Sublingual fentanyl for refractory episodic acute dyspnea in patients with advanced chronic obstructive pulmonary disease (COPD): A real-world study

Abstract BACKGROUND Dyspnea is an extremely prevalent and debilitating symptom in chronic obstructive pulmonary disease (COPD), affecting up to 74% of patients despite optimal medical therapy. Sublingual fentanyl citrate (SLF) has a fast onset of action and a short half-life, both interesting characteristics to treat acute breakthrough dyspnea without inducing metabolite accumulation. The Montreal Chest Institute (MCI) COPD specialty clinic has been using low-dose SLF for patients with advanced COPD experiencing significant episodic dyspnea despite high intensity inhaled therapy. We present here a retrospective chart review, the largest to date, to report on a “real life” experience. METHODS All included patients had a formal diagnosis of COPD and were seen in the MCI COPD specialty clinic between January 1, 2015 and January 1, 2021. All patients prescribed SLF, irrespective of the duration of use, were enrolled in this chart review. Extent of symptom relief, categorized into either major, intermediate or no improvements, and adverse effects were inferred from in-person or telephone follow-up appointment clinical notes. An exacerbation was defined as a self-reported acute increase in symptoms leading to oral corticosteroid use or hospitalization. Rates of exacerbation and hospitalization in the 12 months before SLF initiation and during SLF use were compared. RESULTS In total, 17 COPD patients were given SLF during the study period. The mean FEV1 was 0.51 L (21% predicted). All participants reported MRC5/5 dyspnea and were prescribed regular low-dose oral morphine for daily breathlessness prior to SLF initiation. Most patients used SLF for more than 6 months, and 76.5% of the study group found intermediate or major improvement in breathlessness episodes. There was no significant change in the rates of exacerbation and admission for acute respiratory failure while on SLF. CONCLUSION In this review, we report real-life, long-term data on severe COPD patients using self-controlled as-needed SLF, showing patient acceptability, an improvement in dyspnea, and limited side effects. Hence, this represents an important step toward the first effective alternative rescue medication for the relief of breakthrough dyspnea since short-acting inhalers. Further study using a randomized trial design is required to confirm the efficacy of this therapy.