Endotyping pediatric obesity-related asthma: contribution of anthropometrics, metabolism, nutrients, and CD4+ lymphocytes, to pulmonary function
The Journal of allergy and clinical immunology
Obesity; Th lymphocytes; asthma; fat distribution; metabolic abnormalities; nutrients
BACKGROUND: Obesity-related complications including visceral fat, metabolic abnormalities, nutrient deficiencies, and immune perturbations are interdependent but have been individually associated with childhood asthma. OBJECTIVE: To endotype childhood obesity-related asthma by quantifying contributions of obesity-related complications to symptoms and pulmonary function. METHODS: Multi-omics analysis using Similarity Network Fusion followed by mediation analysis were performed to quantify prediction of obese asthma phenotype by different combinations of anthropometric, metabolic, nutrient, and Th cell transcriptome and DNA methylome datasets. RESULTS: Two clusters (n=28 and 26) distinct in their anthropometric (neck and midarm circumference, waist to hip ratio (WHR) and BMI z-score), metabolic, nutrient, and Th cell transcriptome and DNA methylome footprint predicted 5 or more pulmonary function indices across 7 different dataset combinations. Metabolic measures attenuated the association of neck, WHR and BMI z-score with FEV/FVC ratio and ERV, of neck, midarm, and BMI z-score with FRC, but only of WHR with IC. Nutrient levels attenuated the association of neck, midarm circumference, and BMI z-score with FRC, and of WHR with FEV/FVC ratio, ERV and IC. Th cell transcriptome attenuated the association of all four anthropometric measures with FEV/FVC ratio, but only of WHR with ERV and IC. The DNA methylome attenuated the association of all four anthropometric measures with FEV/FVC ratio and ERV, but only of WHR with IC. CONCLUSION: Anthropometric, metabolic, nutrient, and immune perturbations have individual but interdependent contributions to obese asthma phenotype, with the most consistent effect of WHR, highlighting the role of truncal adiposity in endotyping childhood obesity-related asthma.
Thompson, David; Wood, Lisa G.; Williams, Evan J.; McLoughlin, Rebecca F.; and Rastogi, Deepa, "Endotyping pediatric obesity-related asthma: contribution of anthropometrics, metabolism, nutrients, and CD4+ lymphocytes, to pulmonary function" (2022). GW Authored Works. Paper 904.