Obstructive Sleep Apnoea (OSA) is a disease characterised by repetitive upper airway obstructions which are manifest by desaturation and arousal from sleep. It has been known for many years that this interruption to the normal architecture of sleep may present to the clinician as excessive daytime somnolence often with a complaint of difficulties with concentration and short term memory. Previous work had demonstrated a relationship between variables of cognitive dysfunction in patients with obstructive sleep apnoea, however, little was known about which components of the syndrome contributed to this outcome and whether specific clinical thresholds of sleep disordered breathing could be defined for the development of cognitive dysfunction. In the context of this body of work cognitive dysfunction is defined as: a level of cognitive performance below normal derived values for a given cognitive test, when the subjects performance is controlled for age, sex and level of education.

Obstructive sleep apnoea (OSA) is characterised by repetitive reductions or pauses in breathing during sleep due to upper airway narrowing or closure. Due to disruption to normal sleep patterns, many patients with OSA suffer from increased daytime sleepiness. Epidemiological studies have established a link between OSA and driver fatigue and accidents, generally showing a two to seven times increased risk of road traffic accidents in non-commercial drivers with OSA. There is emerging evidence that commercial drivers have a higher prevalence of OSA than the general population, being predominately male, middle-aged and overweight, three important risk factors for OSA. However, little is known about the relationship between OSA and driver sleepiness in commercial drivers, whether road accidents are increased in commercial drivers with OSA, and whether OSA interacts with other fatigue promoting factors, such as sleep deprivation, to further escalate road accident risk. One thousand randomly selected commercial drivers were surveyed in the field. In addition, 61 randomly selected NSW commercial drivers had in hospital sleep studies and daytime performance testing, including a PC based driving simulator task. The prevalence of OSA, defined as Respiratory Disturbance Index (RDI) < 10, was approximately 50% in NSW commercial drivers. Approximately one quarter of the drivers reported pathological daytime sleepiness, and 12-14% had both OSA and pathological daytime sleepiness. A diagnosis of OSA was the most important factor predicting excessive daytime sleepiness in these drivers: OSA was more important than 15 other work-related, lifestyle and medical factors that could be expected to promote, or be associated with, daytime sleepiness. Drivers with sleep apnoea syndrome (both OSA and pathological daytime sleepiness) had an increased driving accident risk, using driving simulator and daytime performance testing as proxy measures for accident risk. These results demonstrate the importance of OSA as a cause of driver fatigue in commercial drivers and suggest that all commercial drivers should be screened for the presence of sleep apnoea syndrome in order to potentially reduce road accident risk through treatment. A separate, but related body of work examined the combined effects of mild OSA and other fatigue promoting factors (sleep deprivation and circadian influences) on driving performance. Twenty nine subjects, consisting of a group with mild OSA and a group of non-OSA controls, were tested on several occasions throughout the night and day using an intensive performance battery, under both baseline conditions and after a period of 36 hours of total sleep deprivation. The results suggest that drivers with mild OSA are not different to the control group in their response to sleep deprivation or time of day influences. However, the subjects with mild OSA were less aware of their impairment due to sleep deprivation, which is of concern if drivers with OSA are relying on their subjective awareness of fatigue to make decisions about when to stop driving. A final perspective on OSA and driver fatigue is provided through a clinical case series of seven fall-asleep fatality associated MVA�s associated with unrecognised or under-treated sleep disorders. As well as demonstrating the day to day potential for devastating road accidents due, at least in part, to un-recognised or untreated sleep disorders, these cases also serve to highlight some of the current medico-legal controversies and difficulties in this area of driver fatigue. In conclusion, this body of work has provided novel information about the epidemiology and implications of OSA in commercial drivers, and about how OSA interacts with other fatigue promoting factors. Finally, it has explored some of the medico-legal issues that relate to sleep disorders and driver fatigue. As well as providing much needed information in the area of driver fatigue, at the same time this work raises many more questions and suggests areas of future research. For instance, such research should examine the relationship between objective accident rates and OSA/sleep apnoea syndrome in commercial drivers, the interaction between mild sleep apnoea syndrome and other fatigue risk factors, and driver perception of sleepiness prior to sleep onset in drivers with sleep disorders.

Although a broad range of neuropsychological deficits have been reported to occur in patients with Obstructive Sleep Apnea Syndrome (OSAS), few studies have examined the executive functions in this patient group. The executive functions provide conscious control of the more basic cognitive functions and play an important role in daily living. They include capacities such as concept formation, planning, cognitive flexibility and resistance to interference. This study compared the performance of groups of moderate and severe OSAS patients with a group of unaffected individuals (N=24), on five tests of executive functioning. Two indices of sleep disordered breathing, sleep fragmentation and . hypoxemia, obtained from overnight polysomnography, were respectively used to categorise participants. ID patients with severe OSAS, executive function deficits were evident, while in those with moderate OSAS these abilities appeared largely intact. Further analyses revealed that the observed findings could not be attributed to differences in vigilance. These results suggest a discontinuity in the manifestation of executive function deficits between moderate and severe OSAS patients. There may be a threshold of OSAS severity, which if exceeded, impairments tend to occur. The magnitude of the impairment in patients with severe OSAS may be sufficient to interfere with daily cognitive functioning. Further research is needed both to replicate these findings and to establish the underlying pathogenesis of these deficits. / Thesis (M.A.)-University of Natal, Pietermaritzburg, 2001.

No description available.

This thesis presents a framework for the deployment of algorithms that support the correlation and real-time classification of physiological data streams through the development of clinically meaningful alerts using a blend of expert knowledge in the domain and pattern recognition programming based on clinical rules. Its relevance is demonstrated via a real world case study within the context of neonatal intensive care to provide real-time classification of neonatal spells. Events are first detected in individual streams independently; then synced together based on timestamps; and finally assessed to determine the start and end of a multi-signal episode. The episode is then processed through a classifier based on clinical rules to determine a classification. The output of the algorithms has been shown, in a single use case study with 24 hours of patient data, to detect clinically significant relative changes in heart rate, blood oxygen saturation levels and pauses in breathing in the respiratory impedance signal. The accuracy of the algorithm for detecting these is 97.8%, 98.3% and 98.9% respectively. The accuracy for correlating the streams and determining spells classifications is 98.9%. Future research will focus on the clinical validation of these algorithms and the application of the framework for the detection and classification of signals in other clinical contexts.

Obstructive sleep apnoea (OSA) is a common condition characterized by recurrent complete and partial upper airway obstruction. OSA sufferers have been shown to have a significantly smaller upper airway lumen compared to non-OSA sufferers. However, non-anatomical factors of sleep stage, arousability and neuromechanical responses to airway occlusion and chemosensitivity are likely to play a significant part in influencing OSA severity across the night. An exploration of these non-anatomical factors forms the basis for the experiments in this thesis. In the first experimental chapter presented in this thesis, a detailed retrospective epoch by epoch analysis of nocturnal polysomnography in 253 patients referred to a clinical sleep service was performed to examine differences in sleep apnoea severity and arousal indices across the different stages of sleep, while controlling for posture. Both patients with and without OSA demonstrated significant reductions in respiratory and arousal event frequencies from stage 1 to 4 with intermediate frequencies in REM sleep. Lateral posture was also associated with significant improvements in OSA and arousal frequencies, with an effect size comparable to that of sleep stage. The majority of patients showed significant reductions in OSA severity during slow wave sleep. In non-REM sleep, there was a strong correlation between OSA severity and arousal frequency. These results confirm in a large group of patients, a strong sleep stage dependence of both OSA and arousal frequencies. The second study in this thesis explores the development of a CO2 stabilising or ‘clamp’ device to enable the provision of positive airway pressure, and by proportional rebreathing, the maintenance of relatively constant end-tidal CO2 despite significant hyperventilation. Healthy volunteers performed brief periods of significant voluntary hyperventilation at 2 levels of CPAP with the rebreathing function off and with active CO2 clamping in randomized order. Compared to CPAP alone, the device substantially attenuated hypocapnia associated with hyperventilation. The third study of the thesis was designed to investigate if increasing and stabilizing end-tidal CO2 could improve obstructive breathing patterns during sleep. 10 patients with severe OSA underwent rapid CPAP dialdown from therapeutic to a sub-therapeutic level to experimentally induce acute, partial upper airway obstruction over 2 minute periods repeated throughout the night. The CO2 clamp device developed and validated in Study 2 was used to determine whether during periods of partial upper airway obstruction with severe flow limitation, (1) increased end-tidal CO2 resulted in improved airflow and ventilation and (2) clamping end-tidal CO2 lessened post-arousal ventilatory undershoot. Three conditions were studied in random order: no clamping of CO2, clamping of end-tidal CO2 3-4 mmHg above eucapnic levels during the pre-dialdown baseline period only, and clamping of CO2 above eucapnia during both baseline and dialdown periods. Elevated CO2 in the baseline period alone or in the baseline and dialdown periods together resulted in significantly higher peak inspiratory flows and ventilation compared to the no clamp condition. Breath-by-breath analysis immediately pre- and post-arousal showed higher end-tidal CO2 despite hyperventilation immediately post-arousal and attenuation of ventilatory undershoot in CO2 versus non-CO2 clamped conditions. These results support that modulation of ventilatory drive by changes in pre- and post-arousal CO2 are likely to importantly influence upper airway and ventilatory stability in OSA. The fourth study was designed to explore several possible pathophysiological mechanisms whereby obstructive sleep apnoea is improved in stages 3 & 4 (slow wave) versus stage 2 sleep. 10 patients with severe OSA who demonstrated significant reductions in OSA frequency during slow wave sleep on diagnostic investigation were studied. Patients underwent rapid dialdowns from therapeutic CPAP to 3 different pre-determined sub-therapeutic pressures to induce partial airway obstruction and complete airway occlusions in a randomised sequence during the night in both stage 2 and slow wave sleep. Partial airway obstructions and complete occlusions were maintained until arousal occurred or until 2 minutes had elapsed, whichever came first. After airway occlusions, time to arousal, peak pre-arousal negative epiglottic pressure and the rate of ventilatory drive augmentation were significantly greater, suggesting a higher arousal threshold and ventilatory responsiveness to respiratory stimuli during slow wave compared to stage 2 sleep. Post dialdowns, the likelihood of arousal was lower with less severe dialdowns and in slow wave compared to stage 2 sleep. Respiratory drive measured by epiglottic pressure progressively increased post-dialdown, but did not translate into increases in peak flow or ventilation pre-arousal and was not different between sleep stages. These data suggest that while arousal time and propensity following respiratory challenge are altered by sleep depth, there is little evidence to support that upper airway and ventilatory compensation responses to respiratory load are fundamentally improved in slow wave compared to stage 2 sleep. In summary, sleep stage, arousal threshold and chemical drive appear to strongly influence upper airway and ventilatory stability in OSA and are suggestive of important non-anatomical pathogenic mechanisms in OSA.

Obstructive sleep apnoea (OSA) is a common disorder characterized by repetitive closure of the upper airway during sleep and associated with significant adverse health effects including hypertension, heart disease and stroke. Current treatment with continuous positive airway pressure (CPAP) is highly effective but reduced compliance levels have resulted in suboptimal outcomes. Oral appliances such as mandibular advancement splints (MAS) are an alternative treatment and have potential advantages including greater patient compliance, comfort and portability. Although they have been shown to be successful across all categories of OSA severity, overall they are less effective than CPAP. A key limitation to its more widespread use has been the inability to predict which patients will be a treatment success. Prediction of treatment outcome would greatly enhance both MAS utilization and overall OSA management. However, little is known about the mechanisms of action of MAS therapy and a more detailed understanding is likely to improve patient selection and outcome. The aim of this thesis is to improve the prediction of treatment outcome through improved understanding of the mechanisms and site(s) of action of MAS therapy during sleep, through extrapolating this knowledge into daytime prediction tests and by developing prediction equations which can be tested prospectively. The work in this thesis presents novel ideas and findings. It is the first to examine and find that MAS therapy improves upper airway collapsibility during sleep. The site(s) of upper airway collapse was also examined and found to predict treatment outcome. Primary oropharyngeal collapse during sleep predicted treatment success and this was extrapolated into a simple daytime test hypothesized to reflect oropharyngeal function. These primary oropharyngeal collapsers were found to have characteristic awake flow-volume curves and this was then studied prospectively. Cephalometric X-rays and anthropomorphic measurements were also evaluated to formulate prediction equations for treatment outcome with MAS. These new findings together with their implications for clinical practice and future research are then summarized. It is concluded, however, that although many advancements have been made, the mechanisms of MAS action and prediction of treatment outcome remain incompletely understood reflecting the complex pathophysiology of the upper airway.

Obstructive sleep apnoea (OSA) is characterised by repetitive reductions or pauses in breathing during sleep due to upper airway narrowing or closure. Due to disruption to normal sleep patterns, many patients with OSA suffer from increased daytime sleepiness. Epidemiological studies have established a link between OSA and driver fatigue and accidents, generally showing a two to seven times increased risk of road traffic accidents in non-commercial drivers with OSA. There is emerging evidence that commercial drivers have a higher prevalence of OSA than the general population, being predominately male, middle-aged and overweight, three important risk factors for OSA. However, little is known about the relationship between OSA and driver sleepiness in commercial drivers, whether road accidents are increased in commercial drivers with OSA, and whether OSA interacts with other fatigue promoting factors, such as sleep deprivation, to further escalate road accident risk. One thousand randomly selected commercial drivers were surveyed in the field. In addition, 61 randomly selected NSW commercial drivers had in hospital sleep studies and daytime performance testing, including a PC based driving simulator task. The prevalence of OSA, defined as Respiratory Disturbance Index (RDI) < 10, was approximately 50% in NSW commercial drivers. Approximately one quarter of the drivers reported pathological daytime sleepiness, and 12-14% had both OSA and pathological daytime sleepiness. A diagnosis of OSA was the most important factor predicting excessive daytime sleepiness in these drivers: OSA was more important than 15 other work-related, lifestyle and medical factors that could be expected to promote, or be associated with, daytime sleepiness. Drivers with sleep apnoea syndrome (both OSA and pathological daytime sleepiness) had an increased driving accident risk, using driving simulator and daytime performance testing as proxy measures for accident risk. These results demonstrate the importance of OSA as a cause of driver fatigue in commercial drivers and suggest that all commercial drivers should be screened for the presence of sleep apnoea syndrome in order to potentially reduce road accident risk through treatment. A separate, but related body of work examined the combined effects of mild OSA and other fatigue promoting factors (sleep deprivation and circadian influences) on driving performance. Twenty nine subjects, consisting of a group with mild OSA and a group of non-OSA controls, were tested on several occasions throughout the night and day using an intensive performance battery, under both baseline conditions and after a period of 36 hours of total sleep deprivation. The results suggest that drivers with mild OSA are not different to the control group in their response to sleep deprivation or time of day influences. However, the subjects with mild OSA were less aware of their impairment due to sleep deprivation, which is of concern if drivers with OSA are relying on their subjective awareness of fatigue to make decisions about when to stop driving. A final perspective on OSA and driver fatigue is provided through a clinical case series of seven fall-asleep fatality associated MVA�s associated with unrecognised or under-treated sleep disorders. As well as demonstrating the day to day potential for devastating road accidents due, at least in part, to un-recognised or untreated sleep disorders, these cases also serve to highlight some of the current medico-legal controversies and difficulties in this area of driver fatigue. In conclusion, this body of work has provided novel information about the epidemiology and implications of OSA in commercial drivers, and about how OSA interacts with other fatigue promoting factors. Finally, it has explored some of the medico-legal issues that relate to sleep disorders and driver fatigue. As well as providing much needed information in the area of driver fatigue, at the same time this work raises many more questions and suggests areas of future research. For instance, such research should examine the relationship between objective accident rates and OSA/sleep apnoea syndrome in commercial drivers, the interaction between mild sleep apnoea syndrome and other fatigue risk factors, and driver perception of sleepiness prior to sleep onset in drivers with sleep disorders.

Sleep related breathing disorders in childhood are increasingly recognised as contributors to morbidity as well as suboptimal physical, mental and social development. The associated cost in social and economic terms is clearly significant. Detection and diagnosis of such disorders can be costly and technically difficult. Multi-parameter monitoring like polysomnography is expensive and inappropriate for mass screening or investigations remote from tertiary centres. A simple and non-invasive cardiovascular approach termed pulse transit time (PTT) is useful in determining the status of upper airways during sleep. This approach employs the measurement of the time delay in the arterial pulse pressure wave from the aortic valve of the heart to a peripheral site. PTT has shown promise to provide quantify inspiratory effort in adults with sleep disordered breathing (SDB) and can then be an effective monitoring tool in children. Initial investigations explore the parameters that can confound the PTT measurements of a child. This work provides an estimate of the expected PTT ranges from infancy to childhood. Thereafter, overnight PTT recordings were performed in conjunction with PSG studies to corroborate evidence for its capability in paediatric respiratory studies. The results show that PTT has the ability to identify abnormal respiratory events during sleep. Furthermore, the use of PTT can differentiate the nature of respiratory events as obstructive or central. Technological considerations to improve the robustness of PTT measure to be used not only in cardiorespiratory but also cardiovascular studies on children were also illustrated. Preliminary findings obtained here suggest that the properties of PTT show promise as a predictor for obstructive sleep apnoea. There is a need to bridge the gap of providing quality SDB diagnosis and yet accommodating requirements for a robust screening measure. PTT has demonstrated its suitability and utility as a measure to play a role in the investigation and monitoring of treatment in this area.

Orientador: Valfrido Antônio Pereira Filho, Márcio de Moraes / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-17T04:27:50Z (GMT). No. of bitstreams: 1 CastroeSilva_LucasMartinsde_M.pdf: 1071076 bytes, checksum: 478d606eb114721dbe5d1ecf344dd908 (MD5) Previous issue date: 2010 / Resumo: A configuração e as dimensões da via aérea superior são determinadas pelas estruturas anatômicas como: tecidos moles, musculatura e esqueleto craniofacial, que compõem ou circundam a faringe. As alterações anatômicas dos tecidos moles e/ou do esqueleto craniofacial poderão tornar a via aérea superior (VAS) mais estreita. Estes pontos são os principais fatores etiológicos de um distúrbio cada vez mais diagnosticado na população brasileira conhecida como síndrome da apnéia e hipoapnéia obstrutiva do sono (SAHOS). A cirurgia ortognática, que é utilizada na correção das deformidades dento-esqueléticas, tem se mostrado como o tratamento mais eficiente nos casos graves de SAHOS. Boa parte dos pacientes portadores da síndrome apresenta deformidade dento-esquelética. A síndrome é mais comum nos pacientes portadores de deformidade do tipo classe II. Pacientes com deformidade dento-esquelética de classe III resultante do prognatismo mandibular e/ou deficiência maxilar apresentam uma diminuição da VAS após a cirurgia ortognática de recuo mandibular, embora seja menos tratada na literatura, não deixando claras as consequências dos recuos mandibulares isolados, bem como das cirurgias combinadas de avanço maxilar e recuo mandibular na via aérea superior a longo prazo. Em vista dos fatos apresentados, o presente estudo teve como objetivo avaliar as alterações da via aérea superior em pacientes com deformidade dento-esquelética classe III submetidos à cirurgia ortognática e se há diferença na resposta da via aérea superior quando comparados os gêneros. Para tanto, foi realizada uma avaliação cefalométrica de 45 pacientes divididos em três grupos: grupo 1- cirurgia bimaxilar (23 pacientes); grupo 2- cirurgia de avanço maxilar (15 pacientes) e grupo 3- cirurgia de recuo mandibular (7 pacientes). Desses 45 pacientes, 25 são do gênero masculino e 20 do gênero feminino. A via aérea superior foi avaliada utilizando a análise cefalométrica de Arnett-Gunson FAB-Surgery e o software Dolphin Imaging 11 (Dolphing Imaging and Management Solutions, Chatsworth CA, EUA) em 3 períodos distintos: T0 - pré-operatório; T1 - pós-operatório de 1 semana e T2 - pós-operatório de no mínimo 1 ano. Nos pacientes submetidos à cirurgia bimaxilar houve alteração da VAS no pós-operatório imediato, porém, a longo prazo, a medida da orofaringe voltou ao valor pré-operatório. No grupo 2 existiu um aumento da VAS que se manteve por longo tempo. Nos pacientes submetidos ao recuo mandibular não houve alterações da VAS. Quando se comparou a VAS entre os gêneros, observou-se que tanto os homens quanto as mulheres apresentaram alteração na região da nasofaringe, porém só as mulheres apresentaram uma alteração significativa na aérea da orofaringe. Como conclusão foi possível afirmar que: nos pacientes submetidos à cirurgia bimaxilar o avanço maxilar compensou as alterações na VAS acarretadas pelo recuo mandibular; os pacientes submetidos à cirurgia de recuo mandibular não apresentaram mudanças na VAS; o grupo submetido ao avanço maxilar apresentou um ganho significativo da VAS que se manteve estável pelo período avaliado e que as mulheres registraram alterações na região da nasofaringe e orofaringe, enquanto os homens somente na região da nasofaringe. / Abstract: The configuration and dimensions of the upper airway are determined by the anatomical structures such as soft tissue, muscles and craniofacial skeleton, which comprise or surround the pharynx. Anatomic abnormalities of the soft tissue and/or the craniofacial skeleton may narrow the upper airway leading to obstructive sleep apnea. Class III patients, after orthognathic surgery frequently show a decrease in upper airway which has been less evaluated in the literature. These points are the main factors influencing a disorder increasingly being diagnoses in our population known as obstructive sleep apnea. Orthognathic surgery that is used in the correction of dento-skeletal deformities has been shown to be the most effective treatment in severe cases of obstructive sleep apnea. Many of the patients with the syndrome have dento-skeletal deformities in various degrees. The syndrome is more common in patients with class II deformity. However patients with class III deformity resulting from mandibular prognathism and/or maxillary deficiency after a mandibular setback orthognathic surgery showed a decrease in upper airway which has been less evaluated in the literature. The influence of not making clear the influenced of isolated mandibular setbacks and bimaxillary surgery on the upper airway lacks long-term evaluation. This study aimed to evaluate the changes of upper airway dimensions in patients with class III dento-skeletal deformity treated with orthognathic surgery and the difference in the response of the upper airway between genders. A cephalometric evaluation of 45 patients was performed. The subjects were divided into three groups: group 1 - bimaxillary surgery (23 patients), group 2 - maxillary advancement surgery (15 patients) and group 3 - mandibular setback surgery (7 patients). Of these 45 patients 25 were males and 20 females. The upper airway was evaluated through the cephalometric analysis of Arnett-Gunson FAB-Surgery and the software Dolphin Imaging 11 (Dolphing Imaging and Management Solutions, Chatsworth CA, EUA) in three distinct periods: T0 - preoperative, T1 - one week postoperative and T2 - at least one year postoperative. In patients undergoing bimaxillary surgery we observed changes in the upper airway in the immediate postoperative period, but long-term measures the oropharynx returned to preoperative values. In maxillary advancement there was an increase in the upper airway that remained long-term. In patients who underwent mandibular setback no changes in the upper airway was observed. When comparing the upper airway between the genders we found that both men and women showed abnormalities in the nasopharynx, but only women showed a significant change in the oropharynx area. As conclusion, it was possible to state that: in patients who underwent bimaxillary surgery the jaw advancement compensated the changes of the upper airway brought about by the mandibular setback, the patients who received mandibular setback surgery showed no changes in the upper airway, and the group submitted to maxillary advancement showed a significant increase of the upper airway and that remained stable for the evaluation period. Women had abnormalities in the nasopharynx and oropharynx while men presented abnormalities only in the nasopharynx. / Mestrado / Cirurgia e Traumatologia Buco-Maxilo-Faciais / Mestre em Clínica Odontológica