Endotyping pediatric obesity-related asthma: Contribution of anthropometrics, metabolism, nutrients, and CD4+ lymphocytes to pulmonary function

David Thompson; Lisa G Wood; Evan J Williams; Rebecca F McLoughlin; Deepa Rastogi

doi:10.1016/j.jaci.2022.04.033

Endotyping pediatric obesity-related asthma: Contribution of anthropometrics, metabolism, nutrients, and CD4⁺ lymphocytes to pulmonary function

J Allergy Clin Immunol. 2022 Oct;150(4):861-871. doi: 10.1016/j.jaci.2022.04.033. Epub 2022 May 30.

Authors

David Thompson¹, Lisa G Wood², Evan J Williams², Rebecca F McLoughlin², Deepa Rastogi³

Affiliations

¹ Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC.
² Priority Research Centre for Healthy Lungs, University of Newcastle, New Lambton Heights, Australia.
³ Children's National Hospital, George Washington University School of Medicine and Health Sciences, Washington, DC. Electronic address: drastogi@childrensnational.org.

Abstract

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 T_H-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 T_H-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. T_H-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.

Keywords: Obesity; T(H) cells; asthma; fat distribution; metabolic abnormalities; nutrients.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Adiposity
Asthma*
Body Mass Index
CD4-Positive T-Lymphocytes
Humans
Nutrients
Pediatric Obesity* / complications
Waist-Hip Ratio

Abstract

Publication types

MeSH terms

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