Body mass and glucocorticoid response in asthma

Abstract

Rationale: Obesity may alter glucocorticoid response in asthma.

Objectives: 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.

Measurements and main 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.

Figure 1.

(A) Reduced dexamethasone (DEX)-induced mitogen-activated protein kinase phosphatase (MKP)-1 expression in peripheral blood mononuclear cells (PBMCs) from overweight/obese (gray) versus lean (black) subjects with asthma. Data are presented as mean ± SEM. (B) PBMCs from patients with asthma demonstrates significantly reduced DEX-induced MKP-1 expression with increased body mass index (BMI). Lines represent regression with (solid line) and without outlying data point (arrow).

Figure 1.

(A) Reduced dexamethasone (DEX)-induced mitogen-activated protein kinase phosphatase (MKP)-1 expression in peripheral blood mononuclear cells (PBMCs) from overweight/obese (gray) versus lean (black) subjects with asthma. Data are presented as mean ± SEM. (B) PBMCs from patients with asthma demonstrates significantly reduced DEX-induced MKP-1 expression with increased body mass index (BMI). Lines represent regression with (solid line) and without outlying data point (arrow).

Figure 2.

(A) Dexamethasone (DEX)-induced MKP-1 expression in peripheral blood mononuclear cells (PBMCs) of lean (black) versus overweight/obese (gray) subjects without asthma. Data are presented as mean ± SEM. (B) PBMCs from subjects without asthma do not demonstrate significantly reduced DEX-induced MKP-1 expression with increased body mass index (BMI).

Figure 2.

(A) Dexamethasone (DEX)-induced MKP-1 expression in peripheral blood mononuclear cells (PBMCs) of lean (black) versus overweight/obese (gray) subjects without asthma. Data are presented as mean ± SEM. (B) PBMCs from subjects without asthma do not demonstrate significantly reduced DEX-induced MKP-1 expression with increased body mass index (BMI).

Figure 3.

(A) Peripheral blood mononuclear cells (PBMCs) from patients with asthma demonstrate significantly increased log (TNF-α) mRNA expression with increasing body mass index (BMI). (B) PBMCs from subjects without asthma do not demonstrate significantly increased log (TNF-α) mRNA expression with increasing BMI.

Figure 3.

(A) Peripheral blood mononuclear cells (PBMCs) from patients with asthma demonstrate significantly increased log (TNF-α) mRNA expression with increasing body mass index (BMI). (B) PBMCs from subjects without asthma do not demonstrate significantly increased log (TNF-α) mRNA expression with increasing BMI.

Figure 4.

(A) Peripheral blood mononuclear cells (PBMCs) from patients with asthma demonstrate a significantly increased ratio of log (TNF-α) mRNA to dexamethasone (DEX)-induced MKP-1 expression with increasing body mass index (BMI). (B) PBMCs from subjects without asthma do not demonstrate a significantly increased ratio of log (TNF-α) mRNA to DEX-induced MKP-1 expression with increasing BMI.

Figure 4.

(A) Peripheral blood mononuclear cells (PBMCs) from patients with asthma demonstrate a significantly increased ratio of log (TNF-α) mRNA to dexamethasone (DEX)-induced MKP-1 expression with increasing body mass index (BMI). (B) PBMCs from subjects without asthma do not demonstrate a significantly increased ratio of log (TNF-α) mRNA to DEX-induced MKP-1 expression with increasing BMI.

Figure 5.

(A) Reduced dexamethasone (DEX)-induced MKP-1 expression in bronchoalveolar lavage (BAL) cells from overweight/obese (gray) versus lean (black) patients with asthma. Data are presented as mean ± SEM. (B) BAL cells from patients with asthma demonstrate significantly reduced DEX-induced MKP-1 with increasing body mass index (BMI).

Figure 5.

(A) Reduced dexamethasone (DEX)-induced MKP-1 expression in bronchoalveolar lavage (BAL) cells from overweight/obese (gray) versus lean (black) patients with asthma. Data are presented as mean ± SEM. (B) BAL cells from patients with asthma demonstrate significantly reduced DEX-induced MKP-1 with increasing body mass index (BMI).