Vitamin D deficiency and reduced lung function in connective tissue-associated interstitial lung diseases

Abstract

Background: Vitamin D is a steroid hormone with pleiotropic effects including immune system modulation, lung tissue remodeling, and bone health. Vitamin D deficiency has been implicated in the development of autoimmune diseases. We sought to evaluate the prevalence of vitamin D deficiency in a cohort of patients with interstitial lung disease (ILD) and hypothesized that vitamin D deficiency would be associated with an underlying connective tissue disease (CTD) and reduced lung function.

Methods: Patients in the University of Cincinnati ILD Center database were evaluated for serum 25-hydroxyvitamin D levels as part of a standardized protocol. Regression analysis evaluated associations between 25-hydroxyvitamin D levels and other variables.

Results: One hundred eighteen subjects were included (67 with CTD-ILD, 51 with other forms of ILD). The overall prevalence of vitamin D deficiency and insufficiency in the study population was 38% and 59%, respectively. Those with CTD-ILD were more likely to have vitamin D deficiency (52% vs 20%, P < .0001) and insufficiency (79% vs 31%, P < .0001) than other forms of ILD. Diminished FVC was associated with lower 25-hydroxyvitamin D(3) levels (P = .01). The association between vitamin D insufficiency and CTD-ILD persisted (OR, 11.8; P < .0001) after adjustment for potential confounders. Among subjects with CTD-ILD, reduced 25-hydroxyvitamin D(3) levels were strongly associated with reduced lung function (FVC, P = .015; diffusing capacity for carbon monoxide, P = .004).

Conclusions: There is a high prevalence of vitamin D deficiency in patients with ILD, particularly those with CTD-ILD, and it is associated with reduced lung function. Vitamin D may have a role in the pathogenesis of CTD-ILD.

Figure 1.

Histogram of serum vitamin D (25(OH)D₃, ng/mL) by patient subgroup (analysis of variance [ANOVA], P < .00001). 25(OH)D₃ = 25-hydroxyvitamin D₃; CTD-ILD = connective tissue disease-associated interstitial lung disease; granulomatous disease = sarcoidosis and hypersensitivity pneumonitis; IIP  =  idiopathic interstitial pneumonias; Misc = miscellaneous ILD.

Figure 2.

A, Plot of serum vitamin D(25(OH)D₃, ng/mL) by FVC tertiles (first < 64% predicted, second = 64%-83% predicted, third > 83% predicted) among subjects with CTD-ILD (ANOVA, P = .045). B, Plot of serum vitamin D (25(OH)D₃, ng/mL) by diffusing capacity for carbon monoxide tertiles (first < 45% predicted, second = 45%-58% predicted, third > 58% predicted) among subjects with CTD-ILD. (ANOVA, P = .032). DLCO = diffusing capacity for carbon monoxide. See Figure 1 legend for expansion of the other abbreviations.