Endotyping Pediatric Obesity-related Asthma: Contribution of Anthropometrics, Metabolism, Nutrients, and CD4 Lymphocytes to Pulmonary Function

Overview

Journal J Allergy Clin Immunol

Specialty Allergy & Immunology

Date 2022 Jun 2

PMID 35654239

Authors

David Thompson

Lisa G Wood

Evan J Williams

Rebecca F McLoughlin

Deepa Rastogi

Affiliations

Soon will be listed here.

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-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-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 FEV/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 FEV/FVC ratio, ERV, and inspiratory capacity. T-cell transcriptome attenuated the association of all 4 anthropometric measures with FEV/FVC ratio, but only of WHR with ERV and inspiratory capacity. The DNA methylome attenuated the association of all 4 anthropometric measures with FEV/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.

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References

Wood L . Diet, Obesity, and Asthma. Ann Am Thorac Soc. 2017; 14(Supplement_5):S332-S338. DOI: 10.1513/AnnalsATS.201702-124AW. View

Scott H, Gibson P, Garg M, Pretto J, Morgan P, Callister R . Determinants of weight loss success utilizing a meal replacement plan and/or exercise, in overweight and obese adults with asthma. Respirology. 2014; 20(2):243-50. DOI: 10.1111/resp.12423. View

Tse S, Li L, Butler M, Fung V, Kharbanda E, Larkin E . Statin exposure is associated with decreased asthma-related emergency department visits and oral corticosteroid use. Am J Respir Crit Care Med. 2013; 188(9):1076-82. PMC: 3863744. DOI: 10.1164/rccm.201306-1017OC. View

Wildfire J, Gergen P, Sorkness C, Mitchell H, Calatroni A, Kattan M . Development and validation of the Composite Asthma Severity Index--an outcome measure for use in children and adolescents. J Allergy Clin Immunol. 2012; 129(3):694-701. PMC: 3294274. DOI: 10.1016/j.jaci.2011.12.962. View

Alexeeff S, Litonjua A, Sparrow D, Vokonas P, Schwartz J . Statin use reduces decline in lung function: VA Normative Aging Study. Am J Respir Crit Care Med. 2007; 176(8):742-7. PMC: 2020828. DOI: 10.1164/rccm.200705-656OC. View

Tong L, Tergaonkar V . Rho protein GTPases and their interactions with NFκB: crossroads of inflammation and matrix biology. Biosci Rep. 2014; 34(3). PMC: 4069681. DOI: 10.1042/BSR20140021. View

Thomas A, Giesler T, White E . p53 mediates bcl-2 phosphorylation and apoptosis via activation of the Cdc42/JNK1 pathway. Oncogene. 2000; 19(46):5259-69. DOI: 10.1038/sj.onc.1203895. View

Wang B, Mezlini A, Demir F, Fiume M, Tu Z, Brudno M . Similarity network fusion for aggregating data types on a genomic scale. Nat Methods. 2014; 11(3):333-7. DOI: 10.1038/nmeth.2810. View

Conrad L, Cabana M, Rastogi D . Defining pediatric asthma: phenotypes to endotypes and beyond. Pediatr Res. 2020; 90(1):45-51. PMC: 8107196. DOI: 10.1038/s41390-020-01231-6. View

10.

Schatz M, Sorkness C, Li J, Marcus P, Murray J, Nathan R . Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J Allergy Clin Immunol. 2006; 117(3):549-56. DOI: 10.1016/j.jaci.2006.01.011. View

11.

Rastogi D, Suzuki M, Greally J . Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma. Sci Rep. 2013; 3:2164. PMC: 3712321. DOI: 10.1038/srep02164. View

12.

Rastogi D, Canfield S, Andrade A, Isasi C, Hall C, Rubinstein A . Obesity-associated asthma in children: a distinct entity. Chest. 2011; 141(4):895-905. DOI: 10.1378/chest.11-0930. View

13.

Xi B, Zong X, Kelishadi R, Litwin M, Hong Y, Poh B . International Waist Circumference Percentile Cutoffs for Central Obesity in Children and Adolescents Aged 6 to 18 Years. J Clin Endocrinol Metab. 2019; 105(4). PMC: 7059990. DOI: 10.1210/clinem/dgz195. View

14.

Baffi C, Wood L, Winnica D, Strollo Jr P, Gladwin M, Que L . Metabolic Syndrome and the Lung. Chest. 2016; 149(6):1525-34. PMC: 4944780. DOI: 10.1016/j.chest.2015.12.034. View

15.

Haro C, Montes-Borrego M, Rangel-Zuniga O, Alcala-Diaz J, Gomez-Delgado F, Perez-Martinez P . Two Healthy Diets Modulate Gut Microbial Community Improving Insulin Sensitivity in a Human Obese Population. J Clin Endocrinol Metab. 2015; 101(1):233-42. DOI: 10.1210/jc.2015-3351. View

16.

Rougerie P, Delon J . Rho GTPases: masters of T lymphocyte migration and activation. Immunol Lett. 2011; 142(1-2):1-13. DOI: 10.1016/j.imlet.2011.12.003. View

17.

Oddy W, de Klerk N, Kendall G, Mihrshahi S, Peat J . Ratio of omega-6 to omega-3 fatty acids and childhood asthma. J Asthma. 2004; 41(3):319-26. DOI: 10.1081/jas-120026089. View

18.

Chen Y, Tu Y, Huang K, Chen P, Chu D, Lee Y . Pathway from central obesity to childhood asthma. Physical fitness and sedentary time are leading factors. Am J Respir Crit Care Med. 2014; 189(10):1194-203. DOI: 10.1164/rccm.201401-0097OC. View

19.

McGarry M, Castellanos E, Thakur N, Oh S, Eng C, Davis A . Obesity and bronchodilator response in black and Hispanic children and adolescents with asthma. Chest. 2015; 147(6):1591-1598. PMC: 4451713. DOI: 10.1378/chest.14-2689. View

20.

Rastogi D, Bhalani K, Hall C, Isasi C . Association of pulmonary function with adiposity and metabolic abnormalities in urban minority adolescents. Ann Am Thorac Soc. 2014; 11(5):744-52. PMC: 4225805. DOI: 10.1513/AnnalsATS.201311-403OC. View