The role of ambulatory oxygen to improve skeletal muscle gene expression in Chronic Obstructive Pulmonary Disease in patients with exercise induced hypoxaemia

Ejiofor, Stanley Ikenna (2018). The role of ambulatory oxygen to improve skeletal muscle gene expression in Chronic Obstructive Pulmonary Disease in patients with exercise induced hypoxaemia. University of Birmingham. M.D.

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Abstract

Rationale: Hypoxaemia plays a role in the aetiology of abnormal skeletal muscle function in Chronic obstructive pulmonary disease (COPD) via abnormal protein synthesis and mitochondrial function. Patients exhibiting exercise-induced desaturation (EID) have exercise intolerance, perhaps a consequence of muscle hypoxia. Ambulatory oxygen therapy (AOT) is indicated in these patients; however the evidence is derived from single assessment studies. This thesis explores the role of longer term AOT and whether it favourably alters skeletal muscle gene expression in patients with COPD and EID. Methods: A 12 week randomised controlled trial of AOT against air in 25 patients with COPD and EID was undertaken. Participants underwent skeletal muscle biopsies and exercise assessments. In parallel a systematic review of published literature from 1980-2014 for trials in which AOT was compared to placebo in COPD was completed. Results: The systematic review showed that AOT had no statistical effect on improving exercise capacity (6 minute walk or endurance shuttle walk tests); p=0.44 and p=0.29 respectively. Gene set enrichment analysis show the KEGG pathways of oxidative phosphorylation, PPAR signalling and fatty acid metabolism to be up-regulated following AOT (q<2%) in the clinical trial of AOT versus Air. Conclusion: AOT has limited long term benefit in improving functional exercise capacity. It may however favourably alter gene expression in patients with COPD and EID.

Type of Work:

Thesis (Higher Doctorates > M.D.)

Award Type:

Higher Doctorates > M.D.

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