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Published on: August 7, 2017
Early-preschool wheeze trajectories are predominantly nonallergic with distinct biologic and microbiome traits
Zihang Lu1, Charisse Petersen2, Ruixue Dai3
1Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada; Department of Mathematics and Statistics, Queen's University, Kingston, Ontario, Canada.
Insights
This study identified six distinct preschool wheezing phenotypes. Non-allergic wheeze phenotypes, though common, drive significant healthcare use and asthma diagnoses, highlighting a need for better treatment strategies.
Area of Science:
- Pediatric Respiratory Medicine
- Immunology
- Microbiome Research
Background:
- Preschool wheezing is heterogeneous, complicating effective interventions.
- Understanding distinct wheeze and allergy patterns is crucial for targeted treatments.
- Early life respiratory phenotypes impact long-term health outcomes.
Purpose of the Study:
- To define distinct respiratory phenotypes based on wheeze and atopic sensitization patterns in early childhood.
- To analyze risk factors, healthcare utilization, and biological determinants for each phenotype.
- To identify microbiome biomarkers associated with specific wheezing trajectories.
Main Methods:
- Group-based trajectory analysis of longitudinal wheeze and sensitization data from the CHILD Cohort study.
- Evaluation of clinical outcomes, healthcare utilization, and biological markers (lung function, blood eosinophils).
- Shotgun metagenomic sequencing of infant stool samples to analyze microbiome profiles.
Main Results:
- Six distinct respiratory phenotypes were identified in 2902 children.
- Allergic wheeze phenotypes had higher asthma risk, but non-allergic phenotypes accounted for most 5-year asthma diagnoses and healthcare utilization.
- Phenotypes were associated with differences in lung function, blood eosinophils, comorbidities, and distinct infant gut microbiome signatures at 1 year.
Conclusions:
- Novel early childhood respiratory phenotypes were identified, clarifying distinct pathways to preschool wheezing.
- Non-atopic wheeze phenotypes are clinically significant, contributing substantially to asthma diagnoses and healthcare burden.
- Current undertreatment of non-atopic wheeze phenotypes necessitates revised clinical strategies.
Background:
Disentangling preschool wheezing heterogeneity in terms of clinical traits, temporal patterns, and collective health care burden is critical for precise and effective interventions.
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.
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