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Exercise intolerance and exertional dyspnoea are hallmarks of fibrosing interstitial lung disease (FILD) and are associated with worse prognosis and quality of life. Activation of pulmonary vagal afferents influences the ventilatory pattern and contributes to the sensation of dyspnoea. We tested the hypothesis that nebulized fentanyl, which might attenuate aberrant pulmonary afferent activity in FILD, reduces ventilation and dyspnoea while extending exercise endurance time (EET). In this randomized, single‐blind, placebo‐controlled study, eight FILD patients (two males, 71 ± 6 years of age) performed incremental cardiopulmonary cycle exercise tests following nebulization of either fentanyl citrate (100 µg) or 0.9% saline. Previous work indicated that this dose was unlikely to produce central effects. Comparisons between treatment conditions at rest were undertaken using Student's paired t‐test, and exercise data were evaluated with two‐way ANOVA with repeated measures. Dyspnoea was assessed using the Borg dyspnoea scale. Resting respiratory variables were not different following treatment with fentanyl and saline; however, resting heart rate was lower following fentanyl (P = 0.002) and remained lower throughout exercise compared with placebo (P = 0.008). Fentanyl did not increase EET (placebo 334 ± 117 s vs. fentanyl 348 ± 126 s, P = 0.250) although overall minute ventilation was reduced slightly (mean difference: −0.97 L/min, P = 0.022). There were no differences in ratings of dyspnoea intensity or unpleasantness between the conditions either at rest or at end‐exercise. Nebulized fentanyl did not improve EET or exercise dyspnoea but did decrease minute ventilation during exercise, although the extent of this reduction appears clinically insignificant. These findings suggest that nebulized fentanyl is unlikely to offer significant benefits for enhancing exercise capacity in FILD. What is the central question of this study?Fibrotic interstitial lung disease is associated with dyspnoea and exercise intolerance. The role of bronchopulmonary vagal afferents is not completely understood. We asked whether nebulized fentanyl could attenuate sensory feedback and improve exercise capacity.What is the main finding and its importance?Nebulized fentanyl reduced exercise ventilation compared with placebo; however, the small magnitude of this reduction means that it is unlikely to be clinically significant. Exercise endurance time, peak ventilation and dyspnoea scores were unchanged. Nebulized fentanyl is therefore unlikely to offer significant benefits for enhancing exercise capacity in fibrotic interstitial lung disease. [ABSTRACT FROM AUTHOR]