Effects of opioids on breathlessness and exercise capacity in chronic obstructive pulmonary disease. A systematic review

Ann Am Thorac Soc. 2015 Jul;12(7):1079-92. doi: 10.1513/AnnalsATS.201501-034OC.


Rationale: Patients with chronic obstructive pulmonary disease (COPD) commonly suffer from breathlessness, deconditioning, and reduced health-related quality of life (HRQL) despite best medical management. Opioids may relieve breathlessness at rest and on exertion in COPD.

Objectives: We aimed to estimate the efficacy and safety of opioids on refractory breathlessness, exercise capacity, and HRQL in COPD.

Methods: This was a systematic review and metaanalysis using Cochrane methodology. We searched Cochrane Central Register of Controlled Trials, MEDLINE, and Embase up to 8 September, 2014 for randomized, double-blind, placebo-controlled trials of any opioid for breathlessness, exercise capacity, or HRQL that included at least one participant with COPD. Effects were analyzed as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random effect models.

Measurements and main results: A total of 16 studies (15 crossover trials and 1 parallel-group study, 271 participants, 95% with severe COPD) were included. There were no serious adverse effects. Breathlessness was reduced by opioids overall: SMD, -0.35 (95% CI, -0.53 to -0.17; I(2), 48.9%), by systemic opioids (eight studies, 118 participants): SMD, -0.34 (95% CI, -0.58 to -0.10; I(2), 0%), and less consistently by nebulized opioids (four studies, 82 participants): SMD, -0.39 (95% CI, -0.71 to -0.07; I(2), 78.9%). The quality of evidence was moderate for systemic opioids and low for nebulized opioids on breathlessness. Opioids did not affect exercise capacity (13 studies, 149 participants): SMD, 0.06 (95% CI, -0.15 to 0.28; I(2), 70.7%). HRQL could not be analyzed. Findings were robust in sensitivity analyses. Risk of study bias was low or unclear.

Conclusions: Opioids improved breathlessness but not exercise capacity in severe COPD.

Keywords: breathlessness; chronic obstructive pulmonary disease; exercise capacity; opioids; quality of life.

Publication types

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

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / therapeutic use*
  • Dyspnea / drug therapy*
  • Exercise Tolerance / drug effects*
  • Humans
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Quality of Life
  • Randomized Controlled Trials as Topic


  • Analgesics, Opioid