A mutated vitamin D receptor in hereditary vitamin D-resistant rickets prevents induction of bronchial hyperreactivity and inflammation

Context: Previous studies have reported an association between vitamin D deficiency and asthma. Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) patients provide a natural model to assess the role of the vitamin D receptor (VDR) in regulating human lung immune responses and airway hyperreactivity.

Objectives: The aim of the study was to determine the role of the VDR on lung functions, airways, and systemic markers of inflammation and allergy in HVDRR patients.

Conclusions: HVDRR patients show diverse exhaled cytokine profiles but seem to be protected against provoked bronchial hyperreactivity and clinical asthma. These findings suggest that an intact VDR has an important role in asthma pathophysiology.

Results: All HVDRR patients had negative MCT results, whereas six controls (35.3%) had positive MCT results (P < .014). Serum IgE levels, eosinophil counts, and fractional exhaled nitric oxide and allergy skin test results were similar for the HVDRR patients and controls, as were the serum cytokine concentrations. The HVDRR patients had different cytokine levels in their exhaled breath condensate (increased IL-4 and IL-17 and decreased IL-5, IL-10, and interferon-β levels) compared to the controls (P < .005).

Design and Methods: Thirteen HVDRR patients (aged 6-37 y) and 17 normal controls (aged 6-38 y) underwent spirometry, a methacholine challenge test (MCT), blood tests, allergy skin tests, determination of fractional exhaled nitric oxide, and measurement of serum and exhaled breath condensate cytokines, including IL-4, IL-5, IL-10, IL-17, and interferon-γ levels.