Vitamin D status and chronic obstructive pulmonary disease risk: a prospective UK Biobank study

Abstract

BackgroundLow vitamin D status has been linked to an increased risk for various inflammatory diseases. Conflicting results have been reported regarding chronic obstructive pulmonary disease (COPD). This study aims to investigate the associations of serum 25-hydroxyvitamin D (25(OH)D) concentrations with COPD risk and survival.MethodsWe included 403 648 participants with serum 25(OH)D measurements and free of COPD at baseline from UK Biobank. Follow-up was until 30 September 2021. Multivariable-adjusted cox regression models were applied to estimate HRs and 95% CIs for the associations of season-standardised 25(OH)D concentrations with COPD risk and survival. The restricted cubic splines were used to assess dose–response relationship. Kaplan-Meier estimation was used to create graphs of the survival curves.ResultsDuring a median follow-up of 12.3 (IQR: 11.4–13.2) years, 11 008 cases of COPD were recorded. We observed a non-linear inverse association between 25(OH)D concentrations and COPD risk. Compared with participants in the fourth quintile of 25(OH)D, those in the lowest quintile were associated with a 23% higher risk (HR, 1.23; 95% CI, 1.16 to 1.31). Stronger associations were observed for the risk in men and current smokers (Both p for interaction <0.05). In survival analyses, compared with the fourth quintile, cases in the lowest quintile had a 38% higher risk for overall death (HR, 1.38; 95% CI, 1.22 to 1.56).ConclusionOur findings indicate that serum 25(OH)D concentrations are non-linearly negatively associated with incidence and mortality of COPD, suggesting a potential protective role of vitamin D in the pathogenesis of COPD.

The Role of Nutrition in the Development and Management of Chronic Obstructive Pulmonary Disease

“…In accordance with the American Association of Clinical Endocrinologists, vitamin D deficiency is defined as a serum level of 25-hydroxyvitamin D (25(OH)D) lower than 75 nanomolar per liter (nmol/L) [ 70 ]. By this definition, as much as 23% of the United States population is at risk of vitamin D deficiency [ 71 ]; vitamin D deficiency is frequently identified in patients with COPD [ 72 , 73 , 74 , 75 , 76 ]. The etiology of this deficiency in COPD seems to be multifactorial, including poor dietary intake [ 77 ], reduced exposure to sunlight [ 77 ], catabolism by common medications prescribed for the management of COPD (i.e., glucocorticoids) [ 77 ], or the effects of comorbid conditions such as chronic kidney disease [ 77 ].…”

“…Vitamin D deficiency has been identified as a risk factor for the development of COPD [ 72 , 78 , 79 ], specifically levels lower than 32 nmol/L, which have been associated with a 23% increased risk of developing COPD [ 72 ]. Multiple studies have found that vitamin D deficiency is linked with poor lung function in patients with COPD (GOLD stage I–IV) as measured by FEV 1 [ 76 , 80 ] and FVC [ 76 , 77 ].…”

“…Therefore, it is plausible that studies that did not find benefit in vitamin D supplementation consisted of patients with COPD whose disease state was more attributable to chronic bronchitis rather than emphysema [ 83 ]. Besides lung health, vitamin D deficiency has also been linked to an increased risk of mortality in people with COPD [ 72 ]. Indeed, vitamin D levels lower than 32 nmol/L were associated with a 38% increased risk of overall mortality and 57% greater COPD-specific mortality when compared to patients with COPD with higher vitamin D levels [ 72 ].…”

“…Besides lung health, vitamin D deficiency has also been linked to an increased risk of mortality in people with COPD [ 72 ]. Indeed, vitamin D levels lower than 32 nmol/L were associated with a 38% increased risk of overall mortality and 57% greater COPD-specific mortality when compared to patients with COPD with higher vitamin D levels [ 72 ].…”

“…The American Association of Clinical Endocrinologists defines optimal serum vitamin D levels as those greater than 75 nmol/L [ 70 ], although that cutoff is not agreed upon by the literature nor regulatory agencies [ 70 , 88 ]. However, evidence supports that serum levels of 25(OH)D of 50 nmol/L or greater may reduce mortality from respiratory diseases [ 89 ], and levels above 55 nmol/L were linked to the greatest reduction in risk of COPD development [ 72 ]. Indeed, multiple studies recommend considering vitamin D supplementation in patients with COPD [ 11 , 73 , 75 ], with some studies finding optimal serum 25(OH)D levels as those greater than 50 nmol/L [ 72 , 73 , 89 ].…”