METHODS: Data were collected as part of the longitudinal, general Canadian population CHILD Study. LRTIs during the first 18 months of life were identified through parental symptom report at regular study visits. Systemic antibiotic use was defined as at least one dose of oral/intravenous antibiotics between birth and the 18-month visit and were further categorized by indication as either given for a respiratory indication (upper or lower respiratory symptoms) or non-respiratory indication. Asthma was diagnosed by in-study pediatricians at the 5-year study visit. Adjusted logistic regression models and mediation analyses via systemic antibiotics use were performed.
RESULTS: Among 2,073 participants included in our analysis, 72 (4.9%) had asthma age 5, and 609 (29.3%) used systemic antibiotics before the 18-month visit. Among children who had taken antibiotics, 61.6% also had an LRTI in that period compared to 49.7% among children without exposure to systemic antibiotics (p
OBJECTIVE: We aimed to collectively define contributions and distinct characteristics of respiratory phenotypes based on longitudinal wheeze and atopic sensitization patterns in the first 5 years of life.
METHODS: Group-based trajectory analysis was performed in the CHILD Cohort Study to identify distinct wheeze and allergic sensitization trajectories. Trajectories were evaluated for associated risk factors, health care utilization, biologic determinants, and clinical outcomes. Stool samples for shotgun metagenomic sequencing profiles of infant microbiomes collected at ages 3 months and 1 year were assessed for phenotype-specific biomarkers.
RESULTS: A total of 6 distinct respiratory phenotypes were identified on the basis of samples from 2902 children; the phenotypes differed by temporal wheeze and allergic sensitization patterns. Although allergic wheeze phenotypes (found in 11.6% of participants) carried the highest risk of asthma diagnosis, the more common nonallergic phenotypes (in 88.3% of participants) contributed to the majority of 5-year asthma diagnoses (61.4% of diagnoses). Most importantly, nonallergic phenotypes accounted for more than two-thirds of health care utilization in this age group. Phenotypes differed by lung function, blood eosinophil counts, allergic comorbidities, and weight-for-age z score. Moreover, microbiome profiles developed from 1439 infants revealed that largely nonoverlapping microbial signatures at age 1 year are associated with each phenotype.
CONCLUSION: We identified novel early-childhood respiratory phenotypes to disentangle nonoverlapping paths to preschool wheezing. Our findings highlight the continued clinical relevance of nonatopic wheeze phenotypes, which remain undertreated despite accounting for a substantial proportion of health care utilization and asthma diagnoses.