Aims: LDL oxidation plays an important role in the initiation and progression of atherosclerosis. HDL impedes oxidation, glycation and glycoxidation in vitro and there is evidence to suggest paraoxonase-1 (PON1) plays an important role in this. 1. In patients with dyslipidaemia treated with statins, I assessed the relationship of serum PON1 activity with in vitro HDL antioxidant capacity, susceptibility of LDL to oxidation and the protection offered by HDL. 2. I studied the effect of the presence and severity of obstructive sleep apnoea (OSA) in morbidly obese patients on HDL anti-oxidant and anti-inflammatory functions. 3. I investigated the influence of extended release niacin/ laropiprant (ERN/LRP) versus placebo in patients who had persistent dyslipidaemia despite receiving high doses of potent statins. I assessed the effect of ERN/LRP on mediators of vascular inflammation and HDL's in vitro anti-oxidant function. Methods: 1. LDL isolated from dyslipidemic patients was incubated with and without HDL, in the presence of Cu2+. Similarly isolated HDL was incubated alone. Lipid peroxides (LPO) generated over 3 hours were measured. Patients were divided into 2 groups based on median serum PON1 activity. 2. 41 morbidly obese patients were divided into two groups based on the presence or absence of OSA ("OSA" and "no OSA" group) or on severity of OSA (high or low apnoea-hypoapnoea index (AHI) groups). I studied HDL's ability to protect itself from in vitro oxidation and measured serum PON1 activity, tumor necrosis factor alpha (TNFalpha) and intercellular adhesion molecule 1 (ICAM1). 3. This was a randomised double blind cross over trial, where I studied the effect of ERN/LRP compared to placebo in 27 patients who had high LDL-C inspite of maximum tolerated doses of statins. I measured lipid profile, apolipoproteins, cholesteryl ester transport protein (CETP) activity, paraoxonase 1 activity (PON1), oxidised LDL (oxLDL) and related mediators of vascular inflammation. I also examined the capacity of HDL to protect LDL from in vitro oxidation. Results and conclusion: 1. In statin treated dyslipidemic patients the capacity of HDL to protect itself and LDL from oxidation in vitro is significantly better in individuals with higher serum PON1 activity. 2. The capacity of HDL to protect itself from in vitro oxidation in morbidly obese patients is reduced with onset and severity of OSA. The differences in TNFalpha and ICAM1 levels may suggest endothelial dysfunction due to OSA. Oxidative damage of PON1 attributable to OSA could be a mechanism for HDL and endothelial dysfunction. 3. Treatment with ERN/LRP resulted in a significant improvement in HDL-C but did not affect HDL's in vitro anti-oxidant function in patients who had persistent dyslipidaemia despite high doses of potent statins. For the first time I have shown that ERN/LRP reduces mediators of vascular inflammation.

Background. Obstructive Sleep Apnoea (OSA) is associated with an increase in nocturnal gastro-oesophageal reflux (nocturnalGOR) events and symptoms, however the mechanism for this remains undefined. Treatment of OSA with continuous positive airway pressure (CPAP) has been shown to reduce nocturnalGOR in individuals with OSA however the reasons for this reduction are not clear. The combination of OSA and nocturnalGOR could be particularly problematic for individuals who have had a lung transplant in whom Bronchiolitis Obliterans Syndrome (BOS) limits survival. It is thought that GOR plays a role in the development of BOS in these individuals. Methods and Results. Five interrelated studies were undertaken. The first two studies sought to determine and compare the prevalence and risk factors of nocturnalGOR in OSA patients with the general population. To do this, a GOR questionnaire was completed by 2,042 members of the general community as part of the Busselton Health Survey and by 1,116 patients with polysomnography-diagnosed OSA. Risk of OSA in the general population was determined using a standardised sleep questionnaire. 137 of the OSA patients completed the questionnaire before and after treatment with CPAP. The prevalence of nocturnalGOR symptoms reported more than once a week (frequent symptoms) was greater in OSA patients (10.1%) than the general population (5.8%) (p<0.001), in individuals from the general population at high (11.2%) than low risk of OSA (4.5%) (p<0.001) and in patients with severe (14.7%) than mild OSA (5.2%) (p<0.001). Treatment of OSA with CPAP decreased the prevalence of frequent nocturnalGOR from 9.0% to 3.8% (p=0.04). In the general population, high risk of OSA was independently associated with a 2.4-fold increased risk of frequent ABSTRACT vi nocturnalGOR symptoms than low risk. In the OSA group, disease severity was independently associated with nocturnalGOR symptoms, with an adjusted odds ratio of 1.7 for frequent nocturnalGOR symptoms.

Content removed due to copyright restrictions: Marshall, N. S., Neill, A. M., Campbell, A. J., & Sheppard, D. S. (2005). Randomised controlled crossover trial of humidified continuous positive airway pressure in mild obstructive sleep apnoea. Thorax, 60(5), 427-432. Marshall, N. S., Gander, P. H., & Neill, A. M. (2003). Obstructive sleep apnoea and risk of motor vehicle accident: A perspective. New Zealand Medical Journal, 116(1176) / The practice of sleep medicine is expanding and evolving rapidly, often ahead of the evidence base to support clinical practice. Obstructive Sleep Disordered Breathing (SDB) is a condition characterised by repetitive airway collapse causing harmful intermittent blood oxygen desaturations and fragmented sleep. When combined with daytime sleepiness it is known as Obstructive Sleep Apnoea Syndrome (OSAS). Continuous Positive Airway Pressure (CPAP) eliminates SDB by pneumatically splinting open the airway with positive air pressure applied through the nose and/or mouth. CPAP effectively reduces daytime sleepiness in patients with severe OSAS. However, doubt remains as to the effectiveness of CPAP in the majority of patients with mild-moderate OSAS. The effects of CPAP were compared to a placebo CPAP during a three week crossover Randomised Controlled Trial (RCT) that included 31 mild-moderate OSAS patients. CPAP effectively eliminated SDB (when worn) and moderately improved subjective sleepiness. But. it did not improve objective wakefulness, mood, psychomotor function, or quality of life. Patients who were extremely sleepy at baseline tended to gain the most placebo adjusted benefit from treatment. A systematic review and meta-analysis aimed to gather and objectively combine all relevant RCT studies to find our whether CPAP reduced sleepiness in patients with mild-moderate OSAS. Seven trials were combined and showed that both subjective sleepiness and objective wakefulness were slightly improved by CPAP therapy. Objective sleepiness was not improved by CPAP. It is not clear from these two studies that treating mild-moderate OSAS with CPAP is an effective use of resources. CPAP effectiveness might be limited by sub-optimal compliance. C-Flex aims to improve compliance by modulating pressure during exhalation. C-Flex was compared to CPAP during a pilot RCT that included 19 patients with severe OSAS. C-Flex was associated with a non-significant increase in compliance of 1.7 hours/night compared to CPAP. However, this increase in compliance was not associated with better daytime patient outcomes. Further experiments are proposed as a result of our pilot RCT. This thesis helps expand evidence-based sleep medicine. Practitioners need to be vigilant, ensuring that treatments are effective in the patients groups in which they are being used (clinical drift), and that new treatments are not adopted without superiority over existing treatments (technological drift).

Content removed due to copyright restrictions: Marshall, N. S., Neill, A. M., Campbell, A. J., & Sheppard, D. S. (2005). Randomised controlled crossover trial of humidified continuous positive airway pressure in mild obstructive sleep apnoea. Thorax, 60(5), 427-432. Marshall, N. S., Gander, P. H., & Neill, A. M. (2003). Obstructive sleep apnoea and risk of motor vehicle accident: A perspective. New Zealand Medical Journal, 116(1176) / The practice of sleep medicine is expanding and evolving rapidly, often ahead of the evidence base to support clinical practice. Obstructive Sleep Disordered Breathing (SDB) is a condition characterised by repetitive airway collapse causing harmful intermittent blood oxygen desaturations and fragmented sleep. When combined with daytime sleepiness it is known as Obstructive Sleep Apnoea Syndrome (OSAS). Continuous Positive Airway Pressure (CPAP) eliminates SDB by pneumatically splinting open the airway with positive air pressure applied through the nose and/or mouth. CPAP effectively reduces daytime sleepiness in patients with severe OSAS. However, doubt remains as to the effectiveness of CPAP in the majority of patients with mild-moderate OSAS. The effects of CPAP were compared to a placebo CPAP during a three week crossover Randomised Controlled Trial (RCT) that included 31 mild-moderate OSAS patients. CPAP effectively eliminated SDB (when worn) and moderately improved subjective sleepiness. But. it did not improve objective wakefulness, mood, psychomotor function, or quality of life. Patients who were extremely sleepy at baseline tended to gain the most placebo adjusted benefit from treatment. A systematic review and meta-analysis aimed to gather and objectively combine all relevant RCT studies to find our whether CPAP reduced sleepiness in patients with mild-moderate OSAS. Seven trials were combined and showed that both subjective sleepiness and objective wakefulness were slightly improved by CPAP therapy. Objective sleepiness was not improved by CPAP. It is not clear from these two studies that treating mild-moderate OSAS with CPAP is an effective use of resources. CPAP effectiveness might be limited by sub-optimal compliance. C-Flex aims to improve compliance by modulating pressure during exhalation. C-Flex was compared to CPAP during a pilot RCT that included 19 patients with severe OSAS. C-Flex was associated with a non-significant increase in compliance of 1.7 hours/night compared to CPAP. However, this increase in compliance was not associated with better daytime patient outcomes. Further experiments are proposed as a result of our pilot RCT. This thesis helps expand evidence-based sleep medicine. Practitioners need to be vigilant, ensuring that treatments are effective in the patients groups in which they are being used (clinical drift), and that new treatments are not adopted without superiority over existing treatments (technological drift).

Methadone is a long acting mu-opioid and is the most effective treatment for heroin addiction. However, opioids depress respiration and methadone maintenance treatment (MMT) patients have a higher mortality rate than the general population. Teichtahl et al conducted a pilot study and found 6 out of 10 MMT patients had central sleep apnea (CSA). But no definite conclusions were made regarding the prevalence and possible pathogenesis of CSA in the patients due to the small sample size and lack of blood toxicology data. The present project aims to confirm the preliminary results and further quantify the sleep disordered breathing (SDB) in stable MMT patients and to delineate the pathogenesis involved. (For complete abstract open document)

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.