Persistent breathlessness in advanced disease – what can we do about it?

An article written by Dr. Diana Ferreira

Some people with advanced illness may experience breathlessness that persists despite receiving the best treatments for the disease causing it (e.g., cancer, chronic obstructive pulmonary disease). Persistent breathlessness is often progressive and debilitating, limiting people’s mobility and independence. It also has a significant impact on loved ones who try to compensate for the limitations experienced by the person with persistent breathlessness.

Improving the wellbeing of patients and carers includes:

• Increasing the recognition of this symptom, which is often hidden in plain sight. Unlike other symptoms, people with persistent breathlessness may experience guilt about a symptom that is perceived as self-inflicted (i.e., due to smoking). They also tend to avoid activities triggering breathlessness and may not disclose the symptom to their physicians voluntarily until the symptom becomes severe.
• Increasing the scientific evidence for symptomatic treatments that can improve people’s wellbeing and quality of life.

In this context, we conducted a literature review to summarise the evidence supporting the use of pharmacological strategies for persistent breathlessness associated with advanced illnesses. [1] Before introducing medication with the aim to improve breathlessness, it is recommended to:

1. optimise the treatment for the disease causing breathlessness, and
2. initiate non-pharmacological interventions supported by good quality evidence (e.g., pulmonary rehabilitation, hand-held fan).

If breathlessness persists despite these treatments, it is recommended to initiate regular opioids in low doses. Sustained-release morphine is currently approved in Australia for persistent breathlessness associated with advanced disease (doses 10-30mg/daily), regardless of the cause. [2] However, morphine is far from being a panacea for persistent breathlessness. For example, the latest trial conducted in this field has shown that morphine did not show benefit compared to a placebo and produced more harm. [3]

The challenge with large trials is that they report the summary effects seen for the group, but they do not show the effect for individual participants. Qualitative studies reporting on people’s experiences suggest that some people with breathlessness experience great benefits from morphine, which can greatly increase their ability to engage in daily tasks that are essential for them. Other people may not feel any improvements or experience only side effects, such as sedation and constipation. Unfortunately, we still do not fully know what leads to these different responses to the same medication, which needs to be the focus of future research.

Considering the impact of persistent breathlessness for patients and their carers, there is certainly a need to investigate new and more effective medications for this symptom. Until then, we need to ensure people with persistent breathlessness are not denied a potentially beneficial treatment. In the absence of contraindications, initiating sustained-release morphine (10 mg daily) while carefully monitoring side effects is a reasonable approach. In the absence of unacceptable side effects, the dose can be increased by 10 mg weekly until a maximum of 30 mg per week. Currently, no other pharmacological treatments, including antidepressants and benzodiazepines, are indicated for the reduction of persistent breathlessness.

References

1. Ferreira DH, Kochovska S, McNeill R, Currow DC. Current pharmacological strategies for symptomatic reduction of persistent breathlessness - a literature review. Expert Opin Pharmacother. 2023 Feb;24(2):233-244. doi: 10.1080/14656566.2022.2160239. Epub 2022 Dec 28.
2. Therapeutic Goods Administration (TGA). Australian Public Assessment Report for Morphine sulphate pentahydrate (1.63MB pdf). Woden, ACT: TGA; 2019 Mar.
3. Ekström M, Ferreira D, Chang S, Louw S, Johnson MJ, Eckert DJ, et al; Australian National Palliative Care Clinical Studies Collaborative. Effect of Regular, Low-Dose, Extended-release Morphine on Chronic Breathlessness in Chronic Obstructive Pulmonary Disease: The BEAMS Randomized Clinical Trial. JAMA. 2022 Nov 22;328(20):2022-2032. doi: 10.1001/jama.2022.20206. Erratum in: JAMA. 2023 Feb 28;329(8):687.

Dr. Diana Ferreira
Research Fellow
Faculty of Science, Medicine and Health,
University of Wollongong, NSW