American Journal of Respiratory and Critical Care Medicine Vol 181. pp. 699-704, (2010)
doi: 10.1164/rccm.200911-1710OC
E. Rand Sutherland1,2, Elena Goleva3,4, Leisa P. Jackson3, Allen D. Stevens1 and Donald Y. M. Leung3,4
1 Department of Medicine, and 3 Department of Pediatrics, National Jewish Health, Denver, Colorado; and 2 Department of Medicine, and 4 Department of Pediatrics, University of Colorado, Denver, Colorado
Correspondence and requests for reprints should be addressed to E. Rand Sutherland, M.D., M.P.H., 1,400 Jackson Street, J-201, Denver, CO 80206. E-mail: sutherlande at njhealth.org
Rationale: Patients with asthma exhibit variable response to inhaled corticosteroids (ICS). Vitamin D is hypothesized to exert effects on phenotype and glucocorticoid (GC) response in asthma.
Objectives: To determine the effect of vitamin D levels on phenotype and GC response in asthma.
Methods: Nonsmoking adults with asthma were enrolled in a study assessing the relationship between serum 25(OH)D (vitamin D) concentrations and lung function, airway hyperresponsiveness (AHR), and GC response, as measured by dexamethasone-induced expression of mitogen-activated protein kinase phosphatase (MKP)-1 by peripheral blood mononuclear cells.
Measurements and Main Results: A total of 54 adults with asthma (FEV1, 82.9 ± 15.7% predicted mean ± SD, serum vitamin D levels of 28.1 ± 10.2 ng/ml) were enrolled. Higher vitamin D levels were associated with greater lung function, with a 22.7 (±9.3) ml (mean ± SE) increase in FEV1 for each nanogram per milliliter increase in vitamin D (P = 0.02).
Participants with vitamin D insufficiency (<30 ng/ml) demonstrated increased AHR, with a provocative concentration of methacholine inducing a 20% fall in FEV1 of 1.03 (±0.2) mg/ml versus 1.92 (±0.2) mg/ml in those with vitamin D of 30 ng/ml or higher (P = 0.01). In ICS-untreated participants, dexamethasone-induced MKP-1 expression increased with higher vitamin D levels, with a 0.05 (±0.02)-fold increase (P = 0.02) in MKP-1 expression observed for each nanogram per milliliter increase in vitamin D, a finding that occurred in the absence of a significant increase in IL-10 expression.
Conclusions: In asthma, reduced vitamin D levels are associated with impaired lung function, increased AHR, and reduced GC response, suggesting that supplementation of vitamin D levels in patients with asthma may improve multiple parameters of asthma severity and treatment response.
Clinical trials registered with www.clinicaltrials.gov (NCT00495157, NCT00565266, and NCT00557180).
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