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 and 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.

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