The European Respiratory Society convened a multidisciplinary respiratory task force group in 2024 to create a clinical practice guideline including recommendations for symptomatic treatment of advanced respiratory diseases. Ravijyot Saggu, co-author of the guideline, summarises the findings and details how holistic, patient-centred care is required.
A 2019 report highlighted that chronic respiratory diseases were the third leading cause of death and had a high prevalence of 454.6 million cases globally.1 What’s more, the burden of chronic respiratory disease can be significant for patients and carers, adversely impacting health-related quality of life (HRQoL).
The symptoms of respiratory disease are not exhaustive. Exacerbations aside, they often include anxiety and depression, but fatigue and breathlessness are prominent features in more advanced disease.
Many patients with advanced lung disease suffer from breathlessness, which can be limiting.
Breathlessness can be frightening and debilitating and lead to both psychological and functional decline,2 propagating inactivity and deconditioning, which further increases risks of falls and mortality.3 It is also associated with high healthcare utilisation. In England, for example, it accounts for 5% of presentations to emergency departments and approximately 4% of general practitioner consultations, as well as being reported by patients in 12% of medical admissions.4
A combination of pharmacological and non-pharmacological approaches to management is often beneficial. Breathlessness is not always due to hypoxia, which can sometimes be misunderstood by patients. Education is important to manage expectations and concerns.
Addressing a shortage of evidence
There is often a lack of large randomised controlled trials in advanced symptom management of lung disease. Any available evidence for interventions, which may include palliation, is mixed, of varying quality or conflicting.
To address this need, the European Respiratory Society (ERS) convened a multiprofessional respiratory task force group to undertake a review, create a clinical practice guideline and set out recommendations for the symptomatic treatment of advanced respiratory illness. The group also included patients affected by severe respiratory illness and informal carers. The resulting clinical practice guideline was published in the European Respiratory Journal in May 2024.5
Guideline methodology and interventions
The task force defined ‘serious respiratory illness’ as a respiratory condition that carries a high risk of mortality; negatively impacts quality of life and daily function; and/or is burdensome in symptoms, treatments, or caregiver stress.5,6
The task force adopted a rigorous approach, following ERS methodology and setting out Population, Intervention, Comparison, Outcome (PICO) questions for six interventions and one narrative question. Systematic reviews were undertaken, and as expected, there were some limitations on the included populations, the methods and the quality of evidence available.
The patient population in the trials reviewed included mixed lung diseases but chronic obstructive pulmonary disease (COPD) and interstitial lung disease were mainly represented. Patients in these studies had moderate to severe lung disease.
The ERS guideline reviewed six interventions, which were intended as ‘add-ons’ to complement the usual standard of care for the respective lung conditions: multicomponent services, graded exercise therapy, hand-held fans, breathing techniques, opioid use and supplemental oxygen.
PICO questions
Question 1: Should a multicomponent service be used to reduce symptoms in people with serious respiratory illness?
Question 2: Should GET be used to reduce fatigue in people with serious respiratory illness?
Question 3: Should increased airflow be used to reduce breathlessness in people with serious respiratory illness?
Question 4: Should supplemental oxygen be used to reduce symptoms in people with serious respiratory illness?
Question 5: Should opioids be used to reduce symptoms in people with serious respiratory illness?
Question 6: Should breathing techniques be used to reduce symptoms in people with serious respiratory illness?
Guideline review and recommendations
Evidence was reviewed using ‘grading of recommendation, assessment, development and evaluation’ (GRADE) – a systematic approach for rating the certainty of evidence.
Recommendations were made based on the available included evidence, as well as noting the strength and certainty of these and the fact that the relevance of interventions may vary over time along a patient’s disease trajectory.
1. Multicomponent services
A multicomponent model of care offers more than one intervention and includes at least one non-pharmacological intervention. Pulmonary rehabilitation (PR) was outside the scope of the review. Patients are enrolled in multicomponent services due to their symptoms, not diagnoses.
As a lower-risk and lower-cost intervention, the multicomponent model of care addresses a gap in healthcare, however, such services may not be widespread across all countries.
2. Graded exercise therapy
Graded exercise therapy (GET)is part of PR programmes, supervised over 12 weeks in an outpatient setting. It may include aerobic or water-based exercise and usually does not require specific equipment but usually needs staff supervision. It can also be delivered remotely.
Patients may have to wait a long time to access PR programmes or may be ineligible to be referred to PR if their lung disease is too advanced. They may also have a personal lack of confidence and reservations about participating in PR. The guideline serves as a lever to promote physical activity in patients and increase the availability and access of GET across countries.
3. Hand-held fans
A hand-held fan to ease the feeling of breathlessness is already established as part of COPD care in parallel to the use of usual inhaled treatments and breathing techniques.
Usually held six inches from the face, a fan generating cool air reduces the sensation and modulates the perception of, and patient response to, breathlessness.7 Use of a hand-held fan requires little patient training and is portable with virtually no associated adverse effects. However, there may be variations in the frequency, positioning and timing of patients’ use.
The guideline reaffirms its benefits and will hopefully promote greater uptake of this relatively inexpensive and accessible intervention.
4. Breathing techniques
People with lung disease may hyperventilate or have shallower or mouth breathing. Anxiety can also contribute to a dysfunctional breathing pattern, which can be further compounded by the side effects of beta-agonist medication use and overuse in lung disease.
Breathing techniques essentially slow breathing, enabling deeper breathing and increased mindfulness of respiration. This can be useful when a person undertakes an activity to help expel air and pace themselves. Breathing exercises also help manage panic attacks and are an established part of COPD care.
5. Opioid use
Opioids are commonly prescribed for pain but sometimes for a non-analgesic effect in lung disease. To look at this in more detail, the ERS task force reviewed studies which mainly included patients with COPD (and none that were at end of life) comparing opioids to placebo for the treatment of breathlessness or cough when used for >4 days.
Based on the evidence included in the review, the guideline recommends against opioid use for breathlessness or improving HRQoL, which is contrary to current practice in some countries.
The review found that regular use of opioids also had no significant effect on cough scores. Opioids have a range of adverse effects associated with their use; these may be heightened in people with advanced lung disease who may be more sensitive to their effects, for example, due to older age or if there is renal or liver dysfunction.
Before the guideline, patients with more advanced lung disease might have been prescribed low-dose morphine (such as 1.25–2.5 mg orally) for breathlessness, which is an unlicensed use of opioids; however, the evidence of benefit is variable.
This practice may be harder to change but publication of the guideline offers an opportunity to deprescribe and reduce unnecessary medication burden, or equally prevent the prescribing in the first place where it may not be beneficial.
This is also in line with national patient safety concerns related to opioid use in the UK. There may be a role for morphine in the palliation of refractory breathlessness in advanced or terminal illnesses.8
6. Supplemental oxygen
The ERS practice guidance reviewed supplemental oxygen use at rest or exertion. It points out that there is little reliable evidence that oxygen positively affects HRQoL or breathlessness scores in daily life. Hence, oxygen should not be routinely prescribed for breathlessness.
It has utility in an emergency setting or for longer-term use, such as in respiratory failure or palliative care, but also has risks relating to the oxygen itself but also equipment, which include local side effects, trip hazards and burns. Therefore, it should be prescribed as per national guidelines to ensure safe and clinically appropriate use.
Although the guidance suggests not using oxygen, there may be individuals who may derive small benefit and these patients should be reviewed on a case-by-case basis. For selected patients with severe breathlessness and exertional desaturation, and who will be able to use it safely, a trial of oxygen can be instituted. If so, the lowest concentration and flow rate to ease symptoms should be trialled.
Recommendation summary
Positive recommendation:
- GET was given a positive recommendation to reduce fatigue (conditional, low certainty of evidence).
Conditional recommendations, very low certainty of evidence:
- Multicomponent services
- Breathing techniques
- Increased airflow via fan (handheld or table) to ease breathlessness.
Negative recommendations:
- Use of opioids (conditional, very low certainty evidence)
- Use of supplemental oxygen (unequivocal recommendation to administer or not administer – conditional, low certainty evidence).
The guideline‘s robust review process
The task force wanted to maintain rigour and a robust review process and acknowledge that the certainty of the available evidence for review was often low or very low. Certainty of evidence was impacted by various factors in the studies, including the risk of bias, imprecision and reporting bias.
Sometimes, a variety of scales for measuring a clinical difference were used, and sometimes multiple measures within a study were used at inconsistent times. Scores did not always correlate with an improved perception of symptoms or have a positive impact on other non-study-specified outcomes.
Acute improvements and reductions in breathlessness may be more clinically meaningful than a change over time.
HRQoL is impacted by various factors, including when it is measured and by breathlessness, which were, in some cases, measured separately and by the same and different scales, making results challenging to interpret. This reiterates that the studies reviewed had heterogeneity and that patients’ symptoms and the relevance of interventions change over time.
Additionally, the task force noted ‘the low certainty of evidence, modest impact of interventions on patient-centred outcomes, and absence of effective strategies to ameliorate cough highlight the need for new approaches to reduce symptoms and enhance wellbeing for individuals who live with serious respiratory illness.’5
Implications for practice and future priorities
The guideline highlights several research priorities and priorities for future work.
It is intended to complement the usual good practice management of respiratory diseases in line with national and international guidelines. The standard fundamentals of care should be applied, including, where relevant, optimising medicines, inhaler technique and adherence to therapy; ensuring uptake of vaccinations such as pneumococcal and influenza; and the optimal management of co-morbidities.
Smoking cessation is a key intervention at any stage, and patients should be supported to achieve this. In some countries, smoking status may impact eligibility for oxygen therapy.
Considerations of different payers and how healthcare is accessed in different countries are also important in influencing the uptake of care and interventions, recognising that this may widen health inequalities and poor health outcomes if people cannot afford to pay for treatments.
The guideline highlights the need for shared decision-making conversations with patients and a balance of benefit versus risk and adverse events on an individual basis alongside regular review and monitoring, including trialling and stopping interventions if they are not beneficial. This is important to manage patient expectations and personalise care and may be included in advanced care planning conversations.
Additionally, equity of access to interventions, such as oxygen, may be variable depending on the set-up of healthcare in different countries and an individual’s ability to pay for and access care, but, equally, the availability of services and treatments. It is also influenced by geographical location – be that coastal, rural or urban. The guidance hopefully levels this inequity by dissuading the use of oxygen, although it can be difficult to change historical practices.
There is also the opportunity and consideration to employ different models of care for multidisciplinary review and interventions going forward. This is useful in re-imagining pathways of service provision and when considering our respiratory workforce, including growing this for the future; capacity plans; and working in more integrated ways.
Studies of multicomponent services reviewed have been respiratory- or palliative-based and not in primary care. Therefore, the feasibility of implementation in expanded settings must be considered in line with local infrastructure and scope for expansion.
Many of the interventions reviewed are relatively inexpensive and can be implemented with little or no training. Pharmacological interventions, including oxygen, have their own associated potential adverse events and this guideline offers an evidence-based approach to support clinicians with patient discussions as to how and when these interventions may be utilised.
Ultimately, we need to provide holistic, patient-centred care, offering both pharmacological and non-pharmacological interventions which take account of individual needs, balancing risk and benefit to ease symptoms in advanced lung disease.
Author
Ravijyot Saggu
Respiratory pharmacist, London, UK, and chair of the UK Clinical Pharmacy Association Respiratory Committee
References
- GBD 2019 Chronic Respiratory Diseases Collaborators. Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019.eClin Med 2023;59:101936.
- Hutchinson A et al. Living with breathlessness: a systematic literature review and qualitative synthesis. Eur Resp J 2018;51:1701477.
- Hopkinson NS, Baxter N, London Respiratory Network. Breathing SPACE — a practical approach to the breathless patient. NPJ Prim Care Respir Med 2017;27(1):5.
- NHS England Breathlessness pathway. www.england.nhs.uk/long-read/adult-breathlessness-pathway-pre-diagnosis-diagnostic-pathway-support-tool/ (accessed September 2024).
- Holland A et al. European Respiratory Society Clinical Practice Guideline on symptom management for adults with serious respiratory illness. Eur Resp J 2024; May 24.
- Stewart I et al. Patient-reported distress can aid clinical decision-making in idiopathic pulmonary fibrosis: analysis of the PROFILE cohort. Eur Respir J 2019:53(5):1801925.
- Luckett T et al. Contributions of a hand-held fan to self-management of chronic breathlessness. Eur Resp J 2017;50:1700262.
- Barnes H et al. Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database Syst Rev. 2016 Mar 31;3(3):CD011008.
