Factors associated with the severity of Apnoea Hypopnoea Index (AHI) in Obstructive sleep apnoea (OSA)

Electronic versions

Dogfennau

  • Christopher Earing

Abstract

Obstructive sleep apnoea (OSA) is the most prevalent sleep disorder, characterised by repetitive episodes of complete or partial obstructions of the upper airway during sleep. These apnoeic related events have been associated with intermittent hypoventilation, hypoxemia, hypercapnia, recurrent arousals in sleep and the activation of the sympathetic nervous system. Questions arise over the feasibility of a risk factor intervention strategy in reducing the incidence of mild to moderate OSA. Currently the only adequately supported intervention is weight loss. The long term objective of this thesis will be to guide the design of future interventions which are focussed on the specific symptomatology of OSA. The general theme of this thesis is to identify which physiological factors most strongly contribute to the pathogenesis of OSA. A particular interest is first given to the potential effects of the exposure to intermittent hypercapnia and hypoxia during sleep, while newly developed techniques for assessment of chemosensitivity towards carbon dioxide (CO2) and oxygen (O2) was piloted in scuba divers and controls. Following this, the implications of the baroreflex-chemoreflex interactions are assessed before reviewing inflammatory markers present within the patients with OSA. Finally, with the understanding that the occlusive airway and subsequent apnoeas associated with OSA may lead to increased inspiratory efforts whereby the inspiratory muscles are overloaded during sleep, alongside the environment of nocturnal bouts of hypoxia and hypercapnia and systemic inflammation, the prevalence of inspiratory muscle fatigue in OSA is also investigated. The general introduction (Chapter 1) provides the background information and proposes the aims of the research presented in the thesis. Following this, the first study (Chapter 2) investigates the ventilatory response to CO2 amongst scuba divers using a novel methodology. Different populations have displayed altered ventilatory responses to CO2; scuba divers are an example in a healthy population. Investigating scuba divers enabled us to develop and test methodology designed to assess the relative contribution of adaptations to the peripheral and/or central chemoreceptors to their ventilatory response to CO2. Their ventilatory response was also compared to the patients with OSA in chapter 3. The same methodology was then applied in the first OSA Study (Chapter 3) to assess the ventilatory response amongst patients with OSA with the theory that the exposure to intermittent hypercapnia and hypoxia during apnoeic related events may cause a similar modification in the ventilatory response seen in scuba divers. The third study (Chapter 4) assessed the implications of baroreflex sensitivity on the severity of OSA and the ventilatory response to CO2 observed in the third chapter, to increase our understanding of the strength of the baroreflex-chemoreceptor interaction previously reported in the research literature. To increase our knowledge of the inflammatory processes involved in the pathogenesis of OSA, the forth study (Chapter 5) investigates cytokines related to obesity through the quantification of adiponectin, c-reactive protein, leptin and the endocannabinoids (2-arachidonoylglycerol and arachidonoylethanolamide) on the severity of OSA. The endocannabinoids have been shown to mediate anti-inflammatory properties in addition to playing a significant role in the regulation of energy metabolism within adipose tissue. The final study (Chapter 6) assesses the neuromuscular properties of the breathing apparatus with particular interest in studying the fatigability of the inspiratory muscles. This chapter involves the development of an entirely novel protocol which is designed to elicit inspiratory muscle fatigue through submaximal loading. The final chapter (Chapter 7) integrates the findings of all the studies to propose a novel regression model which can be designed to predict the severity of OSA from the physiological processes investigated.

Details

Iaith wreiddiolSaesneg
Sefydliad dyfarnu
Goruchwylydd / Goruchwylwyr / Cynghorydd
Dyddiad dyfarnuIon 2015