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

Abstract

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 (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).

Figures

Figure 1.

Plot of serum vitamin D (25[OH]D, ng/ml) versus prebronchodilator FEV1 (L), representing an increase of 22.7 (±9.3) ml in FEV1 for each nanogram per milliliter increase in vitamin D (P = 0.02; covariate adjusted r = 0.8).

Figure 2.

Airway hyperresponsiveness to methacholine, stratified by serum vitamin D (25[OH]D, ng/ml) concentrations of 30 ng/ml. PC20 FEV1 = provocative concentration of methacholine inducing a 20% fall in FEV1.

Figure 3.

Plot of body mass index (BMI; kg/m2) versus serum vitamin D (25[OH]D, ng/ml), representing a reduction of 0.71 (±0.17) ng/ml in vitamin D for each unit increase in BMI (P = 0.0001; r = −0.5).

Figure 4.

Plot of serum vitamin D (25[OH]D, ng/ml) versus baseline TNF-α, representing a reduction of 0.06 (±0.02) units TNF-α expression for each nanogram per milliliter increase in vitamin D (P = 0.01; covariate adjusted r = −0.3). PBMC = peripheral blood mononuclear cell.

Figure 5.

Plot of serum vitamin D (25[OH]D, ng/ml) versus dexamethasone-induced mitogen-activated protein kinase phosphatase (MKP)-1 expression, representing an increase of MKP-1 of 0.03 (±0.01)-fold for each nanogram per milliliter increase in vitamin D (P = 0.04; covariate adjusted r = 0.4).