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).

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).