Nonpharmacological Interventions for Managing Breathlessness in Patients with Advanced Cancer: A Systematic Review

Arjun Gupta, Ramy Sedhom, Ritu Sharma, Allen Zhang, Julie M. Waldfogel, Josephine L. Feliciano, Jeff Day, Rebecca A. Gersten, Patricia M. Davidson, Eric B. Bass, Sydney M. Dy

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Importance: Breathlessness is a frequent and debilitating symptom in patients with advanced cancer. Often, in the context of breathlessness, aggressive cancer treatment is not beneficial, feasible, or aligned with goals of care. Targeted symptom-focused interventions may be helpful in this scenario. Objective: To evaluate the advantages and harms of nonpharmacological interventions for managing breathlessness in adults with advanced cancer. Evidence Review: PubMed, Embase, CINAHL, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception through May 2020 for published randomized clinical trials (RCTs), nonrandomized controlled trials, and observational studies of the advantages and/or harms of nonpharmacological interventions on alleviating breathlessness in adults with advanced cancer. Only English-language studies were screened for eligibility, titles, abstracts, and full text. Risk of bias and strength of evidence (SOE) were independently assessed. The key outcomes reported in studies were breathlessness, anxiety, exercise capacity, health-related quality of life, and harms. Data were analyzed from October 1, 2019, to June 30, 2020. Findings: A total of 29 RCTs (2423 participants) were included. These RCTs evaluated various types of interventions, such as respiratory (9 RCTs), activity and rehabilitation (7 RCTs), behavioral and psychoeducational (3 RCTs), integrative medicine (4 RCTs), and multicomponent (6 RCTs). Several nonpharmacological interventions were associated with improved breathlessness, including fan therapy (standardized mean difference [SMD],-2.09; 95% CI,-3.81 to-0.37; I2= 94.3%; P for heterogeneity =.02; moderate SOE) and bilevel ventilation (estimated slope difference,-0.58; 95% CI,-0.92 to-0.23; low SOE), lasting for a few minutes to hours, in the inpatient setting. In the outpatient setting, nonpharmacological interventions associated with improved breathlessness were acupressure and reflexology (integrative medicine) (low SOE) and multicomponent interventions (combined activity and rehabilitation, behavioral and psychoeducational, and integrative medicine) (low SOE) lasting for a few weeks to months. Five of the 29 RCTs (17%) reported adverse events, although adverse events and study dropouts were uncommon. Conclusions and Relevance: Findings of this review include the safety and association with improved breathlessness of several nonpharmacological interventions for adults with advanced cancer. Guidelines and clinical practice should evolve to incorporate nonpharmacological interventions as first-line treatment for adults with advanced cancer and breathlessness.

Original languageEnglish (US)
Pages (from-to)290-298
Number of pages9
JournalJAMA Oncology
Issue number2
StatePublished - Feb 1 2021
Externally publishedYes

Bibliographical note

Funding Information:
funded under Contract No. HHSA290201500006I Task Order 75Q80119F32014 from the AHRQ of the US Department of Health and Human Services (HHS).

Funding Information:
reported receiving grants from Agency for Healthcare Research and Quality (AHRQ) during the conduct of the study. Dr Waldfogel reported receiving grants from AHRQ and Patient-Centered Outcomes Research Institute (PCORI) during the conduct of the study as well as personal fees from TRC Healthcare outside the submitted work. Dr Feliciano reported receiving other funding from Eli Lilly, Genentech, and Merck; grants and other funding from AstraZeneca; and grants from Pfizer and Bristol Myers Squibb outside the submitted work. Dr Davidson reported receiving grants from National Health and Medical Research Council during the conduct of the study. Dr Bass reported receiving grants from AHRQ during the conduct of the study. Dr Dy reported receiving grants from AHRQ and PCORI during the conduct of the study. No other disclosures were reported.

Publisher Copyright:
© 2021 American Medical Association. All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, U.S. Gov't, P.H.S.
  • Systematic Review


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