Asthma and lower airway disease
Vitamin D reduces eosinophilic airway inflammation in nonatopic asthma

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Background

Low levels of vitamin D are associated with asthma severity, airway remodeling, and exacerbation rate increase, especially in nonatopic asthma. Reduced steroid responsiveness or impaired antimicrobial defense might be underlying mechanisms.

Objective

We sought to evaluate the effect of vitamin D supplementation on eosinophilic and neutrophilic airway inflammation in patients with nonatopic asthma.

Methods

In a double-blind, randomized, placebo-controlled trial, we investigated the effect of long-acting vitamin D3 (400,000 IU) on sputum neutrophils and eosinophils in 44 patients with nonatopic asthma with neutrophilic (≥53%) and/or eosinophilic (≥3%) airway inflammation. Sputum induction was performed at baseline and after 9 weeks. Other measurements included questionnaires, blood samples, and pulmonary function.

Results

Treatment with vitamin D did not significantly affect sputum neutrophils or eosinophils compared with treatment with placebo in the total group. Regarding sputum eosinophils, the effect of vitamin D appeared to be dependent on baseline sputum eosinophil levels (interaction P = .015). In patients with eosinophil levels of 26.2% or more (median in patients with sputum eosinophilia, >3%), eosinophils decreased from a median of 41.0% to 11.8% after vitamin D treatment as compared with an increase from 51.8% to 63.3% in patients receiving placebo (P = .034). Vitamin D treatment also resulted in slightly better Asthma Control Questionnaire scores (P = .08).

Conclusions

Vitamin D supplementation reduced eosinophilic airway inflammation in patients with nonatopic asthma with severe eosinophilic airway inflammation, but did not affect sputum neutrophils. Also, a small effect on asthma control was observed. These findings suggest that vitamin D might have potential as an add-on treatment option in eosinophilic asthma.

Section snippets

Patients

Patients with asthma aged 18 years or older were included in this study. Asthma diagnosis was confirmed by a documented reversible airway obstruction (improvement in FEV1 ≥12% predicted and ≥200 mL after the administration of 400 μg of salbutamol) or by airway hyperresponsiveness to methacholine (reduction of 20% predicted in FEV1 after the inhalation of up to 8 mg/mL of methacholine). All patients were using standard asthma medication according to international guidelines.20 They were all

Results

Of the 196 patients who were screened for this study, 118 had a successful sputum induction. Of these subjects, 44 patients were eligible for participation in the study (15 patients with sputum eosinophilia and 20 with sputum neutrophilia and 9 with mixed eosinophilia and neutrophilia) and data from these patients were used in the analysis (Fig 1). Baseline characteristics showed no statistically significant differences between patients treated with vitamin D and patients treated placebo (Table

Discussion

In this study, a single high dose of oral vitamin D3 reduced eosinophilic airway inflammation in patients with nonatopic asthma and prominent sputum eosinophilia. Vitamin D3 did not affect sputum neutrophils despite a significant rise in plasma vitamin D3 levels. These results suggest that the beneficial effect of vitamin D3 in asthma may be related to its effect on eosinophilic airway inflammation, thereby identifying an area of potential intervention in the subgroup of patients with most

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    This study was supported by unrestricted grants from GlaxoSmithKline, Medical Centre Leeuwarden research fund, and Frysian Pulmonologists.

    Disclosure of potential conflict of interest: J. C. de Groot has received research support from GlaxoSmithKline (GSK), the Medical Centre Leeuwarden research fund, and Frysian Pulmonologists. P. S. Hiemstra has received research support from Boehringer Ingelheim and Galapagos. E. H. D. Bel is a board member for Novartis (2014); has received consultancy fees from GSK (2012), Regeneron (2013), and Cipla (2013); has received research support from GSK and Chiesi; and has received lecture fees from GSK. A. ten Brinke has received research support from GSK; is a board member for Novartis NL (Advisor Research Board); and has received lecture fees from GSK, Boehringer Ingelheim, and Novartis. The rest of the authors declare that they have no relevant conflicts of interest.

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