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Pharmacologic and Nonpharmacologic Therapies in Adult Patients With Exacerbation of COPD: A Systematic Review

Author/s: 
Dobler, CC, Morrow, AS, Farah, MH, Beuschel, B, Majzoub, AM, Wilson, ME, Hasan, B, Seisa, MO, Daraz, L, Prokop, LJ, Murad, MH, Wang, Z

Objectives. To synthesize existing knowledge about the effectiveness and harms of pharmacologic and nonpharmacologic treatments for exacerbations of chronic obstructive pulmonary disease (ECOPD).

Data sources. Embase®, Epub Ahead of Print, In-Process & Other Non-Indexed Citations, MEDLINE® Daily, MEDLINE, Cochrane Central Registrar of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus from database inception to January 2, 2019.

Review methods. We included randomized controlled trials (RCTs) that evaluated pharmacologic intervention or nonpharmacologic interventions for ECOPD. The strength of evidence (SOE) was graded for critical final health outcomes.

Results. We included 98 RCTs (13,401 patients, mean treatment duration 9.9 days, mean followup 3.7 months). Final health outcomes, including mortality, resolution of exacerbation, hospital readmissions, repeat exacerbations, and need for intubation, were infrequently evaluated and often showed no statistically significant differences between groups. Antibiotic therapy increases the clinical cure rate and reduces the clinical failure rate regardless of the severity of ECOPD (moderate SOE). There is insufficient evidence to support a particular antibiotic regimen. Oral and intravenous corticosteroids improve dyspnea and reduce the clinical failure rate (low SOE). Despite the ubiquitous use of inhaled bronchodilators in ECOPD, we found only a small number of trials that assessed lung function tests, and not final health outcomes. The evidence is insufficient to support the effect of aminophyllines, magnesium sulfate, mucolytics, inhaled corticosteroids, inhaled antibiotics, 5-lipoxygenase inhibitor, and statins on final health outcomes. Titrated oxygen reduces mortality compared with high flow oxygen (low SOE). Low SOE suggested benefit from some nonpharmacologic interventions such as chest physiotherapy using vibration/percussion/massage or breathing technique (on dyspnea), resistance training (on dyspnea and quality of life), early pulmonary rehabilitation commenced before hospital discharge during the initial most acute phase of exacerbation rather than the convalescence period (on dyspnea) and whole body vibration training (on quality of life). Vitamin D supplementation may improve quality of life (low SOE).

Conclusions. Although chronic obstructive pulmonary disease is a common condition, the evidence base for most interventions in ECOPD remains limited. Systemic antibiotics and corticosteroids are associated with improved outcomes in mild and moderate to severe ECOPD. Titrated oxygen reduces mortality. Future research is required to assess the effectiveness of several emerging nonpharmacologic and dietary treatments.

Keywords 
copd chronic obstructive pulmonary disease therapy randomized control trial systematic review

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

Author/s: 
Walters, Julia A.E., Tan, Daniel J., White, Clinton J., Wood-Baker, Richard

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.

Keywords 
copd corticosteroids

Different Durations of Corticosteroid therapy for Exacerbations of Chronic Obstructive Pulmonary Disease

Author/s: 
Walters, Julia A.E., Wang, Wendy, Morley, Carla, Soltani, Amir, Wood-Baker, Richard

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.

Keywords 
corticosteroids copd chronic obstructive pulmonary disease
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