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woman getting Vitamin D from standing in direct sunlight.

NIHR Signal Treating vitamin D deficiency may reduce exacerbations of COPD

Published on 26 February 2019

doi: 10.3310/signal-000737

Vitamin D supplements halve the number of exacerbations of chronic obstructive pulmonary disease (COPD) in people with low levels of the vitamin, from two per year to one per year. The supplements do not affect exacerbations of COPD in people who are not deficient.

This NIHR-funded review is the first to pool individual-level data from randomly controlled trials to see whether taking vitamin D can help reduce exacerbations.

People with moderate to severe COPD may be at risk of low vitamin D levels because their illness reduces their opportunities to get out into the sunlight.

These findings suggest that vitamin D is an effective, safe prevention for those with COPD found to be deficient.  

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Why was this study needed?

Chronic obstructive pulmonary disease (COPD) is one of the top two reasons for UK emergency hospital admission. The condition costs the NHS approximately £1.9 billion annually. It causes 30,000 deaths every year in England.

Vitamin D plays a key role in regulating the body’s calcium levels and is essential for healthy bones and muscles. It has recently been shown to reduce asthma symptoms and chest infections. The vitamin is made in the skin from exposure to sufficient sunlight and can also come from food. However, people with restricted time outdoors can have low levels.

This review aimed to find out whether vitamin D can reduce exacerbations of COPD and to study whether impacts differ according to patient characteristics.

What did this study do?

This systematic review analysed data from three of the four randomised controlled trials carried out to date. Participants in the UK, Belgium and the Netherlands were randomly assigned to receive oral vitamin D or a placebo alongside any COPD treatment. Trial authors were asked to provide full individual-level data sets, giving a combined dataset of 469 adults.

The trials included people with mild, moderate and severe COPD. Vitamin D doses were not combined with other supplements and ranged from 30 micrograms daily for six months to 2,500 micrograms monthly for one year.

All three trials had a low risk of bias and were double-blind, meaning that patients, clinicians and researchers did not know which treatment was given.

What did it find?

  • When pooling individual-level data for people with low vitamin D at the start of the trial (less than 25 nmol/L), those taking a vitamin D supplement experienced on average 1.2 moderate or severe exacerbations of COPD in a year (95% confidence interval [CI] 0.86 to 1.75), compared to 2.1 exacerbations in the placebo group (adjusted incidence rate ratio [aIRR] 0.55, 95% CI 0.36 to 0.84; 3 trials, 87 adults). 
  • There was no significant effect of vitamin D supplementation for those with adequate baseline vitamin D levels (at least 25 nmol/L) (aIRR 1.04, 95% CI 0.85 to 1.27; 3 trials, 382 adults). 
  • When all those who had vitamin D supplementation were compared with all those who had a placebo, there was no difference in exacerbation rates (aIRR 0.94, 95% CI 0.78 to 1.13; 3 trials, 469 adults).
  • Vitamin D did not cause any increase in the proportion of participants experiencing a serious adverse event.

What does current guidance say on this issue?

Public Health England 2016 guidance advises that everyone needs 10 micrograms of vitamin D daily. In the spring and summer, sufficient can come from sunlight and dietary sources. In the autumn and winter, people should consider supplements.

A NICE 2014 guideline on vitamin D for specific population groups advises that vitamin D levels should be tested only when a person is at especially high risk of deficiency, or there is a clinical reason to do so. Prompts for health professionals to recommend supplements should be integrated into health and social care systems.

The NICE 2018 guideline for adults with COPD does not include advice on vitamin D. It states that pulmonary rehabilitation programmes should incorporate nutritional advice.

What are the implications?

Though the number of participants was small and the number of exacerbations relatively low, the results are in keeping with what is already known about vitamin D. That is it can reduce the risk of chest infections in the general population, especially for those with low levels.

The supplements are low cost, but testing for deficiency also has resource implications.  Health practitioners could integrate Public Health England advice into services for people with COPD based on this evidence. This would mean most people with COPD could consider taking supplements through the autumn and winter months.

Flu and pneumococcal vaccinations and pulmonary rehabilitation programmes provide a contact point with COPD patients and an opportunity for health practitioners to give advice on vitamin D intake.

Citation and Funding

Jolliffe D, Greenberg L, Hooper R et al. Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax. 2019; 10 January. doi: 10.1136/thoraxjnl-2018-212092. [Epub ahead of print].

This project was funded by the National Institute for Health Research Health Technology Appraisal programme (project number 13/03/25).

Bibliography

British Lung Foundation. Estimating the economic burden of respiratory illness in the UK. London: British Lung Foundation; 2017.

NHS website. Vitamin D. London: Department of Health and Social Care; updated 2017.

NHS website. Chronic obstructive pulmonary disease (COPD). London: Department of Health and Social Care; updated 2016.

NICE. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. NG115. London: National Institute for Health and Care Excellence; 2018.

NICE. Vitamin D: supplement use in specific population groups. PH56. London: National Institute for Health and Care Excellence; 2014 (updated 2017).

Martineau AR, Cates CJ, Urashima M et al. Vitamin D for the management of asthma. Cochrane Database Syst Rev. 2016;9:CD011511.

Martineau AR, Jolliffe DA, Hooper RL et al. Vitamin D supplementation to prevent acute respiratory tract infections: meta-analysis of individual participant data. BMJ. 2017;356:i6583.

SACN. Vitamin D and health. London: Scientific Advisory Committee on Nutrition; 2016.

Why was this study needed?

Chronic obstructive pulmonary disease (COPD) is one of the top two reasons for UK emergency hospital admission. The condition costs the NHS approximately £1.9 billion annually. It causes 30,000 deaths every year in England.

Vitamin D plays a key role in regulating the body’s calcium levels and is essential for healthy bones and muscles. It has recently been shown to reduce asthma symptoms and chest infections. The vitamin is made in the skin from exposure to sufficient sunlight and can also come from food. However, people with restricted time outdoors can have low levels.

This review aimed to find out whether vitamin D can reduce exacerbations of COPD and to study whether impacts differ according to patient characteristics.

What did this study do?

This systematic review analysed data from three of the four randomised controlled trials carried out to date. Participants in the UK, Belgium and the Netherlands were randomly assigned to receive oral vitamin D or a placebo alongside any COPD treatment. Trial authors were asked to provide full individual-level data sets, giving a combined dataset of 469 adults.

The trials included people with mild, moderate and severe COPD. Vitamin D doses were not combined with other supplements and ranged from 30 micrograms daily for six months to 2,500 micrograms monthly for one year.

All three trials had a low risk of bias and were double-blind, meaning that patients, clinicians and researchers did not know which treatment was given.

What did it find?

  • When pooling individual-level data for people with low vitamin D at the start of the trial (less than 25 nmol/L), those taking a vitamin D supplement experienced on average 1.2 moderate or severe exacerbations of COPD in a year (95% confidence interval [CI] 0.86 to 1.75), compared to 2.1 exacerbations in the placebo group (adjusted incidence rate ratio [aIRR] 0.55, 95% CI 0.36 to 0.84; 3 trials, 87 adults). 
  • There was no significant effect of vitamin D supplementation for those with adequate baseline vitamin D levels (at least 25 nmol/L) (aIRR 1.04, 95% CI 0.85 to 1.27; 3 trials, 382 adults). 
  • When all those who had vitamin D supplementation were compared with all those who had a placebo, there was no difference in exacerbation rates (aIRR 0.94, 95% CI 0.78 to 1.13; 3 trials, 469 adults).
  • Vitamin D did not cause any increase in the proportion of participants experiencing a serious adverse event.

What does current guidance say on this issue?

Public Health England 2016 guidance advises that everyone needs 10 micrograms of vitamin D daily. In the spring and summer, sufficient can come from sunlight and dietary sources. In the autumn and winter, people should consider supplements.

A NICE 2014 guideline on vitamin D for specific population groups advises that vitamin D levels should be tested only when a person is at especially high risk of deficiency, or there is a clinical reason to do so. Prompts for health professionals to recommend supplements should be integrated into health and social care systems.

The NICE 2018 guideline for adults with COPD does not include advice on vitamin D. It states that pulmonary rehabilitation programmes should incorporate nutritional advice.

What are the implications?

Though the number of participants was small and the number of exacerbations relatively low, the results are in keeping with what is already known about vitamin D. That is it can reduce the risk of chest infections in the general population, especially for those with low levels.

The supplements are low cost, but testing for deficiency also has resource implications.  Health practitioners could integrate Public Health England advice into services for people with COPD based on this evidence. This would mean most people with COPD could consider taking supplements through the autumn and winter months.

Flu and pneumococcal vaccinations and pulmonary rehabilitation programmes provide a contact point with COPD patients and an opportunity for health practitioners to give advice on vitamin D intake.

Citation and Funding

Jolliffe D, Greenberg L, Hooper R et al. Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials. Thorax. 2019; 10 January. doi: 10.1136/thoraxjnl-2018-212092. [Epub ahead of print].

This project was funded by the National Institute for Health Research Health Technology Appraisal programme (project number 13/03/25).

Bibliography

British Lung Foundation. Estimating the economic burden of respiratory illness in the UK. London: British Lung Foundation; 2017.

NHS website. Vitamin D. London: Department of Health and Social Care; updated 2017.

NHS website. Chronic obstructive pulmonary disease (COPD). London: Department of Health and Social Care; updated 2016.

NICE. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. NG115. London: National Institute for Health and Care Excellence; 2018.

NICE. Vitamin D: supplement use in specific population groups. PH56. London: National Institute for Health and Care Excellence; 2014 (updated 2017).

Martineau AR, Cates CJ, Urashima M et al. Vitamin D for the management of asthma. Cochrane Database Syst Rev. 2016;9:CD011511.

Martineau AR, Jolliffe DA, Hooper RL et al. Vitamin D supplementation to prevent acute respiratory tract infections: meta-analysis of individual participant data. BMJ. 2017;356:i6583.

SACN. Vitamin D and health. London: Scientific Advisory Committee on Nutrition; 2016.

Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials

Published on 10 January 2019

D Jolliffe, L Greenberg, R Hooper, C Mathyssen, R Rafiq, R de Jongh, C Camargo, C Griffiths, W Janssens, A Martineau

Thorax , 2019

Background Randomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results. Individual participant data meta-analysis could identify factors that explain this variation. Methods PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial. Results Four eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75). Conclusions Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels.

Expert commentary

The authors of this meta-analysis show that vitamin D supplementation in chronic obstructive pulmonary disease patients with frank deficiency (levels <25 nmol/L) was associated with a reduction in exacerbation frequency.

This suggests that in patients with recurrent exacerbations, vitamin D levels should be measured and deficiency corrected where it is identified.

Importantly, vitamin D supplementation did not have any effect on exacerbation in patients who were not deficient.

Dr Nicholas Hopkinson, Reader in Respiratory Medicine and Honorary Consultant Physician, Royal Brompton and Harefield NHS Foundation Trust

The commentator declares no conflicting interests