Table 1 Summary of key evidence for approaches to the management of breathlessness in advanced disease

Bausewein et al. 2008²²

Cochrane systematic review of 47 controlled studies (2532 participants) evaluating non-pharmacological approaches in any advanced disease. Studies evaluating pulmonary rehabilitation, exercise and self-management education excluded

High strength of evidence for neuromuscular electrical stimulation and chest wall vibration

Moderate strength of evidence for walking aids and breathing retraining

Low strength of evidence for acupuncture/pressure

Zwerink et al. 2014

Cochrane systematic review of 28 controlled studies evaluating self-management interventions in COPD

Significant reduction in breathlessness and respiratory-related hospital admissions

Improved health-related quality of life

Howard et al. 2014²¹

Randomised controlled trial involving 222 COPD patients allocated to receive a cognitive-behavioural manual (applying CBT techniques within a self-management framework, with brief telephone support) or an information booklet

Significant improvement in breathlessness at 6 months (secondary outcome)

Reduction in A&E visits by 42% with associated cost-savings, improved anxiety, depression

McCarthy et al. 2015²⁴

Cochrane systematic review of 65 randomised controlled trials evaluating pulmonary rehabilitation in COPD

Moderately large and clinically significant improvement in breathlessness.

Also improvements in fatigue, quality of life and emotional function

Abernethy et al. 2003¹⁹

Randomised controlled crossover trial of oral morphine sustained release 20 mg twice daily for 4 days vs. placebo, involving 48 opioid-naive participants

6.6–9.5% improvement in breathlessness More distressing constipation in the opioid group despite laxatives

Abernethy et al. 2010⁴³

Randomised controlled trial of 239 participants (152 with COPD) with life-limiting illness, 2 l/min oxygen or room air via a concentrator for at least 15 h/day

Improvement in both oxygen and room air group, but no significant differences between groups

Barnes et al. 2016²⁰

Cochrane systematic review of 26 controlled trials evaluating opioids for refractory breathlessness in any advanced disease

Low quality evidence of improvement in post-treatment breathlessness, but no statistically significant change of breathlessness from baseline

Simon et al. 2010¹⁸

Cochrane systematic review of seven controlled trials evaluating benzodiazepines in advanced malignant or non-malignant disease

No beneficial effect of benzodiazepines, including from a meta-analysis of six of the seven studies

Uronis et al. 2008^{16, 44}

Systematic review and meta-analysis of five studies evaluating oxygen for dyspnoea in mildly- or non-hypoxaemic cancer patients

Oxygen did not improve breathlessness

Ekstrom et al. 2016¹⁷

Cochrane systematic review of 33 randomised controlled trials evaluating oxygen for dyspnoea in patients with COPD who do not qualify for home oxygen therapy

Oxygen improved breathlessness by the equivalent of 0.7 cm in a 10 cm visual analogues scale, on exercise only.

There was no benefit from oxygen before exercise, and no improvement in quality of life.

Bredin et al. 1999⁴⁵

Randomised controlled trial of 119 patients with lung cancer receiving a nurse-led, non-pharmacological, outpatient intervention or best supportive care

Significant improvement in breathlessness, as well as performance status, anxiety and depression, at 8 weeks

Farquhar et al. 2014²⁵

Randomised controlled trial involving 67 cancer patients, receiving the Breathlessness Intervention Service (multidisciplinary team providing predominantly home-based, non-pharmacological approaches) or usual care

Distress from breathlessness improved significantly (primary outcome) at 2 weeks

Evidence of cost-effectiveness

Higginson et al. 2014²⁶

Randomised controlled trial involving 105 patients with mixed advanced disease, receiving Breathlessness Support Service (multidisciplinary team providing predominantly outpatient and home-based, predominantly non-pharmacological approaches) or usual care.

Mastery of breathlessness improved significantly by an average of 16% (primary outcome), at 6 weeks

Significant improvement in survival in the intervention group

Johnson et al. 2015²⁷

Randomised controlled trial involving 156 cancer patients receiving either three or a single breathing technique training session

Improvement in worst breathlessness in last 24 h in both groups, but not difference between groups

The single session was cost-effective