Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.

A pediatric randomized, controlled trial of German cockroach subcutaneous immunotherapy.

BACKGROUND: Cockroach allergy contributes to morbidity among urban children with asthma. Few trials address the effect of subcutaneous immunotherapy (SCIT) with cockroach allergen among these at-risk children. OBJECTIVES: We sought to determine whether nasal allergen challenge (NAC) responses to cockroach allergen would improve following 1 year of SCIT. METHODS: Urban children with asthma, who were cockroach-sensitized and reactive on NAC, participated in a year-long randomized double-blind placebo-controlled SCIT trial using German cockroach extract. The primary endpoint was the change in mean Total Nasal Symptom Score (TNSS) during NAC after 12 months of SCIT. Changes in nasal transcriptomic responses during NAC, skin prick test wheal size, serum allergen-specific antibody production, and T-cell responses to cockroach allergen were assessed. RESULTS: Changes in mean NAC TNSS did not differ between SCIT-assigned (n = 28) versus placebo-assigned (n = 29) participants (P = .63). Nasal transcriptomic responses correlated with TNSS, but a treatment effect was not observed. Cockroach serum-specific IgE decreased to a similar extent in both groups, while decreased cockroach skin prick test wheal size was greater among SCIT participants (P = .04). A 200-fold increase in cockroach serum-specific IgG4 was observed among subjects receiving SCIT (P < .001) but was unchanged in the placebo group. T-cell IL-4 responses following cockroach allergen stimulation decreased to a greater extent among SCIT versus placebo (P = .002), while no effect was observed for IL-10 or IFN-γ. CONCLUSIONS: A year of SCIT failed to alter NAC TNSS and nasal transcriptome responses to cockroach allergen challenge despite systemic effects on allergen-specific skin tests, induction of serum-specific IgG4 serum production and down-modulation of allergen-stimulated T-cell responses.

Early-Life Exposure to Air Pollution and Childhood Asthma Cumulative Incidence in the ECHO CREW Consortium.

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.

The impact of prenatal dog keeping on infant gut microbiota development.

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 ß-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.

Incidence rates of childhood asthma with recurrent exacerbations in the US Environmental influences on Child Health Outcomes (ECHO) program.

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.

Associations between outdoor air pollutants and non-viral asthma exacerbations and airway inflammatory responses in children and adolescents living in urban areas in the USA: a retrospective secondary analysis.

BACKGROUND: Asthma prevalence and severity have markedly increased with urbanisation, and children in low-income urban centres have among the greatest asthma morbidity. Outdoor air pollution has been associated with adverse respiratory effects in children with asthma. However, the mechanisms by which air pollution exposure exacerbates asthma, and how these mechanisms compare with exacerbations induced by respiratory viruses, are poorly understood. We aimed to investigate the associations between regional air pollutant concentrations, respiratory illnesses, lung function, and upper airway transcriptional signatures in children with asthma, with particular focus on asthma exacerbations occurring in the absence of respiratory virus. METHODS: We performed a retrospective analysis of data from the MUPPITS1 cohort and validated our findings in the ICATA cohort. The MUPPITS1 cohort recruited 208 children aged 6-17 years living in urban areas across nine US cities with exacerbation-prone asthma between Oct 7, 2015, and Oct 18, 2016, and monitored them during reported respiratory illnesses. The last MUPPITS1 study visit occurred on Jan 6, 2017. The ICATA cohort recruited 419 participants aged 6-20 years with persistent allergic asthma living in urban sites across eight US cities between Oct 23, 2006, and March 25, 2008, and the last study visit occurred on Dec 30, 2009. We included participants from the MUPPITS1 cohort who reported a respiratory illness at some point during the follow-up and participants from the ICATA cohort who had nasal samples collected during respiratory illness or at a scheduled visit. We used air quality index values and air pollutant concentrations for PM2·5, PM10, O3, NO2, SO2, CO, and Pb from the US Environmental Protection Agency spanning the years of both cohorts, and matched values and concentrations to each illness for each participant. We investigated the associations between regional air pollutant concentrations and respiratory illnesses and asthma exacerbations, pulmonary function, and upper airway transcriptional signatures by use of a combination of generalised additive models, case crossover analyses, and generalised linear mixed-effects models. FINDINGS: Of the 208 participants from the MUPPITS1 cohort and 419 participants from the ICATA cohort, 168 participants in the MUPPITS1 cohort (98 male participants and 70 female participants) and 189 participants in the ICATA cohort (115 male participants and 74 female participants) were included in our analysis. We identified that increased air quality index values, driven predominantly by increased PM2·5 and O3 concentrations, were significantly associated with asthma exacerbations and decreases in pulmonary function that occurred in the absence of a provoking viral infection. Moreover, individual pollutants were significantly associated with altered gene expression in coordinated inflammatory pathways, including PM2·5 with increased epithelial induction of tissue kallikreins, mucus hypersecretion, and barrier functions and O3 with increased type-2 inflammation. INTERPRETATION: Our findings suggest that air pollution is an important independent risk factor for asthma exacerbations in children living in urban areas and is potentially linked to exacerbations through specific inflammatory pathways in the airway. Further investigation of these potential mechanistic pathways could inform asthma prevention and management approaches. FUNDING: National Institutes of Health, National Institute of Allergy and Infectious Diseases.

Association of citrulline concentration at birth with lower respiratory tract infection in infancy: Findings from a multi-site birth cohort study.

Assessing the association of the newborn metabolic state with severity of subsequent respiratory tract infection may provide important insights on infection pathogenesis. In this multi-site birth cohort study, we identified newborn metabolites associated with lower respiratory tract infection (LRTI) in the first year of life in a discovery cohort and assessed for replication in two independent cohorts. Increased citrulline concentration was associated with decreased odds of LRTI (discovery cohort: aOR 0.83 [95% CI 0.70-0.99], p = 0.04; replication cohorts: aOR 0.58 [95% CI 0.28-1.22], p = 0.15). While our findings require further replication and investigation of mechanisms of action, they identify a novel target for LRTI prevention and treatment.

African-specific alleles modify risk for asthma at the 17q12-q21 locus in African Americans.

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.

Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: Black and Hispanic children living in urban environments in the USA have an excess burden of morbidity and mortality from asthma. Therapies directed at the eosinophilic phenotype reduce asthma exacerbations in adults, but few data are available in children and diverse populations. Furthermore, the molecular mechanisms that underlie exacerbations either being prevented by, or persisting despite, immune-based therapies are not well understood. We aimed to determine whether mepolizumab, added to guidelines-based care, reduced the number of asthma exacerbations during a 52-week period compared with guidelines-based care alone. METHODS: This is a randomised, double-blind, placebo-controlled, parallel-group trial done at nine urban medical centres in the USA. Children and adolescents aged 6-17 years, who lived in socioeconomically disadvantaged neighbourhoods and had exacerbation-prone asthma (defined as ≥two exacerbations in the previous year) and blood eosinophils of at least 150 cells per µL were randomly assigned 1:1 to mepolizumab (6-11 years: 40 mg; 12-17 years: 100 mg) or placebo injections once every 4 weeks, plus guideline-based care, for 52 weeks. Randomisation was done using a validated automated system. Participants, investigators, and the research staff who collected outcome measures remained masked to group assignments. The primary outcome was the number of asthma exacerbations that were treated with systemic corticosteroids during 52 weeks in the intention-to-treat population. The mechanisms of treatment response were assessed by study investigators using nasal transcriptomic modular analysis. Safety was assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03292588. FINDINGS: Between Nov 1, 2017, and Mar 12, 2020, we recruited 585 children and adolescents. We screened 390 individuals, of whom 335 met the inclusion criteria and were enrolled. 290 met the randomisation criteria, were randomly assigned to mepolizumab (n=146) or placebo (n=144), and were included in the intention-to-treat analysis. 248 completed the study. The mean number of asthma exacerbations within the 52-week study period was 0·96 (95% CI 0·78-1·17) with mepolizumab and 1·30 (1·08-1·57) with placebo (rate ratio 0·73; 0·56-0·96; p=0·027). Treatment-emergent adverse events occurred in 42 (29%) of 146 participants in the mepolizumab group versus 16 (11%) of 144 participants in the placebo group. No deaths were attributed to mepolizumab. INTERPRETATION: Phenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations. FUNDING: US National Institute of Allergy and Infectious Diseases and GlaxoSmithKline.

Human Epidemiology and RespOnse to SARS-CoV-2 (HEROS): Objectives, Design and Enrollment Results of a 12-City Remote Observational Surveillance Study of Households with Children using Direct-to-Participant Methods.

The Human Epidemiology and Response to SARS-CoV-2 (HEROS) is a prospective multi-city 6-month incidence study which was conducted from May 2020-February 2021. The objectives were to identify risk factors for SARS-CoV-2 infection and household transmission among children and people with asthma and allergic diseases, and to use the host nasal transcriptome sampled longitudinally to understand infection risk and sequelae at the molecular level. To overcome challenges of clinical study implementation due to the coronavirus pandemic, this surveillance study used direct-to-participant methods to remotely enroll and prospectively follow eligible children who are participants in other NIH-funded pediatric research studies and their household members. Households participated in weekly surveys and biweekly nasal sampling regardless of symptoms. The aim of this report is to widely share the methods and study instruments and to describe the rationale, design, execution, logistics and characteristics of a large, observational, household-based, remote cohort study of SARS-CoV-2 infection and transmission in households with children. The study enrolled a total of 5,598 individuals, including 1,913 principal participants (children), 1,913 primary caregivers, 729 secondary caregivers and 1,043 other household children. This study was successfully implemented without necessitating any in-person research visits and provides an approach for rapid execution of clinical research.

Risk factors for SARS-CoV-2 infection and transmission in households with children with asthma and allergy: A prospective surveillance study.

BACKGROUND: Whether children and people with asthma and allergic diseases are at increased risk for severe acute respiratory syndrome virus 2 (SARS-CoV-2) infection is unknown. OBJECTIVE: Our aims were to determine the incidence of SARS-CoV-2 infection in households with children and to also determine whether self-reported asthma and/or other allergic diseases are associated with infection and household transmission. METHODS: For 6 months, biweekly nasal swabs and weekly surveys were conducted within 1394 households (N = 4142 participants) to identify incident SARS-CoV-2 infections from May 2020 to February 2021, which was the pandemic period largely before a vaccine and before the emergence of SARS-CoV-2 variants. Participant and household infection and household transmission probabilities were calculated by using time-to-event analyses, and factors associated with infection and transmission risk were determined by using regression analyses. RESULTS: In all, 147 households (261 participants) tested positive for SARS-CoV-2. The household SARS-CoV-2 infection probability was 25.8%; the participant infection probability was similar for children (14.0% [95% CI = 8.0%-19.6%]), teenagers (12.1% [95% CI = 8.2%-15.9%]), and adults (14.0% [95% CI = 9.5%-18.4%]). Infections were symptomatic in 24.5% of children, 41.2% of teenagers, and 62.5% of adults. Self-reported doctor-diagnosed asthma was not a risk factor for infection (adjusted hazard ratio [aHR] = 1.04 [95% CI = 0.73-1.46]), nor was upper respiratory allergy or eczema. Self-reported doctor-diagnosed food allergy was associated with lower infection risk (aHR = 0.50 [95% CI = 0.32-0.81]); higher body mass index was associated with increased infection risk (aHR per 10-point increase = 1.09 [95% CI = 1.03-1.15]). The household secondary attack rate was 57.7%. Asthma was not associated with household transmission, but transmission was lower in households with food allergy (adjusted odds ratio = 0.43 [95% CI = 0.19-0.96]; P = .04). CONCLUSION: Asthma does not increase the risk of SARS-CoV-2 infection. Food allergy is associated with lower infection risk, whereas body mass index is associated with increased infection risk. Understanding how these factors modify infection risk may offer new avenues for preventing infection.

Childhood Asthma Incidence, Early and Persistent Wheeze, and Neighborhood Socioeconomic Factors in the ECHO/CREW Consortium.

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.

Association of mold levels in urban children's homes with difficult-to-control asthma.

BACKGROUND: Mold sensitization and exposure are associated with asthma severity, but the specific species that contribute to difficult-to-control (DTC) asthma are unknown. OBJECTIVE: We sought to determine the association between overall and specific mold levels in the homes of urban children and DTC asthma. METHODS: The Asthma Phenotypes in the Inner-City study recruited participants, aged 6 to 17 years, from 8 US cities and classified each participant as having either DTC asthma or easy-to-control (ETC) asthma on the basis of treatment step level. Dust samples had been collected in each participant's home (n = 485), and any dust remaining (n = 265 samples), after other analyses, was frozen at -20oC. The dust samples (n = 265) were analyzed using quantitative PCR to determine the concentrations of the 36 molds in the Environmental Relative Moldiness Index. Logistic regression was performed to discriminate specific mold content of dust from homes of children with DTC versus ETC asthma. RESULTS: Frozen-dust samples were available from 54% of homes of children with DTC (139 of 253) and ETC asthma (126 of 232). Only the average concentration of the mold Mucor was significantly (P < .001) greater in homes of children with DTC asthma. In homes with window air-conditioning units, the Mucor concentration contributed about a 22% increase (1.6 odds ratio; 95% CI, 1.2-2.2) in the ability to discriminate between cases of DTC and ETC asthma. CONCLUSIONS: Mucor levels in the homes of urban youth were a predictor of DTC asthma, and these higher Mucor levels were more likely in homes with a window air-conditioner.

Infant gut bacterial community composition and food-related manifestation of atopy in early childhood.

BACKGROUND: Immunoglobulin E-mediated food allergy (IgE-FA) has emerged as a global public health concern. Immune dysregulation is an underlying mechanism for IgE-FA, caused by "dysbiosis" of the early intestinal microbiota. We investigated the association between infant gut bacterial composition and food-related atopy at age 3-5 years using a well-characterized birth cohort. METHODS: The study definition of IgE-FA to egg, milk, or peanut was based on physician panel retrospective review of clinical and questionnaire data collected from birth through age 3-5 years. Using 16S rRNA sequencing, we profiled the bacterial gut microbiota present in stool specimens collected at 1 and 6 months of age. RESULTS: Of 447 infants with data for analysis, 44 (9.8%) met physician panel review criteria for IgE-FA to ≥1 of the three allergens. Among children classified as IgE-FA at 3-5 years, infant stool samples showed significantly less diversity of the gut microbiota compared with the samples of children classified as no IgE-FA at age 3-5 years, especially for milk and peanut (all covariate-adjusted p's for alpha metrics <.007). Testing of individual operational taxonomic units (OTUs) revealed 6-month deficiencies in 31 OTUs for IgE-FA compared with no IgE-FA, mostly in the orders Lactobacillales, Bacteroidales, and Clostridiales. CONCLUSIONS: Variations in gut microbial composition in infant stool were associated with a study definition of IgE-FA at 3-5 years of age. This included evidence of a lack of bacterial diversity, deficiencies in specific OTUs, and delayed microbial maturation. Results support dysbiosis in IgE-FA pathogenesis.

Association of Severe Bronchiolitis during Infancy with Childhood Asthma Development: An Analysis of the ECHO Consortium.

Objective: Many studies have shown that severe (hospitalized) bronchiolitis during infancy is a risk factor for developing childhood asthma. However, the population subgroups at the highest risk remain unclear. Using large nationwide pediatric cohort data, namely the NIH Environmental influences on Child Health Outcomes (ECHO) Program, we aimed to quantify the longitudinal relationship of bronchiolitis hospitalization during infancy with asthma in a generalizable dataset and to examine potential heterogeneity in terms of major demographics and clinical factors. Methods: We analyzed data from infants (age <12 months) enrolled in one of the 53 prospective cohort studies in the ECHO Program during 2001−2021. The exposure was bronchiolitis hospitalization during infancy. The outcome was a diagnosis of asthma by a physician by age 12 years. We examined their longitudinal association and determined the potential effect modifications of major demographic factors. Results: The analytic cohort consisted of 11,762 infants, 10% of whom had bronchiolitis hospitalization. Overall, 15% subsequently developed asthma. In the Cox proportional hazards model adjusting for 10 patient-level factors, compared with the no-bronchiolitis hospitalization group, the bronchiolitis hospitalization group had a significantly higher rate of asthma (14% vs. 24%, HR = 2.77, 95%CI = 2.24−3.43, p < 0.001). There was significant heterogeneity by race and ethnicity (Pinteraction = 0.02). The magnitude of the association was greater in non-Hispanic White (HR = 3.77, 95%CI = 2.74−5.18, p < 0.001) and non-Hispanic Black (HR = 2.39, 95%CI = 1.60−3.56; p < 0.001) infants, compared with Hispanic infants (HR = 1.51, 95%CI = 0.77−2.95, p = 0.23). Conclusions: According to the nationwide cohort data, infants hospitalized with bronchiolitis are at a higher risk for asthma, with quantitative heterogeneity in different racial and ethnic groups.

COVID-19 Modulates Inflammatory and Renal Markers That May Predict Hospital Outcomes among African American Males.

BACKGROUND AND OBJECTIVES: African Americans and males have elevated risks of infection, hospitalization, and death from SARS-CoV-2 in comparison with other populations. We report immune responses and renal injury markers in African American male patients hospitalized for COVID-19. METHODS: This was a single-center, retrospective study of 56 COVID-19 infected hospitalized African American males 50+ years of age selected from among non-intensive care unit (ICU) and ICU status patients. Demographics, hospitalization-related variables, and medical history were collected from electronic medical records. Plasma samples collected close to admission (≤2 days) were evaluated for cytokines and renal markers; results were compared to a control group (n = 31) and related to COVID-19 in-hospital mortality. RESULTS: Among COVID-19 patients, eight (14.2%) suffered in-hospital mortality; seven (23.3%) in the ICU and one (3.8%) among non-ICU patients. Interleukin (IL)-18 and IL-33 were elevated at admission in COVID-19 patients in comparison with controls. IL-6, IL-18, MCP-1/CCL2, MIP-1α/CCL3, IL-33, GST, and osteopontin were upregulated at admission in ICU patients in comparison with controls. In addition to clinical factors, MCP-1 and GST may provide incremental value for risk prediction of COVID-19 in-hospital mortality. CONCLUSIONS: Qualitatively similar inflammatory responses were observed in comparison to other populations reported in the literature, suggesting non-immunologic factors may account for outcome differences. Further, we provide initial evidence for cytokine and renal toxicity markers as prognostic factors for COVID-19 in-hospital mortality among African American males.