Impact of nebulized fentanyl on exertional dyspnea in interstitial lung disease

Background: Limited options exist for alleviation of exertional dyspnea in interstitial lung disease (ILD). Exertional dyspnea in ILD is associated with increased inspiratory neural drive (IND) to the diaphragm (Faisal et al, AJRCCM 2016;193(3):299-309). We assessed the impact of nebulized fentanyl on dyspnea intensity, IND and its physiological underpinnings in ILD during constant work rate (CWR) cycle exercise. Methods: This randomized double-blind cross-over study examined the effect of 100mcg nebulized fentanyl vs. placebo on dyspnea (Borg scale), IND using diaphragmatic electromyography (EMGdi/EMGdi, max), pulmonary gas exchange and dynamic respiratory mechanics during 4-min CWR exercise (performed at 75% peak work rate) in ILD subjects. Results: Subjects (n=21) had Baseline Dyspnea Index of 7.8±1.7; TLC 70±12%predicted, FVC 79±17%predicted and DLCO 50±15%predicted (mean±SD). With placebo from rest to end-exercise dyspnea increased to 4.1±1.2 Borg units, IND increased from 17±7% to 61±13%, minute ventilation (V_E) increased from 15.5±3.3L/min to 58.7±11.6L/min and inspiratory reserve volume (IRV) dropped from 1.6±0.5L to 0.6±0.2L (mean±SD). Significant inter-relationships were found between increased dyspnea, increased IND and decreased IRV (all p<0.01). There was no difference in dyspnea, IND, ventilatory equivalent for carbon dioxide (V_E/VCO₂) or IRV with fentanyl vs. placebo. Conclusions: In ILD exertional dyspnea increases in tandem with IND as IRV decreases. Nebulized fentanyl had no effect on dyspnea, IND, dynamic respiratory mechanics or their inter-relationships during exercise.