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Published ahead of print on July 17, 2008, doi:10.1164/rccm.200801-076OC

Am. J. Respir. Crit. Care Med., Volume 178, Number 7, October 2008, 682-687

A more recent version of this article appeared on October 1, 2008
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Submitted on January 11, 2008
Accepted on July 17, 2008

Body Mass and Glucocorticoid Response in Asthma

E. Rand Sutherland1*, Elena Goleva2, Matthew Strand3, David A Beuther1, and Donald YM Leung4

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

* To whom correspondence should be addressed. E-mail: sutherlande{at}njc.org.

Rationale: Obesity may alter glucocorticoid (GC) response in asthma. Objective: To evaluate the relationship between body mass index (BMI, kg/m2) and GC response in subjects with and without asthma. Methods: Nonsmoking adult subjects underwent characterization of lung function, body mass index (BMI, kg/m2) and spirometric response to prednisone. Dexamethasone (DEX, 10-6M)-induced MAP kinase phosphatase-1 (MKP-1) and baseline tumor necrosis factor-{alpha}(TNF-{alpha}) expression were evaluated by PCR in peripheral blood mononuclear (PBMC) and bronchoalveolar lavage (BAL) cells. The relationship between BMI and expression of MKP-1 and TNF-{alpha} was analyzed. Main Results: 45 nonsmoking adults, 33 with asthma (mean (SD) FEV1% of 70.7 (9.8)%) and 12 without were enrolled. DEX-induced PBMC MKP-1 expression was reduced in overweight/obese versus lean asthmatics, with mean (±SEM) fold-induction of 3.11 ± 0.46 vs. 5.27 ± 0.66, respectively (p=0.01). In asthmatics, regression analysis revealed a -0.16 ± 0.08-fold decrease in DEX-induced MKP-1 per unit BMI increase (p=0.04). PBMC TNF-{alpha} expression increased as BMI increased in subjects with asthma, with a 0.27 unit increase in log [TNF-{alpha} (ng/mL)] per unit BMI increase (p=0.01). The ratio of PBMC [log [TNF-{alpha}]:DEX-induced MKP-1] also increased as BMI increased in asthmatics (+0.09 ±0.02, p=0.004). In BAL cells, DEX-induced MKP-1 expression was also reduced in overweight/obese vs. lean asthmatics (1.36 ± 0.09 vs. 1.76 ± 0.15-fold induction, p=0.05). Similar findings were not observed in nonasthmatic controls. Conclusions: Elevated BMI is associated with blunted in vitro response to prednisone in overweight and obese asthmatics.
Key words: asthma, therapy, obesity






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