Abstract
Obesity negatively impacts on asthma response to inhaled corticosteroids by unknown mechanisms. Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma is associated with an impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both improved by weight loss. 23 obese asthmatics (OA) [18 females; median age (interquartile range) 56 (51-59) years], 14 non-obese asthmatics (NOA) [11 females; 53 (43-60) years], 15 obese (O) [13 females; 47 (45-60) years], and 19 healthy controls (HC) [14 females; 43 (34-56) years] were enrolled. 10 OA and 11 O patients were evaluated at baseline (V1) and six months after (V2) bariatric surgery. Corticosteroid response was measured by dexamethasone inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function, serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2. We found a reduced response to dexamethasone in PBMCs of O and OA patients with respect to NOA and HC subjects, that inversely correlated with the diponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in O and OA patients and normalized adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP-1 expression in O and OA patients. We found a reduced response to dexamethasone in PBMCs of O and OA patients with respect to NOA and HC subjects, that inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in O and OA patients and normalized adiponectin/leptin ratio and vitamin D levels. Exposure of PBMCs to vitamin D potentiated the antiproliferative effects of corticosteroids. Dexamethasone and vitamin D induced similar MKP-1 expression in O and OA patients.
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More From: Journal of Investigational Allergy and Clinical Immunology
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