NIHR DC Discover

NIHR Signal One week of steroids may be as effective as two weeks in managing severe COPD

Published on 10 July 2018

doi: 10.3310/signal-000616

A shorter course of steroids lasting 3 to 7 days appears as effective as the recommended 7 to 14-day standard treatment for managing a flare-up of severe chronic obstructive pulmonary disease.

This update to an earlier Cochrane review looked at randomised clinical trials comparing a short course (7 days or fewer) with a longer course (7 to 14 days) of steroids given by mouth or injection. All participants had been admitted to hospital, but none required mechanical ventilation.

The evidence suggests that shorter courses of steroids could be given to people with severe chronic obstructive pulmonary disease where there are concerns about side effects. However, the research was limited by small study sizes and including only 582 people in total. Further research is needed to determine the optimum duration of steroid treatment in flare-ups of mild or moderate chronic obstructive pulmonary disease.

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Why was this study needed?

Chronic obstructive pulmonary disease (COPD) is a group of lung diseases commonly associated with smoking that cause breathing difficulty. The World Health Organization estimates that 64 million people have COPD and that it will become the third leading cause of death worldwide by 2030.

Sudden worsening symptoms (exacerbations) occur with COPD and are a cause of hospitalisation. Frequent exacerbations contribute to a progressive decline in lung function.

The recommended treatment for flare-ups includes a course of corticosteroids given by mouth or injection (not inhaled) for between 7 and 14 days. However, prolonged or frequent use of steroids can cause side effects including fluid retention, high blood pressure, diabetes and osteoporosis.

This analysis aimed to assess whether a shorter course of steroids is as effective at treating COPD flare-ups as the longer course.

What did this study do?

This systematic review and meta-analysis pooled data from eight randomised controlled trials of 582 people with severe or very severe COPD.

All participants had been admitted to hospital, but the study did not include people who required assisted ventilation. The average age was between 65 and 73 years old, and most participants were male. None of the studies were from the UK.

Overall, the evidence was graded as moderate in reliability because of the small sample size and wide range of results. The five studies used in the main analysis were considered to be at low risk of bias. The inclusion of a new, well-conducted, study of 296 people reporting since the evidence was last reviewed in 2011 increased the reviewers’ confidence in the results.

What did it find?

  • There was no significant difference in the likelihood of treatment failure (the need for additional treatment) between the short and longer course of steroids (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.36 to 1.46; four studies, 457 participants). The wide margin of error, though, means there is still some uncertainty about this.
  • There was also no difference between treatments in the likelihood of people suffering a new flare-up during the 14 to 180 days follow-up period (OR 1.04, 95% CI 0.7 to 1.56; four studies, 478 participants).
  • One of the side effects from steroid treatment is diabetes. Two studies with moderate-quality data showed no difference in the likelihood of developing high blood sugar between treatment durations (OR 0.99, 95% CI 0.64 to 1.53; 345 people). Low-quality data from five studies also showed no difference in a range of other drug side effects (OR 0.88, 95% CI 0.46 to 1.69; 503 people).
  • Information on quality of life, an important outcome for people with COPD, was limited as it was only measured in one study.

What does current guidance say on this issue?

NICE guidelines published in 2010 on managing COPD include the following key recommendations with regards to steroid treatment of flare-ups (exacerbations):

In the absence of significant contraindications, oral corticosteroids should be used

  • in conjunction with other therapies, in all patients admitted to hospital with an exacerbation of COPD
  • in patients in the community who have an exacerbation with a significant increase in breathlessness which interferes with daily activities
  • for no longer than 14 days as there is no advantage in prolonged therapy

What are the implications?

This updated review reinforces the existing evidence that a short course of steroids may be just as good as a longer course at treating flare-ups in people with severe or very severe COPD.

There is currently variation in the duration of steroid treatment used for COPD flare-ups in clinical practice. This is likely to continue due to individual factors and response to steroids. Though the review is based on small numbers of people, it does provide some evidence that if there has been an adequate response, the steroids could be stopped sooner.

Citation and Funding

Walters JA, Tan DJ, White CJ, Wood-Baker R. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018;3:CD006897.

This review was funded by the Breathe Well Centre of Research Excellence, University of Tasmania, Australia and the National Health and Medical Research Council, Australia.

Bibliography

NHS Choices. Chronic obstructive pulmonary disease (COPD). London: Department of Health; updated 2016.

NICE. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. CG101. London: National Institute for Health and Care Excellence; 2010.

WHO. Burden of COPD. Geneva: World Health Organization; accessed May 2018.

Why was this study needed?

Chronic obstructive pulmonary disease (COPD) is a group of lung diseases commonly associated with smoking that cause breathing difficulty. The World Health Organization estimates that 64 million people have COPD and that it will become the third leading cause of death worldwide by 2030.

Sudden worsening symptoms (exacerbations) occur with COPD and are a cause of hospitalisation. Frequent exacerbations contribute to a progressive decline in lung function.

The recommended treatment for flare-ups includes a course of corticosteroids given by mouth or injection (not inhaled) for between 7 and 14 days. However, prolonged or frequent use of steroids can cause side effects including fluid retention, high blood pressure, diabetes and osteoporosis.

This analysis aimed to assess whether a shorter course of steroids is as effective at treating COPD flare-ups as the longer course.

What did this study do?

This systematic review and meta-analysis pooled data from eight randomised controlled trials of 582 people with severe or very severe COPD.

All participants had been admitted to hospital, but the study did not include people who required assisted ventilation. The average age was between 65 and 73 years old, and most participants were male. None of the studies were from the UK.

Overall, the evidence was graded as moderate in reliability because of the small sample size and wide range of results. The five studies used in the main analysis were considered to be at low risk of bias. The inclusion of a new, well-conducted, study of 296 people reporting since the evidence was last reviewed in 2011 increased the reviewers’ confidence in the results.

What did it find?

  • There was no significant difference in the likelihood of treatment failure (the need for additional treatment) between the short and longer course of steroids (odds ratio [OR] 0.72, 95% confidence interval [CI] 0.36 to 1.46; four studies, 457 participants). The wide margin of error, though, means there is still some uncertainty about this.
  • There was also no difference between treatments in the likelihood of people suffering a new flare-up during the 14 to 180 days follow-up period (OR 1.04, 95% CI 0.7 to 1.56; four studies, 478 participants).
  • One of the side effects from steroid treatment is diabetes. Two studies with moderate-quality data showed no difference in the likelihood of developing high blood sugar between treatment durations (OR 0.99, 95% CI 0.64 to 1.53; 345 people). Low-quality data from five studies also showed no difference in a range of other drug side effects (OR 0.88, 95% CI 0.46 to 1.69; 503 people).
  • Information on quality of life, an important outcome for people with COPD, was limited as it was only measured in one study.

What does current guidance say on this issue?

NICE guidelines published in 2010 on managing COPD include the following key recommendations with regards to steroid treatment of flare-ups (exacerbations):

In the absence of significant contraindications, oral corticosteroids should be used

  • in conjunction with other therapies, in all patients admitted to hospital with an exacerbation of COPD
  • in patients in the community who have an exacerbation with a significant increase in breathlessness which interferes with daily activities
  • for no longer than 14 days as there is no advantage in prolonged therapy

What are the implications?

This updated review reinforces the existing evidence that a short course of steroids may be just as good as a longer course at treating flare-ups in people with severe or very severe COPD.

There is currently variation in the duration of steroid treatment used for COPD flare-ups in clinical practice. This is likely to continue due to individual factors and response to steroids. Though the review is based on small numbers of people, it does provide some evidence that if there has been an adequate response, the steroids could be stopped sooner.

Citation and Funding

Walters JA, Tan DJ, White CJ, Wood-Baker R. Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2018;3:CD006897.

This review was funded by the Breathe Well Centre of Research Excellence, University of Tasmania, Australia and the National Health and Medical Research Council, Australia.

Bibliography

NHS Choices. Chronic obstructive pulmonary disease (COPD). London: Department of Health; updated 2016.

NICE. Chronic obstructive pulmonary disease in over 16s: diagnosis and management. CG101. London: National Institute for Health and Care Excellence; 2010.

WHO. Burden of COPD. Geneva: World Health Organization; accessed May 2018.

Different durations of corticosteroid therapy for exacerbations of chronic obstructive pulmonary disease

Published on 20 March 2018

Walters, J. A.,Tan, D. J.,White, C. J.,Wood-Baker, R.

Cochrane Database Syst Rev Volume 3 , 2018

BACKGROUND: Current guidelines recommend that patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) should be treated with systemic corticosteroid for seven to 14 days. Intermittent systemic corticosteroid use is cumulatively associated with adverse effects such as osteoporosis, hyperglycaemia and muscle weakness. Shorter treatment could reduce adverse effects. OBJECTIVES: To compare the efficacy of short-duration (seven or fewer days) and conventional longer-duration (longer than seven days) systemic corticosteroid treatment of adults with acute exacerbations of COPD. SEARCH METHODS: Searches were carried out using the Cochrane Airways Group Specialised Register of Trials, MEDLINE and CENTRAL (Cochrane Central Register of Controlled Trials) and ongoing trials registers up to March 2017. SELECTION CRITERIA: Randomised controlled trials comparing different durations of systemic corticosteroid defined as short (i.e. seven or fewer days) or longer (i.e. longer than seven days). Other interventions-bronchodilators and antibiotics-were standardised. Studies with participants requiring assisted ventilation were excluded. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by The Cochrane Collaboration. MAIN RESULTS: Eight studies with 582 participants met the inclusion criteria, of which five studies conducted in hospitals with 519 participants (range 28 to 296) contributed to the meta-analysis. Mean ages of study participants were 65 to 73 years, the proportion of male participants varied (58% to 84%) and COPD was classified as severe or very severe. Corticosteroid treatment was given at equivalent daily doses for three to seven days for short-duration treatment and for 10 to 15 days for longer-duration treatment. Five studies administered oral prednisolone (30 mg in four, tapered in one), and two studies provided intravenous corticosteroid treatment. Studies contributing to the meta-analysis were at low risk of selection, performance, detection and attrition bias. In four studies we did not find a difference in risk of treatment failure between short-duration and longer-duration systemic corticosteroid treatment (n = 457; odds ratio (OR) 0.72, 95% confidence interval (CI) 0.36 to 1.46)), which was equivalent to 22 fewer per 1000 for short-duration treatment (95% CI 51 fewer to 34 more). No difference in risk of relapse (a new event) was observed between short-duration and longer-duration systemic corticosteroid treatment (n = 457; OR 1.04, 95% CI 0.70 to 1.56), which was equivalent to nine fewer per 1000 for short-duration treatment (95% CI 68 fewer to 100 more). Time to the next COPD exacerbation did not differ in one large study that was powered to detect non-inferiority and compared five days versus 14 days of systemic corticosteroid treatment (n = 311; hazard ratio 0.95, 95% CI 0.66 to 1.37). In five studies no difference in the likelihood of an adverse event was found between short-duration and longer-duration systemic corticosteroid treatment (n = 503; OR 0.89, 95% CI 0.46 to 1.69, or nine fewer per 1000 (95% CI 44 fewer to 51 more)). Length of hospital stay (n = 421; mean difference (MD) -0.61 days, 95% CI -1.51 to 0.28) and lung function at the end of treatment (n = 185; MD FEV1 -0.04 L; 95% CI -0.19 to 0.10) did not differ between short-duration and longer-duration treatment. AUTHORS' CONCLUSIONS: Information from a new large study has increased our confidence that five days of oral corticosteroids is likely to be sufficient for treatment of adults with acute exacerbations of COPD, and this review suggests that the likelihood is low that shorter courses of systemic corticosteroids (of around five days) lead to worse outcomes than are seen with longer (10 to 14 days) courses. We graded most available evidence as moderate in quality because of imprecision; further research may have an important impact on our confidence in the estimates of effect or may change the estimates. The studies in this review did not include people with mild or moderate COPD; further studies comparing short-duration systemic corticosteroid versus conventional longer-duration systemic corticosteroid for treatment of adults with acute exacerbations of COPD are required.

Expert commentary

Systemic corticosteroids are recommended for severe acute exacerbations of chronic obstructive pulmonary disease (COPD), but the duration of this treatment varies from one to two weeks in duration. Since systemic corticosteroids have long-term adverse effects, such as osteoporosis, it is important to use the lowest effective treatment duration.

This Cochrane review shows that shorter courses (7 days) are as effective as longer courses (up to 14 days) in terms of the frequency of relapse, duration of hospital admission and recurrence of exacerbations, although the quality of the evidence used was poor in most studies.

The studies included patients with severe COPD who were hospitalised and did not consider duration of oral steroids used in moderate disease or patients treated at home.

Peter Barnes, NHLI, Imperial College London