Body Mass and Glucocorticoid Response in Asthma

• Published in: American journal of respiratory and critical care medicine Vol. 178; no. 7; pp. 682 - 687
• Main Authors: Sutherland, E. Rand, Goleva, Elena, Strand, Matthew, Beuther, David A, Leung, Donald Y. M
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.10.2008; American Lung Association; American Thoracic Society
• Subjects: A. Asthma and Allergy; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Asthma - complications; Asthma - drug therapy; Biological and medical sciences; Body Mass Index; Bronchoalveolar Lavage Fluid - cytology; Case-Control Studies; Chronic obstructive pulmonary disease, asthma; Dexamethasone - pharmacology; Dual Specificity Phosphatase 1 - drug effects; Female; Glucocorticoids - pharmacology; Humans; In Vitro Techniques; Intensive care medicine; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Male; Medical sciences; Middle Aged; Obesity - complications; Pneumology; Tumor Necrosis Factor-alpha - drug effects; Lung disease; Obesity; Intensive care; Respiratory disease; therapy; Nutrition disorder; Glucocorticoid; Asthma; Treatment; Bronchus disease; Obstructive pulmonary disease; Nutritional status; Resuscitation
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.200801-076OC

Obesity may alter glucocorticoid response in asthma. To evaluate the relationship between body mass index (BMI, kg/m(2)) and glucocorticoid response in subjects with and without asthma. 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)-alpha 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-alpha was analyzed. A total of 45 nonsmoking adults, 33 with asthma (mean [SD] FEV(1)% 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-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 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. Elevated BMI is associated with blunted in vitro response to dexamethasone in overweight and obese patients with asthma.