Background 25-hydroxyvitamin D (25(OH)D) may be associated with lung function through modulation of pulmonary protease-antiprotease imbalance, airway inflammation, lung remodelling and oxidative stress. We examined the association of plasma 25(OH)D levels with lung function, lung function decline and risk of chronic obstructive pulmonary disease (COPD).

Methods Plasma 25(OH)D was measured in 10 116 participants in the Copenhagen City Heart Study and in 8391 participants in the Copenhagen General Population Study. In the former study, up to three measurements of lung function spanning 20 years allowed analyses of lung function decline.

Results In both cohorts, forced vital capacity in % of predicted was 7% lower and forced expiratory volume in 1 s in % of predicted was 7–10% lower for lowest versus highest decile of 25(OH)D (p_trend≤1×10⁻²⁸). In prospective analyses, participants in the lower versus higher 25(OH)D quintiles had a faster decline in forced expiratory volume in 1 s % predicted (p_interaction=1×10⁻⁷) and forced vital capacity % predicted (p_interaction=8×10⁻⁸). In cross-sectional analyses, multivariable adjusted ORs for COPD were 2.30 (95% CI 1.55 to 3.41) and 3.06 (1.97 to 4.76) for lowest versus highest quintile in the Copenhagen City Heart Study using Global Initiative for Chronic Obstructive Lung Disease (GOLD) and lower limit of normal criteria. The corresponding ORs were 1.82 (1.13 to 2.92) and 2.23 (1.35 to 3.69) in the Copenhagen General Population Study. In prospective analyses, corresponding multivariable adjusted HRs for developing COPD were 1.58 (1.05 to 2.40) and 2.00 (1.19 to 3.36).

Conclusions We observed a novel association of lower plasma 25(OH)D levels with faster decline in lung function and with a higher risk of COPD in prospective analyses.