Dissertations / Theses on the topic 'Upper airways obstruction'

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária
A Síndrome da Apneia/Hipopneia Obstrutiva do Sono (SAHOS) é uma síndrome com grande prevalência na sociedade actual, constituíndo um grande problema de saúde pública. A SAHOS ocorre pelo repetido estreitamento ou colapso das vias aéreas superiores (VAS) durante o sono provocando como principal síntoma uma hipersonolência diurna exessiva. Os factores de riscos mais comuns incluem o sexo masculino, a obesidade, um palato mole alongado e uma retrognatia maxilar e/ou mandibular. A fisiopatologia da síndrome é multifactorial decorrente, em parte, de alterações das estruturas craniofaciais e dos tecidos moles das VAS associadas a alterações neuromusculares da faringe e a uma maior complacência da faringe. Relativamente ao tratamento, existem actualmente várias modalidades, tanto comportamentais, clínicas e cirúrgicas que devem ser individualizadas e criteriosamente seleccionadas para a situação clínica de cada paciente. Acredita-se que a SAHOS resulta na maioria das vezes de um estreitamento difuso da faringe. Para o seu tratamento é importante detectar os diferentes padrões de obstrução das VAS que parecem determinar o sucesso ou a falha do tratamento cirúrgico. As novas tecnologias permitem a criação de imagems tridimensionais a partir de imagems obtidas por ressonância magnética e tomografia computorizada juntamente com programas de reconstrução em 3 dimensões. Estas imagems tridimensionais possibilitam a avaliação dos locais de obstrução bem como proporcionam medições volumétricas das VAS. A cirurgia de avanço maxilo-mandibular (AMM) é um movimento em cirurgia ortognática que permite o avanço bi-maxilar, aumentando o volume das VAS a nível da velo-oro-hipofaringe. Tem sido descrita como sendo o tratamento cirúrgico mais efetivo para a SAHOS (excluíndo a traqueostomia) com índices de sucesso acima dos 80%. Vários autores comprovaram a eficiência da cirurgia de AMM no aumento do espaço faríngeo, diminuindo ou mesmo eliminando os episódios de colapsos respiratórios e melhorando significativemente a qualidade do sono e de vida dos pacientes. As palavras chaves utilizadas foram: “obstructive sleep apnea syndrome”, “maxillomandibular advancement” e “upper airway obstruction” que foram associados de múltiplas formas. Obstructive Sleep Apnea/Hipopnea Syndrome (OSAH) is a highly prevalent syndrome in the society, characterized as a public health burden. OSAH occurs by recurrent episodes of upper airway (UA) obstruction or collapse during sleep with daytime somnolence as the major symptom. The principal risks factors are : male, obesity, elongated soft palate and maxillary and/or mandibular retrognathia. Pathophysiology of OSAH is multifactorial, due partly to abnormalities of craniofacial stuctures and UA soft tissue associated with neuromuscular alterations of the pharynx and increased UA compliance. Behavioral, clinical and surgical options are available for the treatment of OSAH, which must be individualized and carefully selected for the clinical situation of each patient. Over the time, OSAH has been recognized as an obstructive process with a diffuse narrowing of the pharynx. For its treatment it is important te detect the different patterns of UA obstruction that seems to determine the sucess or failure of surgical treatment. New technologies allow the creation of tridimensional images achieved from magnetic resonance and computed tomography with reconstruction program. This tridimensional images enable the evaluation of obstruction sites and provide volumetric measurments of UA. Maxillomandibular advancement (MMA) is a movement on orthognatic surgery which allows bi-maxillary advancement, increasing the volume of UA at the level of velo-oro-hypopharynx. It has been described as the most effective surgical treatment for OSAH (excluding tracheostomy) with success rates above 80%. Several authors have demonstrated the effectiveness of AMM surgery on increasing the AMM pharyngeal space, reducing or eliminating episodes of respiratory collapse and improving sleep quality and life of patients. The keys words were : “obstructive sleep apnea syndrome”, “maxillomandibular advancement” e “upper airway obstruction” which have been associated in multiple ways.

Repetitive closure of the upper-airway characterises obstructive sleep apnea. It disrupts sleep causing excessive daytime drowsiness, and is linked to hypertension and cardiovascular disease.Previous studies simulating the underlying fluid mechanics of two-dimensional channel flow are based upon velocity-driven boundaries with symmetric positioning of the soft-palate. In the first part of the present work the two-dimensional work of Balint (2001) is extended to a pressure-driven model where the stability solutions space mapped for the soft-palate, symmetrically placed within viscous channel flow. As a result of this work the modelling of Obstructive Sleep Apnoea (OSA) it is proposed that modelling should focus on nasal breathing as the first indicator for the presence of OSA. Numerical simulations reveal the appearance of amplification of soft-palate displacement over several breathing cycles with asymmetric positioning of the soft-plate and for nasal breathing (single channel flow). Such events increase airway hydraulic resistance at the start of inhalation, a vulnerably period of the breathing cycle for collapse of the pharynx.In the second part of the present work three-dimensional studies are conducted for duct flow and flow through an anatomically correct reconstructed geometry, supporting the findings of the two-dimensional work of the first part. Moreover, extending understanding of anatomical interactions, through development of a three-dimensional geometry reconstruction based on an airway at the end of inhalation. Here the geometry is reconstructed from quantitative date linked to the breathing cycle, captured via an in vivo method using an adapted endoscope technique. Simulations reveal flow mechanisms that produce low-pressure regions on the side walls of the pharynx and on the soft-palate within the pharyngeal section of minimum area. Soft-palate displacement and lateral pharynx-wall deformations reduce further the pressures in these regions creating forces that would tend to narrow the airway owing to flow curvature. These phenomena suggest a mechanism for airway closure in the lateral direction as observed in an bronchoscope study conducted as part of this thesis.

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 Apnea (OSA) is a syndrome in which the human Upper Airway (UA) collapses during sleep leading to frequent sleep disruption and inadequate air supply to the lungs. OSA involves Fluid-Structure Interaction (FSI) between a complex airflow regime and intricate mechanics of soft and hard tissue, causing large deformation of the complicated UA geometry. Numerical simulations provide a means for understanding this complex system, therefore, we develop a validated FSI simulation, composed of a 1D fluid model coupled with a 3D FEM solid solver (Artisynth), that is applied to a parameterized airway model providing a fast and versatile system for researching FSI in the UA. The 1D fluid model implements the limited pressure recovery model of Cancelli and Pedley [28] using a dynamic pressure recovery term, area function corrections allowing complete closure and reopening of fluid geometries, and discretization schemes providing robust behavior in highly-uneven geometries. The fluid model is validated against 3D fluid simulations in static geometries and simple dynamic geometries, and proves reliable for predicting bulk flow pressure. Validation of simulation methods in Artisynth is demonstrated by simulating the buckling, complete collapse, and reopening of elastic tubes under static pressure which compare well with experimental results. The FSI simulation is validated against experiments performed for a collapsible channel (a "2D" Starling resistor) designed to have geometry and characteristics similar to the UA. The observed FSI behaviors are described and compared for both experiment and simulation, providing a quantitative validation of the FSI simulation. The simulations and experiments agree quite well, exhibiting the same major FSI behaviors, similar progression from one behavior to another, and similar dynamic range. A parameterized UA model is designed for fast and consistent creation of geometries. Uniform pressure and dynamic flow FSI simulations are performed with this model for numerous parameters associated with OSA. Uniform pressure simulations compare well to clinical data. Dynamic flow results demonstrate airflow limitation and snoring oscillations. The simulations are fast, simulating 1 s of FSI in 30 minutes. This model is a powerful tool for understanding the complex mechanics of OSA.
Applied Science, Faculty of
Mechanical Engineering, Department of
Graduate

本文データは平成22年度国立国会図書館の学位論文(博士)のデジタル化実施により作成された画像ファイルを基にpdf変換したものである
Kyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第7578号
医博第2065号
新制||医||704(附属図書館)
UT51-99-D195
京都大学大学院医学研究科内科系専攻
(主査)教授 一山 智, 教授 人見 滋樹, 教授 泉 孝英
学位規則第4条第1項該当

Introduction: Juvenile onset recurrent respiratory papillomatosis (JoRRP) is the commonest benign paediatric neoplasm. There is no curative treatment, but the condition is self-limiting. Current primary treatment is aimed at symptomatic relief, comprising of serial surgical debulking of obstructive papillomas along the respiratory tract, with voice preservation. Adjuvant therapy is indicated in severe cases. Objective: A review of children with JoRRP presenting to the ENT Department at Red Cross War Memorial Children’s Hospital (RCWMCH) over 2 years. Evaluation of the pattern of disease and factors that may contribute to disease severity were reviewed. Method: Retrospective folder review of children with histologically confirmed laryngeal papillomatosis over above the time period. Results: Twenty children were included. Nine were male, 11 were female. The median age at diagnosis was 2.4 years (11 - 109 months). Presentation at < 3 years was noted in 5/7 of the most severe cases. Nine of 20 were HPV serotyped; 5 were type 11, and 4 were type 6. Eighty percent (16/20) were HIV negative; 10% (2/20) HIV positive; and 10% (2/20) were unknown. A total of 90 surgical procedures were performed; the highest number of surgeries per child was 13. Inter-surgical time was 1 to 164 weeks (median 9 weeks). Four received Gardasil vaccination as adjuvant therapy, 3 of who showed a reduction in disease severity. Conclusion: JoRRP commonly presents around the first 3 years of life. Severe cases can be life-threatening, often with multiple hospital admissions for clearance of surgical papillomata. Severe cases presented before 3 years. Gardasil vaccination as adjuvant therapy has promise. No identifiable risk factors in our review were noted. HIV co-infection and HPV type were not risk factors for severity.

名古屋大学博士学位論文 学位の種類:博士（医療技術学）（課程） 学位授与年月日:平成19年3月23日
"Daytime polysomnography and portable recording device for diagnosis and CPAP therapy in patients with obstructive sleep apnea syndrome" Sleep and Breathing, v.11, n.2 (2007) pp.109-115 を、博士論文として提出したもの。

Includes bibliographical references.
Numerous challenges are faced in investigations aimed at developing a better understanding of the pathophysiology of obstructive sleep apnoea. The anatomy of the tongue and other upper airway tissues, and the ability to model their behaviour, is central to such investigations. In this thesis, details of the construction and development of a three-dimensional finite element model of soft tissues of the human upper airway, as well as a simplified fluid model of the airway, are provided. The anatomical data was obtained from the Visible Human Project, and its underlying micro-histological data describing tongue musculature were also extracted from the same source and incorporated into the model. An overview of the mathematical models used to describe tissue behaviour, both at a macro- and microscopic level, is given. Hyperelastic constitutive models were used to describe the material behaviour, and material incompressibility was accounted for. An active Hill three-element muscle model was used to represent the muscular tissue of the tongue. The neural stimulus for each muscle group to a priori unknown external forces was determined through the use of a genetic algorithm-based neural control model. The fundamental behaviour of the tongue under gravitational and breathing-induced loading is investigated. The response of the various muscles of the tongue to the complex loading developed during breathing is determined, with a particular focus being placed to that of the genioglossus. It is demonstrated that, when a time-dependent loading is applied to the tongue, the neural model is able to control the position of the tongue and produce a physiologically realistic response for the genioglossus. A comparison is then made to the response determined under quasi-static conditions using the pressure distribution extracted from computational fluid-dynamics results. An analytical model describing the time-dependent response of the components of the tongue musculature most active during oral breathing is developed and validated. It is then modified to simulate the activity of the tongue during sleep and under conditions relating to various possible neural and physiological pathologies. The retroglossal movement of the tongue resulting from the pathologies is quantified and their role in the potential to induce airway collapse is discussed.

La estimación del esfuerzo respiratorio durante el sueño es de una importancia crítica para la identificación correcta de eventos respiratorios en los trastornos respiratorios del sueño (TRS), el diagnóstico correcto de las patologías relacionadas con los TRS y las decisiones sobre la terapia correspondiente. Hoy en día el esfuerzo respiratorio suele ser estimado mediante la polisomnografía (PSG) nocturna con técnicas imprecisas y mediante la evaluación manual por expertos humanos, lo cual es un proceso laborioso que conlleva limitaciones significativas y errores en la clasificación.
El objetivo principal de esta tesis es la presentación de nuevos métodos para la estimación automático, invasiva y no-invasiva del esfuerzo respiratorio y cambios en la obstrucción de las vías aéreas superiores (VAS). En especial, la aplicación de estos métodos debería permitir, entre otras cosas, la diferenciación automática invasiva y no-invasiva de eventos centrales y obstructivos durante el sueño.
Con este propósito se diseñó y se obtuvo una base de datos de PSG nocturna completamente nueva de 28 pacientes con medición sistemática de presión esofágica (Pes). La Pes está actualmente considerada como el gold-standard para la estimación del esfuerzo respiratorio y la identificación de eventos respiratorios en los TRS. Es sin embargo una técnica invasiva y altamente compleja, lo cual limita su uso en la rutina clínica. Esto refuerza el valor de nuestra base de datos y la dificultad que ha implicado su adquisición. Todos los métodos de procesado propuestos y desarrollados en esta tesis están consecuentemente validados con la señal gold-standard de Pes para asegurar su validez.
En un primer paso, se presenta un sistema automático invasivo para la clasificación de limitaciones de flujo inspiratorio (LFI) en los ciclos inspiratorios. La LFI se ha definido como una falta de aumento en flujo respiratorio a pesar de un incremento en el esfuerzo respiratorio, lo cual suele resultar en un patrón de flujo respiratorio característico (flattening). Un total de 38,782 ciclos respiratorios fueron automáticamente extraídos y analizados. Se propone un modelo exponencial que reproduzca la relación entre Pes y flujo respiratorio de una inspiración y permita la estimación objetiva de cambios en la obstrucción de las VAS. La capacidad de caracterización del modelo se estima mediante tres parámetros de evaluación: el error medio cuadrado en la estimación de la resistencia en la presión pico, el coeficiente de determinación y la estimación de episodios de LFI. Los resultados del modelo son comparados a los de los dos mejores modelos en la literatura. Los resultados finales indican que el modelo exponencial caracteriza la LFI y estima los niveles de obstrucción de las VAS con la mayor exactitud y objetividad.
Las anotaciones gold-standard de LFI obtenidas, fueron utilizadas para entrenar, testear y validar un nuevo clasificador automático y no-invasivo de LFI basa en la señal de flujo respiratorio nasal. Se utilizaron las técnicas de Discriminant Analysis, Support Vector Machines y Adaboost para la clasificación no-invasiva de inspiraciones con las características extraídas de los dominios temporales y espectrales de los patrones de flujo inspiratorios. Este nuevo clasificador automático no-invasivo también identificó exitosamente los episodios de LFI, alcanzando una sensibilidad de 0.87 y una especificidad de 0.85.
La diferenciación entre eventos respiratorios centrales y obstructivos es una de las acciones más recurrentes en el diagnostico de los TRS. Sin embargo únicamente la medición de Pes permite la diferenciación gold-standard de este tipo de eventos. Recientemente se han propuesto nuevas técnicas para la diferenciación no-invasiva de apneas e hipopneas. Sin embargo su adopción ha sido lenta debido a su limitada validación clínica, ya que la creación manual por expertos humanos de sets gold-standard de validación representa un trabajo laborioso. En esta tesis se propone un nuevo sistema para la diferenciación gold-standard automática y objetiva entre hipopneas obstructivas y centrales. Expertos humanos clasificaron manualmente un total de 769 hypopneas en 28 pacientes para crear un set de validación gold-standard. Como siguiente paso se extrajeron características específicas de cada hipopnea para entrenar y testear clasificadores (Discriminant Analysis, Support Vector Machines y adaboost) para diferenciar entre hipopneas centrales y obstructivas mediante la señal gold-standard Pes. El sistema de diferenciación automática alcanzó resultados prometedores, obteniendo una sensibilidad, una especificad y una exactitud de 0.90. Por lo tanto este sistema parece prometedor para la diferenciación automática, gold-standard de hipopneas centrales y obstructivas.
Finalmente se propone un sistema no-invasivo para la diferenciación automática de hipopneas centrales y obstructivas. Se propone utilizar la señal de flujo respiratorio para la diferenciación utilizando características de los ciclos inspiratorios de cada hipopnea, entre ellos los patrones flattening. Este sistema automático no-invasivo es una combinación de los sistemas anteriormente presentados y se valida mediante las anotaciones gold-standard obtenidas mediante la señal de Pes por expertos humanos. Los resultados de este sistema son comparados a los resultados obtenidos por expertos humanos que utilizaron un nuevo algoritmo no-invasivo para la diferenciación manual de hipopneas. Los resultados del sistema automático no-invasivo son prometedores y muestran la viabilidad de la metodología empleada. Una vez haya sido validado extensivamente, se ha propuesto este algoritmo para su utilización en dispositivos de terapia de TRS desarrollados por uno de los socios cooperantes en este proyecto.
The assessment of respiratory effort during sleep is of major importance for the correct identification of respiratory events in sleep-disordered breathing (SDB), the correct diagnosis of SDB-related pathologies and the consequent choice of treatment. Currently, respiratory effort is usually assessed in night polysomnography (NPSG) with imprecise techniques and manually evaluated by human experts, resulting in a laborious task with significant limitations and missclassifications.
The main objective of this thesis is to present new methods for the automatic, invasive and non-invasive assessment of respiratory effort and changes in upper airway (UA) obstruction. Specifically, the application of these methods should, in between others, allow the automatic invasive and non-invasive differentiation of obstructive and central respiratory events during sleep.
For this purpose, a completely new NPSG database consisting of 28 patients with systematic esophageal pressure (Pes) measurement was acquired. Pes is currently considered the gold-standard to assess respiratory effort and identify respiratory events in SDB. However, the invasiveness and complexity of Pes measurement prevents its use in clinical routine, underlining the importance of this new database. . . All the processing methods developed in this thesis will consequently be validated with the gold-standard Pes-signal in order to ensure their clinical validity.
In a first step, an (invasive) automatic system for the classification of inspiratory flow limitation (IFL) in the inspiratory cycles is presented.
IFL has been defined as a lack of increase in airflow despite increasing respiratory effort, which normally results in a characteristic inspiratory airflow pattern (flattening). A total of 38,782 breaths were extracted and automatically analyzed. An exponential model is proposed to reproduce the relationship between Pes and airflow of an inspiration and achieve an objective assessment of changes in upper airway obstruction. The characterization performance of the model is appraised with three evaluation parameters: mean-squared-error when estimating resistance at peakpressure,
coefficient of determination and assessment of IFL episodes. The model's results are compared to the two best-performing models in the literature. The results indicated that the exponential model characterizes IFL and assesses levels of upper airway obstruction with the highest accuracy and objectivity.
The obtained gold-standard IFL annotations were then employed to train, test and validate a new automatic, non-invasive IFL classification system by means of the nasal airflow signal. Discriminant Analysis, Support Vector Machines and Adaboost algorithms were employed to objectively classify breaths non-invasively with features extracted from the time and frequency domains of the breaths' flow patterns. The new non-invasive automatic classification system also succeeded identifying IFL episodes, achieving a sensitivity of 0.87 and a specificity of 0.85.
The differentiation between obstructive and central respiratory events is one of the most recurrent tasks in the diagnosis of sleep disordered breathing, but only Pes measurement allows the gold-standard differentiation of these events. Recently new techniques have been proposed to allow the non-invasive differentiation of hypopneas. However, their adoption has been slow due to their limited clinical validation, as the creation of manual, gold-standard validation sets by human experts is a cumbersome procedure. In this study, a new system is proposed for an objective automatic, gold-standard differentiation between obstructive and central hypopneas with the esophageal pressure signal. An overall of 769 hypopneas of 28 patients were manually scored by human experts to create a gold-standard validation set. Then, features were extracted from each hypopnea to train and test classifiers (Discriminant Analysis, Support Vector Machines and adaboost classifiers) to differentiate between central and obstructive hypopneas with the gold-standard esophageal pressure signal. The automatic differentiation system achieved promising results, with a sensitivity of 0.82, a specificity of 0.87 and an accuracy of 0.85. Hence, this system seems promising for an automatic, goldstandard differentiation between obstructive and central hypopneas.
Finally, a non-invasive system is proposed for the automatic differentiation of central and obstructive hypopneas. Only the airflow signal is used for the differentiation, as features of the inspiratory cycles of the hypopnea, such as the flattening patterns, is used. The automatic, non-invasive system represents a combination of the systems that have been presented before and it was validated with the gold-standard scorings obtained with the Pes-signal by human experts. The outcome is compared to the results obtained by human scorers that applied a new non-invasive algorithm for the manual differentiation of hypopneas. The non-invasive system's results are promising and show the viability of this technique. Once validated, this algorithm has been proposed to be used in therapy devices developed by one of the partner institutions cooperating in this project.

Thesis (M.S.)--University of Cincinnati, 2007.
Advisor: Dr. Robert Hopkin. Title from electronic thesis title page (viewed June 30, 2010). Includes abstract. Keywords: Pierre Robin Sequence; Mandibular Distraction; Tracheostomy; cost; infant. Includes bibliographical references.

The present PhD investigation is a compendium of five related publications broadening the current state-of-the art and long-term three-dimensional effects of orthognathic surgery on the upper airway (UA) and the sleep-related disorders, such as the Obstructive Sleep Apnea-hypopnea syndrome (OSA). This PhD project, coordinated by Prof. Dr. Federico Hernández-Alfaro and Dr.Adaia Valls-Ontañón at the Universitat Internacional de Catalunya, started in January 2018 as a three-year program, and was granted by the competitive predoctoral fellowship ID: FI_B200134 by the AGAUR (Agencia de Gestió d’ajudes Universitàries i d’investigació) of the Generalitat de Catalunya. With the support of the Secretariat of Universities and Research of the Generalitat de Catalunya and the European Social Fund. Globally, the aim of this whole investigation through a PhD project was to assess the 3D-clinical impact of OS, with regard to direction, magnitude and type of surgical movement, on the upper airway and the clinical improvement and/or cure of the OSA syndrome at long term. Thus, to verify the stability of OS surgical movements when maximizing the PAV and the minimum cross-sectional areas (mCSA), results were evaluated at three time points: pre-, immediate (1-month) and late postoperative (12-months follow-up) throughout the whole investigation. These three time points allowed the authors to be able to state firm conclusions on identifying both the surgical and volumetric gains and possible relapses (short term) and the stability of OS (long-term). Hence, to address the global and specific research purposes, the authors designed and implemented 5 different studies as follows though this rationale: - A systematic review (SR) to study the current the state-of-the art regarding the impact of MMA on the PAV and the AHI in the surgical treatment and definitive cure of OSA (Paper I). Assuming the scarce and lack of homogenic data on this topic: - A retrospective cohort study was performed to demonstrate the relevance of the relationship between the head positioning through the natural head position (NHP) and the Frankfort Horizontal (FH) planes patients with different dentofacial deformities (DFD) (i.e. maxilla/mandibular retrognathia and/or prognathism) and malocclusions (i.e. class I,II or III), thus demonstrating which horizontal plane should be properly executed when planning for OS (Paper II). - As there is no rigorous data regarding the AHI reduction and volumetric, linear and cross-sectional parameters gain after OS, a retrospective longitudinal study of consecutive patients was designed and performed to study the effect of maxillary and mandibular movements (isolated or jointly) on the PAV (nasopharynx, oropharynx, and hypopharynx) and the mCSA on a 3D basis using cone-beam computed tomography (CBCT). In turn, a proposed surgical planning protocol to maximize the UA was designed and validated through this investigation (PaperIII). - On the need of further studies to individualize a required magnitude and direction of surgery-induced movements to patients with DFD, a three case-series study was implemented to validate a protocol and algorithm for the surgical management of DFD in Down syndrome (DS) patients with OSA, when the main concerns are the narrowing of the UA, malocclusion, feeding and speech problems aside from aesthetics (Paper IV). - Finally, the results of a pilot study of an ongoing three arm prospective controlled clinical trial (CCT) (ClinicalTrials.gov ID NCT03796078 registration) are depicted in this PhD project to correlate the magnitude, type, and direction of these skeletal movements with the airway dimension gain or impairment at 12 months follow-up, to propose OS as the definitive and first line treatment armamentarium in selected patients to cure OSA (in terms of AHI and sleep patient-centered parameters) (Paper V).

Obstructive sleep apnea (OSA) is a disease process characterized by collapse of the upper airway during periods of sleep leading to the cessation airflow despite persistent respiratory efforts. The aim of this research project is to investigate for associations and correlations between OSA and other clinical entities using two separate prospective studies. The initial objective was to evaluate the prevalence of laryngopharyngeal reflux (LPR) in patients with OSA. LPR was present in 26/28 (93%) of OSA patients. Moreover, there were significant correlations between LPR and OSA severity (eg. r = 0.57, p = 0.001). The second objective of this research study was to determine the prevalence of OSA in patients with cancer of the oral cavity and oropharynx, and to correlate the presence of OSA and the occurrence of postoperative morbidities. OSA was present in 76% of patients. Overall, postoperative complications were observed in 67% of OSA and 25% of non-OSA patients, although this difference was not yet significant (p = 0.27, Fisher exact test).

Introdução: Dependendo da magnitude da má oclusão de Classe III, esta é uma alteração difícil de ser tratada apenas com a correção ortodôntica. Tanto as cirurgias de recuo mandibular quanto as bimaxilares promovem uma melhora na oclusão, na função mastigatória e na estética facial, ao corrigirem as posições da mandíbula e/ou maxila, mas um importante aspecto da cirurgia ortognática, que não pode ser negligenciado, são os efeitos que os movimentos esqueléticos das bases ósseas podem provocar na região das vias aéreas, ao alterar a posição do osso hióide e da língua. O estreitamento das vias aéreas superiores (VAS) pode comprometer o sono dos pacientes submetidos à correção cirúrgica e predispor ao desenvolvimento da apneia/hipopneia obstrutiva do sono (AOS). Objetivos: O presente trabalho tem como objetivo avaliar as alterações de volume e área axial mínima do espaço aéreo faringeo em pacientes com má oclusão de Classe III esquelética, submetidos à cirurgia ortognática bimaxilar, pela técnica de osteotomia Le Fort I da maxila e osteotomia sagital bilateral da mandíbula. Material e Métodos: As avaliações foram feitas em tomografias computadorizadas Cone-beam, utilizando-se o Programa Dolphin Imaging 11.7. As tomografias de 50 pacientes, de ambos os sexos, com média de idade de 33,40 (± 9,38) anos, foram analisadas nos períodos pré e pósoperatório e as medidas de volume e área axial mínima foram mensuradas. Foi utilizado o teste t pareado e os testes foram realizados utilizando-se o programa Statistica 7.0, adotando-se um nível de significância de 5%. Resultados: ao calcular o erro do método, não foram encontrados erros casuais e nem sistemáticos (p> 0,05 em todas as medidas). As cirurgias bimaxilares para correção da Classe III esquelética promoveram um aumento de 16,68% (±22,61) no volume e 23,58% (± 31,46) na área axial mínima. Conclusões: Mesmo que os efeitos da cirurgia de avanço maxilar e recuo mandibular sobre as vias aéreas não sejam completamente previsíveis, podemos observar que a maioria dos pacientes não apresentaram prejuízos na anatomia faringeana que resulte em diminuição do volume aéreo e área axial mínima, predispondo-o ao desenvolvimento da AOS.
Introduction: Depending on the extend of Class III malocclusion, it becomes difficult to be treated only with orthodontic correction. Both mandibular setback surgery as bimaxillary surgery, promote an improvement in occlusion, masticatory function and facial aesthetics, correcting the position of the mandible and/or maxilla. But an important aspect of orthognathic surgery that cant be overlooked, are the effects that the skeletal movements of the bone bases causes in the airway space, since they change the position of the hyoid bone and tongue. The narrowing of the pharingeal airway space (PAS) may impair the patient\'s sleep and predispose to the development of obstructive sleep apnea (OSA). Purpose: This study aims to evaluate surgical changes in the airway volume and minimal cross-sectional area in the pharyngeal airway space (PAS) in patients with skeletal Class III malocclusion, submitted to bimaxillary surgery, using a Le Fort I maxillary osteotomy and bilateral sagittal split ramus osteotomy technique. Material and Methods: The evaluations were made through Cone-beam computed tomography (CBCT), using Dolphin Imaging program version 11.7. The CT scans of 50 patients of both genders, with a mean age of 33.40 (± 9.38), were analyzed pre and postoperatively and volume and minimum axial area were measured. Paired t test was used and tests were performed using Statistica 7.0 software, adopting a 5% significance level. Results: Method error were done and no random or systematic errors were found (p> 0.05 for all measures). Bimaxillary surgery for skeletal Class III correction promoted an increase of 16.68% (± 22.61) in volume and 23.58% (± 31.46) at the minimum axial area. Conclusion: Even if the effects of the maxillary advancement and mandibular setback surgery on the airway are not completely predictable, we observed that most patients didnt have pharyngeal airway anatomy damage, that could result decreased on airway volume and minimum axial area predisposing to OSA development.

Le Syndrome d’Apnée Obstructive du Sommeil affecte 4 à 6 % de la population en France soit près de 3 millions de personnes. Toutefois, les techniques de diagnostic usuelles ne permettent pas de déterminer de façon précise les sites d’occlusion ni de décrire les interactions fluide-paroi qui jouent un rôle important dans les processus de fermeture des voies aériennes supérieures. Au cours de ce travail, un ensemble d’outil a été mis en œuvre pour explorer les mécanismes sous-jacents conduisant à une apnée obstructive. La détermination géométrique et la caractérisation mécanique des voies aériennes supérieures, d’une part, la mesure des écoulements dans ces dernières, d’autre part, ont été réalisées par imagerie par résonance magnétique de l’hydrogène, pour les tissus, de l’hélium-3 et du fluor-19 pour les gaz. Les données obtenues ont été exploitées tout d’abord dans un modèle numérique statique pour estimer les lois d’état locales et caractériser la compliance des voies aériennes supérieures, puis, dans un modèle monodimensionnel, prenant en compte l’interaction fluide-structure et la limitation de débit au cours de l’inspiration, pour localiser les sites potentiellement responsables d’un éventuel collapsus. Par ailleurs, les écoulements de gaz d’hélium-3 et d’hexafluorure de soufre ont été simulés afin de déterminer le potentiel de ces deux modalités d’imagerie de gaz pour l’étude des obstructions des voies aériennes. La faisabilité d’une imagerie statique et dynamique par résonance magnétique du fluor a été démontrée. Avec une densité du gaz traceur bien plus importante, cette dernière technique présente une plus grande sensibilité à l’obstruction. Cette thèse ouvre ainsi une nouvelle voie de diagnostic et de guide thérapeutique personnalisé pour ce syndrome
Obstructive Sleep Apnea (OSA) is a common disorder occurring in almost 3 million French people. However, current diagnosis methods are not sufficient to precisely define obstructing sites and doesn't take into account the fluid structure coupling which plays an important role during upper airway closing. During this thesis, we developed a series of tools exploring upper airway closing process. On the one hand, a screening tool of the structure and the mechanical properties of the upper airway, and on the other hand, a screening tool exploring with dynamic images of inert gases flow into the upper airway, were obtained using conventional hydrogen MRI coupled to magnetic resonance elastography (MRE) and helium-3 or fluor-19 gases MRI, respectively. Geometric and biomechanical data obtained using MRI/MRE are injected into a numerical model given the compliance and the state law of upper airway. Contributions of anatomical restriction on airway collapse are also investigated using a multi-compartmental two-dimensional fluid structure interaction model during a breath inspiration to predicted airway mechanical changes and collapse pressures. Furthermore, helium 3 and sulfur hexafluoride flow was modeled at steady state using commercial finite volume software to evaluate potential feasibility to image upper airway collapsibility during OSA. First dynamic MR imaging using sulfur hexafluoride (SF6) was obtained showing the feasibility of this technique. Using SF6, 6 times denser than air, shows a higher sensibility to upper airway obstruction. This thesis opens a new imaging modality to probe and to diagnose upper airway obstruction

Le syndrome des apnées obstructives du sommeil (SAOS) est caractérisé par des épisodes répétitifs de collapsus des voies aériennes supérieures (VAS) durant le sommeil. Au cours du SAOS les propriétés mécaniques des voies aériennes supérieures sont altérées, dans le sens d'une réduction de leur capacité à laisser passer l'air, ce qui peut être assimilé à une "charge" inspiratoire. Les apnées obstructives ne se produisent jamais à l'éveil, suggérant qu'il existe, des mécanismes protecteurs d'origine corticale, de type " compensation de charge ", liés à l'éveil. Ce travail permis de caractériser ces mécanismes chez le sujet sain et le patient SAOS. Une première étude a décrit la relation pression/débit des VAS à l'éveil afin d'approcher le phénomène de compensation de charge, avant et après un traitement modulant le contrôle neurovégétatif des VAS par la compression du ganglion ptérygopalatin. La deuxième étude a mis en évidence à l'éveil chez les patients SAOS, une activité corticale motrice liée à la respiration (présence de potentiels électroencephalographiques - PPI), dont l'origine semble liée à la dysfonction des VAS, et qui est susceptible d'expliquer l'augmentation du niveau de contrôle respiratoire central connu dans le SAOS. La troisième étude a mis en évidence un phénomène de filtrage des sensations respiratoires à l'éveil chez des patients SAOS, avec restauration des ces sensations sous orthèse d'avancée mandibulaire, permettant de relier l'amélioration des propriétés mécaniques des VAS à l'intégration centrale des sensations respiratoires. Enfin la relation pression/débit a fait l'objet de deux modélisations
The obstructive sleep apnoea syndrome (OSAS) involves recurrent sleep-related upper airways (UA) collapse. UA mechanical properties and neural control are altered imposing a mechanical load on inspiration. UA collapse does not occur during wakefulness, hence arousal-dependent compensation. Three studies in healthy and apnoeic patients allowed characterizing it. From upper-airway pressure-flow relationships, the first study described local compensation mechanisms, before and after a neurovegetative modulation based on ptérygopalatin node compression. The second study showed a respiratory-related cortical activity that could contribute to the increased neural drive to upper airway and to inspiratory muscles that has previously been described in OSAS, and could therefore contribute to the arousal-dependent compensation of upper airway abnormalities. The third study showed a sensory gating-out process of breathing sensations in OSAS that could be reversed by mandibular advancement device, allowing linking upper-airway stability improvement to central integration of respiratory sensations. Finally, upper-airway pressure-flow relationship was approached by two models

Introdução: O descontentamento com a estética facial é considerado o fator motivador mais frequente na procura pela cirurgia ortognática, visto que este é o procedimento indicado nos casos de severas discrepâncias dentoesqueléticas em pacientes adultos. A anatomia das vias aéreas superiores (VAS) permite que fatores como obesidade, hipotonia muscular e deficiência mandibular favoreçam sua obstrução, podendo gerar a Apneia Obstrutiva do Sono (AOS), caracterizada por episódios recorrentes de obstrução parcial ou completa das VAS durante o sono. As cirurgias de avanço bimaxilar estão associadas ao aumento do espaço aéreo, no entanto, as alterações morfológicas e volumétricas ainda não são bem conhecidas. Objetivos: Avaliar as alterações em 3D do espaço aéreo faríngeo frente aos procedimentos de cirurgia ortognática de avanço bimaxilar em pacientes Classe I e II esqueléticos. Material e Métodos: A análise da área axial mínima e do volume da aérea superior foi realizada em pré-operatório (T0) e pós-operatório (T1) de 56 pacientes, sendo 21 do sexo masculino e 35 do sexo feminino, com média de idade de 35,8 (±10,7) anos, submetidos ao avanço bimaxilar pela técnica da osteotomia sagital de mandíbula bilateral associada ao avanço de maxila por meio de osteotomia Le Fort I. As avaliações foram feitas através de tomografia computadorizada Cone-beam, utilizando-se o Programa Dolphin Imaging 11.7. Foi utilizado o teste t pareado para comparar os dados pré e pós-operatórios. Todos os testes foram realizados com o programa Statistica, adotando-se um nível de significância de 5%. Resultados: No estudo do erro do método, não houve erro casual nem sistemático entre a primeira e a segunda medição das variáveis (p >0,05 em todas as medidas). A cirurgia de avanço bimaxilar apresentou uma média de 73,6% (± 74,75%) de aumento volumétrico e 113,5% (±123,87%) de aumento na área axial mínima. Conclusões: Podemos concluir que a cirurgia de avanço bimaxilar proporciona um aumento volumétrico significativo no espaço aéreo superior, bem como na área axial mínima, no entanto, esse ganho nem sempre ocorre na mesma magnitude para todos os pacientes.
Introduction: Facial aesthetics dissatisfaction is considered the most common motivating factor in the search for orthognathic surgery. This procedure may be used in cases of severe dental and skeletal discrepancies in adult patients. The restricted space anatomy of the upper airway space (UAS) allows features such as obesity, muscular hypotonia and mandibular deficiency favor clogging, which may lead to obstructive sleep apnea (OSA), characterized by recurrent episodes of partial or complete obstruction of the UAS during sleep. Surgeries of bimaxillary advancement are associated with increased UAS, however, the morphological and volumetric changes are not well known. Objectives: to evaluate changes in 3D pharyngeal airway in front of orthognathic surgery procedures of skeletal Class I and II subjects. Material and Methods: 3D pharyngeal airway was evaluated preoperative (T0) and postoperative (T1), with the aid of the analysis of the minimum axial area and airway volume. Fifty-six patients 21 male and 35 female, with a mean age of 35.8 (± 10.7) years undergo bimaxillary advancement by the technique of bilateral sagittal split osteotomy of the mandible associated with maxillary advancement through Le Fort I osteotomy. Measurements were made using Cone-beam Computed Tomography, using the Dolphin Imaging program 11.7. Paired t test was used to compare to the data between T0 and T1. All tests were performed with the Statistica Program, adopting a 5% significance level. Results: In the method error of the study, there was no casual or systematic error between the first and second measurement variables (p > 0.05 for all measures). The bimaxillary advancement surgery showed an average of 73.6% (± 74.75%) of increase in volume and 113.5% (±123.87%) increase in the minimum axial area. Conclusions: We concluded that the maxillomandibular advancement surgery provides a significant increase in volume in the UAS as well as the minimum axial area; however, this gain is not always in the same magnitude for all patients.

El diagnòstic de la síndrome d’Apnea-Hipopnea Obstructiva del Son (SAHOS) s’efectua amb la demostració objectiva de l’alteració respiratòria que provoca l’obstrucció de les vies respiratòries superiors durant el son i dels despertars relacionats amb els esforços respiratoris. La valoració clínica i exploració física exhaustives no prediuen adequadament ni la presencia o absència d’apnees o hipopnees nocturnes, ni la severitat, si existeix, del SAHOS. D’altra banda, la subjectivitat de l’avaluació i la variabilitat en la nomenclatura de les troballes clíniques dificulten la comparació. La Videofibrosomnoscòpia proporciona informació sobre la dinàmica de la via aèria superior en els pacients amb Trastorns Respiratoris del Son, millorant les indicacions terapèutiques. Malgrat això, encara no s’ha pogut demostrar que millori l’èxit terapèutic. L’objectiu principal d’aquesta tesi ha estat comprovar si aquesta tècnica diagnòstica millora els resultats terapèutics en pacients amb la síndrome d’Apnea-Hipopnea Obstructiva del Son. Els nostres resultats indiquen que hi ha diferències en les indicacions terapèutiques dels pacients avaluats amb i sense videofibrosomnoscòpia. Malgrat això, no podem afirmar que aquest mètode d’exploració millori els resultats terapèutics en pacients amb la síndrome d’Apnea-Hipopnea Obstructiva del Son, encara que la trobem útil en alguns casos seleccionats.
El diagnóstico de síndrome de Apnea-Hipopnea Obstructiva del Sueño (SAHOS) se efectúa mediante la demostración objetiva de la alteración respiratoria que provoca la obstrucción de las vías respiratorias superiores durante el sueño y los despertares relacionados con los esfuerzos respiratorios. La valoración clínica y exploración física exhaustivas no predicen adecuadamente ni la presencia o ausencia de apneas o hipopneas nocturnas, ni la severidad, si existe, del SAHOS. Por otra parte, la subjetividad de la evaluación y la variabilidad de la nomenclatura de los hallazgos clínicos dificultan su comparación. La Videofibrosomnoscopia proporciona información sobre la dinámica de la vía aérea superior en los pacientes con Trastornos Respiratorios del Sueño, mejorando las indicaciones terapéuticas. Sin embargo, aún no ha podido demostrarse que mejore el éxito terapéutico. El objetivo principal de esta tesis ha sido comprobar si esta técnica diagnóstica mejora los resultados terapéuticos en pacientes con síndrome de Apnea-Hipopnea Obstructiva del sueño. Nuestros resultados indican que hay diferencias en las indicaciones terapéuticas de los pacientes evaluados con y sin videofibrosomnoscopia. A pesar de ello, no podemos afirmar que este método exploratorio mejore los resultados terapéuticos en pacientes con síndrome de Apnea-Hipopnea Obstructiva del sueño, aunque lo consideramos útil en algunos casos seleccionados.
The diagnosis of Obstructive Sleep Apnea-hypopnea syndrome (OSAS) is effected by the objective demonstration of a respiratory disorder that causes obstruction of the upper airway during sleep and the awakenings (cessations of sleep)related to respiratory effort. Using clinical and physical assessment it is not easy to predict the presence or absence of apneas or nocturnal hypopneas, nor the severity of OSAS. Moreover, the subjectivity of the evaluation and the variability of the nomenclature of clinical findings make it difficult to make comparisons. The DISE (drug induced sleep endoscopy) provides information on the dynamics of the upper airway in patients with sleep-disordered breathing, improving the therapeutic indications. However, it has not been demonstrated that it improves therapeutic success. The main objective of this thesis was to determine whether this diagnostic technique improves treatment outcomes in patients with obstructive apnea-hypopnea sleep syndrome. Our results indicate that there are differences in the therapeutic indications of patients evaluated with and without DISE. However, we cannot claim that this screening method improves treatment outcomes in patients with obstructive sleep apnea-hypopnea syndrome, although we consider it useful in selected cases.

Dissertação de Mestrado Integrado em Medicina Veterinária
The respiratory system plays a limiting role for maximum performance in exercising horses, actually, noncontagious respiratory diseases rank second as a cause of poor performance. Most of the functional obstructions of the airway are only accurately diagnosed at exercise. With the introduction of overground endoscopy, dynamic upper respiratory tract (URT) obstructions are now easier to diagnose, particularly due to its ease of application, safety, tolerance by the horse and its ability to image the upper airway during normal working conditions. Nowadays, overground endoscopy is widely used in Thoroughbred racehorses, representing a fundamental tool to diagnose and develop clinical treatment. The aim of this study was to characterize a population of 81 Thoroughbred racehorses presented for poor performance and/or respiratory noise, the protocol exam, the diagnostic findings, its prevalence and also, the relation between findings and symptoms. The results were comparable to most of the pre-existing studies, with a high prevalence of URT findings, where most horses were affected by multiple disorders, being the dorsal displacement of the soft palate the most represented one. In conclusion, this study subscribed the importance of the URT assessment in performing horses, enforcing the value of dynamic examinations to reach maximum welfare, health and performance.
RESUMO - ACHADOS À ENDOSCPIA DINÂMICA EM PURO SANGUE INGLESES DE CORRIDA REFERIDOS POR MAU DESEMPENHO DESPORTIVO OU/E RUÍDO RESPIRATÓRIO - O trato respiratório representa um fator limitante na performance de cavalos de desporto, sendo que as doenças respiratórias não contagiosas são a segunda maior causa de mau desempenho desportivo. A maioria das obstruções funcionais das vias aéreas só são diagnosticadas durante o exercício. Com a introdução da endoscopia dinâmica, obstruções dinâmicas do trato respiratório superior (TRS) tornaram-se mais fáceis de diagnosticar, especialmente devido à sua fácil utilização, segurança, tolerância pelo cavalo e pela sua capacidade de filmar o TRS durante condições normais de trabalho. Atualmente, a endoscopia dinâmica é largamente utilizada em cavalos de corrida, representando uma ferramenta fundamental de diagnóstico e desenvolvimento do tratamento. O objetivo deste estudo foi caraterizar uma população de 81 cavalos puro sangue ingleses de corrida com mau desempenho desportivo ou/e ruído respiratório, o protocolo, os diagnósticos, a sua prevalência e a sua relação com os sintomas. Os resultados obtidos foram similares aos da maioria dos estudos pré-existentes, com uma grande prevalência de diagnósticos do TRS, onde a maioria dos cavalos foi afetada por múltiplas patologias, sendo que o deslocamento dorsal do palato mole foi a mais comum. Concluindo, este estudo reforçou a importância da avaliação do TRS em cavalos de desporto, fortalecendo o valor das avaliações dinâmicas com o fim de atingir máximo bem-estar, saúde e performance.
N/A

Le syndrome d’apnées obstructives du sommeil (SAOS) se caractérise par un collapsus répété des voies aériennes supérieures (VAS) durant le sommeil. Il résulte d’anomalies anatomiques des VAS qui constituent une charge inspiratoire et d’un défaut de réponse neuromusculaire à cette charge durant le sommeil. A l’éveil, il n’y a jamais de collapsus des VAS ce qui suggère l’existence de mécanismes compensatoires. Cette thèse explore ces mécanismes en étudiant la réponse à la charge imposée par le décubitus dorsal chez des sujets sains et des patients SAOS à l’éveil. Nous retrouvons chez 42% des patients SAOS éveillés en position assise une activité corticale liée à la ventilation (potentiels pré-inspiratoires, PPI) qui est absente chez les sujets sains (étude 1) et qui pourrait traduire une augmentation de la commande ventilatoire en réponse aux anomalies des VAS. Le passage en décubitus dorsal s’accompagne de l’apparition d’un PPI chez 46% des sujets sains vraisemblablement en lien avec une augmentation de la charge liée au déplacement de liquides des membres inférieurs vers la région cervicale (étude 2). A l’inverse, chez les patients SAOS, le décubitus dorsal est associé à une diminution significative de l’incidence des PPI mais à une augmentation de l’activité du génioglosse, muscle dilatateur des VAS (étude 3), probablement réflexe à une augmentation de la pression négative pharyngée générée par la charge imposée par le décubitus. Ces données montrent une réponse corticale différente des sujets sains et des patients SAOS face à la charge induite par le décubitus dorsal, ce qui contribue à mieux comprendre le contrôle des VAS et la physiopathologie du SAOS
The obstructive sleep apnea syndrome (OSAS) is characterized by recurrent upper airway (UA) collapse during sleep. It involves UA anatomical abnormalities accompanied by increased inspiratory load and defect in compensatory neuromuscular response to this load during sleep. UA collapse does not occur during wakefulness, suggesting that wakefulness-dependant neuromuscular response compensates for the increased inspiratory load. This thesis investigates these compensatory mechanisms by studying the response to the load imposed by the supine position in healthy subjects and OSAS patients during wakefulness. We found in 42% of awake OSAS patients studied in sitting position, a respiratory-related cortical activity (pre-inspiratory potentials, PIP). This activity was absent in healthy subjects (study 1) and could correspond to an increased neural drive in response to UA abnormalities. Moving to supine position was associated with the occurrence of PIP in 46% of healthy subjects probably related to an increase in fluid shift from the legs to the neck (study 2). Conversely, in OSAS patients, supine position was associated with a significant decrease in the incidence of PIP but with an increase in the genioglossus activity, an UA dilator muscle, (study 3), probably reflex to the increase in pharyngeal negative pressure induced by the load imposed by supine position. These data show a different cortical response of healthy subjects and OSAS patients to an increased load induced by supine position. It contributes to better understand the respiratory control of UA and the pathophysiology of OSAS

An examination of the nature of sleep fragmentation in children with upper airway obstruction. Introduction – Sleep related upper airway obstruction (UAO) in children disrupts breathing in sleep, resulting in sleep fragmentation and subsequent neurocognitive and behavioural deficits. Unfortunately the nature of this fragmentation in children is poorly understood and a universally accepted, clinically valid, measure of sleep fragmentation has been elusive. This limits our ability to accurately determine and measure the consequences of sleep fragmentation on a child’s development due to UAO, as well as the success of any treatment administered. General Aims - The aim of the current study was to (i) examine the nature of sleep fragmentation in children with upper airway obstruction and (ii) to develop a new sleep fragmentation index for use in paediatric clinical populations with upper airway obstruction. When this study began no such index existed that was widely accepted and utilized. A range of sleep fragmentation measures already trialed in children with upper airway obstruction were reviewed to identify problems and limitations with current and previous methods of measuring sleep fragmentation in these children. An attempt was also made to identify other possible additional factors that mediate sleep fragmentation so as to develop a workable and generally applicable sleep fragmentation index for children with upper airway obstruction. Methods – We performed a series of analyses on sleep and neurocognitive data from children with upper airway obstruction to identify and quantify neural activity associated with sleep fragmentation. We then used these measures and other mediating factors to create a composite measure of sleep fragmentation in children. Results – We found that children with upper airway obstruction had characteristically altered neural activity as measured by electroencephalogram (e.g. changes in sleep spindle density, decreased alpha and sigma power around spontaneous arousals from sleep). They also had an altered movement distribution in sleep (increased exponential distribution coefficient when sleep runs between movements are modeled on a survival curve), when compared to normal controls. The studies also demonstrated the potential ability of a composite measure of such sleep fragmentation markers and mediating vulnerability factors to more accurately and usefully quantify the negative impacts of upper airway obstruction. Conclusions - Sleep fragmentation is a significant consequence of UAO in children, however the current measure of UAO severity is insufficient for determining the overall impact on a child’s development. As this study demonstrates, the impact of sleep fragmentation is dependent on a complicated set of variables including: age, health factors (e.g. BMI), exposure time, disease severity (e.g. AHI), genetics, trait-like factors, social factors (e.g. SES) and family history. The arousals, or disruptions to sleep, are also altered in children with UAO compared to normal controls. We therefore propose a composite measure of these important factors as a more accurate tool for determining the impact of sleep fragmentation and overall severity of UAO in children.
Thesis (Ph.D.) (Research by Publication) -- University of Adelaide, School of Medicine, 2015.

碩士
國立臺灣大學
臨床牙醫學研究所
97
Objectives The narrowing of the upper airway caliber during sleep is believed to be essential to the pathogenesis of obstructive sleep apnea syndrome (OSAS). Nasal continuous positive airways pressure (nCPAP) is the therapy of choice especially for treating severe OSAS patients. We hypothesized that after continuous using of nCPAP, it could yield some persist changes of the upper airway. The aim of this study was to evaluate the changes of upper airway and its surrounding soft tissues of severe OSAS patients before and after nCPAP therapy. Material and method 76 severe OSAS patients were randomly assigned into two groups. In experimental group the patients have received nCPAP treatment with optimal pressure, i.e. effective nCPAP; and nCPAP with sub-therapeutic pressure, i.e. sham nCPAP, in control group. Static and dynamic MRI were used to image the upper airways in awakening supine posture of all subjects at baseline and 3 months after nCPAP therapy. The volume of the upper airway and the lateral pharyngeal wall were measured by using the serial static MRI. The area changes of the upper airway caliber sectioned at retro-palatal and retro-glossal levels were obtained from dynamic MRI to represent the collapsibility of the upper airway. The possible persist effects of nCPAP therapy on the upper airway were then analyzed by using these measurements. Results 35 subjects in the experimental group and 27 subjects in the control group have completed all the measurements. The total and retro-palatal upper airway volume were significantly increased after using effective nCPAP, but not occurred in controls. The retro-palatal upper airway volume was also correlated with the optimal pressure of the nCPAP (r=0.314, p<0.05). The volume of the lateral pharyngeal wall was significantly correlated with neck circumference (r=0.456) and BMI (0.590); and the lateral pharyngeal volume seemed not to be changed after both effective and sham nCPAP treatments. By comparing the maximal, minimal, and mean area of the upper airway caliber, effective nCPAP treatment didn’t yield collapsibility change in the retro-palatal level but in the retro-glossal level. The collapsibility of the airway both in the retro-palatal and retro-glossal levels were significantly correlated with the optimal pressure of the nCPAP. Conclusion In severe OSAS patients, the upper airway volume but not the lateral pharyngeal volume was increased after 3 months of effective nCPAP treatments. It seemed to indicate that such improvement might be due to strengthening of the tissue tone. The collapsibility of the upper airway in the retro-glossal level seemed to be also improved, but our study is not able to provide explanations. The upper airway resistance seemed to be correlated with the ratio between minimal and mean upper airway caliber. Its clinical implication needs future studies.

Obstructive sleep apnea (OSA) severity is strongly associated with the degree of overnight peripharyngeal fluid accumulation. We hypothesized that intravenous fluid loading would cause upper airway (UA) narrowing or increase the frequency of apneas and hypopneas per hour of sleep (apnea-hypopnea index; AHI). We employed a controlled, randomized double-crossover experiment in 9 healthy men aged 23-46 years. In the control, subjects were administered approximately 80 ml of normal saline intravenously during sleep. In the intervention, subjects were administered approximately 1850 ml of saline during sleep while wearing compression stockings to localize fluid rostrally. The intervention induced nuchal fluid accumulation, resulting in an increase in neck circumference (+0.1 cm during control, +0.6 cm during intervention, P< 0.01 ) and a decrease in UA cross-sectional area (-0.08 cm2 during control, -0.43 cm2 during intervention, P = 0.023). Although the intervention did not increase the AHI (control AHI = 19.5, intervention AHI = 30.3, P = 0.249), the AHI during the intervention correlated with age (r = 0.8, P < 0.01). Thus, intravenous saline loading during sleep can narrow the UA, which in older men may induce or worsen OSA. Further studies are needed to test this hypothesis.

碩士
國立清華大學
動力機械工程學系
103
Numerical method is employed to simulate the muscle material characteristics of obstructive sleep apnea (OSA) patients. A set of averaged muscle material characteristics for the range of body mass index (BMI) examined is concluded to predict the expansion of the patient’s upper airway after surgery for the clinic reference before the surgery. Firstly, the mandibular bone, chin, neck and upper airway models of three patients, whose BMI are similar, are reconstructed based on the computed tomography (CT) images before and after surgery. Then, the model structures before and after “virtual surgery” are simulated by computational solid mechanics (CSM) with the assumptions of elasticity, anisotropy and homogeneous muscle material characteristics. Iterations are subsequently performed through comparing the model outlines obtained by “virtual surgery” simulation and the clinical surgery to acquire the appropriate muscle material characteristics of patients. A set of proper muscle material characteristics of patients is thus attained for 21