Clinical Impact and Therapeutic Outcomes in Obesity-Related Hypoventilation Disorders

Abstract

This thesis explores the clinical impact and therapeutic outcomes of obesity-related hypoventilation disorders to address some of the research unknowns in this area. It addresses two main clinical questions. Firstly, the symptom burden, neurocognitive and cardiovascular impact of disease at diagnosis and following positive airway pressure (PAP) therapy are evaluated. Secondly, the efficacy of different modes of PAP therapy in addressing respiratory failure is examined.

An overview of the effects of obesity, obesity hypoventilation syndrome, and the impact of obesity on COPD is covered in Chapter 2.

Chapter 3 examines the neurocognitive symptom outcomes between two obesity-related hypoventilation disorders, either with or without airways disease. Despite differences in baseline demographics, lung function, and polysomnographic data, the two disorders have a similar symptom burden and deficiencies in neurocognitive assessment at baseline and similar responses to 3 months of PAP therapy.

Chapter 4 includes a study that showed that at baseline, participants with obesity hypoventilation syndrome had high rates of abnormal cardiovascular biomarkers, even in those without an established cardiovascular diagnosis. Furthermore, PAP therapy over 3-months did not result in significant changes in these cardiovascular biomarkers, including markers of arterial stiffness.

Chapter 5 is a randomised, parallel study that compares bilevel PAP and fixed CPAP in improving respiratory failure in obesity-related hypoventilation with concurrent airways disease. The study found that bilevel PAP was superior to fixed CPAP in improving hypercapnic respiratory failure over 3 months of therapy.

Chapter 6 is a pilot, randomised, parallel study that explored the use of auto-titrating CPAP in obesity hypoventilation syndrome. The study found that non-inferiority to fixed pressure CPAP could not be confirmed, but several clinically important outcomes favoured fixed CPAP over auto-titrating CPAP.