Article

Body Mass and Glucocorticoid Response in Asthma

Department of Medicine, National Jewish Medical and Research Center, 1400 Jackson Street, J-220 Denver, CO 80206, USA.
American Journal of Respiratory and Critical Care Medicine (Impact Factor: 13). 10/2008; 178(7):682-7. DOI: 10.1164/rccm.200801-076OC
Source: PubMed

ABSTRACT

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.

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    • "LT synthesis has been shown to be increased in peripheral blood leukocytes [11] [12], airway macrophages, and eosinophils [13] from asthmatics compared to cells from healthy controls. Asthma with obesity is often difficult to control and manifests steroid resistance [14]. Interestingly, obese subjects that had reduced responsiveness to inhaled corticosteroids with increasing body mass index (BMI) demonstrated a stable response to treatment with the LT modifier, montelukast [15]. "
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    ABSTRACT: . The prevalence of obesity has increased dramatically over the last decades, and its association with asthma is being increasingly recognized. Aims . Our hypothesis is that increased leptin and decreased adiponectin levels in obese subjects play a direct role in regulating inflammation in asthmatics. We wanted to examine the hypothesis that cysteinyl leukotrienes (cys-LT), inflammatory mediators that are regulated by adipokines, are involved in the pathogenesis of asthma. Methods . We studied a population of asthmatics and nonasthmatics, who in turn were divided into obese and nonobese categories. We examined leptin and its ratio to adiponectin, in asthmatics and nonasthmatics, with and without obesity. In addition, we measured cys-LT levels in exhaled breath condensate (EBC) and in peripheral blood monocytes (PBM) in these groups. Results . Leptin levels were increased in obese asthmatics compared to obese nonasthmatics. The leptin/adiponectin (L/A) ratio was higher in obese asthmatics compared to obese nonasthmatics. EBC cys-LT levels were elevated in asthmatics compared to nonasthmatics. Discussion . Proinflammatory adipokines, released from adipose tissue, may promote an asthma phenotype through enhanced cys-LT production that may result in more prevalent and difficult to control airway disease.
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    • "Not only is obesity a risk factor for asthma, but asthma in the obese has distinct features compared to disease in the non-obese. Obese asthmatics tend to have more severe disease [2] [3] respond less well to standard controller therapy, [4] and have evidence of cellular glucocorticoid resistance [5]. This despite the fact they do not appear to have worsened airway inflammation as measured by either sputum eosinophils or neutrophils [6]. "
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    ABSTRACT: Asthma in the obese represents a growing epidemic of pulmonary disease, and these patients are distinct from non obese asthmatics. Accordingly, studies on the pathogenesis of asthma in the obese are critical to guide our understanding of this disease process; such studies will ultimately guide the development of new therapies to treat the obese asthmatic population.
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    • "Obese asthmatic patients are often described as severe and poorly controlled4,5 perhaps because they are less responsive to corticosteroids and exhibit a different (e.g., less atopic) inflammatory phenotype.6 Obesity is associated with chronic low-grade systemic inflammation that is thought to enhance systemic complications.7 It is known that adipose tissue can regulate systemic inflammation through the production of a variety of adipokines which may link the two disorders mechanistically.8 "
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    ABSTRACT: Increasing epidemiological data identify a link between obesity and asthma incidence and severity. Based on experimental data, it is possible that shared inflammatory mechanisms play a role in determining this linkage. Although controversial, the role of adipokines may be central to this association and the maintenance of the asthma phenotype. While leptin and adiponectin have a causal link to experimental asthma in mice, data in humans are less conclusive. Recent studies demonstrate that adipokines can regulate the survival and function of eosinophils and that these factors can affect eosinophil trafficking from the bone marrow to the airways. In addition, efferocytosis, the clearance of dead cells, by airway macrophages or blood monocytes appears impaired in obese asthmatics and is inversely correlated with glucocorticoid responsiveness. This review examines the potential mechanisms linking obesity to asthma.
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