Body mass and glucocorticoid response in asthma.
BACKGROUND
Obesity may alter glucocorticoid response in asthma.


OBJECTIVE
To evaluate the relationship between body mass index (BMI, kg/m(2)) 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)-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.


RESULTS
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.


CONCLUSIONS
Elevated BMI is associated with blunted in vitro response to dexamethasone in overweight and obese patients with asthma.
Sutherland
E Rand
ER
Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, J-220 Denver, CO 80206, USA. sutherlande@njc.org
Goleva
Elena
E
Strand
Matthew
M
Beuther
David A
DA
Leung
Donald Y M
DY
D000328:Adult; D001249:Asthma / Q000150:complications / Q000188:drug therapy*; D015992:Body Mass Index; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016022:Case-Control Studies; D003907:Dexamethasone / Q000494:pharmacology*; D054638:Dual Specificity Phosphatase 1 / Q000187:drug effects*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects*
D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1