Obstructive Sleep Apnoea (OSA) is a common sleep disorder for which Continuous Positive Airway Pressure Therapy (CPAP) is the standard treatment. Despite the effectiveness of this treatment, CPAP acceptance and adherence rates are generally suboptimal. The aim of this dissertation was to validate a new, inclusive Health Belief Model (HBM) for the prediction of CPAP acceptance and adherence. It was argued that the HBM could predict future adherence even before patients have experienced the treatment, thus providing valid intervention targets to improve CPAP acceptance as well as adherence. Modifiable constructs that are proximal to the decision making process for OSA patients, were identified from the literature (Chapter 1). Along with the generic HBM constructs of perceived benefits, barriers, severity, risk, self-efficacy and cues to action, additional predictors were incorporated in the OSA specific model. These included biomedical indices of objective disease severity and measures of psychological distress. Study One assessed 77 newly diagnosed, CPAP naïve OSA patients on a questionnaire battery at baseline (prior to CPAP treatment). The questionnaire included HBM measures which were available in the literature; benefits perception, self-efficacy, functional severity, and perceived risk of negative health outcomes. CPAP adherence was assessed at four month follow-up. This initial investigation found that health beliefs alone explained 21.8% of the variance in CPAP adherence, whilst health beliefs and biomedical indices together explained 31.8% of the variance in CPAP adherence. The greatest proportion of CPAP adherence was explained by higher benefits perception, greater severity and lower risk perception. Study Two reported on the development and validation of a measure of the barriers construct (as no measure of this existed). A sample of 113 newly diagnosed, CPAP naïve OSA patients completed a questionnaire containing potential items of the Barriers to CPAP Use questionnaire (BACQ) at baseline. Exploratory Factor Analysis (EFA) showed a two factor structure of the eight-item BACQ, with ‘Barriers’ and ‘Cost of Treatment’ subscales identified. The BACQ had an internal consistency of 0.82 and readability at a fifth grade reading level. The aim of Study Three was to develop a valid and reliable measure of the cues to action construct. A sample of 63 OSA patients (from the total 113 patients assessed in Study Two) completed a questionnaire containing potential items of the Cues to CPAP Use questionnaire (CCUQ) one month after being prescribed CPAP. EFA showed a three factor structure of the nine-item CCUQ, with ‘Health Cues’, ‘Partner Cues’ and ‘Health Professional Cues’ subscales identified. The CCUQ demonstrated modest internal consistency and split-half reliability, and readability at a seventh grade level. Study Four incorporated three sub-studies which assessed the accuracy of the fully articulated HBM (including the BACQ and CCUQ measures) in predicting CPAP adherence at two months. Study Four A reported on the same sample of 113 CPAP naïve patients (from Study Two). Structural Equation Modelling demonstrated the complex relationship between health beliefs, psychological variables, and biomedical indices in CPAP adherence. The full HBM predicted 24% of the variance in CPAP adherence at two months. Adherence was directly predicted by lower perception of treatment cost as a barrier to CPAP use, higher self-efficacy, and higher BMI. Study Four B reported on 63 patients who completed HBM questionnaires at one month. The model predicted 42% of the variance in CPAP adherence at two months. Adherence was directly predicted by greater benefits perception, greater psychological distress, and lower perception of the Health Professional as the important cue to action. Study Four C investigated changes in health beliefs between baseline and one month. By one month patients generally reported more positive attitudes to CPAP, and better overall functioning. These changes did not correlate with CPAP adherence. Those who used CPAP more than four hours per night demonstrated greater improvement in functional severity and in anxiety score. Study Five used the findings of the HBM studies in developing a theory-driven Motivational Intervention (MI) to target specific beliefs associated with poor adherence. 101 newly diagnosed, CPAP naïve OSA patients were randomly assigned to nurse-led MI + Standard Care (50 participants), or to Standard Care only (51 participants). MI patients received two sessions before starting CPAP, and one session one month after CPAP prescription. By three months, the MI group used CPAP 50% more of the time, and were six times less likely to reject CPAP. The MI group demonstrated greater self-efficacy and a lower perception of barriers to CPAP use. The findings were largely supportive of the HBM theory of CPAP adherence. The substantive findings of this dissertation were that patients do need relevant, timely and targeted support in order for them to effectively commence on CPAP and then continue to adequately adhere. At a minimum, psychological intervention, such as a Motivational Intervention, is likely to be needed for the subset of patients who report beliefs associated with poor adherence at pre-treatment.

This thesis investigates the feasibility of using the non-invasive biomedical signal of oxygen saturation, or SpO₂ , to diagnose a sleep disorder known as Obstructive Sleep Apnoea Hypopnoea Syndrome (OSAHS). Epidemiologically, OSAHS is the most common condition investigated by sleep clinics. In a patient suspected of having the disorder, the upper airway is obstructed during sleep and a cessation in respiration results. An apnoea is defined as a temporary cessation of breathing. Similarly, a hypopnoea is defined as any reduction in breathing (i.e., less severe than an apnoea). The work has three main objectives; the first being to establish automated evaluation procedures for methods of quantifying apnoeic activity from the SpO₂ signal, the second being to accurately identify apnoeic and normal activity on a minute-by-minute basis, the third being to create a Respiratory Disturbance Index (RDI) based on the analysis which is comparable to the gold-standard Apnoea Hypopnoea Index (AHI) derived by experts. The detection of apnoeic activity is determined using three separate analyses: time domain, frequency domain, and autoregressive modelling with an incorporated amplitude criterion. A training dataset is utilised for algorithm development, and an independent dataset is employed for testing . All three methods result in comparable overall classification accuracies of: 81.2% (time domain), 82.1% (frequency domain), and 80.0% (autoregressive modelling with amplitude). In addition, particular attention is given to the resultant sensitivity, specificity, and accuracy values partitioned according to patient category; i.e., patients with OSAHS may be divided into normal, mild, moderate and severe. Lastly, a simple RDI is computed based on the automated analyses; i.e., the number of apnoeic segments detected divided by the total number of segments used. A comparison between computed RDI and AHI values for the test database show correlation values above 0.8. In conclusion, this thesis shows that through the automated analysis of the SpO₂ signal, OSAHS severity in patients suspected of having the disorder can be quantified. The AR-modelling with an incorporated amplitude criterion, in particular, shows the most promise for further work in this area.

Driver sleepiness is known to be a major contributor to road traffic incidents (RTIs). An initial literature review identified many studies reporting untreated obstructive sleep apnoea (OSA) sufferers as having impaired driving performance and increased RTI risk. It is consistently reported that treatment with continuous positive air pressure (CPAP) improves driving performance and decreases RTI risk, although most of these studies are conducted less than one year after starting treatment. UK law allows treated OSA patients to continue driving if their doctor states that treatment has been successful. Despite the wealth of publications surrounding OSA and driving, 6 key areas were identified from the literature review as not fully investigated, the: (i) prevalence of undiagnosed OSA in heavy goods vehicle (HGV) drivers in the UK; (ii) impact of sleep restriction on long term CPAP treated OSA compared with healthy controls; (iii) ability of treated OSA participants to identify sleepiness when driving; (iv) impact of one night CPAP withdrawal on driving performance; (v) individual difference in driving performance of long term CPAP treated OSA participants; (vi) choice of countermeasures to driver sleepiness by two groups susceptible to driver sleepiness, OSA and HGV drivers. Key areas (i) and (vi) were assessed using questionnaires. 148 HGV drivers were surveyed to assess OSA symptoms and preference of countermeasures to driver sleepiness. All participants completing the driving simulator study were also surveyed. 9.5% of HGV drivers were found to have symptoms of suspected undiagnosed OSA. Additionally the OSA risk factors were more prevalent for HGV drivers than reported in national statistics reports for the general population. The most effective countermeasures to driver sleepiness (caffeine and a nap) were not the most popular. Being part of a susceptible group (OSA or HGV driver) and prior experience of driver sleepiness did not promote effective choice of countermeasure. Key areas (ii) to (v) were assessed using a driving simulator. Driving simulators present a safe environment to test participants in a scenario where they may experience sleepiness without endangering other road users.

Introdução: A apneia obstrutiva do sono (AOS) é uma condição subdiagnosticada na prática clínica. A falta relativamente frequente de sintomas típicos para a AOS bem como a restrição da oferta da polissonografia (considerado o exame de escolha para o diagnóstico da AOS) são responsáveis em parte pelo subdiagnóstico desta doença. Diversos estudos exploraram o desenvolvimento de métodos de triagem para identificação de indivíduos com AOS. O excesso de peso é um fator de risco bem estabelecido para a AOS. As medidas antropométricas globais (índice de massa corporal, IMC) e regionais (por exemplo: circunferências do pescoço e cintura) de adiposidade são ferramentas simples e de baixo custo que têm sido correlacionadas com a AOS. Além disto, questionários de triagem da AOS, embora validados, tem uma acurácia não ideal em detectar este distúrbio do sono. No entanto, não está claro se a combinação de duas ou mais destas medidas antropométricas melhorariam o desempenho em identificar indivíduos com AOS. Portanto, o objetivo principal deste estudo foi o de comparar o desempenho de diversas medidas antropométricas isoladamente ou de forma combinada na identificação da AOS em adultos não referidos para o Laboratório do Sono derivados da coorte do Estudo Longitudinal da Saúde do Adulto (ELSA-Brasil). Métodos: Trata-se de um estudo transversal que recrutou adultos de ambos gêneros, participantes do ELSA-Brasil, centro São Paulo. Os participantes realizaram avaliações do sono com a poligrafia portátil domiciliar (Embletta GoldTM) e questionários que avaliam risco para a AOS (questionário de Berlim e escore NoSAS). As medidas antropométricas - IMC, circunferência do pescoço (CC), circunferência da cintura abdominal (CC), circunferência do quadril (CQ), razão cinturaestatura (RCE), razão cintura-quadril (RCQ) e índice de forma corporal (IFC) - foram feitas de forma padronizada e sem o conhecimento sobre os dados do sono. A análise da curva Receiver Operating Characteristic (ROC) foi realizada e a área sob a curva (AUC) foi calculada para avaliar a acurácia das medidas antropométricas na detecção da AOS. A análise de regressão logística foi realizada combinando as medidas antropométricas globais com as regionais (cervical e/ou abdominal) ajustando para dois outros importantes fatores de risco para a AOS: a idade e o sexo. Além disto, comparamos o desempenho das medidas antropométricas com o questionário de Berlim e o escore NoSAS. Resultados: No período de dois anos recrutamos inicialmente 2.334 participantes, dos quais 2.059 completaram todas as avaliações propostas. A amostra geral era predominantemente do sexo feminino (56%) e a média de idade foi de 49 ± 8 anos. A frequência da AOS foi de 32,3%, sendo que a porcentagem de homens (58 vs. 37%) e a idade (51 ± 8 vs. 48 ± 8 anos) foi significantemente maior no grupo com versus sem AOS, respectivamente. Aproximadamente um terço da amostra total era composta por indivíduos com sobrepeso ou obesidade. Participantes com AOS tiveram maior frequência de sobrepeso/obesidade e maiores valores das medidas antropométricas do que aqueles sem AOS. Todas as medidas antropométricas isoladamente apresentaram razoável capacidade de identificar a AOS (AUC aproximadamente de 0,700). Houve uma discreta melhora na acurácia após o ajuste para a idade e o sexo, sendo que a maior AUC foi encontrada para o IMC (AUC=0,760 [IC 95%: 0,739 - 0,781]), seguido por RCE (AUC=0,758 [IC 95%: 0,737 - 0,780]), CC (AUC=0,753 [IC 95%: 0,732 - 0,775]), CP (AUC=0,733 [IC 95%: 0,711 - 0,755]), RCQ (AUC=0,722 [IC 95%: 0,699 - 0,745]) e IFC (AUC=0,680 [IC 95%: 0,656 - 0,704]). Não foi observado diferenças significantes nas AUCs exceto para o menor valor observado para o IFC (p < 0,05 vs. demais medidas). A combinação de diferentes medidas antropométricas não resultou em melhora da acurácia em descriminar a AOS. Na comparação das medidas antropométricas com os questionários de triagem, não observamos diferenças significativas no desempenho do IMC ajustado para a idade e o sexo (AUC=0,748 [IC 95%: 0,727 - 0,770]) em relação ao escore NoSAS (AUC=0,760 [IC 95%: 0,739 - 0,781]). No entanto, o questionário de Berlim (AUC=0,676 [IC 95%: 0,653 - 0,699]) apresentou um desempenho inferior em relação ao IMC ajustado e ao escore NoSAS (p < 0,05 para cada comparação). Conclusões: Entre diversas medidas antropométricas globais e regionais de adiposidade, o IMC ajustado para a idade e sexo teve a melhor acurácia para detectar a AOS em uma coorte de indivíduos não referidos para estudo do sono. A combinação de medidas de adiposidade regional ou a combinação destas com o IMC não melhorou a capacidade de detectar a AOS. No entanto, considerando os valores das AUCs para as variáveis antropométricas bem como as AUCs dos questionários de sono disponíveis, esses dados reforçam a necessidade de ferramentas adicionais para reduzir o subdiagnóstico da AOS / Introduction: Obstructive sleep apnea (OSA) is an undiagnosed condition in clinical practice. The lack of typical symptoms in a subset of OSA patients as well as the limited availability of polysomnography (considered the gold standard method for diagnosing OSA) may partly explained this underdiagnosis. Several studies have explored the development of screening methods for identifying individuals with OSA. Overweight is a well-established risk factor for OSA. Global (body mass index, BMI) and regional (e.g., neck and waist circumferences) anthropometric measurements of adiposity are simple and low-cost tools that correlate with OSA. In addition, OSA screening questionnaires, although validated, have a non-ideal accuracy in detecting this sleep-disordered breathing. However, it is unclear whether the combination of two or more of these anthropometric measures would improve performance in identifying individuals with OSA. Therefore, the main aim of this study was to compare the performance of several anthropometric measurements alone or in combination to identify OSA in adults not referred to the Sleep Laboratory derived from the cohort of the Longitudinal Study of Adult Health (ELSA-Brasil). Methods: This is a cross-sectional study that recruited adults of both genders, participants of the ELSA-Brasil, Sao Paulo center. The participants performed sleep assessments with portable polygraphy (Embletta GoldTM) and questionnaires assessing the risk of OSA (Berlin questionnaire and NoSAS score). The anthropometric measures - body mass index (BMI), neck circumference (NC), waist circumference (WC), waist-to-height ratios (WHtR), waist-hip ratio (WHR) and body shape index (BSI) - were performed in a standardized way with no access to the sleep data. A receiver operating characteristic curve analysis was performed, and the area under the curve (AUC) was calculated to evaluate the accuracy of the anthropometric measurements to detect OSA. A logistic regression analysis was performed combining the global anthropometric measures with other regional (cervical and/or abdominal) measures adjusting for the two other important risk factors for OSA: age and gender. We also compared the performance of the anthropometric measurements with the Berlin questionnaire and the NoSAS score. Results: During two years, 2,334 participants were initially recruited and 2,059 completed all evaluations. Overall, our sample comprised predominantly females (56%) and the mean age was 49 ± 8 years. The frequency of OSA was 32.3% and the percentage of men (58 vs. 37%) and age (51 ± 8 vs. 48 ± 8 years) were significantly higher in the OSA group compared to their counterparts, respectively. Approximately one third of our sample consisted of overweight or obese individuals. Participants with OSA had a higher frequency of overweight/obesity and higher values of anthropometric measures than subjects without OSA. All anthropometric measurements alone showed a reasonable ability to identify OSA (approximately AUC 0.700). There was a modest improvement in the accuracy to identify OSA after adjustment for sex and age, and the highest AUC was found for BMI (AUC=0.760 [95% CI: 0.739 - 0.781]), followed by WHtR (AUC=0.758 [95% CI: 0.737 - 0.780]), WC (AUC=0.753 [95% CI: 0.732 - 0.775]), NC (AUC=0.733 [95% CI: 0.711 - 0.755]), WHR (AUC=0.722 [95% CI: 0.699 - 0.745]) and BSI (AUC=0.680 [95% CI: 0.656 - 0.704]). No significant differences were observed in AUCs except for the lower value of BSI (p < 0.05 vs. other measurements). The combination of different anthropometric measurements did not improve the accuracy in discriminating OSA. In the comparisons of anthropometric measurements with the screening questionnaires, we did not observe significant differences in the performance of for age- and gender-adjusted BMI (AUC=0.748 [95% CI: 0.727 - 0.770]) compared to the NoSAS score (AUC=0.760 [95% CI: 0.739 - 0.781]). However, the Berlin questionnaire (AUC=0.666 [95% CI: 0.653 - 0.699]) had a lower performance than adjusted BMI and the NoSAS score (p < 0.05 for each comparison). Conclusions: Among several global and regional anthropometric measurements of adiposity, age- and gender-adjusted BMI had the best accuracy to detect OSA in a cohort of individuals not referred to the sleep study. The combination of regional adiposity measurements or the combination of these with BMI did not improve the ability to detect OSA. However, considering the AUC values for the anthropometric variables as well as the AUC of the available sleep questionnaires, these data underscore the need of additional tools to reduce the underdiagnosis of OSA

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is characterised by repeated cycles of upper airway obstruction during sleep, leading to diurnal symptoms. Individuals with Down syndrome (DS) are predisposed to this as the DS phenotype overlaps with OSAHS risk factors. Around 2-4% of the general adult population and 55% of children with DS have OSAHS but, to date, no large-scale study has assessed OSAHS prevalence or efficacy of treatment in DS adults. This study aimed to: 1) Systematically assess subjective and objective OSAHS prevalence; 2) Assess the effectiveness of continuous positive airway pressure (CPAP) in an adult DS population. Standard questionnaires including pictorial Epworth Sleepiness Scale (pESS) and Developmental Behaviour Checklist for Adults (DBC-A) were sent to UK adults aged ≥16yr with DS and their caregivers. All questionnaire responders were invited to undergo home polygraphy. Symptomatic adults with DS with ≥10 apnoeas/hypopnoeas per hour in bed (AH) on home polygraphy were invited to participate in a prospective randomised controlled trial (RCT) of CPAP v. lifestyle advice, with review at 1, 3, 6 and 12m. Participants in the lifestyle arm were offered CPAP at 1m. Standard measurements of sleepiness, behaviour, cognitive function and general health were undertaken. Standard statistical analyses were conducted, with significance set at p < 0.001 to control for multiple testing. Of 5270 questionnaires sent, 1105 responses were valid (21%). Responders (55% males) were overweight/obese young adults: mean BMI 29.0±6.8kg/m2; mean age 28±9 years. Women had a higher BMI (p < 0.0001), but collar size was greater in men (p < 0.0001). Mean pESS scores were broadly within the normal range (7±5/24). No significant gender differences in OSAHS symptoms were noted. Individuals with probable OSAHS had higher pESS and DBC-A scores, and significantly more symptoms of OSAHS. Subjective OSAHS prevalence was estimated at 35%. Of the 790 individuals invited, 149 underwent polygraphy, with 134 valid studies obtained: mean AH 21.8(10.9-42.7); mean oximetry desaturation index (ODI) 6.6(2.3-20.0). No significant gender differences were observed. Forty-two percent of participants met standard clinical diagnostic criteria for OSAHS. Twenty-eight eligible adults with DS (19 male) were randomised: age 28±9yr; BMI 31.5±7.9kg/m2; AH 28.6(14.8-47.9); ODI 7.3(1.8-21.9); pESS 11±6/24. Groups did not differ significantly at baseline. By 12m, 4 participants had withdrawn (all remaining participants on CPAP). The pESS (p=0.001), DBC-A Disruptive (p < 0.0001) and Kaufmann Brief Intelligence Test verbal subscale (p=0.001) scores improved significantly. This first large study of OSAHS prevalence in the adult DS population estimates a prevalence of 35-42% - around 10 times higher than in the general adult population. Sustained, significant improvements in sleepiness, cognitive function and behavioural/emotional outcomes with CPAP use over a 12m period were demonstrated during this first RCT of CPAP in adults with DS. A larger trial of CPAP in this population is warranted.

Introduction: Obstructive sleep apnoea (OSA) is common and is caused by repetitive obstruction of the upper airway during sleep. OSA is associated with increased cardiovascular morbidity and mortality and is an independent risk factor for hypertension. The immediate physiological effects of OSA include intermittent hypoxia, repeated arousal from sleep and intra-thoracic pressure swings. The resulting activation of the sympathetic nervous system, systemic inflammation and oxidative stress may result in increased arterial stiffness and endothelial dysfunction, potentially explaining any causal link between OSA and cardiovascular disease (CVD). Continuous positive airway pressure (CPAP) therapy improves excessive daytime sleepiness (EDS) and in non-randomised studies, reduces cardiovascular mortality. Prior to starting this study, there was a limited amount of evidence suggesting that CPAP therapy improved arterial stiffness and endothelial function, but the effects in subjects without pre-existing CVD were unclear. Aims: i) to determine whether CPAP therapy has an effect upon measures of arterial stiffness and endothelial function in patients with OSA, in the absence of known CVD. ii) To compare arterial stiffness and endothelial function in a subset of patients with OSAHS (defined as OSA and EDS), with a group of well-matched control subjects. Methods: Fifty three patients with OSA, defined as an apnoea/hypopnoea index of ≥15, and without known CVD, entered a double-blind placebo-controlled crossover trial of 12 weeks CPAP therapy, of whom forty three completed the study protocol. Sham CPAP was used in the placebo arm of the study and vascular assessments were made at baseline and after each arm of the study. Arterial stiffness was determined by measuring aortic distensibility using cardiovascular magnetic resonance imaging and by measuring the augmentation index (AIx) and aortic pulse wave velocity (PWV) by applanation tonometry. Endothelial function was assessed non-invasively by measuring vascular reactivity after administration of salbutamol and glyceryl trinitrate. In a subset of twenty patients with OSAHS, arterial stiffness and endothelial function at baseline were compared to readings obtained from healthy control subjects, matched on a one-to-one basis for age, sex and BMI. Results: Patients with OSAHS (n=20) had increased arterial stiffness [AIx 19.3(10.9) vs. 12.6(10.2) %; p=0.017] and impaired endothelial function, measured as the change in AIx following salbutamol [-4.3(3.2) vs. -8.0(4.9) %; p=0.02] compared to controls. Twelve weeks of CPAP therapy had no significant effect upon any measure of arterial stiffness or endothelial function in patients with OSA (n=43). A trend towards a reduction in AIx following CPAP therapy was seen, but this was non-significant. There was a reduction in systolic blood pressure following CPAP therapy [126(12) vs. 129(14) mmHg]. Sub group analysis showed CPAP to have no effect on arterial stiffness or endothelial function in patients with EDS or in patients using CPAP for ≥4 hours per night. Conclusions: This study demonstrates that even in the absence of known CVD, patients with OSAHS have evidence of increased arterial stiffness and impaired endothelial function. However, in patients with OSA, free from CVD, CPAP therapy did not lead to an improvement in any measure of arterial stiffness or endothelial function after 12 weeks.

This thesis addresses the organisation of drive to human upper airway and inspiratory pump muscles. The characterisation of single motor unit activity is important as the discharge frequency or timing of discharge of each motor unit directly reflects the output of single motoneurones. Thus, the firing properties of a population of motor units is indicative of the neural drive to the motoneurone pool. The experiments presented in Chapter 2 measured the recruitment time of five inspiratory pump muscles (diaphragm, scalene, second parasternal intercostal, and third and fifth dorsal external intercostal muscles) during normal quiet breathing and quantified the timing and magnitude of drive reaching each muscle. Chapter 3 examined the EMG activity of a major upper airway muscle (the genioglossus). The single motor units of the genioglossus display activity that can be grouped into six types based on its association or lack of association with respiration. The types of activity are termed: Inspiratory Phasic, Inspiratory Tonic, Expiratory Phasic, Expiratory Tonic, Tonic, and Tonic Other. A new method is presented in Chapter 4 to illustrate large amounts of data from single motor units recorded from respiratory muscles in a concise manner. This single figure displays for each motor unit, the recruitment time and firing frequency, the peak discharge frequency and its time, and the derecruitment time and its frequency. This method, termed the time-and-frequency plot, is used to demonstrate differences in behaviour between populations of diaphragm (Chapter 2) and genioglossus (Chapter 3) motoneurones. In Chapter 5, genioglossus activity during quiet breathing is compared between a group of patients with severe OSA and healthy control subjects. The distribution of central drive is identical between the OSA and control subjects with the same proportion of the six types of motor unit activity in both groups. However, there are alterations in the onset time of Inspiratory Phasic and Inspiratory Tonic motor units in OSA subjects and their peak discharge rates are also altered. Single motor unit action potentials in OSA subjects showed an increased area. This suggests the presence of neurogenic changes and may provide a pathophysiological explanation for the increased multiunit electromyographic activity reported in OSA subjects during wakefulness.

While the importance of assessing the occupational consequences of insomnia and other sleep disorders is emphasised in clinical nosologies and research guidelines, there is little consensus on which aspects of occupational performance should be assessed, how such impairment should be measured, and how outcomes should be reported. The research programme described in this thesis aimed to address this issue. Chapter 1 presents a systematic review and methodical critique of studies reporting those aspects of occupational performance most impacted by (or most frequently associated with) insomnia symptoms and degraded sleep quality. Equivocal results, wide variations in reporting conventions, and the overall lack of comparability among studies, strongly indicated the need to develop a standardised metric able to quantify sleep related occupational performance and serve as an assessment and outcome instrument suitable for use in research and clinical settings. Informed by the literature review, Chapters 2-4 describe the development and validation of the Loughborough Occupational Impact of Sleep Scale ( LOISS ), a unidimensional 19 item questionnaire that captures sleep-related occupational impairment across a number of workplace domains over a 4-week reference period. Chapters 5-7 describe LOISS outcomes from: i) surveys in a random population sample; ii) a representative sample of the UK workforce; and iii) a clinical sample of patients with obstructive sleep apnoea (before and after treatment with CPAP). Overall, the scale showed strong internal consistency (Cronbach s alpha range=0.84-0.94) and test-retest reliability (r=0.77, r2=0.59, p<0.001), high levels of criterion validity (significantly discriminating between good and poor sleepers), and proved an effective outcome measure in OSA. From the survey data reported in Chapters 2-7, LOISS score distributions showed no consistent gender difference but did show a significant ageing gradient, with sleep-related occupational impairment declining with increasing age. In conclusion, the work presented here supports the usability, validity and reliability of the LOISS as an assessment and outcome instrument, and also demonstrates the utility of this instrument in exploring the dynamics of sleep-related occupational performance

This thesis addresses the organisation of drive to human upper airway and inspiratory pump muscles. The characterisation of single motor unit activity is important as the discharge frequency or timing of discharge of each motor unit directly reflects the output of single motoneurones. Thus, the firing properties of a population of motor units is indicative of the neural drive to the motoneurone pool. The experiments presented in Chapter 2 measured the recruitment time of five inspiratory pump muscles (diaphragm, scalene, second parasternal intercostal, and third and fifth dorsal external intercostal muscles) during normal quiet breathing and quantified the timing and magnitude of drive reaching each muscle. Chapter 3 examined the EMG activity of a major upper airway muscle (the genioglossus). The single motor units of the genioglossus display activity that can be grouped into six types based on its association or lack of association with respiration. The types of activity are termed: Inspiratory Phasic, Inspiratory Tonic, Expiratory Phasic, Expiratory Tonic, Tonic, and Tonic Other. A new method is presented in Chapter 4 to illustrate large amounts of data from single motor units recorded from respiratory muscles in a concise manner. This single figure displays for each motor unit, the recruitment time and firing frequency, the peak discharge frequency and its time, and the derecruitment time and its frequency. This method, termed the time-and-frequency plot, is used to demonstrate differences in behaviour between populations of diaphragm (Chapter 2) and genioglossus (Chapter 3) motoneurones. In Chapter 5, genioglossus activity during quiet breathing is compared between a group of patients with severe OSA and healthy control subjects. The distribution of central drive is identical between the OSA and control subjects with the same proportion of the six types of motor unit activity in both groups. However, there are alterations in the onset time of Inspiratory Phasic and Inspiratory Tonic motor units in OSA subjects and their peak discharge rates are also altered. Single motor unit action potentials in OSA subjects showed an increased area. This suggests the presence of neurogenic changes and may provide a pathophysiological explanation for the increased multiunit electromyographic activity reported in OSA subjects during wakefulness.

Background: Compliance with CPAP treatment for OSA is not reliably predicted by the severity of symptoms or physiological variables. I conducted a series of studies to examine a range of factors that may affect compliance with CPAP. Methods: I performed a retrospective study examining association of demographic factors and OSA severity with long-term CPAP compliance. In a prospective study, I looked at the correlation of short and long-term CPAP compliance with socio-economic status, education, type D personality, demographics, disease severity, mood and clinician's prediction. I undertook a prospective, cross-over trial comparing the impact of Bi-level PAP therapy in individuals with low tolerance of CPAP. Results: In a retrospective analysis, an improvement in subjective daytime somnolence was correlated with optimal compliance. In the prospective study, median compliance with CPAP at 6 months was 5.6 (3.4- 7.1) hours/night with 73% of subjects using CPAP ≥ 4 hours/night. Compliance with CPAP was not found to be associated with socio-economic class for people in work, type D personality, education, sex, age, baseline sleepiness (ESS score) or disease severity (ODI). The clinician's initial impression had no predictive value for individual patients. Subjects who were long-term unemployed or reporting mood disorders (High Beck's Depression Index scores) were likely to have poor compliance and sub-optimal CPAP usage (OR 4.6, p = 0.011 and OR 1.4. p=0.04 respectively). Subjects experiencing side effects after the first night on treatment showed lower acceptance and subsequent compliance. In the cross-over trial, changing to Bi-level PAP in individuals with suboptimal compliance due to pressure related intolerance, did not lead to an improvement in CPAP compliance. In post-hoc analysis, compliance and comfort were better in the subgroup that complained of difficulty with exhalation on CPAP. Conclusion: My research as presented in this thesis, did not find an association between disease severity (ODI), socio-economic status (for people in employment), education or personality type and CPAP compliance. My research demonstrated that subjects with long-term unemployment, mood disorders and those experiencing side effects on the first night of treatment were likely to have sub-optimal compliance. Changing to Bi-level PAP is only likely to be useful for a sub-group of subjects experiencing pressure related intolerance. More research is needed to explore whether intensive support to individuals with OSA and long term unemployment, as well as mood disorders, may improve compliance.