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Weight Loss and Vitamin D Improve Hyporesponsiveness to Corticosteroids in Obese Asthma
Bantulà M1, Tubita V1, Roca-Ferrer J1,2, Mullol J1,2,3, Valero A1,2,4, Bobolea I1,2,4, Pascal M5, de Hollanda A1,6,7, Vidal J1,6,8, Picado C1,2,4*, Arismendi E1,2,4*
1Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
2Centro de Investigaciones Biomédicas en Red de Enfermedades Respiratorias (CIBERES), Madrid, Spain
3Rhinology Unit & Smell Clinic, ENT Department, Hospital Clinic, Barcelona, Spain
4Pulmonology and Allergy Department, Hospital Clinic, Barcelona, Spain
5Immunology Department, Hospital Clinic, Barcelona, Spain
6Obesity Unit, Endocrinology and Nutrition Department, Hospital Clínic, Barcelona, Spain
7Centro de Investigaciones Biomédicas en Red de Fisopatología de la Obesidad y Nutrición (CIBEROBN), Madrid, Spain
8Centro de Investigaciones Biomédicas en Red en Diabetes y Enfermedades Metabólicas (CIBERDEM), Madrid, Spain
*Both authors contributed equally to this work with senior responsibilities.
J Investig Allergol Clin Immunol 2023; Vol 33(6)
: 464-473
doi: 10.18176/jiaci.0861
Background: Obesity negatively impacts on the response of asthma patients to inhaled corticosteroids. The mechanisms underlying this impact are unknown.
Objective: To demonstrate that the poor response to inhaled corticosteroids in obese asthma patients is associated with impaired anti-inflammatory activity of corticosteroids and vitamin D deficiency, both of which are improved by weight loss.
Methods: The study population comprised 23 obese asthma patients (OA) (18 females; median (IQR) age 56 [51-59] years), 14 nonobese asthma patients (NOA) (11 females; 53 [43-60] years), 15 obese patients (OP) (13 females; 47 [45-60] years), and 19 healthy controls (HC) (14 females; 43 [34-56] years). Ten OA and 11 OP were evaluated at baseline (V1) and 6 months after bariatric surgery (V2). Corticosteroid response was measured using dexamethasone-induced inhibition of peripheral blood mononuclear cell (PBMC) proliferation. Lung function and serum levels of leptin, adiponectin, and vitamin D were measured at V1 and V2.
Results: We found a reduced response to dexamethasone in PBMCs of OP and OA with respect to NOA and HC; this inversely correlated with the adiponectin/leptin ratio and vitamin D levels. Bariatric surgery improved corticosteroid responses in OP and OA and normalized the 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 MKP1 expression in OP and OA.
Conclusions: The efficacy of weight loss to improve symptoms and lung function in OA may be due, at least in part, to the recovered anti-inflammatory effects of corticosteroids. Vitamin D deficiency may contribute to corticosteroid hyporesponsiveness in OA.
Key words: Asthma, Bariatric surgery, Corticosteroid, Obesity, Vitamin D
