Am J Respir Crit Care Med. 2022 Jun 10. doi: 10.1164/rccm.202112-2745OC. Online ahead of print.
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 was categorized as without (< 3.0), moderate (3.0-5.0), or severe (>5.0). Lung function included forced expired volume in one second (FEV1) and forced vital capacity (FVC) measured before and after treatment with inhaled albuterol and intramuscular triamcinolone acetonide (TA) 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 to patients without IR, those with IR had significantly lower values for forced expired volume in one second (FEV1) and forced vital capacity (FVC), and these lower values were not attributable to obesity effects. Compared to patients without IR, those with IR had lower FEV1 responses to beta adrenergic agonists and systemic corticosteroids. The annualized decline in FEV1 was significantly greater in patients with moderate IR (-41 mLs/year) and severe IR (-32 mLs/year,) than in patients without IR (-13mLs/year, p< 0.001 for both comparisons).
CONCLUSION: 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.