• Kathryn M Milne, Megha Ibrahim-Masthan, Robin E Scheeren, Matthew D James, Devin B Phillips, Onofre Moran-Mendoza, Neder Ja, and Denis E O'Donnell.
• Department of Medicine, Queen's University, Kingston Health Sciences Centre, Kingston, Ontario, Canada; Clinician Investigator Program, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
• Respir Physiol Neurobiol. 2020 Nov 1; 282: 103511.

BackgroundExertional dyspnea in interstitial lung disease (ILD) remains difficult to manage despite advances in disease-targeted therapies. Pulmonary opioid receptors present a potential therapeutic target for nebulized fentanyl to provide dyspnea relief.MethodsILD patients were characterized with reference to healthy volunteers. A randomized, double-blind, placebo-controlled crossover comparison of 100 mcg nebulized fentanyl vs placebo on dyspnea intensity and inspiratory neural drive (IND) during constant work rate (CWR) cycle exercise was performed in 21 ILD patients.ResultsDyspnea intensity in ILD increased in association with an increase in IND (diaphragm activation) from a high resting value of 16.66 ± 6.52 %-60.04 ± 12.52 % of maximum (r = 0.798, p < 0.001). At isotime during CWR exercise, Borg dyspnea intensity ratings with fentanyl vs placebo were 4.1 ± 1.2 vs 3.8 ± 1.2, respectively (p = 0.174), and IND responses were also similar.ConclusionIND rose sharply during constant work rate exercise in association with dyspnea intensity in mild to moderate ILD but was not different after nebulized fentanyl compared with placebo.Copyright © 2020 Elsevier B.V. All rights reserved.

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