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Physiological Assessment of the Load-Capacity-Drive Relationship in Chronic Respiratory Failure and Outcomes following Domiciliary Non-Invasive Ventilation

Student thesis: Doctoral ThesisDoctor of Philosophy

Background: Acute and chronic respiratory failure occurs as a consequence of an imbalance in the load-capacity-drive relationship of the respiratory system. Despite the high morbidity and mortality of these patients, clear clinical strategies for assessment and subsequent management have been lacking due to the limited high quality data available. The aim of this thesis was to evaluate novel techniques to monitor patients with acute respiratory deterioration as well as the use of specific monitoring and non-invasive ventilation strategies in patients with chronic respiratory failure, which could translate into important clinical benefits.
Methods: Three clinical physiological studies were performed. Firstly, a randomised controlled trial evaluated an automated novel hybrid pressure-volume mode of non-invasive ventilation to treat obesity hypoventilation syndrome. Although the primary outcome measure was gas exchange at three months, important physiological measures including physical activity, sleep quality and their relationship to weight loss were also investigated. Secondly, an observational cohort trial investigated the role of a novel advanced physiological biomarker, neural respiratory drive, to identify treatment failure and readmission risk in patients admitted to hospital with an acute exacerbation of chronic obstructive pulmonary disease. The third physiological trial investigated, in patients with persistent hypercapnic respiratory failure following an acute exacerbation of COPD as part of a large randomised controlled trial, the efficacy and mechanism of action of home mechanical ventilation and its effect on sleep quality compared with standard oxygen therapy.
Results: The automated volume targeted mode of ventilation demonstrated no advantage in physiological and clinical outcomes above a nurse-led protocolised standard set up of non-invasive ventilation in the management of obesity hypoventilation syndrome. The trial was the first to demonstrate that the management of sleep disordered breathing and chronic respiratory failure in obesity hypoventilation syndrome confers an improvement in objectively assessed physical activity as well as weight loss, which has important clinical implications. In the second trial, neural respiratory drive was validated as a
novel physiological biomarker to monitor acute clinical change during hospital treated exacerbations of COPD. Furthermore, patients in whom neural respiratory drive failed to fall in response to treatment prior to hospital discharge had a significantly higher risk of hospital readmission within 14 days, again, highlighting the important clinical implications of detailed physiological observations. The third physiological trial confirmed previous data indicating that an important mechanism of action of home mechanical ventilation in COPD is through improvements in central respiratory drive, but this conclusion was given greater confidence by the use of advanced physiological monitoring.
Conclusion: The data presented in this thesis provide clinically important information on the physiological targeting of set-up of non-invasive ventilation in patients with chronic respiratory failure secondary to obesity hypoventilation syndrome and severe COPD. Important markers of treatment success in the management of chronic respiratory failure in obesity hypoventilation syndrome have been identified including physical activity, sleep quality and weight loss. These data have also established the potential clinical role of advanced physiological biomarkers of neural respiratory drive to monitor clinical change and to risk stratify patients during acute exacerbations of COPD. Finally, the data in this thesis provides further evidence that the major mechanism of action of home mechanical ventilation in hypercapnic COPD patients is the modification of central respiratory drive.
Original languageEnglish
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Award date2015

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