Healthcare and Societal Costs in Patients with COPD and Breathlessness after Completion of a Comprehensive Rehabilitation Program.

Breathlessness is one of the most frequent symptoms in chronic obstructive pulmonary disease (COPD). COPD may result in disability, decreased productivity and increased healthcare costs. The presence of comorbidities increases healthcare utilization. However, the impact of breathlessness burden on healthcare utilization and daily activities is unclear. This study's goal was to analyze the impact of breathlessness burden on healthcare and societal costs. In this observational single-center study, patients with COPD were followed-up for 24 months after completion of a comprehensive pulmonary rehabilitation program. Every three months participants completed a cost questionnaire, covering healthcare utilization and impact on daily activities. The results were compared between participants with low (modified Medical Research Council (mMRC) grade <2; LBB) and high baseline breathlessness burden (mMRC grade ≥2; HBB). Healthcare costs in year 1 were €7302 (95% confidence interval €6476-€8258) for participants with LBB and €10,738 (€9141-€12,708) for participants with HBB. In year 2, costs were €8830 (€7372-€10,562) and €14,933 (€12,041-€18,520), respectively. Main cost drivers were hospitalizations, contact with other healthcare professionals and rehabilitation. Costs outside the healthcare sector in year 1 were €682 (€520-€900) for participants with LBB and €1520 (€1210-€1947) for participants with HBB. In year 2, costs were €829 (€662-€1046) and €1457 (€1126-€1821) respectively. HBB in patients with COPD is associated with higher healthcare and societal costs, which increases over time. This study highlights the relevance of reducing costs with adequate breathlessness relief. When conventional approaches fail to improve breathlessness, a personalized holistic approach is warranted.

Morphine for chronic breathlessness in COPD: improvement predictors-cross-sectional study.

OBJECTIVE: Morphine is used as palliative treatment of chronic breathlessness in patients with chronic obstructive pulmonary disease (COPD). Part of the patients does not experience a clinically meaningful improvement of breathlessness and it is unclear which characteristics are related to a clinically meaningful improvement of breathlessness after morphine. Therefore, this study assessed whether sensory breathlessness description, demographic and clinical characteristics are related with this improvement. METHODS: Cross-sectional secondary analysis of the intervention arm of a randomised controlled trial. 45 patients with COPD and moderate-to-very severe chronic breathlessness despite optimal treatment received 20-30 mg oral sustained-release morphine daily for 4 weeks. Using binary logistic regression, the relationship between a clinically meaningful improvement in breathlessness (≥1 point on 0-10 numeric rating scale) and the baseline variables sensory breathlessness descriptors, age, breathlessness and body mass index (BMI) was assessed. RESULTS: Twenty-one participants (42%) showed a clinically meaningful improvement. Baseline breathlessness (OR 1.51, 95% CI 1.04 to 2.21, p=0.03) and BMI (OR 1.13, 95% 1.02-1.28, p=0.02) were significant associated to a clinically meaningful improvement of breathlessness, while age and sensory breathlessness descriptors were not. CONCLUSIONS: Worse baseline breathlessness and higher BMI are associated to a clinically meaningful improvement of breathlessness in patients using 20-30 mg oral sustained-release morphine. Opioid treatment should be considered in patients with COPD with severe breathlessness, taking into account the patient's BMI.

Cost-effectiveness of sustained-release morphine for refractory breathlessness in COPD: A randomized clinical trial.

BACKGROUND: Chronic breathlessness is a frequent symptom in advanced Chronic Obstructive Pulmonary Disease (COPD) and has major impact on quality of life, daily activities and healthcare utilization. Morphine is used as palliative treatment of chronic breathlessness. The aim is to analyze cost-effectiveness of regular, low-dose morphine in patients with advanced COPD from a healthcare and societal perspective. METHODS: In a randomized controlled trial, participants with advanced COPD were assigned to 10 mg regular, oral sustained-release morphine or placebo twice daily for four weeks. Quality of life (COPD Assessment Test; CAT), quality-adjusted life years (QALY's; EQ-5D-5L), healthcare costs, productivity, and patient and family costs were collected. Incremental cost-effectivity ratio's (ICERs) using healthcare costs and CAT scores, and incremental cost-utility ratio's (ICURs) using societal costs and QALY's were calculated. RESULTS: Data of 106 of 124 participants were analyzed, of which 50 were in the morphine group (mean [SD] age 65.4 [8.0] years; 58 [55%] male). Both ICER and ICUR indicated dominance for morphine treatment. Sensitivity analyses substantiated these results. From a healthcare perspective, the probability that morphine is cost-effective at a willingness to pay €8000 for an minimal clinically important difference of 2 points increase in CAT score is 63%. From a societal perspective, the probability that morphine is cost-effective at a willingness to pay €20,000 per QALY is 78%. CONCLUSION: Morphine for four weeks is cost-effective regarding the healthcare and the societal perspective. To estimate the long-term costs and effects of morphine treatment, a study of longer follow-up should be performed. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02429050).

Effect of Sustained-Release Morphine for Refractory Breathlessness in Chronic Obstructive Pulmonary Disease on Health Status: A Randomized Clinical Trial.

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 Participants: The 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 Measures: Primary outcomes were CAT score (higher scores represent worse health status) and arterial partial pressure of carbon dioxide (Paco2). 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 Paco2 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 Relevance: In 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 Paco2 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02429050.

Fentanyl nasal spray in a patient with end-stage COPD and severe chronic breathlessness.

Insufficient control of chronic breathlessness may induce excessive use of fentanyl nasal spray in COPD patients. Prescription of fentanyl nasal spray for breathlessness should only be done as part of palliative treatment and requires close follow-up. http://bit.ly/2YdOjJ1.