Pharmacologic Therapies in Patients With Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review With Meta-analysis

Ann Intern Med. 2020 Mar 17;172(6):413-422. doi: 10.7326/M19-3007. Epub 2020 Feb 25.


Background: Chronic obstructive pulmonary disease (COPD) is characterized by frequent exacerbations.

Purpose: To evaluate the comparative effectiveness and adverse events (AEs) of pharmacologic interventions for adults with exacerbation of COPD.

Data sources: English-language searches of several bibliographic sources from database inception to 2 January 2019.

Study selection: 68 randomized controlled trials that enrolled adults with exacerbation of COPD treated in out- or inpatient settings other than intensive care and compared pharmacologic therapies with placebo, "usual care," or other pharmacologic interventions.

Data extraction: Two reviewers independently extracted data and rated study quality and strength of evidence (SOE).

Data synthesis: Compared with placebo or management without antibiotics, antibiotics given for 3 to 14 days were associated with increased exacerbation resolution at the end of the intervention (odds ratio [OR], 2.03 [95% CI, 1.47 to 2.80]; moderate SOE) and less treatment failure at the end of the intervention (OR, 0.54 [CI, 0.34 to 0.86]; moderate SOE), independent of severity of exacerbations in out- and inpatients. Compared with placebo in out- and inpatients, systemic corticosteroids given for 9 to 56 days were associated with less treatment failure at the end of the intervention (OR, 0.01 [CI, 0.00 to 0.13]; low SOE) but also with a higher number of total and endocrine-related AEs. Compared with placebo or usual care in inpatients, other pharmacologic interventions (aminophyllines, magnesium sulfate, anti-inflammatory agents, inhaled corticosteroids, and short-acting bronchodilators) had insufficient evidence, showing either no or inconclusive effects (with the exception of the mucolytic erdosteine) or improvement only in lung function.

Limitation: Scant evidence for many interventions; several studies had unclear or high risk of bias and inadequate reporting of AEs.

Conclusion: Antibiotics and systemic corticosteroids reduce treatment failure in adults with mild to severe exacerbation of COPD.

Primary funding source: Agency for Healthcare Research and Quality. (PROSPERO: CRD42018111609).

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Disease Progression
  • Humans
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Randomized Controlled Trials as Topic
  • Treatment Failure


  • Adrenal Cortex Hormones
  • Anti-Bacterial Agents