Pediatric Asthma Risk Research Articles

Causal effects of pediatric asthma on psychiatric disorders: a bidirectional Mendelian randomization study

Background Previous studies have suggested a potential link between pediatric asthma and psychiatric disorders. However, the causal relationship between pediatric asthma and psychiatric disorders is unclear. Therefore, we used Mendelian randomization to explore causal relationships between pediatric asthma and depression, anxiety disorders, and attention deficit and hyperactivity disorder (ADHD). Methods Genome-wide association studies (GWAS) meta-analyses with the largest possible sample size and independent individuals from European ancestry were selected. The genetic data for depression and anxiety are from FinnGen consortium, while the genetic data for ADHD is from the Psychiatric Genomics Consortium. Inverse variance weighted (IVW) was the main analysis method. The heterogeneity of the instrumental variables (IVs) was assessed using IVW, and the horizontal pleiotropy of the IVs was assessed using MR-Egger. Result The IVW results showed a significant causal relationship between pediatric asthma and depression (OR = 1.08, 95% CI = 1.02–1.15; p = 0.013). However, there is no evidence to suggest a causal relationship between pediatric asthma, anxiety, and ADHD. Reverse MR suggests a significant causal relationship (OR = 1.27, 95% CI [1.14–1.41], p = 9.64E − 06) between ADHD and pediatric asthma using the IVW method. Conclusions Our findings suggest a causal relationship between pediatric asthma and an increased risk of depression. Additionally, we found that ADHD is significantly associated with a higher risk of pediatric asthma.

Challenging unverified assumptions in causal claims: Do gas stoves increase risk of pediatric asthma?

The use of unverified models for risk estimates and policy recommendations can be highly misleading, as their predictions may not reflect real-world health impacts. For example, a recent article states that NO2 from gas stoves “likely causes ∼50,000 cases of current pediatric asthma from long-term NO2 exposure alone” annually in the United States. This explicitly causal claim, which is contrary to several methodology and review articles published in this journal, among others, reflects both (a) An unverified modeling assumption that pediatric asthma burden is approximately proportional to NO2; and (b) An unverified causal assumption that the assumed proportionality between exposure and response is causal. The article is devoid of any causal analysis showing that these assumptions are likely to be true. It does not show that reducing NO2 exposure from gas stoves would reduce pediatric asthma risk. Its key references report no significant associations – let alone causation – between NO2 and pediatric asthma. Thus, the underlying data suggests that the number of pediatric asthma cases caused by gas stoves in the United States is indistinguishable from zero. This highlights the need to rigorously validate modeling assumptions and causal claims in public health risk assessments to ensure scientifically sound foundations for policy decisions.

COVID-19 and Asthma Onset in Children.

Respiratory viral infections increase risk of asthma in infants and children. Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus can cause severe lung inflammation and prolonged respiratory symptoms. We sought to determine whether SARS-CoV-2 infection modified pediatric incident asthma risk. This retrospective cohort study examined children ages 1 to 16 within the Children's Hospital of Philadelphia Care Network who received polymerase chain reaction (PCR) testing for SARS-CoV-2 between March 1, 2020 and February 28, 2021. Multivariable Cox regression models assessed the hazard ratio of new asthma diagnosis between SARS-CoV-2 PCR positive and SARS-CoV-2 PCR negative groups within an 18-month observation window. Models were adjusted for demographic characteristics, socioeconomic variables, and atopic comorbidities. There were 27 423 subjects included in the study. In adjusted analyses, SARS-CoV-2 PCR positivity had no significant effect on the hazard of new asthma diagnosis (hazard ratio [HR]: 0.96; P = .79). Black race (HR: 1.49; P = .004), food allergies (HR: 1.26; P = .025), and allergic rhinitis (HR: 2.30; P < .001) significantly increased the hazard of new asthma diagnosis. Preterm birth (HR: 1.48; P = .005) and BMI (HR: 1.13; P < .001) significantly increased the hazard of new asthma diagnosis for children <5 years old. SARS-CoV-2 PCR positivity was not associated with new asthma diagnosis in children within the observation period, although known risk factors for pediatric asthma were confirmed. This study informs the prognosis and care of children with a history of SARS-CoV-2 infection.

Sphingolipid classes and the interrelationship with pediatric asthma and asthma risk factors.

While dysregulated sphingolipid metabolism has been associated with risk of childhood asthma, the specific sphingolipid classes and/or mechanisms driving this relationship remain unclear. We aimed to understand the multifaceted role between sphingolipids and other established asthma risk factors that complicate this relationship. We performed targeted LC-MS/MS-based quantification of 77 sphingolipids in plasma from 997 children aged 6 years from two independent cohorts (VDAART and COPSAC2010 ). We examined associations of circulatory sphingolipids with childhood asthma, lung function, and three asthma risk factors: functional SNPs in ORMDL3, low vitamin D levels, and reduced gut microbial maturity. Given racial differences between these cohorts, association analyses were performed separately and then meta-analyzed together. We observed elevations in circulatory sphingolipids with asthma phenotypes and risk factors; however, there were differential associations of sphingolipid classes with clinical outcomes and/or risk factors. While elevations from metabolites involved in ceramide recycling and catabolic pathways were associated with asthma and worse lung function [meta p-value range: 1.863E-04 to 2.24E-3], increased ceramide levels were associated with asthma risk factors [meta p-value range: 7.75E-5 to .013], but not asthma. Further investigation identified that some ceramides acted as mediators while some interacted with risk factors in the associations with asthma outcomes. This study demonstrates the differential role that sphingolipid subclasses may play in asthma and its risk factors. While overall elevations in sphingolipids appeared to be deleterious overall; elevations in ceramides were uniquely associated with increases in asthma risk factors only; while elevations in asthma phenotypes were associated with recycling sphingolipids. Modification of asthma risk factors may play an important role in regulating sphingolipid homeostasis via ceramides to affect asthma. Further function work may validate the observed associations.

Association between IL10 rs1800896 polymorphism and risk of pediatric asthma: A meta-analysis.

Asthma is a common chronic condition in children. Several studies have explored the potential association between IL10 rs1800896 polymorphism and the risk of asthma in children, but the findings have been inconsistent. To address these discrepancies, we conducted a systematic review and meta-analysis to assess the relationship between IL10 rs1800896 polymorphisms and the susceptibility to pediatric asthma. A literature search was conducted in PubMed, Scopus, Web of Science, and CNKI databases to identify eligible studies through April 2022. Meta-analysis was then performed using five genetic models: dominant, recessive, homozygous, heterozygous, and allele. A total of 12 studies comprising 1645 cases along with 1447 controls were included in this meta-analysis. It was found that rs1800896 was not associated significantly with susceptibility to childhood asthma in all genetic models investigated. Subgroup analysis based on the ethnic background of the subjects revealed that rs1800896 was significantly linked to a lower risk of pediatric asthma among Asians in the homozygous model (OR = 0.311, 95% CI = 0.152-0.637, P = 0.001) and in the recessive model (OR = 0.585, 95% CI = 0.405-0.846, P = 0.004), whereas no significant relationship was observed in Egyptians (P > 0.05). In conclusion, IL10 rs1800896 polymorphism may be useful as a predictive marker for childhood asthma in Asians, although further studies are needed to validate the study results.

A lifecourse Mendelian randomization study uncovers age-dependent effects of adiposity on asthma risk

Evaluating the long-term consequences of childhood lifestyle factors on asthma risk can be exceptionally challenging in epidemiology given that cases are typically diagnosed at various timepoints throughout the lifecourse. In this study, we used human genetic data to evaluate the effects of childhood and adulthood adiposity on risk of pediatric (n= 13,962 cases) and adult-onset asthma (n= 26,582 cases) with a common set of controls (n= 300,671) using a technique known as lifecourse Mendelian randomization. We found that childhood adiposity directly increases risk of pediatric asthma (OR= 1.20, 95% CI= 1.03-1.37, p=0.03), but limited evidence that it has an effect on adult-onset asthma after accounting for adiposity during adulthood (OR= 1.05, 95% CI= 0.93-1.17, p= 0.39). Conversely, there was strong evidence that adulthood adiposity increases asthma risk in midlife (OR= 1.37, 95% CI= 1.28-1.46, P= 7×10-12). These findings suggest that childhood and adulthood adiposity are independent risk factors for asthma at each of their corresponding timepoints in the lifecourse.

Application of Asthma Prediction Tools in a Cohort of Infants with Severe Bronchiolitis.

Background: Severe bronchiolitis is a strong childhood asthma risk factor. Early and accurate asthma prediction is key. We applied the Asthma Predictive Index (API), the modified Asthma Predictive Index (mAPI), and the Pediatric Asthma Risk Score (PARS) in a cohort of high-risk infants to predict asthma at age 6 years. Methods: We conducted a 17-center cohort of infants (age <1 year) hospitalized with severe bronchiolitis during 2011-2014. We used only infancy data to predict asthma at age 6 years. Results: The prevalence of parent-reported asthma at age 6 years was 328/880 (37%). The prevalences of a positive index/score for stringent and loose API, mAPI, and PARS were 21%, 51%, 11%, and 34%, respectively. Area under the receiver operating characteristic curves [95% confidence interval (CI)] ranged from 0.57 (95% CI 0.55-0.60) for mAPI to 0.66 (95% CI 0.63-0.70) for PARS. Conclusions: An asthma prediction tool for high-risk infants is needed to identify those who would benefit most from asthma prevention interventions.

Performance of the Pediatric Asthma Risk Score across Diverse Populations

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.)

The Pediatric Asthma Risk Score: A New Gold Standard for Asthma Prediction

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.

Breastfeeding enrichment of B. longum subsp. infantis mitigates the effect of antibiotics on the microbiota and childhood asthma risk

Early antibiotic exposure is linked to persistent disruption of the infant gut microbiome and subsequent elevated pediatric asthma risk. Breastfeeding acts as a primary modulator of the gut microbiome during early life, but its effect on asthma development has remained unclear. We harnessed the CHILD cohort to interrogate the influence of breastfeeding on antibiotic-associated asthma risk in a subset of children (n= 2,521). We then profiled the infant microbiomes in a subset of these children (n= 1,338) using shotgun metagenomic sequencing and compared human milk oligosaccharide and fatty acid composition from paired maternal human milk samples for 561 of these infants. Children who took antibiotics without breastfeeding had 3-fold higher asthma odds, whereas there was no such association in children who received antibiotics while breastfeeding. This benefit was associated with widespread "re-balancing" of taxonomic and functional components of the infant microbiome. Functional changes associated with asthma protection were linked to enriched Bifidobacterium longum subsp. infantis colonization. Network analysis identified a selection of fucosylated human milk oligosaccharides in paired maternal samples that were positively associated with B.infantis and these broader functional changes. Our data suggest that breastfeeding and antibiotics have opposing effects on the infant microbiome and that breastfeeding enrichment of B.infantis is associated with reduced antibiotic-associated asthma risk. This work was supported in part by the Canadian Institutes of Health Research; the Allergy, Genes and Environment Network of Centres of Excellence; Genome Canada; and Genome British Columbia.

Association of the IL-4R Q576R Polymorphism with Pediatric Asthma: a meta-analysis.

The relationship between Q576R polymorphism of IL-4 receptor (IL-4R) gene and pediatric asthma risk is still undefined. To this end, this meta-analysis was performed to explore the above controversy. In this study, we systemically retrieved CNKI, EMBASE, Web of Science, Scopus, Science direct and Pub Med to collect relevant researches, followed by calculation of odds ratio (OR) along with 95% confidence intervals (CIs). STATA 12.0 software was employed in this meta-analysis. We found an association between IL-4R Q576R polymorphism and pediatric asthma risk (GG vs AA: OR = 3.75, 95% CI = 1.89-7.45; AG vs AA: OR = 2.15, 95% CI = 1.36-3.39; the dominant model: OR = 2.25, 95% CI = 1.42-3.57;the recessive model: OR = 3.05, 95% CI = 1.54-6.05). Moreover, there was no obvious publication bias. Our findings suggested that G allele of IL-4R Q576R polymorphism is associated with increased risk of pediatric asthma. Anyhow, delicately-designed, large-scale studies should be conducted to further confirm the current outcomes.

Maternal exposure to urinary polycyclic aromatic hydrocarbons (PAH) in pregnancy and childhood asthma in a pooled multi-cohort study

BackgroundPrenatal exposure to polycyclic aromatic hydrocarbons (PAH) may increase risk of pediatric asthma, but existing human studies are limited. ObjectivesWe estimated associations between gestational PAHs and pediatric asthma in a diverse US sample and evaluated effect modification by child sex, maternal asthma, and prenatal vitamin D status. MethodsWe pooled two prospective pregnancy cohorts in the ECHO PATHWAYS Consortium, CANDLE and TIDES, for an analytic sample of N = 1296 mother–child dyads. Mono-hydroxylated PAH metabolites (OH-PAHs) were measured in mid-pregnancy urine. Mothers completed the International Study on Allergies and Asthma in Childhood survey at child age 4–6 years. Poisson regression with robust standard errors was used to estimate relative risk of current wheeze, current asthma, ever asthma, and strict asthma associated with each metabolite, adjusted for potential confounders. We used interaction models to assess effect modification. We explored associations between OH-PAH mixtures and outcomes using logistic weighted quantile sum regression augmented by a permutation test to control Type 1 errors. ResultsThe sociodemographically diverse sample spanned five cities. Mean (SD) child age at assessment was 4.4 (0.4) years. While there was little evidence that either individual OH-PAHs or mixtures were associated with outcomes, we observed effect modification by child sex for most pairs of OH-PAHs and outcomes, with adverse associations specific to females. For example, a 2-fold increase in 2-hydroxy-phenanthrene was associated with current asthma in females but not males (RRfemale = 1.29 [95 % CI: 1.09, 1.52], RRmale = 0.95 [95 % CI: 0.79, 1.13]; pinteraction = 0.004). There was no consistent evidence of modification by vitamin D status or maternal asthma. DiscussionThis analysis, the largest cohort study of gestational PAH exposure and childhood asthma to date, suggests adverse associations for females only. These preliminary findings are consistent with hypothesized endocrine disruption properties of PAHs, which may lead to sexually dimorphic effects.

Size-segregated particle number concentrations and outpatient-department visits for pediatric respiratory diseases in Shanghai, China

BackgroundFew studies have simultaneously explored which size of particles has the greatest impact on the risk for pediatric asthma, bronchitis and upper respiratory tract infections (URTIs). ObjectivesTo investigate the short-term association between size-segregated particle number concentrations (PNCs) and outpatient-department visits (ODVs) for major pediatric respiratory diseases. MethodsDaily counts of pediatric ODVs for asthma, bronchitis and URTIs were obtained from 66 hospitals in Shanghai, China, from 2016 to 2018. Pollutant effects were estimated using Poisson generalized additive models combined with polynomial distributed lag models. We also fitted co-pollutant cumulative effects models included six criteria air pollutants and conducted stratifying analyses by gender, age, season and geographic distances. ResultsWe identified a total of 430,103 patients with asthma, 1,547,013 patients with bronchitis, and 2,155,738 patients with URTIs from the hospitals. Effect estimates increased with decreasing particle size. Ultrafine particle (UFP) and PNCs of 0.10–0.40 µm particles (PNC0.10–0.40) were associated with increased ODVs for asthma, bronchitis and URTIs at cumulative lags up to 3d. Associations tended to appear stable after adjusting for criteria air pollutants. At the cumulative lag 0–2d, each interquartile range increase in UFP was associated with increased ODVs due to asthma (relative risk 1.21, 95% CI: 1.07, 1.38), bronchitis (1.20, 95% CI: 1.07, 1.34) and URTI (1.17, 95% CI: 1.06, 1.30), whereas the associations for PNC0.10–0.40 remained significant but attenuated in magnitude. ConclusionsUFP may be a leading contributor to the adverse respiratory effects of particulate air pollution and the effects increased with decreasing particle size.

Racial Fairness in Precision Medicine: Pediatric Asthma Prediction Algorithms.

Quantify and examine the racial fairness of two widely used childhood asthma predictive precision medicine algorithms: the asthma predictive index (API) and the pediatric asthma risk score (PARS). Apply the API and PARS and evaluate model performance overall and when stratified by race. Cincinnati, OH, USA. A prospective birth cohort of 590 children with clinically measured asthma diagnosis by age seven. Model diagnostic criteria included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Significant differences in model performance between Black and white children were considered to be present if the P-value associated with a t-test based on 100 bootstrap replications was less than .05. Compared to predictions for white children, predictions for Black children using the PARS had a higher sensitivity (.88 vs .57), lower specificity (.55 vs .83), higher PPV (.42 vs .33), but a similar NPV (.93 vs .93). Within the API and compared to predictions for white children, predictions for Black children had a higher sensitivity (.63 vs .53), similar specificity (.81 vs .80), higher PPV (.54 vs .28), and lower NPV (.86 vs .92). Overall, racial disparities in model diagnostic criteria were greatest for sensitivity and specificity in the PARS, but racial disparities existed in three of the four criteria for both the PARS and the API.

The Pediatric Asthma Risk Score: More does not mean better

Asthma is a chronic inflammatory lung disease that affects 6.2 million children worldwide.1 The vast heterogeneity in endotypes makes it difficult to predict which children will develop asthma. The Pediatric Asthma Risk Score (PARS) is a quantitative risk score for asthma developed using clinical and demographic data that can be used by health care providers, parents, and researchers.2 PARS was developed using data from the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) birth cohort3 to identify risk factors predicting asthma development at age 7 years.

Daily Associations of Air Pollution and Pediatric Asthma Risk Using the Biomedical REAI-Time Health Evaluation (BREATHE) Kit.

Background: Exposure to air pollution is associated with acute pediatric asthma exacerbations, including reduced lung function, rescue medication usage, and increased symptoms; however, most studies are limited in investigating longitudinal changes in these acute effects. This study aims to investigate the effects of daily air pollution exposure on acute pediatric asthma exacerbation risk using a repeated-measures design. Methods: We conducted a panel study of 40 children aged 8–16 years with moderate-to-severe asthma. We deployed the Biomedical REAI-Time Health Evaluation (BREATHE) Kit developed in the Los Angeles PRISMS Center to continuously monitor personal exposure to particulate matter of aerodynamic diameter < 2.5 µm (PM2.5), relative humidity and temperature, geolocation (GPS), and asthma outcomes including lung function, medication use, and symptoms for 14 days. Hourly ambient (PM2.5, nitrogen dioxide (NO2), ozone (O3)) and traffic-related (nitrogen oxides (NOx) and PM2.5) air pollution exposures were modeled based on location. We used mixed-effects models to examine the association of same day and lagged (up to 2 days) exposures with daily changes in % predicted forced expiratory volume in 1 s (FEV1) and % predicted peak expiratory flow (PEF), count of rescue inhaler puffs, and symptoms. Results: Participants were on average 12.0 years old (range: 8.4–16.8) with mean (SD) morning %predicted FEV1 of 67.9% (17.3%) and PEF of 69.1% (18.4%) and 1.4 (3.5) puffs per day of rescue inhaler use. Participants reported chest tightness, wheeze, trouble breathing, and cough symptoms on 36.4%, 17.5%, 32.3%, and 42.9%, respectively (n = 217 person-days). One SD increase in previous day O3 exposure was associated with reduced morning (beta [95% CI]: −4.11 [−6.86, −1.36]), evening (−2.65 [−5.19, −0.10]) and daily average %predicted FEV1 (−3.45 [−6.42, −0.47]). Daily (lag 0) exposure to traffic-related PM2.5 exposure was associated with reduced morning %predicted PEF (−3.97 [−7.69, −0.26]) and greater odds of “feeling scared of trouble breathing” symptom (odds ratio [95% CI]: 1.83 [1.03, 3.24]). Exposure to ambient O3, NOx, and NO was significantly associated with increased rescue inhaler use (rate ratio [95% CI]: O3 1.52 [1.02, 2.27], NOx 1.61 [1.23, 2.11], NO 1.80 [1.37, 2.35]). Conclusions: We found significant associations of air pollution exposure with lung function, rescue inhaler use, and “feeling scared of trouble breathing.” Our study demonstrates the potential of informatics and wearable sensor technologies at collecting highly resolved, contextual, and personal exposure data for understanding acute pediatric asthma triggers.

Association of IL-10-1082G>A, -819C>T and -592C>A Polymorphisms with susceptibility to asthma in children: a Systematic Review and Meta-Analysis.

Studies evaluating the association of Interleukin 10 (IL-10) polymorphisms with risk of pediatric asthma found inconsistent data. Here, we performed a meta-analysis to get a precise estimation of the associations. Relevant studies identified in the PubMed, Scopus, CNKI databases were used to perform a meta-analysis. A total of 23 case-control studies including nine studies with 1298 cases and 1079 controls on IL-10-1082G>A, four studies with 622 cases and 603 controls on -819C>T and ten studies with 1480 case and 1462 controls on -592C>A were selected. Overall, there was no significant association between IL-10 polymorphisms with pediatric asthma risk in global population. When stratified by ethnicity, there was a significant association of IL-10-1082G>A with pediatric asthma in Asians and Chinese. This meta-analysis result revealed that IL-10-1082G>A, -819C>T and -592C>A polymorphisms were not associated with pediatric asthma risk in the global population.

Pediatric asthma risk score and asthma prediction index in risk prediction of asthma in recurrent wheezing children

Pediatric asthma risk score and asthma prediction index in risk prediction of asthma in recurrent wheezing children

Performance of Three Asthma Predictive Tools in a Cohort of Infants Hospitalized With Severe Bronchiolitis.

Childhood asthma develops in 30–40% of children with severe bronchiolitis but accurate prediction remains challenging. In a severe bronchiolitis cohort, we applied the Asthma Predictive Index (API), the modified Asthma Predictive Index (mAPI), and the Pediatric Asthma Risk Score (PARS) to predict asthma at age 5 years. We applied the API, mAPI, and PARS to the 17-center cohort of infants hospitalized with severe bronchiolitis during 2011–2014 (35th Multicenter Airway Research Collaboration, MARC-35). We used data from the first 3 years of life including parent interviews, chart review, and specific IgE testing to predict asthma at age 5 years, defined as parent report of clinician-diagnosed asthma. Among 875/921 (95%) children with outcome data, parent-reported asthma was 294/875 (34%). In MARC-35, a positive index/score for stringent and loose API, mAPI, and PARS were 24, 68, 6, and 55%, respectively. The prediction tools' AUCs (95%CI) ranged from 0.57 (95%CI 0.54–0.59) to 0.68 (95%CI 0.65–0.71). The positive likelihood ratios were lower in MARC-35 compared to the published results from the original cohorts. In this high-risk population of infants hospitalized with severe bronchiolitis, API, mAPI, and PARS had sub-optimal performance (AUC <0.8). Highly accurate (AUC >0.8) asthma prediction tools are desired in infants hospitalized with severe bronchiolitis.

Longitudinal atopic dermatitis endotypes: An atopic march paradigm that includes Black children

The atopic march has been studied mostly in White populations, biasing our current paradigms. We sought to define the atopic march in Black and White children and explore mechanisms for racial differences. Utilizing the Mechanisms of Progression of Atopic Dermatitis to Asthma in Children (MPAACH) cohort (n= 601), we assessed longitudinal sensitization, food allergy (FA), allergic rhinitis, risk of asthma development (through the Pediatric Asthma Risk Score), Scoring for Atopic Dermatitis (SCORAD), transepidermal water loss, skin filaggrin (FLG) expression, exposures, and genetic heritability to define AD progression endotypes in Black and White children. White MPAACH children were more likely to be sensitized to aero and food allergens (P= .0001) and over 3 times more likely to develop FA and/or allergic rhinitis (AR) without asthma risk (P< .0001). In contrast, Black children were over 6 times more likely to proceed to high asthma risk without FA, sensitization, or AR (P< .0001). White children had higher lesional and nonlesional transepidermal water loss (both P< .001) as well as decreased nonlesional keratinocyte FLG expression (P= .02). Black children had increased genetic heritability for asthma risk and higher rates of exposures to secondhand smoke and traffic-related air pollution. Black and White children with AD have distinct allergic trajectories defined by different longitudinal endotypes. Black children exhibit higher asthma risk despite a more intact skin barrier and less sensitization, FA, and AR. White children have less asthma risk, despite a more dysfunctional skin barrier, and more FA, AR, and sensitization. The observed racial differences are likely due in part to increased genetic heritability for asthma risk and harmful environmental exposures in Black children. Collectively, our findings provide a new paradigm for an atopic march that is inclusive of Black children.