Better Treatments for Refractory Breathlessness
Chronic breathlessness is a distressing and highly prevalent symptom of advanced chronic respiratory diseases. It is associated with social isolation, high healthcare costs and poor prognosis. Currently, there are few effective drug treatments thus, chronic breathlessness represents a huge unmet need.
At the core of the Better Treatments for Refractory Breathlessness project (BETTER-B) is an international, multicentre, randomised controlled trial testing the effectiveness of mirtazapine, an established antidepressant, in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD).
The BETTER-B programme of work also includes an online survey of physicians to understand current clinical management of breathlessness, the production of European wide guidance on the management of breathlessness in palliative and end of life care, and qualitative interviews with trial participants (patients and caregivers) to further understand their experiences.
Aims
To deliver a step-change in the evidence-based management of breathlessness in palliative and end of life care.
Methods
The interventions we identified have been offered to patients as part of a Breathlessness Support Service. The service provides two outpatient clinic visits to the Cicely Saunders Institute and a home assessment over a six-week period. Patients are seen by respiratory and palliative care physicians, and their carer has access to a social worker. Patients are followed up by a home visit with an occupational therapist and a physiotherapist. Patients were provided with a toolkit including the following fact sheets.
Breathlessness Support Service Toolkit
Impact
BETTER-B provides a wide-reaching impact by translating the trial and research results to produce recommendations, educational materials and clinical improvements for clinicians and policymakers in palliative, supportive, respiratory, primary and end-of-life care.
Publications
Integrating home-based exercise training with a hospital at home service for patients hospitalised with acute exacerbations of COPD: Developing the model using accelerated experience-based co-design. https://www.dovepress.com/integrating-home-based-exercise-training-with-a-hospital-at-home-servi-peer-reviewed-fulltext-article-COPD
Integrating Comprehensive Geriatric Assessment for people with COPD and frailty starting pulmonary rehabilitation: the Breathe Plus feasibility trial protocol. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005693/
COPD discharge bundle and pulmonary rehabilitation referral and uptake following hospitalisation for acute exacerbation of COPD. https://thorax.bmj.com/content/early/2021/03/02/thoraxjnl-2020-215464.long
Supervised pulmonary rehabilitation using minimal or specialist exercise equipment in COPD: a propensity-matched analysis. https://thorax.bmj.com/content/76/3/264.long
Pharmacological and nonpharmacological interventions to improve symptom control, functional exercise capacity and quality of life in interstitial lung disease: an evidence synthesis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836673/
Management of breathlessness in patients with cancer: ESMO Clinical Practice Guidelines†. Electronic address: clinicalguidelines@esmo.org. https://www.esmoopen.com/article/S2059-7029(20)32759-9/fulltext
Trajectories of disability in activities of daily living in advanced cancer or respiratory disease: a systematic review. https://www.tandfonline.com/doi/abs/10.1080/09638288.2020.1820587
Palliative care and the management of common distressing symptoms in advanced cancer: Pain, breathlessness, nausea and vomiting and fatigue. https://ascopubs.org/doi/10.1200/JCO.19.00470?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&
Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility) https://thorax.bmj.com/content/75/2/176
To What Extent Do the NRS and CRQ Capture Change in Patients' Experience of Breathlessness in Advanced Disease? Findings From a Mixed-Methods Double-Blind Randomized Feasibility Trial. https://www.jpsmjournal.com/article/S0885-3924(19)30309-4/fulltext
Mirtazapine for chronic breathlessness? A review of mechanistic insights and therapeutic potential. https://www.tandfonline.com/doi/abs/10.1080/17476348.2019.1563486
Holistic services for people with advanced disease and chronic breathlessness: a systematic review and meta-analysis. https://thorax.bmj.com/content/74/3/270
Control and context are central for people with advanced illness experiencing breathlessness: A systematic review and thematic synthesis. https://www.sciencedirect.com/science/article/pii/S0885392418305050
Recommendations for services for people living with chronic breathlessness in advanced disease: results of a transparent expert consultation Chronic Respiratory Disease.
https://journals.sagepub.com/doi/full/10.1177/1479973118816448
Use of mirtazapine in patients with chronic breathlessness: A case series. https://journals.sagepub.com/doi/10.1177/0269216318787450
Trials
BETTER-B: An International, Multicentre, Randomised Controlled Pragmatic Trial of Mirtazapine to alleviate Breathlessness in Palliative and End of Life Care
The aim of the trial is to assess the effectiveness and cost-effectiveness of mirtazapine for the reduction of chronic or refractory breathlessness and quality of life in patients with COPD or ILD over a 56-day period and with an extended follow-up period of 180 days. Caregivers (as nominated by participating patients) are also encouraged to take part so that their own experience can also be assessed. Eligible patients meet the following criteria • diagnosed with COPD or ILD with mMRC breathlessness score 3 or 4 • ≥18 years old • on optimal treatment for their condition • management of condition unchanged for the previous 2 weeks • no exclusion criteria For further details please contact beter-b@kcl.ac.uk or visit our website https://betterbreathe.eu/
Publications
Integrating home-based exercise training with a hospital at home service for patients hospitalised with acute exacerbations of COPD: Developing the model using accelerated experience-based co-design. https://www.dovepress.com/integrating-home-based-exercise-training-with-a-hospital-at-home-servi-peer-reviewed-fulltext-article-COPD
Integrating Comprehensive Geriatric Assessment for people with COPD and frailty starting pulmonary rehabilitation: the Breathe Plus feasibility trial protocol. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005693/
COPD discharge bundle and pulmonary rehabilitation referral and uptake following hospitalisation for acute exacerbation of COPD. https://thorax.bmj.com/content/early/2021/03/02/thoraxjnl-2020-215464.long
Supervised pulmonary rehabilitation using minimal or specialist exercise equipment in COPD: a propensity-matched analysis. https://thorax.bmj.com/content/76/3/264.long
Pharmacological and nonpharmacological interventions to improve symptom control, functional exercise capacity and quality of life in interstitial lung disease: an evidence synthesis.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836673/
Management of breathlessness in patients with cancer: ESMO Clinical Practice Guidelines†. Electronic address: clinicalguidelines@esmo.org. https://www.esmoopen.com/article/S2059-7029(20)32759-9/fulltext
Trajectories of disability in activities of daily living in advanced cancer or respiratory disease: a systematic review. https://www.tandfonline.com/doi/abs/10.1080/09638288.2020.1820587
Palliative care and the management of common distressing symptoms in advanced cancer: Pain, breathlessness, nausea and vomiting and fatigue. https://ascopubs.org/doi/10.1200/JCO.19.00470?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed&
Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility) https://thorax.bmj.com/content/75/2/176
To What Extent Do the NRS and CRQ Capture Change in Patients' Experience of Breathlessness in Advanced Disease? Findings From a Mixed-Methods Double-Blind Randomized Feasibility Trial. https://www.jpsmjournal.com/article/S0885-3924(19)30309-4/fulltext
Mirtazapine for chronic breathlessness? A review of mechanistic insights and therapeutic potential. https://www.tandfonline.com/doi/abs/10.1080/17476348.2019.1563486
Holistic services for people with advanced disease and chronic breathlessness: a systematic review and meta-analysis. https://thorax.bmj.com/content/74/3/270
Control and context are central for people with advanced illness experiencing breathlessness: A systematic review and thematic synthesis. https://www.sciencedirect.com/science/article/pii/S0885392418305050
Recommendations for services for people living with chronic breathlessness in advanced disease: results of a transparent expert consultation Chronic Respiratory Disease.
https://journals.sagepub.com/doi/full/10.1177/1479973118816448
Use of mirtazapine in patients with chronic breathlessness: A case series. https://journals.sagepub.com/doi/10.1177/0269216318787450
Trials
BETTER-B: An International, Multicentre, Randomised Controlled Pragmatic Trial of Mirtazapine to alleviate Breathlessness in Palliative and End of Life Care
The aim of the trial is to assess the effectiveness and cost-effectiveness of mirtazapine for the reduction of chronic or refractory breathlessness and quality of life in patients with COPD or ILD over a 56-day period and with an extended follow-up period of 180 days. Caregivers (as nominated by participating patients) are also encouraged to take part so that their own experience can also be assessed. Eligible patients meet the following criteria • diagnosed with COPD or ILD with mMRC breathlessness score 3 or 4 • ≥18 years old • on optimal treatment for their condition • management of condition unchanged for the previous 2 weeks • no exclusion criteria For further details please contact beter-b@kcl.ac.uk or visit our website https://betterbreathe.eu/
Our Partners
University College Dublin
The University of Leeds Clinical Trials Research Unit
University of Nottingham
Trinity College Dublin
Principal Investigator
Irene Higginson
Executive Dean, Florence Nightingale Faculty of Nursing, Midwifery & Palliative Care
Investigators
Sabrina Bajwah
Clinical Senior Lecturer and Honorary Consultant in Palliative Care
Nilay Hepgul
Senior Trial Manager
Adejoke Oluyase
Research Associate
Charles Normand
Professor of Economics of Palliative Care & Rehabilitation
Affiliations
Project websites
Funding
Funding Body: European Commission
Amount: €3.7million
Period: January 2019 - June 2023