Obesity Is Associated with Sustained Symptomatology and Unique Inflammatory Features in Children with Asthma

• Type of Material: Article
• Authors: Anne Fitzpatrick, Emory University; Jocelyn Grunwell, Emory University; Abby Mutic, Emory University; AF Mohammad, Emory University; ST Stephenson, Emory University
• Language: English
• Date: 2022-03-07
• Publisher: ELSEVIER
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2021 American Academy of Allergy, Asthma & Immunology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jaip.2021.10.020
• Title of Journal or Parent Work: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE
• Volume: 10
• Issue: 3
• Start Page: 815
• End Page: +
• Grant/Funding Information: R01NR012021, R01NR013700, R01NR018666, K24NR018866, and the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number UL1TR002378
• Keywords: CHILDHOOD; QUALITY-OF-LIFE; Glutathione; Lung function; Immunology; Allergy; Oxidant stress; GESTATIONAL WEIGHT-GAIN; Life Sciences & Biomedicine; PULMONARY-FUNCTION; OXIDATIVE STRESS; Amino acids; Obesity; LUNG-FUNCTION; CONSEQUENCES; OVERWEIGHT; BODY-MASS INDEX; L-ARGININE SUPPLEMENTATION; Asthma; Exacerbation; Arginine; Science & Technology; Children; Inflammation

Abstract

Background: Obesity complicates the clinical manifestations of asthma in children. However, few studies have examined longitudinal outcomes or markers of systemic inflammation in obese asthmatic children. Objective: We hypothesized that obese children with asthma would have: (1) poorer clinical outcomes over 12 months, (2) decreased responsiveness to systemic corticosteroid administration, (3) greater markers of systemic inflammation, and (4) unique amino acid metabolites associated with oxidative stress. Methods: Children 6 to 17 years of age (lean, N = 257; overweight, N = 99; obese, N = 138) completed a baseline visit and follow-up visit at 12 months. Outcome measures included asthma control, quality of life, lung function, and exacerbations. A subset received intramuscular triamcinolone and were re-evaluated at 7(+7) days. Leptin, adiponectin, C-reactive protein, total cholesterol, interleukin (IL)-1β, IL-6, IL-17, interferon gamma, tumor necrosis factor alpha, monocyte-chemoattractant protein-1, and amino acid metabolites were also quantified in plasma as potential biomarkers of outcomes in obese children. Results: Obesity was associated with more symptoms, poorer quality life, and more exacerbations that persisted over 1 year despite greater medication requirements. Obese children also had minimal clinical improvement in asthma control and lung function after intramuscular triamcinolone. Leptin, C-reactive protein, and amino acid metabolites associated with glutathione synthesis and oxidative stress differed in obese children. Within the obese group, lower concentrations of arginine-related metabolites also distinguished uncontrolled from controlled asthma at 12 months. Conclusion: Obesity is associated with poorer asthma outcomes and unique systemic inflammatory features that may not be adequately modified with conventional asthma therapies. Novel approaches may be needed given increased symptoms and unique inflammation and oxidative stress in obese children with asthma.