Vitamin D levels, lung function, and steroid response in adult asthma.
BACKGROUND
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.


OBJECTIVE
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.


RESULTS
A total of 54 adults with asthma (FEV(1), 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 FEV(1) 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 FEV(1) 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).
Sutherland
E Rand
ER
Department of Medicine, University of Colorado, Denver, Colorado, USA. sutherlande@njhealth.org
Goleva
Elena
E
Jackson
Leisa P
LP
Stevens
Allen D
AD
Leung
Donald Y M
DY
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D015992:Body Mass Index; D016535:Bronchial Hyperreactivity / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000009:adverse effects; D048708:Cell Growth Processes / Q000187:drug effects / Q000502:physiology; D003430:Cross-Sectional Studies; D003907:Dexamethasone / Q000008:administration & dosage; D004347:Drug Interactions; D054638:Dual Specificity Phosphatase 1 / Q000096:biosynthesis; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D008168:Lung / Q000503:physiopathology*; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood; D014807:Vitamin D / Q000008:administration & dosage / Q000097:blood*; D014808:Vitamin D Deficiency / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology
D001993:Bronchodilator Agents; D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride; D016753:Interleukin-10; D014807:Vitamin D; D003907:Dexamethasone; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1