Effects of hyperoxia on dyspnoea and exercise endurance in fibrotic interstitial lung disease

Abstract

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.

Neurophysiological mechanisms of exertional dyspnoea in fibrotic interstitial lung disease

“…This is consistent with our findings, suggesting that increased NRD largely contributes to increased dyspnoea intensity in patients with fibrotic ILD, at least during normoxic incremental exercise. We recently demonstrated significant reductions in iso-time dyspnoea intensity ratings during constant-load exercise with hyperoxia versus room air [7]. However, no signification correlations were found between the reduction in dyspnoea intensity ratings and the between-treatment changes in standard ventilatory measures during exercise.…”

“…This study included 14 fibrotic ILD patients with isolated lung involvement that simultaneously participated in a previously published study (n=20) examining the effects of hyperoxia on cycle endurance time and dyspnoea [7]. All patients had resting arterial oxygen saturation ⩾92%.…”

“…Treatment options to reduce dyspnoea in ILD are limited; however, recent evidence suggests that breathing a hyperoxic inspirate (inspiratory oxygen fraction (FIO 2 ) =0.60) significantly reduces dyspnoea intensity ratings and can eliminate or delay the onset of 'unsatisfied inspiration' during exercise [7]. To our knowledge, no study has investigated the effect of supplemental oxygen on NRD and/or NMU in ILD in order to determine which outcome is more strongly associated with reduced exertional dyspnoea ratings.…”

Cardiopulmonary Exercise Testing in Patients With Interstitial Lung Disease

“…The increased dyspnea is thought to reflect the awareness of an increased neural respiratory drive necessitated by the aforementioned pathophysiological alterations in respiratory mechanics and pulmonary gas exchange efficiency (Schaeffer et al, 2018). This notion is supported by the fact that when patients with ILD are given supplemental oxygen during constant-load exercise, the neural respiratory drive to the diaphragm decreases along with their perception of dyspnea (Schaeffer et al, 2017b). Neural respiratory drive to the diaphragm can be estimated during CPET using esophageal electromyography (Faisal et al, 2016;Schaeffer et al, 2018).…”

Supplemental oxygen and dypsnoea in interstitial lung disease: absence of evidence is not evidence of absence

“…We recently completed a study that addresses the aforementioned limitations in order to evaluate the effect of supplemental oxygen on dyspnoea during exercise in patients with ILD [13]. During this single-blind, randomised, placebo-controlled crossover study, 20 ILD patients performed two symptom-limited constant work-rate cycle exercise tests at 75% of peak work rate while breathing room air or supplemental oxygen (60% oxygen) in randomised order.…”