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Study finds link between vitamin D deficiency and decline in lung function among patients with chronic obstructive pulmonary disease

Posted on: April 17, 2015   by  John Cannell, MD


Chronic obstructive pulmonary disease (COPD) is a type of obstructive lung disease characterized by chronically poor airflow. It typically worsens over time (chronic), but progression of the disease varies greatly. The main symptoms include shortness of breath, cough, and sputum production.  Tobacco smoking is the most common cause of COPD, with a number of other factors such as air pollution and genetics playing a smaller role.

The progression of COPD varies greatly between afflicted subjects, in terms of lung function decline, exacerbation frequency, and development of other illnesses. The reasons for the difference in disease progression among afflicted individuals are unknown, but vitamin D may play a role.

In cross-sectional studies, vitamin D deficiency (VDD) is common in COPD patients, and has been associated with lower lung function both in COPD patients and in the general population. Recently, a large longitudinal population based study found an association between lower plasma 25(OH)D levels with faster decline in lung function and a higher risk of COPD.

There are plausible mechanisms by which vitamin D could impact COPD pathogenesis, as the vitamin D receptor (VDR) is a nuclear transcription factor regulating the expression of more than 2000 genes, many with immune functions. Laboratory studies have found associations between vitamin D and a strengthened innate immune response against airway infections by the production of antimicrobial peptides (AMPs) together with enhanced immune activity, improved lung development and lung tissue repair. Additionally, vitamin D may down-regulate inflammation through decreased T-cell reactivity and pro-inflammatory response.

A group from the University of Bergen in Bergen, Norway, recently tried to duplicate some of these findings.

Persson LJ, Aanerud M, Hiemstra PS, Michelsen AE, Ueland T, Hardie JA, Aukrust P, Bakke PS, Eagan TM. Vitamin D, Vitamin D Binding Protein, and Longitudinal Outcomes in COPD. PLoS One. 2015 Mar 24;10(3):e0121622.

They studied 426 subjects for three years, obtaining pulmonary data on the patients every six months. At baseline, COPD patients with VDD (<20ng/mL, n = 142) were more often current smokers, had more severe COPD, were more likely to have frequent exacerbations and were more often either underweight (cachectic) or obese compared to patients with 25(OH)D levels above 20 ng/ml (n = 284). There was no association of vitamin D binding protein (VDBP) at baseline with any clinical parameter. They found that low entry 25(OH)D levels predicted a greater decline in pulmonary functions tests (FEV1 and FVC), but baseline VDBP had no relationship with clinical outcomes. Baseline 25(OH)D status did not predict exacerbation rate or mortality, but P values were close to significant.

Below is a chart in the decline of lung function tests according to baseline vitamin D levels:

COPD chart

The authors concluded:

“Severe vitamin D deficiency predicted later decline in lung function in COPD patients, an important parameter of COPD disease progression. 25(OH)D or VDBP levels did otherwise not predict markers of disease progression. This may imply that the effects of vitamin D in COPD disease progression are so small as to be clinically less relevant, or that vitamin D deficiency is a later event rather than a potentially causal factor.”

The authors found that the majority of COPD patients had baseline 25(OH)D levels above 20 ng/ml. However, the authors did not say if they analyzed their data to see if levels above 30 or 40 ng/ml were more protective than simply being above 20 ng/ml. I emailed the authors that question but received no response.

As pulmonary function tests are a key indicator of disease severity, it seems logical, based on the study, for COPD subjects to have their 25(OH)D levels measured. We suggest anyone with COPD keep their 25(OH)D around 80 ng/ml, which is the upper limit of both normal (averages of thousands of blood tests) and natural (those levels obtained by working and living outside). As always, we think the best way to get vitamin D is through safe sensible full-body noontime sunbathing (when your shadow is shorter that you are)to get vitamin D. Otherwise, COPD patients should take 10,000 IU of vitamin D3 daily. Also, as always, we suggest getting the first 5,000 IU/day of vitamin D by taking 3 capsules per day of D3Plus.

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