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We hypothesize that children characterized by deprived factors have poorer health outcomes. We aim to identify clustering of determinants and estimate risk of early childhood diseases. This 1993–2019 longitudinal cohort study combines three Canadian pediatric cohorts and their families. Mothers and children are clustered using latent class analysis (LCA) by 16 indicators in three domains (maternal and newborn; socioeconomic status [SES] and neighbourhood; environmental exposures). Hazard ratios (HR) of childhood asthma, allergic rhinitis (AR), and eczema are quantified with Cox proportional hazard (PH) regression. Rate ratios (RR) of children's health services use (HSU) are estimated with Poisson regression. Here we report the inclusion of 15,724 mother–child pairs; our LCA identifies four mother-clusters. Classes 1 and 2 mothers are older (30–40 s), non-immigrants with university education, living in high SES neighbourhoods; Class 2 mothers have poorer air quality and less greenspace. Classes 3 and 4 mothers are younger (20–30 s), likely an immigrant/refugee, with high school-to-college education, living in lower SES neighborhoods with poorer air quality and less greenspace. Children's outcomes differ by Class, in comparison to Class 1. Classes 3 and 4 children have higher risks of asthma (HR 1.24, 95% CI 1.11–1.37 and HR 1.39, 95% CI 1.22–1.59, respectively), and similar higher risks of AR and eczema. Children with AR in Class 3 have 20% higher all-cause physician visits (RR = 1.20, 95% CI 1.10–1.30) and those with eczema have 18% higher all-cause emergency department visits (RR = 1.18, 95% CI 1.09–1.28) and 14% higher all-cause physician visits (RR = 1.14, 95% CI 1.09–1.19). Multifactorial-LCA mother-clusters may characterize associations of children's health outcomes and care, adjusting for interrelationships. [ABSTRACT FROM AUTHOR]

Background. Di-(2-ethylhexyl) phthalate (DEHP), which is ubiquitous in indoor environments, was the predominant phthalate measured in house dust in the Canadian CHILD Cohort and was found to be associated with a large increased risk of childhood asthma. Objective. To inform interventions by identifying sources of DEHP in dust and assessing behaviors related to DEHP concentrations in house dust. Methods. DEHP levels were measured in 726 dust samples collected at ~3 months of age in CHILD as well as in ~50 homes at two time points (June and November) in the CHILD pilot study. DEHP metabolites were measured in urine for a subset of the ~3-month-old infants. Housing characteristics were assessed at the time of dust and urine collection. Numerous factors from these surveys were investigated as potential sources of DEHP using univariate analyses and multivariable regressions. Correlations between DEHP in dust and urinary metabolites and between repeat dust samples were examined to study the relationship between dust measurement and DEHP exposure. Results. Overall, DEHP dust concentrations were higher for lower-income families. Homes with vinyl flooring in the kitchen and bathroom showed higher levels of DEHP than those without vinyl flooring. The quantity of vinyl furniture and the presence of mold were associated with higher DEHP concentrations, while the use of mattress covers reduced concentration. No other significant associations were found. DEHP concentrations in dust were consistent over 6 months, although the correlation between dust and DEHP metabolites in urine was low. Conclusion. DEHP in house dust persisted over multiple months, contributed to infant internal exposure, and was associated with specific housing characteristics. These findings may inform the public on their choice of building materials and products, as well as future policies, aimed at reducing the health risk associated with exposures in the indoor environment especially for children. [ABSTRACT FROM AUTHOR]

Background: The infant fecal microbiome is known to impact subsequent asthma risk, but the environmental exposures impacting this association, the role of the maternal microbiome, and how the microbiome impacts different childhood asthma phenotypes are unknown. Methods: Our objective was to identify associations between features of the prenatal and early‐life fecal microbiomes and child asthma phenotypes. We analyzed fecal 16 s rRNA microbiome profiling and fecal metabolomic profiling from stool samples collected from mothers during the third trimester of pregnancy (n = 120) and offspring at ages 3–6 months (n = 265), 1 (n = 436) and 3 years (n = 506) in a total of 657 mother–child pairs participating in the Vitamin D Antenatal Asthma Reduction Trial. We used clinical data from birth to age 6 years to characterize subjects with asthma as having early, transient or active asthma phenotypes. In addition to identifying specific genera that were robustly associated with asthma phenotypes in multiple covariate‐adjusted models, we clustered subjects by their longitudinal microbiome composition and sought associations between fecal metabolites and relevant microbiome and clinical features. Results: Seven maternal and two infant fecal microbial taxa were robustly associated with at least one asthma phenotype, and a longitudinal gut microenvironment profile was associated with early asthma (Fisher exact test p =.03). Though mode of delivery was not directly associated with asthma, we found substantial evidence for a pathway whereby cesarean section reduces fecal Bacteroides and microbial sphingolipids, increasing susceptibility to early asthma. Conclusion: Overall, our results suggest that the early‐life, including prenatal, fecal microbiome modifies risk of asthma, especially asthma with onset by age 3 years. [ABSTRACT FROM AUTHOR]

Purpose: This is a pilot study that describes the feasibility and clinical course of a cohort of preschool children with severe asthma undergoing a combined adenotonillectomy (TA), bronchoscopy (B), and bronchoalveolar lavage (BAL) procedure. Methods: A retrospective cohort study of preschool patients with severe asthma who underwent a combined TA-B-BAL procedure between 2012 and 2019. Subjects were treated at a tertiary care asthma clinic and had a diagnosis of preschool asthma according to the Canadian Thoracic Society Guidelines. Data on demographics, clinical characteristics, medication use, virology and microbiology from bronchoalveolar lavage, and asthma control questionnaires were collected. Variables were analyzed using paired t test. Results: Eighteen preschool subjects (mean age 3.19 ± 1.13 years) with severe asthma were identified through the asthma clinic. Patients treated with standard asthma care and a combined TA-B-BAL procedure experienced a decrease in the number of oral steroid courses (p = 0.017), emergency department visits (p = 0.03) and wheezing exacerbations (p = 0.026) following the procedure. Ten patients experienced clinically meaningful improvements in TRACK scores after the procedure (p < 0.001). Conclusion: This pilot study provides early evidence that a combined TA-B-BAL procedure is feasible in preschool children with severe asthma and that the procedure may reduce asthma medication use and hospital visits. [ABSTRACT FROM AUTHOR]

Childhood asthma incidence is decreasing in some parts of Europe and North America. Antibiotic use in infancy has been associated with increased asthma risk. In the present study, we tested the hypothesis that decreases in asthma incidence are linked to reduced antibiotic prescribing and mediated by changes in the gut bacterial community. This study comprised population-based and prospective cohort analyses. At the population level, we used administrative data from British Columbia, Canada (population 4·7 million), on annual rates of antibiotic prescriptions and asthma diagnoses, to assess the association between antibiotic prescribing (at age <1 year) and asthma incidence (at age 1–4 years). At the individual level, 2644 children from the Canadian Healthy Infant Longitudinal Development (CHILD) prospective birth cohort were examined for the association of systemic antibiotic use (at age <1 year) with the diagnosis of asthma (at age 5 years). In the same cohort, we did a mechanistic investigation of 917 children with available 16S rRNA gene sequencing data from faecal samples (at age ≤1 year), to assess how composition of the gut microbiota relates to antibiotic exposure and asthma incidence. At the population level between 2000 and 2014, asthma incidence in children (aged 1–4 years) showed an absolute decrease of 7·1 new diagnoses per 1000 children, from 27·3 (26·8–28·3) per 1000 children to 20·2 (19·5–20·8) per 1000 children (a relative decrease of 26·0%). Reduction in incidence over the study period was associated with decreasing antibiotic use in infancy (age <1 year), from 1253·8 prescriptions (95% CI 1219·3–1288·9) per 1000 infants to 489·1 (467·6–511·2) per 1000 infants (Spearman's r =0·81; p<0·0001). Asthma incidence increased by 24% with each 10% increase in antibiotic prescribing (adjusted incidence rate ratio 1·24 [95% CI 1·20–1·28]; p<0·0001). In the CHILD cohort, after excluding children who received antibiotics for respiratory symptoms, asthma diagnosis in childhood was associated with infant antibiotic use (adjusted odds ratio [aOR] 2·15 [95% CI 1·37–3·39]; p=0·0009), with a significant dose–response; 114 (5·2%) of 2182 children unexposed to antibiotics had asthma by age 5 years, compared with 23 (8·1%) of 284 exposed to one course, five (10·2%) of 49 exposed to two courses, and six (17·6%) of 34 exposed to three or more courses (aOR 1·44 [1·16–1·79]; p=0·0008). Increasing α-diversity of the gut microbiota, defined as an IQR increase (25th to 75th percentile) in the Chao1 index, at age 1 year was associated with a 32% reduced risk of asthma at age 5 years (aOR for IQR increase 0·68 [0·46–0·99]; p=0·046). In a structural equation model, we found the gut microbiota at age 1 year, characterised by α-diversity, β-diversity, and amplicon sequence variants modified by antibiotic exposure, to be a significant mediator between outpatient antibiotic exposure in the first year of life and asthma diagnosis at age 5 years (β=0·08; p=0·027). Our findings suggest that the reduction in the incidence of paediatric asthma observed in recent years might be an unexpected benefit of prudent antibiotic use during infancy, acting via preservation of the gut microbial community. British Columbia Ministry of Health, Pharmaceutical Services Branch; Canadian Institutes of Health Research; Allergy, Genes and Environment (AllerGen) Network of Centres of Excellence; Genome Canada; and Genome British Columbia. [ABSTRACT FROM AUTHOR]

Here, using data from the Canadian CHILD Cohort Study, we performed a sex-stratified analysis of human milk adiponectin, leptin, and insulin concentrations and their association with possible or probable asthma development by 3 years of age. For this analysis, asthma was classified as "possible or probable asthma" or "no asthma." Milk hormone concentrations did not differ in milk produced for sons vs. daughters (Table, Figure A); however, sex-specific associations were observed between milk hormone concentrations and child asthma (Table, Figure B). It is known that circulating leptin can stimulate the production of pro-inflammatory cytokines, potentially mediating the asthma-obesity axis; however, it is not known whether leptin in human milk can trigger similar responses. [Extracted from the article]

Background: Comprehensive longitudinal studies are important for understanding the complex risk factors, pathways, exposures and interactions that lead to the development and persistence of asthma. We aimed to examine associations between use of household cleaning products in early life and childhood respiratory and allergic disease using data from the Canadian Healthy Infant Longitudinal Development (CHILD) Cohort Study.Methods: We summed responses from parental questionnaires that indicated the frequency of use of 26 household cleaning products in the homes of 2022 children from this birth cohort when they were 3-4 months of age to create a cumulative Frequency of Use Score (FUS). We used multivariable logistic regression models to assess whether frequent compared with less frequent use was associated with recurrent wheeze, atopy or asthma diagnosis, as defined by the questionnaire and clinical assessments at age 3 years. Data were collected between 2008 and 2015.Results: Children in homes with a higher frequency of use of cleaning products in infancy, as determined by an interquartile range increase, had higher odds of recurrent wheeze (adjusted odds ratio [OR] 1.35, 95% confidence interval [CI] 1.11-1.64), recurrent wheeze with atopy (adjusted OR 1.49, 95% CI 1.02-2.16) and asthma diagnosis (adjusted OR 1.37, 95% CI 1.09-1.70), but no increase in the odds of atopy at age 3 years (adjusted OR 1.14, 95% CI 0.96-1.35). Compared with the lowest tertile of FUS exposure, infants in the highest tertile had higher odds of acquiring asthma. Stratification of the results showed that females had higher ORs than males for all outcomes, although the p values for this sex difference did not reach statistical significance.Interpretation: Frequent use of household cleaning products in early life was associated with an increased risk for childhood wheeze and asthma but not atopy at age 3 years. Our findings add to the understanding of how early life exposures to cleaning products may be associated with the development of allergic airway disease and help to identify household behaviours as a potential area for intervention. [ABSTRACT FROM AUTHOR]

In contrast to other environmental allergens, the association with atopic dermatitis was present for Fel d 1, which may suggest that the skin is an important route of sensitization for this allergen. GLO:1X5/01dec19:all13927-fig-0002.jpg PHOTO (COLOR): Hierarchical clustering performed on patient sensitization profiles and allergen components indicating clusters by allergen source and biochemical family (sensitized: N = 37; nonsensitized: N = 18). In conclusion, we provide data describing a potentially high-risk preschool asthma cohort in Canada using a comprehensive approach capturing sensitization to allergens of paramount importance. By applying both allergen extracts and components, we identified that peanut and animal allergens from cat and dog were major allergen sources in this North American cohort of preschool asthmatics. [Extracted from the article]

Asthma is a chronic disease of the airways affecting one in ten children in Westernized countries. Recently, our group showed that specific bacterial genera in early life are associated with atopy and wheezing in 1-year-old children. However, little is known about the link between the early life gut microbiome and the diagnosis of asthma in preschool age children. To determine the role of the gut microbiota in preschool age asthma, children up to 4 years of age enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) study were classified as asthmatic (n=39) or matched healthy controls (n=37). 16S rRNA sequencing and quantitative PCR (qPCR) were used to analyse the composition of the 3-month and 1-year gut microbiome of these children. At 3 months the abundance of the genus, Lachnospira (L), was decreased (P=0.008), whereas the abundance of the species, Clostridium neonatale (C), was increased (P=0.07) in asthmatics. Quartile analysis of stool composition at 3-months revealed a negative association between the ratio of these two bacteria (L/C) and asthma risk by 4 years of age [quartile 1: odds ratio (OR)=15, P=0.02, CI (confidence interval) =1.8-124.7; quartile 2: OR=1.0, ns; quartile 3: OR=0.37, ns]. We conclude that opposing shifts in the relative abundances of Lachnospira and C. neonatale in the first 3 months of life are associated with preschool age asthma, and that the L/C ratio may serve as a potential early life biomarker to predict asthma development. [ABSTRACT FROM AUTHOR]

The Canadian Healthy Infant Longitudinal Development birth cohort was designed to elucidate interactions between environment and genetics underlying development of asthma and allergy. Over 3600 pregnant mothers were recruited from the general population in four provinces with diverse environments. The child is followed to age 5 years, with prospective characterization of diverse exposures during this critical period. Key exposure domains include indoor and outdoor air pollutants, inhalation, ingestion and dermal uptake of chemicals, mold, dampness, biological allergens, pets and pests, housing structure, and living behavior, together with infections, nutrition, psychosocial environment, and medications. Assessments of early life exposures are focused on those linked to inflammatory responses driven by the acquired and innate immune systems. Mothers complete extensive environmental questionnaires including time-activity behavior at recruitment and when the child is 3, 6, 12, 24, 30, 36, 48, and 60 months old. House dust collected during a thorough home assessment at 3-4 months, and biological specimens obtained for multiple exposure-related measurements, are archived for analyses. Geo-locations of homes and daycares and land-use regression for estimating traffic-related air pollution complement time-activity-behavior data to provide comprehensive individual exposure profiles. Several analytical frameworks are proposed to address the many interacting exposure variables and potential issues of co-linearity in this complex data set. [ABSTRACT FROM AUTHOR]

The article offers insight to Canadian Healthy Infant Longitudinal Development Study focusing on the impact of early infancy microbial and metabolic alterations on the risk of childhood asthma. Topics discussed include link between gut microbial dysbiosis; microbe-derived functional changes in infants; and the role of Faecalibacterium, Lachnospira, Veillonella-mediated amelioration of murine lung inflammation.

Bacterial members of the infant gut microbiota and bacterial-derived short-chain fatty acids (SCFAs) have been shown to be protective against childhood asthma, but a role for the fungal microbiota in asthma etiology remains poorly defined. We recently reported an association between overgrowth of the yeast Pichia kudriavzevii in the gut microbiota of Ecuadorian infants and increased asthma risk. In the present study, we replicated these findings in Canadian infants and investigated a causal association between early life gut fungal dysbiosis and later allergic airway disease (AAD). In a mouse model, we demonstrate that overgrowth of P. kudriavzevii within the neonatal gut exacerbates features of type-2 and -17 inflammation during AAD later in life. We further show that P. kudriavzevii growth and adherence to gut epithelial cells are altered by SCFAs. Collectively, our results underscore the potential for leveraging inter-kingdom interactions when designing putative microbiota-based asthma therapeutics. [ABSTRACT FROM AUTHOR]

Studies have demonstrated an association between phthalate exposure and childhood asthma, although results have been inconsistent. No epidemiological studies have examined exposure during the first year of life. To investigate the association between phthalate exposures in the home environment during the first year of life, and subsequent development of childhood asthma and related symptoms. This study used a case-cohort design including 436 randomly selected children and all additional cases of asthma at 5 years (n total = 129) and recurrent wheeze between 2 and 5 years (n total = 332) within the CHILD Cohort Study, a general population Canadian birth cohort of 3455 children. Phthalate exposure was assessed using house dust samples collected during a standardized home visit when children were 3-4 months of age. All children were assessed by specialist clinicians for asthma and allergy at 1, 3 and 5 years. Logistic regression was used to assess the association between exposure to five phthalates and asthma diagnosis at 5 years, and recurrent wheeze between 2 and 5 years, with further stratification by wheeze subtypes (late onset, persistent, transient) based on the timing of onset and persistence of wheeze symptoms. Di(2-ethylhexyl) phthalate (DEHP) had the highest concentration in dust (median subcohort = 217 μg/g), followed by benzyl butyl phthalate (BzBP) (20 μg/g). A nearly four-fold increase in risk of developing asthma was associated with the highest concentration quartile of DEHP (OR = 3.92, 95% CI: 1.87–8.24) including a positive dose-response relationship. A two-fold increase in risk of recurrent wheeze was observed across all quartiles compared to the lowest quartile of DEHP concentrations. Compared to other wheeze subtypes, stronger associations for DEHP were observed with the late onset wheezing subtype, while stronger associations for di-iso-butyl phthalate (DiBP) and BzBP were observed with the transient subtype. DEHP exposure at 3-4 months, at concentrations lower than other studies that reported an association, were associated with increased risks of asthma and recurrent wheeze among children at 5 years. These findings suggest the need to assess whether more stringent regulations are required to protect children's health, which can be informed by future work exploring the main sources of DEHP exposure. • DEHP, BzBP, DnBP, DiBP and DEP were detected in nearly all house dust samples. • Early life DEHP exposure was associated with a large increased risk of asthma at 5 years. • Early life DEHP exposure associated with increased risk of recurrent wheeze between 2 and 5 years. • Increased risk with DEHP observed at concentrations lower than other studies. [ABSTRACT FROM AUTHOR]