower z-scores for FEV1 and FVC but similar values for FEV1/FVC, thus increasing the proportion of children classified with low FEV1 by 14%. Although both equations yielded strong inverse relationships between FEV1 and FEV1/FVC z-scores and asthma outcomes, these relationships varied across racial and ethnic groups (P < 0.05). For any given FEV1 or FEV1/FVC z-score, asthma diagnosis and emergency department visits were higher among Black and Hispanic than among White children (P < 0.05). For FEV1, GLI-Global equations estimated asthma outcomes that were more uniform across racial and ethnic groups. Conclusions: Parent-reported race and ethnicity influenced relationships between lung function and asthma outcomes. Our data show no advantage to race-specific equations for evaluating childhood asthma, and the potential for race-specific equations to obscure lung impairment in disadvantaged children strongly supports using race-neutral equations.

BACKGROUND:Environmental exposures and social determinants likely influence specific childhood asthma phenotypes. OBJECTIVE:We hypothesized that the Child Opportunity Index (COI) at birth, measuring multiple neighborhood opportunities, influences incidence rates (IRs) for asthma with recurrent exacerbations (ARE). METHODS:We tested for COI associations with ARE IRs in 15,877 children born between 1990 and 2018 in the ECHO (Environmental Influences on Child Health Outcomes) program. Parent-reported race and ethnicity and other demographics were assessed as effect modifiers. RESULTS:The IRs of ARE for children born in very low COI neighborhoods was higher (IR = 10.98; 95% CI: 9.71, 12.25) than for other COI categories. Rates for non-Hispanic Black (NHB) children were significantly higher than non-Hispanic White children in every COI category. The ARE IRs for children born in very low COI neighborhoods were several-fold higher for NHB and Hispanic Black children (IR = 15.30; 95% CI: 13.10, 17.49; and IR = 18.48; 95% CI: 8.80, 28.15, respectively) when compared to White children. Adjusting for individual-level characteristics, children born in very low COI neighborhoods demonstrated an ARE IR ratio of 1.26 (95% CI: 0.99, 1.59) with a higher incidence of cases among children ages 2 to 4 years and with a parental history of asthma. CONCLUSIONS:Rates of ARE were higher among children born in under-resourced communities, and this relationship is strongest for young minoritized children with a parental history of asthma. Higher rates for NHB even in the highest COI categories suggest that risk associated with race persists regardless of social disadvantage.

BACKGROUND:Nocturnal cough affects approximately 1 in 3 children, can negatively affect child health, and is often attributable to asthma. The association of the gut microbiome with nocturnal cough has not been investigated. OBJECTIVE:We investigated the association between early-life gut microbiome composition and nocturnal cough overall and in the context of asthma. METHODS:Gut microbiota 1-month (neonate) and 6-month (infant) specimens from 512 children in the Wayne County, Health, Environment, Allergy, and Asthma Longitudinal Study were profiled using 16S ribosomal RNA V4 sequencing. Nocturnal cough (parental report) and asthma (parent-reported doctor's diagnosis) were assessed at age 4 years. Microbiome regression-based kernel association tests (MiRKAT) were used to assess the relationship between gut microbiota composition and nocturnal cough overall and in the context of asthma. Operational taxonomic unit (OTU) associations were conducted using negative binomial regression, adjusting for multiple comparisons using the false discovery rate. RESULTS:Stool microbial composition differences during infancy were associated with nocturnal cough (weighted UniFrac P = .045); 78 OTUs were significantly associated with nocturnal cough overall (false discovery rate < 0.05); and 110 OTUs were significantly associated with nocturnal cough and differed by asthma status (interaction false discovery rate < 0.05), with a predominance of Lachnospiraceae genera Blautia and Dorea. Thirty-two OTU were identified as having both overall effects and differences by asthma status. Among OTUs with significant nocturnal cough-by-asthma interactions, 84 retained significance in children with asthma, with 45 exclusive to those with asthma (predominance of Bacteroidaceae genus Bacteroides and Lachnospiraceae genus Dorea). CONCLUSION:Infantile gut microbiome development is associated with nocturnal cough and differed by asthma status by age 4 years. Further studies are needed to determine if the gut microbiome may provide additional information for the early identification of children at risk for nocturnal cough, with and without asthma.

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.

Atopic conditions are common and represent a substantial healthcare burden. Investigation of cord blood IgE as a predictor of future atopic disease has yielded varying results. We aimed to investigate these associations in a racially diverse population through our Wayne County Health, Environment and Allergy Longitudinal (WHEALS) population-based birth cohort.

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.

Early life gut microbiome composition has been correlated with childhood obesity, though microbial functional contributions to disease origins remain unclear. Here, using an infant birth cohort (n = 349) we identify a distinct fecal microbiota composition in 1-month-old infants with the lowest rate of exclusive breastfeeding, that relates with higher relative risk for obesity and overweight phenotypes at two years. Higher-risk infant fecal microbiomes exhibited accelerated taxonomic and functional maturation and broad-ranging metabolic reprogramming, including reduced concentrations of neuro-endocrine signals. In vitro, exposure of enterocytes to fecal extracts from higher-risk infants led to upregulation of genes associated with obesity and with expansion of nutrient sensing enteroendocrine progenitor cells. Fecal extracts from higher-risk infants also promoted enterocyte barrier dysfunction. These data implicate dysregulation of infant microbiome functional development, and more specifically promotion of enteroendocrine signaling and epithelial barrier impairment in the early-life developmental origins of childhood obesity.

BACKGROUND:Descriptive epidemiological data on incidence rates (IRs) of asthma with recurrent exacerbations (ARE) are sparse. OBJECTIVES:This study hypothesized that IRs for ARE would vary by time, geography, age, and race and ethnicity, irrespective of parental asthma history. METHODS:The investigators leveraged data from 17,246 children born after 1990 enrolled in 59 US with 1 Puerto Rican cohort in the Environmental Influences on Child Health Outcomes (ECHO) consortium to estimate IRs for ARE. RESULTS:The overall crude IR for ARE was 6.07 per 1000 person-years (95% CI: 5.63-6.51) and was highest for children aged 2-4 years, for Hispanic Black and non-Hispanic Black children, and for those with a parental history of asthma. ARE IRs were higher for 2- to 4-year-olds in each race and ethnicity category and for both sexes. Multivariable analysis confirmed higher adjusted ARE IRs (aIRRs) for children born 2000-2009 compared with those born 1990-1999 and 2010-2017, 2-4 versus 10-19 years old (aIRR = 15.36; 95% CI: 12.09-19.52), and for males versus females (aIRR = 1.34; 95% CI 1.16-1.55). Black children (non-Hispanic and Hispanic) had higher rates than non-Hispanic White children (aIRR = 2.51; 95% CI 2.10-2.99; and aIRR = 2.04; 95% CI: 1.22-3.39, respectively). Children born in the Midwest, Northeast and South had higher rates than those born in the West (P < .01 for each comparison). Children with a parental history of asthma had rates nearly 3 times higher than those without such history (aIRR = 2.90; 95% CI: 2.43-3.46). CONCLUSIONS:Factors associated with time, geography, age, race and ethnicity, sex, and parental history appear to influence the inception of ARE among children and adolescents.

IntroductionDelivery via caesarean section (C-section) has been associated with an increased risk of childhood chronic diseases such as obesity and asthma, which may be due to underlying systemic inflammation. However, the impact of specific C-section types may be differential, as emergency C-sections typically involve partial labor and/or membrane rupture. Our objectives were to determine if mode of delivery associates with longitudinal profiles of high sensitivity CRP (hs-CRP) -a marker of systemic inflammation-from birth through preadolescence, and to examine if CRP mediates the association between mode of delivery and preadolescent body mass index (BMI).MethodsData from the WHEALS birth cohort (N = 1,258) were analyzed; 564 of the 1,258 children in the cohort had data available for analysis. Longitudinal plasma samples (birth through 10-years of age) from 564 children from were assayed for hs-CRP levels. Maternal medical records were abstracted to obtain mode of delivery. Growth mixture models (GMMs) were used to determine classes of hs-CRP trajectories. Poisson regression with robust error variance was used to calculate risk ratios (RRs).ResultsTwo hs-CRP trajectory classes were identified: class 1 (76% of children) was characterized by low hs-CRP, while class 2 (24% of children) was characterized by high and steadily increasing hs-CRP. In multivariable models, children delivered via planned C-section had 1.15 times higher risk of being in hs-CRP class 2, compared to vaginal deliveries (p = 0.028), while no association was found for unplanned C-section deliveries [RR (95% CI) = 0.96 (0.84, 1.09); p = 0.49]. Further, the effect of planned C-section on BMI z-score at age 10 was significantly mediated by hs-CRP class (percent mediated = 43.4%).ConclusionsThese findings suggest potentially beneficial effects of experiencing partial or full labor, leading to a lower trajectory of systemic inflammation throughout childhood and decreased BMI during preadolescence. These findings may have implications for chronic disease development later in life.

To the Editor, Pediatric atopic dermatitis (AD) is a chronic, pruritic, inflammatory skin disorder that affects up to 20% of children worldwide.1 Often the earliest sign of atopy, AD has been recognized as the start of the “atopic march,” described as the progression of AD to allergic respiratory diseases (ARD) including asthma and allergic rhinitis.2 Although these atopic conditions often share a common T2enriched pathway influenced by both genetic and environmental factors, not all children with AD have subsequent risk of ARD. Additionally, recent investigations dispute the theory that the temporal progression of the atopic march occurs in a sequential pattern.3 Early AD can facilitate allergen sensitization due to a dysfunctional skin barrier.4 Both aeroallergen and food sensitization have been associated with risk of ARD,5 but it is less clear whether AD may partially mediate that risk. Additionally, food allergy has been recognized to be part of the atopic march; however, its role in the march to ARD is less wellidentified. It is also unclear how these risks may appear in ethnically diverse populations. Distinct atopic phenotypes may better predict risk of ARD. Our objective was to identify whether associations between early food sensitization, aeroallergen sensitization, or food allergy (FA) and the subsequent risk of ARD by age 10 were modified by the development of early AD by age 2 years. We analyzed data from our racially and socioeconomically diverse birth cohort, Wayne County Health, Environment, Allergy, and Asthma Longitudinal Study (WHEALS) that enrolled pregnant women 21– 45 years of age and their offspring. Recruitment period was from September 2003 to December 2007. Eligibility and recruitment are described in previous publications,6 and all study protocols were approved by the Henry Ford Health System Institutional Review Board. Offspring sensitization to aeroallergens (Alternaria, cat, cockroach, dog, Dermatophagoides farina, ragweed, timothy grass), milk, egg, or peanut was determined at 2 years of age by sIgE ≥ 0.35 IU/ mL and skin prick testing (SPT; wheal size ≥3 mm larger than the saline control defined a positive test). As sensitization does not always translate to clinical allergy, we also formed an algorithm to determine those most likely to have true IgEmediated food allergy.7 Two allergists reviewed subjects with at least one of the following criteria: (1) at least one food (milk, egg, or peanut) with sIgE ≥ 0.35 IU/mL; (2) a positive SPT; or (3) parental report of infant symptoms potentially related to food allergy plus at least one sIgE > 0.10 IU/mL. To standardize classifying infants to the presence of IgEmediated food allergy (IgEFA), physicians were asked to combine professional experience with investigatordeveloped protocols based on the Guidelines for the Diagnosis and Management of Food Allergy in the United States.8 A third allergist independently reviewed and ruled on discordant decisions. Data on asthma and AR by age 10 diagnosed by the study physician were collected using clinical history, physical examination, spirometry, and methacholine test. Adjusted relative risk (aRR) was calculated using Poisson regression with robust error variance and following adjustment for sex, child's race, parental history of asthma, parental history of AR, BMI zscore at age 2, delivery mode, 1month breastfeeding status,

INTRODUCTION:Prenatal and early-life dog exposure has been linked to reduced childhood allergy and asthma. A potential mechanism includes altered early immune development in response to changes in the gut microbiome among dog-exposed infants. We thus sought to determine whether infants born into homes with indoor dog(s) exhibit altered gut microbiome development.METHODS:Pregnant women living in homes with dogs or in pet-free homes were recruited in southeast Michigan. Infant stool samples were collected at intervals between 1 week and 18 months after birth and microbiome was assessed using 16S ribosomal sequencing. Perinatal maternal vaginal/rectal swabs and stool samples were sequenced from a limited number of mothers. Mixed effect adjusted models were used to assess stool microbial community trajectories comparing infants from dog-keeping versus pet-free homes with adjustment for relevant covariates.RESULTS:Infant gut microbial composition among vaginally born babies became less similar to the maternal vaginal/rectal microbiota and more similar to the maternal gut microbiota with age-related accumulation of bacterial species with advancing age. Stool samples from dog-exposed infants were microbially more diverse (p = .041) through age 18 months with enhanced diversity most apparent between 3 and 6 months of age. Statistically significant effects of dog exposure on β-diversity metrics were restricted to formula-fed children. Across the sample collection period, dog exposure was associated with Fusobacterium genera enrichment, as well as enrichment of Collinsella, Ruminococcus, Clostridaceae and Lachnospiraceae OTUs.CONCLUSION:Prenatal/early-life dog exposure is associated with an altered gut microbiome during infancy and supports a potential mechanism explaining lessened atopy and asthma risk. Further research directly linking specific dog-attributable changes in the infant gut microbiome to the risk of allergic disorders is needed.

ABSTRACT Combining and comparing microbiome data from distinct infant cohorts has been challenging because such data are inherently multidimensional and complex. Here, we used an ensemble of machine-learning (ML) models and studied 16S rRNA amplicon sequencing data from 4,099 gut microbiome samples representing 12 prospectively collected infant cohorts. We chose the childbirth delivery mode as a starting point for such analysis because it has previously been associated with alterations in the gut microbiome in infants. In cross-study ensemble models, Bacteroides was the most important feature in all machine-learning models. The predictive capacity by taxonomy varied with age. At the age of 1–2 months, gut microbiome data were able to predict delivery mode with an area under the curve of 0.72 to 0.83. In contrast, ML models trained on taxa were not able to differentiate between the modes of delivery, in any of the cohorts, when the infants were between 3 and 12 months of age. Moreover, no ML model, alternately trained on the functional pathways of the infant gut microbiome, could consistently predict mode of delivery at any infant age. This study shows that infant gut microbiome data sets can be effectively combined with the application of ML analysis across different study populations. IMPORTANCE There are challenges in merging microbiome data from diverse research groups due to the intricate and multifaceted nature of such data. To address this, we utilized a combination of machine-learning (ML) models to analyze 16S sequencing data from a substantial set of gut microbiome samples, sourced from 12 distinct infant cohorts that were gathered prospectively. Our initial focus was on the mode of delivery due to its prior association with changes in infant gut microbiomes. Through ML analysis, we demonstrated the effective merging and comparison of various gut microbiome data sets, facilitating the identification of robust microbiome biomarkers applicable across varied study populations.

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.)

High-quality evidence from prospective longitudinal studies in humans is essential to testing hypotheses related to the developmental origins of health and disease. In this paper, the authors draw upon their own experiences leading birth cohorts with longitudinal follow-up into adulthood to describe specific challenges and lessons learned. Challenges are substantial and grow over time. Long-term funding is essential for study operations and critical to retaining study staff, who develop relationships with participants and hold important institutional knowledge and technical skill sets. To maintain contact, we recommend that cohorts apply multiple strategies for tracking and obtain as much high-quality contact information as possible before the child's 18(th) birthday. To maximize engagement, we suggest that cohorts offer flexibility in visit timing, length, location, frequency, and type. Data collection may entail multiple modalities, even at a single collection timepoint, including measures that are self-reported, research-measured, and administrative with a mix of remote and in-person collection. Many topics highly relevant for adolescent and young adult health and well-being are considered to be private in nature, and their assessment requires sensitivity. To motivate ongoing participation, cohorts must work to understand participant barriers and motivators, share scientific findings, and provide appropriate compensation for participation. It is essential for cohorts to strive for broad representation including individuals from higher risk populations, not only among the participants but also the staff. Successful longitudinal follow-up of a study population ultimately requires flexibility, adaptability, appropriate incentives, and opportunities for feedback from participants.

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.