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Physiological mechanisms of dyspnoea in patients with fibrotic interstitial lung disease and the role of hyperoxia as an exercise intervention Schaeffer, Michele Rebecca


Problem: Dyspnoea is a common and debilitating symptom in patients with fibrotic interstitial lung disease (ILD). Unfortunately, there are no therapies that consistently reduce exertional dyspnoea in this population. Hyperoxia is a potential intervention to acutely address many of the pathophysiological mechanisms thought to be associated with dyspnoea and exercise intolerance in fibrotic ILD. However, additional research is needed to clarify the role and specific physiological and perceptual effects of hyperoxia during exercise in these patients. Methods: Study 1: Twenty fibrotic ILD patients performed two symptom limited constant work-rate cycle exercise tests at 75% of peak work-rate while breathing room air or hyperoxia, in randomized order. Ventilatory responses as well as both the intensity and qualitative dimensions of dyspnoea were measured throughout exercise. Study 2: Fourteen patients with fibrotic ILD completed an incremental cycle exercise test while breathing room air and two constant work-rate cycle exercise tests while breathing room air or hyperoxia. Diaphragmatic electromyography (EMGdi), a surrogate of neural respiratory drive (NRD), was measured with an oesophageal catheter. Neuromechanical uncoupling (NMU) was calculated as the ratio between EMGdi (% max) and tidal volume (% vital capacity). Dyspnoea intensity was recorded throughout exercise. Study 3: Sixteen patients with fibrotic ILD performed incremental and constant work-rate cycle exercise tests while breathing room air until exhaustion, wherein dyspnoea quality was evaluated throughout exercise. Conclusions: Study 1 demonstrated that hyperoxia results in clinically significant improvements in exercise tolerance, dyspnoea intensity, and dyspnoea quality. Study 2 found that dyspnoea intensity was more strongly associated with estimates of NRD than NMU during normoxic incremental cycling. However, improvements in dyspnoea intensity with hyperoxia were more strongly correlated with NMU than NRD. Study 3 showed increased work/effort was the dominant descriptor of dyspnoea throughout incremental and constant work-rate cycle exercise, but there was an increase in the selection of unsatisfied inspiration once further tidal volume expansion was constrained. Collectively, these results may contribute to the development and enhancement of symptom management in patients with ILD. In the context of rehabilitation, this may translate into improvements in patient outcomes from exercise training programs.

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