- Title
- Endotyping pediatric obesity–related asthma: Contribution of anthropometrics, metabolism, nutrients, and CD4+ lymphocytes to pulmonary function
- Creator
- Thompson, David; Wood, Lisa G.; Williams, Evan J.; McLoughlin, Rebecca F.; Rastogi, Deepa
- Relation
- Journal of Allergy and Clinical Immunology Vol. 150, Issue 4, p. 861-871
- Publisher Link
- http://dx.doi.org/10.1016/j.jaci.2022.04.033
- Publisher
- Elsevier
- Resource Type
- journal article
- Date
- 2022
- Description
- 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: We sought to endotype childhood obesity–related asthma by quantifying contributions of obesity-related complications to symptoms and pulmonary function. Methods: Multiomics 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 data sets. Results: Two clusters (n = 28 and 26) distinct in their anthropometric (neck and midarm circumference, waist to hip ratio [WHR], and body mass index [BMI] z score), metabolic, nutrient, and TH-cell transcriptome and DNA methylome footprint predicted 5 or more pulmonary function indices across 7 different data set combinations. Metabolic measures attenuated the association of neck, WHR, and BMI z score with FEV1/forced vital capacity (FVC) ratio and expiratory reserve volume (ERV), of neck, midarm, and BMI z score with functional residual capacity, but only of WHR with inspiratory capacity. Nutrient levels attenuated the association of neck, midarm circumference, and BMI z score with functional residual capacity, and of WHR with FEV1/FVC ratio, ERV, and inspiratory capacity. TH-cell transcriptome attenuated the association of all 4 anthropometric measures with FEV1/FVC ratio, but only of WHR with ERV and inspiratory capacity. The DNA methylome attenuated the association of all 4 anthropometric measures with FEV1/FVC ratio and ERV, but only of WHR with inspiratory capacity. Conclusions: 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.
- Subject
- obesity; asthma; fat distribution; metabolic abnormalities; nutrients; TH cells; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1488194
- Identifier
- uon:52374
- Identifier
- ISSN:0091-6749
- Language
- eng
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