Dyspnoea is a major source of distress and is the hallmark symptom of patients with interstitial lung disease (ILD). Supplemental oxygen may alleviate dyspnoea by attenuating arterial oxygen desaturation, increasing oxygen delivery and reducing the drive to breathe; however, previous studies show conflicting results on the effectiveness of supplemental oxygen on dyspnoea and exercise performance in ILD [1][2][3][4][5][6]. Methodological factors in these studies likely led to underestimation of the potential magnitude of improvement, including an insufficient fraction of inspired oxygen (FIO 2 ) and/or the use of self-paced walking tests and incremental cycle tests rather than constant-load exercise protocols [3][4][5][6][7][8]. Dyspnoea was also either not evaluated or only evaluated at peak exercise [1,[3][4][5][6], which is insensitive to change compared to more clinically relevant submaximal exercise [8]. Finally, some studies were retrospective and did not include a blinded room-air exercise trial, making it difficult to rule out the potential placebo effect [4,5]. The purpose of this study was to determine the effects of hyperoxia on exercise endurance as well as the intensity and qualitative dimensions of exertional dyspnoea in patients with fibrotic ILD.This prospective, single-blind, randomised, placebo-controlled, crossover study (ClinicalTrials.gov: NCT01781793) received ethical approval and included 20 fibrotic ILD patients with isolated lung involvement (age 66±9 yrs; body mass index 29±5 kg·m −2 ; forced vital capacity 72±16% predicted; total lung capacity (TLC) 64±11% predicted; diffusing capacity of the lung for carbon monoxide 46±13% predicted; peak oxygen uptake 68±22% predicted). Visit 1 included medical history, pulmonary function testing and a symptom-limited incremental cycle test for familiarisation purposes. Visit 2 included the same incremental test to determine peak work-rate. Visits 3 and 4 each included symptom-limited constant-load cycle tests at 75% of peak work-rate while breathing room air (FIO 2 21%) or hyperoxia (FIO 2 60%), in randomised order. Subjects were blinded to the gas mixtures, which were delivered into a non-diffusing Douglas bag connected to a two-way non-rebreathing valve. Breath-by-breath metabolic and ventilatory responses were measured using a commercially available metabolic cart.

Our understanding of the mechanisms of dyspnoea in fibrotic interstitial lung disease (ILD) is incomplete. The aims of this study were two-fold: 1) to determine whether dyspnoea intensity is better predicted by neural respiratory drive (NRD) or neuromechanical uncoupling (NMU) of the respiratory system in fibrotic ILD, and 2) to examine the effect of breathing 60% oxygen on NRD, NMU and dyspnoea ratings.Fourteen patients with fibrotic ILD were included. Visit 1 comprised a familiarisation incremental cycle exercise test, Visit 2 comprised a normoxic incremental cycling test to address Aim 1, and Visits 3 and 4 consisted of constant-load cycling while breathing room air or 60% oxygen to address Aim 2. Diaphragmatic electromyography (EMGdi) was used as a surrogate of NRD. NMU was calculated as the ratio between EMGdi (%max) and tidal volume (%vital capacity).On adjusted analysis, NMU and its constituents were all significantly associated with dyspnoea ratings during incremental cycling, with EMGdi having the strongest correlation. The between-treatment change in dyspnoea ratings during constant load cycling was only correlated with change in exercise endurance time and NMU.Dyspnoea more strongly reflected the level of EMGdi than NMU in fibrotic ILD. However, the improvement in dyspnoea with 60% oxygen was better predicted by improvements in NMU.