Back to Journals » Journal of Asthma and Allergy » Volume 14

Dysregulated Metabolism in the Pathophysiology of Non-Allergic Obese Asthma

Authors McCravy M, Ingram JL, Que LG

Received 25 September 2020

Accepted for publication 1 January 2021

Published 4 March 2021 Volume 2021:14 Pages 179—186


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Amrita Dosanjh

Matthew McCravy, Jennifer L Ingram, Loretta G Que

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Durham, NC, 27710, USA

Correspondence: Matthew McCravy
Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Duke University Medical Center, Box 102349, Durham, NC, 27710, USA
Tel +1 731-571-4816
Email [email protected]

Abstract: Asthma is an obstructive airway disease that is characterized by reversible airway obstruction and is classically associated with atopic, TH 2 driven inflammation. Landmark studies in the second half of the twentieth century identified eosinophils as a key mediator of inflammation and steroids, both inhaled and systemic, as a cornerstone of therapy. However, more recently other phenotypes of asthma have emerged that do not respond as well to traditional therapies. In particular, obese patients who develop asthma as adults are less likely to have eosinophilic airway inflammation and do not respond to traditional therapies. Obese patients often have metabolic comorbidities such as impaired glucose tolerance and dyslipidemias, also known as metabolic syndrome (MetS). The unified pathophysiology of metabolic syndrome is not known, however, several signaling pathways, such as the neuropeptide glucagon-like peptide-1 (GLP-1) and nitric oxide (NO) signaling have been shown to be dysregulated in MetS. These pathways are targeted by commercially available medications. This review discusses the potential roles that dysregulation of the GLP-1 and NO signaling pathways, along with arginine metabolism, play in the development of asthma in obese patients. GLP-1 receptors are found in high density in the lung and are also detectable in bronchoalveolar lavage fluid. NO has long been associated with asthma. We hypothesize that these derangements in metabolic signaling pathways underpin the asthmatic phenotype seen in obese patients with non-eosinophilic airway inflammation and poor response to established therapies. While still an active area of research, novel interventions are needed for this subset of patient who respond poorly to available asthma therapies.

Keywords: asthma, obesity, metabolic syndrome, glucagon-like peptide-1, nitric oxide

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]