American Journal of Respiratory and Critical Care Medicine

Rationale: The role of obesity-associated insulin resistance (IR) in airflow limitation in asthma is uncertain.

Objectives: Using data in the Severe Asthma Research Program 3 (SARP-3), we evaluated relationships between homeostatic measure of IR (HOMA-IR), lung function (cross-sectional and longitudinal analyses), and treatment responses to bronchodilators and corticosteroids.

Methods: HOMA-IR values were categorized as without (<3.0), moderate (3.0–5.0), or severe (>5.0). Lung function included FEV1 and FVC measured before and after treatment with inhaled albuterol and intramuscular triamcinolone acetonide and yearly for 5 years.

Measurements and Main Results: Among 307 participants in SARP-3, 170 (55%) were obese and 140 (46%) had IR. Compared with patients without IR, those with IR had significantly lower values for FEV1 and FVC, and these lower values were not attributable to obesity effects. Compared with patients without IR, those with IR had lower FEV1 responses to β-adrenergic agonists and systemic corticosteroids. The annualized decline in FEV1 was significantly greater in patients with moderate IR (−41 ml/year) and severe IR (−32 ml/year,) than in patients without IR (−13 ml/year, P < 0.001 for both comparisons).

Conclusions: IR is common in asthma and is associated with lower lung function, accelerated loss of lung function, and suboptimal lung function responses to bronchodilator and corticosteroid treatments. Clinical trials in patients with asthma and IR are needed to determine if improving IR might also improve lung function.

Correspondence and requests for reprints should be addressed to Michael C. Peters, M.D., Division of Pulmonary and Critical Care Medicine, Department of Medicine, University of California San Francisco, 400 Parnassus Ave., San Francisco, CA 94143-0130. E-mail: .

A complete list of National Heart, Lung, and Blood Institute Severe Asthma Research Program-3 members may be found before the beginning of the References.

Supported by NIH grant K23 HL138303, AstraZeneca, Boehringer Ingelheim, Genentech, and GlaxoSmithKline.

Author Contributions: M.C.P., D.T.M., and J.V.F. are the guarantors of the paper, taking responsibility for the integrity of the work as a whole from inception to published article. M.C.P., M.L.S., J.C.C., M.W.J., R.S., M.D.D., E.R.B., D.A.M., M.C., K.S., S.C.E., M.C.T., J.G.Z., A.T.H., W.M., B.D.L., E.I., M.D.D., B.R.P., D.T.M., S.E.W., M.L.F., S.K.K., L.C.D., P.G.W., N.N.J., and J.V.F. conceived and designed the study. M.C.P. and D.T.M. did the primary analysis and made substantial contributions to the design of the study and interpretation of data. M.C.P. and D.T.M. had access to and verified the underlying data. M.C.P. and J.V.F. prepared the first draft of the manuscript, and all authors revised the draft critically for important intellectual content. All authors gave final approval for the manuscript version to be published.

This article has a related editorial.

This version of the article was corrected on March 1, 2023 (see

This article has an online supplement, which is accessible from this issue’s table of contents at

Originally Published in Press as DOI: 10.1164/rccm.202112-2745OC on June 10, 2022

Author disclosures are available with the text of this article at

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