IMPORTANCE Morphine is used as palliative treatment of chronic breathlessness in patients with advanced chronic obstructive pulmonary disease (COPD). Evidence on respiratory adverse effects and health status is scarce and conflicting.OBJECTIVE To assess the effects of regular, low-dose, oral sustained-release morphine on disease-specific health status (COPD Assessment Test; CAT), respiratory outcomes, and breathlessness in patients with COPD.INTERVENTIONS Participants were randomly assigned to 10 mg of regular, oral sustained-release morphine or placebo twice daily for 4 weeks, with the possibility to increase to 3 times daily after 1 or 2 weeks. DESIGN, SETTING, AND PARTICIPANTSThe Morphine for Treatment of Dyspnea in Patients With COPD (MORDYC) study was a randomized, double-blind, and placebo-controlled study of a 4-week intervention. Patients were enrolled between November 1, 2016, and January 24, 2019. Participants were recruited in a pulmonary rehabilitation center and 2 general hospitals after completion of a pulmonary rehabilitation program. Outpatients with COPD and moderate to very severe chronic breathlessness (modified Medical Research Council [mMRC] breathlessness grades 2-4) despite optimal pharmacological and nonpharmacological treatment were included. A total of 1380 patients were screened, 916 were ineligible, and 340 declined to participate. MAIN OUTCOMES AND MEASURESPrimary outcomes were CAT score (higher scores represent worse health status) and arterial partial pressure of carbon dioxide (PaCO 2 ). Secondary outcome was breathlessness in the previous 24 hours (numeric rating scale). Data were analyzed by intention to treat. Subgroup analyses in participants with mMRC grades 3 to 4 were performed.RESULTS A total of 111 of 124 included participants were analyzed (mean [SD] age, 65.4 [8.0] years; 60 men [54%]). Difference in CAT score was 2.18 points lower in the morphine group (95% CI, -4.14 to -0.22 points; P = .03). Difference in PaCO 2 was 1.19 mm Hg higher in the morphine group (95% CI, -2.70 to 5.07 mm Hg; P = .55). Breathlessness remained unchanged. Worst breathlessness improved in participants with mMRC grades 3 to 4 (1.33 points lower in the morphine group; 95% CI, -2.50 to -0.16 points; P = .03). Five participants of 54 in the morphine group (9%) and 1 participant of 57 in the placebo group (2%) withdrew because of adverse effects. No morphine-related hospital admissions or deaths occurred. CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, regular, low-dose, oral sustained-release morphine for 4 weeks improved disease-specific health status in patients with COPD without affecting PaCO 2 or causing serious adverse effects. The worst breathlessness improved in participants with mMRC grades 3 to 4. A larger randomized clinical trial with longer follow-up in patients with mMRC grades 3 to 4 is warranted.

Previous studies have shown that opioids can reduce chronic breathlessness in advanced disease. However, physicians remain reluctant to prescribe opioids for these patients, commonly due to fear of respiratory adverse effects. The aim of this study was to systematically review reported respiratory adverse effects of opioids in patients with advanced disease and chronic breathlessness.PubMed, Embase, the Cochrane Central Register of Controlled Trials, CINAHL, ClinicalTrials.gov and the reference lists of relevant systematic reviews were searched. Two independent researchers screened against predefined inclusion criteria and extracted data. Meta-analysis was conducted where possible.We included 63 out of 1990 articles, describing 67 studies. Meta-analysis showed an increase in carbon dioxide tension (0.27 kPa, 95% CI 0.08-0.45 kPa,) and no significant change in oxygen tension and oxygen saturation (both p>0.05). Nonserious respiratory depression (definition variable/not stated) was described in four out of 1064 patients. One cancer patient pretreated with morphine for pain needed temporary respiratory support following nebulised morphine for breathlessness (single case study).We found no evidence of significant or clinically relevant respiratory adverse effects of opioids for chronic breathlessness. Heterogeneity of design and study population, and low study quality are limitations. Larger studies designed to detect respiratory adverse effects are needed.

Background: Despite recommendations, people with heart failure have poor access to palliative care. Aim: To identify the evidence in relation to palliative care for people with symptomatic heart failure. Design: Systematic review and narrative synthesis. (PROSPERO CRD42016029911) Data sources: Databases (Medline, Cochrane database, CINAHL, PsycINFO, HMIC, CareSearch Grey Literature), reference lists and citations were searched and experts contacted. Two independent reviewers screened titles and abstracts and retrieved papers against inclusion criteria. Data were extracted from included papers and studies were critically assessed using a risk of bias tool according to design. Results: Thirteen interventional and 10 observational studies were included. Studies were heterogeneous in terms of population, intervention, comparator, outcomes and design rendering combination inappropriate. The evaluation phase studies, with lower risk of bias, using a multi-disciplinary specialist palliative care intervention showed statistically significant benefit for patient-reported outcomes (symptom burden, depression, functional status, quality of life), resource use and costs of care. Benefit was not seen in studies with a single component/discipline intervention or with higher risk of bias. Possible contamination in some studies may have caused under-estimation of effect and missing data may have introduced bias. There was no apparent effect on survival. Conclusion: Overall, the results support the use of multi-disciplinary palliative care in people with advanced heart failure but trials do not identify who would benefit most from specialist palliative referral. There are no sufficiently robust multi-centre evaluation phase trials to provide generalisable findings. Use of common population, intervention and outcomes in future research would allow meta-analysis.

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The limits of agreement of the IC measured by OM and OP were +/-10%, which is recommended for interdevice reproducibility. We conclude that OM and OP can be used interchangeably for measuring IC at rest and during steady-state exercise.

Breathlessness is the most common symptom in advanced chronic lung disease or chronic heart failure (CHF) [1]. Opioids are recommended for palliative treatment of breathlessness persisting despite optimal pharmacological and non-pharmacological treatment [2, 3]. However, physicians don't always consider opioids for chronic breathlessness [4,5] and experience barriers when considering opioids, such as resistance of patients [6]. This can limit effective palliative treatment. Qualitative studies in patients with COPD and CHF revealed fear of dependence and fear of imminent death as the most important barriers to opioid use. The reason to start treatment was to do as much as possible [7][8][9]. These qualitative studies were only conducted in small patient populations. Therefore, our aims were to assess the willingness of patients with chronic lung disease or CHF to use opioids for breathlessness, irrespective of a current indication for opioid treatment; and to assess their barriers towards opioid use and reasons to use opioids. Finally, we aimed to compare willingness differences according to sex, age, educational level, diagnosis and breathlessness severity.An exploratory convenience sample of 175 patients referred for a baseline assessment prior to pulmonary or heart failure rehabilitation was recruited, independent of their level of breathlessness. Patients were excluded if they could not read or write, had not mastered Dutch, were aged <18 years or were unable to give informed consent. The Maastricht University Medical Centre (MUMC+, Maastricht, the Netherlands) medical ethical committee, reviewed the study protocol and concluded that the study didn't fall under the Medical Research Involving Human Subjects Act (METC 2018-0790). Patients completed a survey including demographic characteristics, educational level, previous and current opioid use (opioid, dosage and reason for prescription) and willingness to use opioids for breathlessness. Patients willing to use opioids and patients who had experience with opioids were asked to indicate their reasons to use opioids; patients unwilling to use opioids were asked to indicate their barriers. Patients who were indecisive were asked to indicate their barriers against and the reasons to use opioids. In addition, patients were invited to report reasons other than those predefined using a free-text field. The predefined reasons were selected based on previous research [7][8][9], expert opinion of the project group and experience from patient inclusion for an opioid trial (MORDYC) [10]. Disease characteristics (diagnosis, disease history, lung function, 6-min walk distance (6MWD) [11]) and breathlessness severity (modified Medical Research Council (mMRC) scale) [12] were recorded using chart review. Data were described using mean±SD or median (interquartile range (IQR)) for continuous variables and n (%) for categorical variables. We compared the willingness to use opioids between sexes, age (<65 years or ⩾65 years), educational level (lower education, defined as having...

Chronic breathlessness syndrome, defined as breathlessness that persists despite optimal treatment of the underlying pathophysiology, resulting in disability, is a major problem for patients with advanced chronic lung disease, and can be difficult to manage [1, 2]. Opioids should be considered for treatment of these patients [3]. Episodic breathlessness is severe worsening of breathlessness intensity, which can be predictable or unpredictable [4]. Episodic breathlessness can have a major impact on activities of daily life, but ∼90% of episodes last for 20 min or less [5]. Therefore, the selection of appropriate palliative pharmacological therapy is a complex issue. Indeed, the onset of action of short-acting oral opioids is between 15 and 30 min [6]. The rapid onset of action (between 1 and 4 min [7]) is the major advantage of fentanyl nasal spray. This case report relates the experience and insight gained when fentanyl nasal spray was prescribed to a patient with end-stage chronic obstructive pulmonary disease (COPD) and the lessons we have learned. Written informed consent for publication of the clinical details was obtained from the deceased patient's spouse.

• The Fox-walk test is a new method to estimate aerobic capacity and could be performed walking or running. • The test is self administered without expensive equipment and is available in 150 public places in Sweden and several other European countries. • The Fox-walk test is a reliable test for use among people with rheumatoid arthritis monitoring the progress of their physical activity.