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Body Mass and Glucocorticoid Response in Asthma

¹ Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado; ² Department of Medicine, University of Colorado, Denver, Colorado; ³ Department of Pediatrics, and ⁴ Division of Biostatistics, National Jewish Medical and Research Center, Denver, Colorado; and ⁵ Department of Preventive Medicine and Biometrics, and ⁶ Department of Pediatrics, University of Colorado, Denver, Colorado

Correspondence and requests for reprints should be addressed to E. Rand Sutherland, M.D., M.P.H., National Jewish Health Center, 1400 Jackson Street, J-220 Denver, CO 80206. E-mail: sutherlande{at}njc.org

Rationale: Obesity may alter glucocorticoid response in asthma.

Objectives: To evaluate the relationship between body mass index (BMI, kg/m²) and glucocorticoid response in subjects with and without asthma.

Methods: Nonsmoking adult subjects underwent characterization of lung function, BMI, and spirometric response to prednisone. Dexamethasone (DEX, 10^–6 M)-induced mitogen-activated protein kinase phosphatase-1 (MKP-1) and baseline tumor necrosis factor (TNF)- expression were evaluated by polymerase chain reaction in peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage cells. The relationship between BMI and expression of MKP-1 and TNF- was analyzed.

Measurements and Main Results: A total of 45 nonsmoking adults, 33 with asthma (mean [SD] FEV₁% of 70.7 [9.8]%) and 12 without asthma were enrolled. DEX-induced PBMC MKP-1 expression was reduced in overweight/obese versus lean patients with asthma, with mean (± SEM) fold-induction of 3.11 (±0.46) versus 5.27 (±0.66), respectively (P = 0.01). In patients with asthma, regression analysis revealed a –0.16 (±0.08)-fold decrease in DEX-induced MKP-1 per unit BMI increase (P = 0.04). PBMC TNF- expression increased as BMI increased in subjects with asthma, with a 0.27 unit increase in log (TNF- [ng/ml]) per unit BMI increase (P = 0.01). The ratio of PBMC log (TNF-):DEX-induced MKP-1 also increased as BMI increased in patients with asthma (+0.09 ± 0.02; P = 0.004). In bronchoalveolar lavage cells, DEX-induced MKP-1 expression was also reduced in overweight/obese versus lean patients with asthma (1.36 ± 0.09-fold vs. 1.76 ± 0.15-fold induction; P = 0.05). Similar findings were not observed in control subjects without asthma.

Conclusions: Elevated BMI is associated with blunted in vitro response to dexamethasone in overweight and obese patients with asthma.

Key Words: asthma • therapy • obesity

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Obesity may alter glucocorticoid (GC) response in asthma. What This Study Adds to the Field These data suggest that in vitro response to GCs is reduced in overweight and obese patients with asthma. This phenomenon may lead to reduced clinical efficacy of GC therapy in patients with asthma who are overweight or obese.