Supplemental Oxygen Therapy in Patients with Early Interstitial Lung Disease: Physiological Effects during Exercise and Sleep

Abstract

Background and goals: The interstitial lung diseases (ILD) are characterised by inflammation and fibrosis of the lung, resulting in poor gas exchange and restricted lung mechanics. Hypoxaemia during exercise and sleep are frequently observed, impacting on effort tolerance, sleep architecture, quality of life and survival. Intermittent hypoxaemia during exercise and sleep may be important in the development of pulmonary hypertension (PH) in this patient population. Currently in Australia, supplemental oxygen is largely prescribed for ILD patients with severe resting hypoxaemia. In this thesis, we hypothesised that oxygen provided for ILD patients with exercise- or sleep-desaturation would provide significant benefits, with potential for improvement in pulmonary vascular function and markers of oxidative stress. Results: Both significant nocturnal oxygen desaturation (NOD, i.e. 10% or more of total sleep time spent with oxygen saturation below 90%) and sleep disordered breathing (SDB) occurred frequently during sleep in a large unselected ILD population. Significant NOD independently predicted the presence of PH at 6 months, and was the only sleep index to be prognostic of overall and progression-free survival. Supplemental oxygen during sleep for 4 weeks led to a significant improvement in sleep oxygenation and indices of SDB, compared with medical air for the same period. Furthermore, plasma brain natriuretic peptide (BNP), a biomarker of pulmonary vascular dysfunction, was reduced with oxygen use in ILD patients with significant NOD. Oxygen during shuttle walk testing and cardiopulmonary exercise testing (CPET) significantly improved endurance in ILD patients with known exercise-desaturation. During CPET, oxygen attenuated minute ventilation (VE) and reduced the ventilatory equivalent for carbon dioxide (VE/VCO2), a surrogate for PH in this population. A subgroup who did not improve their endurance with oxygen were seen to have higher VE at all stages of exercise, with no reduction during oxygen testing. Right ventricular (RV) function, studied directly during exercise with real-time cardiac magnetic resonance imaging, was significantly depressed in patients, compared with healthy controls. Oxygen enhanced RV contractility in the patient group, with a strong correlation found between the degree of improvement in RV function and the response in endurance time seen during CPET using oxygen. In both the patients with sleep and exercise-desaturation, there was evidence of chronic oxidative stress, with specific correlation between redox indices and pulmonary vascular dysfunction. These markers of oxidative stress were improved with the use of oxygen in the Sleep and Exercise-ILD cohorts. Conclusion: Desaturation during sleep and exercise is associated with the development of PH and reduced overall survival in the ILD population. Supplemental oxygen prevents nocturnal desaturation and sleep–disordered breathing, improves exercise performance, enhances RV function, and reduces the burden of oxidative stress. The amelioration of pulmonary vascular dysfunction with oxygen may impact on the long-term outlook for patients with ILD.