Higher Vitamin D Concentrations Linked to Improved COPD Survival

Higher concentrations of vitamin D, specifically serum 25-hydroxyvitamin D (25(OH)D), are associated with improved survival with chronic obstructive pulmonary disease (COPD), according to a study published in BMJ Open Respiratory Research.

Researchers concluded that COPD survival increased with higher 25(OH)D concentrations, and the lowest risk of COPD incidence was seen in participants with concentrations at 55 nmol/L.

To conduct this study, researchers utilized the UK Biobank, which recruited over 500,000 participants aged 40 to 69 years from 2006 to 2010 across 22 assessment centers. The researchers included 403,648 participants, all with serum 25(OH)D measurements, who were free of COPD at baseline. Of the included participants, 185,840 were men, and 217,808 were women. The researchers excluded those with airway obstruction or unavailable 25(OH)D measurements.

The authors explained that “participants contributed person-time from the date of recruitment until the date of the initial diagnosis of COPD, lost to follow-up, death, or the end of the study, whichever occurred first.” They added that Cox proportional hazard models were used to estimate 95% CIs and HRs for the connection of 25(OH)D with COPD risk in participants, both overall and stratified by whether they are smokers or never-smokers.

“We classified serum 25(OH)D into quintiles and estimated the HRs using the fourth quintile reflected the typical vitamin D level in UK population as the reference in the primary analysis,” the authors wrote. “We considered 3 analytic models.”

Within model 1, the researchers adjusted for age, sex, ethnicity, and assessment center. Additionally, model 2 adjusted for educational degree, smoking status, Townsend deprivation index (a measure of material deprivation), physical activity, body mass index (BMI), alcohol drinking, oily fish intake, regular use of vitamin D supplements, prevalent asthma, family history of respiratory diseases, and female-specific factors. Lastly, model 3 adjusted for occupations at risk of COPD, passive smoking, and particulate matter (PM2.5).

During a median (IQR) follow-up of 12.3 (11.4-13.2) years, the researchers documented 11,008 COPD cases, 5956 being men and 5052 being women. Of those with COPD, 2773 died, 255 from COPD, within a median (IQR) survival time of 3.8 (1.6-6.6) years. Additionally, researchers found that the intraclass correlation coefficient (ICC) in serum 25(OH)D between the initial and repeated assessment was 0.59 (95% CI, 0.58-0.60).

Overall, researchers found that participants with increased 25(OH)D concentrations had higher economic standards, oily fish intake, and use of vitamin D supplements. They also found that the proportion of prevalent asthma cases and current smokers was lower among those with higher 25(OH)D concentrations.

Researchers explained that there was a nonlinear inverse relationship between 25(OH)D concentrations and COPD incidence among all participants, never-smokers, and smokers.

“In the fully adjusted model, compared with the fourth quintile, the lowest quintile groups increase a 23% risk (HR, 1.23; 95% CI, 1.16-1.31) in total participants, a 25% risk (HR, 1.25; 95% CI, 1.16-1.42) in never-smokers, and a 23% risk (HR, 1.23; 95% CI, 1.15-1.32) in smokers,” the authors wrote.

The survival analyses revealed that cases in the lowest quintile of 25(OH)D level had a 38% higher risk of overall death (HR, 1.38; 95% CI, 1.22-1.56) and a 57% higher risk of COPD-specific death (HR, 1.57; 95% CI, 1.03-2.40) in the fully adjusted models.

Consequently, the researchers’ findings imply that vitamin D plays a role in COPD progression; they found that lower 25(OH)D concentrations could be related to higher COPD risk. They also found the optimal concentrations associated with lower COPD risk to be 50 to 60 nmol/L. As for smoking, their findings indicate that lower 25(OH)D concentrations significantly elevate the risk of COPD in current smokers.

The researchers noted that their study had several limitations, one of which was that they could not exclude reverse causality. Additionally, a single measurement of 25(OH)D at recruitment might not represent long-term exposure concentrations. Also, researchers collected blood samples at recruitment to minimize selection bias but excluded 20% of participants; they excluded 10% because of a missing available measurement for 25(OH)D and the other 10% due to airway obstruction at baseline. Lastly, findings from this study may not apply to other populations as most participants were from the United Kingdom.

In the future, the researchers encouraged further research to expand upon their findings.

“Whether lower concentrations of 25(OH)D are causal or contributory to COPD risk may spur future long-duration and large-scale [randomized controlled trials],” the authors concluded.

Reference

Zhu Z, Wan X, Liu J, et al. Vitamin D status and chronic obstructive pulmonary disease risk: a prospective UK Biobank study. BMJ Open Respir Res. 2023;10:e001684. doi:10.1136/bmjresp-2023-001684