Vitamin D deficiency, smoking, and lung function in the Normative Aging Study

Abstract

Rationale: Vitamin D has immunomodulatory and antiinflammatory effects that may be modified by cigarette smoke and may affect lung function.

Objectives: To examine the effect of vitamin D deficiency and smoking on lung function and lung function decline.

Methods: A total of 626 men from the Normative Aging Study had 25-hydroxyvitamin D levels measured at three different times between 1984 and 2003 with concurrent spirometry. Vitamin D deficiency was defined as serum level ≤ 20 ng/ml. Statistical analysis was performed using multivariable linear regression and mixed effects models.

Measurements and main results: In the overall cohort, there was no significant effect of vitamin D deficiency on lung function or on lung function decline. In both cross-sectional and longitudinal multivariable models, there was effect modification by vitamin D status on the association between smoking and lung function. Cross-sectional analysis revealed lower lung function in current smokers with vitamin D deficiency (FEV(1), FVC, and FEV(1)/FVC; P ≤ 0.0002), and longitudinal analysis showed more rapid rates of decline in FEV(1) (P = 0.023) per pack-year of smoking in subjects with vitamin D deficiency as compared with subjects who were vitamin D sufficient.

Conclusions: Vitamin D deficiency was associated with lower lung function and more rapid lung function decline in smokers over 20 years in this longitudinal cohort of elderly men. This suggests that vitamin D sufficiency may have a protective effect against the damaging effects of smoking on lung function. Future studies should seek to confirm this finding in the context of smoking and other exposures that affect lung function.

Figure 1.

Three-way relationship between FEV₁, vitamin D levels, and smoking (pack-years). Shown here is the unadjusted relationship between FEV₁, pack-years of smoking, and vitamin D levels as a continuous variable, viewed from the side of the graph where pack-years are highest. This suggests that FEV₁ is higher in subjects with higher vitamin D levels compared with subjects with lower vitamin D levels and the same number of pack-years of smoking.

Figure 2.

Relationship between lung function, vitamin D deficiency, and smoking (pack-years). Shown here is the cross-sectional relationship between FEV₁% predicted and pack-years of smoking in subjects who were vitamin D deficient (vitamin D ≤ 20 ng/ml) compared with those who were not (vitamin D > 20 ng/ml). In subjects who were vitamin D deficient, the effect of pack-years of smoking on FEV₁ was twice as severe as in subjects without vitamin D deficiency.