Dobler CC, Morrow AS, Farah MH, et al. Pharmacologic and Nonpharmacologic Therapies in Adult Patients With Exacerbation of COPD: A Systematic Review Rockville (MD): Agency for Healthcare Research and Quality (US); 2019 Oct. Report No.: 19(20)-EHC024-EF. (Systematic review)

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.

Discipline Area Score
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Emergency Medicine 6 / 7
General Internal Medicine-Primary Care(US) 5 / 7
Respirology/Pulmonology 5 / 7
Family Medicine (FM)/General Practice (GP) 5 / 7
Comments from MORE raters

Emergency Medicine rater

This extensive review mostly highlights the paucity of high-quality evidence to support current therapies for acute COPD exacerbations. Although the summary highlights that antibiotics appear to decrease "treatment failure" (at some timeframes but not others) - a term with variable meanings and clinical relevance - evidence also shows that they don't decrease other outcomes, such as readmissions, quality-of-life, or mortality (except perhaps in ICU patients). Systemic steroids show similar results. Even inhaled beta-agonists and muscarinics have not been adequately studied to determine their actual effectiveness, although I'm sure we will all continue to use them.

Emergency Medicine rater

Astonishing that bread-and-butter emergency conditions like acute exacerbation of COPD (encountered multiple times daily by every ED) lacks sufficient evidence to justify any interventions (bronchodilators and perhaps benefit for steroids and occasionally antibiotics) that most physicians believe are effective.

General Internal Medicine-Primary Care(US) rater

This is a very long meta-analysis of treatments for COPD. It states antibiotics are helpful but no particular one is better. Steroids help dyspnea. Postural drainage helps as well as other mechanical aids to clear the mucus.

General Internal Medicine-Primary Care(US) rater

Although this review isn`t going to grab headlines, I find it valuable because it illustrates how little we often know about common problems. That alone may help foster humility and help temper the zealots who compel us to "get with the guidelines." In a sense, this kind of review helps to de-stress decisions: we can turn our focus to the patient.

Internal Medicine rater

Interesting what low-level evidence we have for much of what we do.

Respirology/Pulmonology rater

A very long and detailed treatise finds a lack of strong evidence for many of the standard therapies used to treat exacerbations of COPD. The paper highlights potential areas for future study, but adds little to change current practice.

Respirology/Pulmonology rater

This is a very comprehensive review of the different therapeutic agents (pharmacologic and non-pharmacologic). The PICO questions are patient-centered and the conclusions are relevant to practicing clinicians. This document is a very good resource. The section on Key messages is high yield for the busy clinicians.

Respirology/Pulmonology rater

Systematic comparative effectiveness review by AHRQ of treatments for COPD exacerbations that finds support for antibiotics, systemic steroids, and careful titration of oxygen, with low-to-moderate strength of evidence. All analyses based on 1 or a few trials that were mostly underpowered. Meta-analysis does not appear to add new information (although hard to assess as no forest plot presented). This information is already well known to clinicians.
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