<p>Obstructive sleep apnea (OSA) appears to affect up to 5% of the population. The extent to what pulmonary function awake and during sleep relates to obstructive breathing and hypoxemia during sleep in these patients is unclear. The aim of this study was to investigate respiratory function in patients with varying degree of snoring and OSA and to analyse regional lung aeration during sleep.</p><p>In all, 35 healthy subjects and 90 patients with snoring and OSA were studied. The ventilatory response to CO₂ (VRCO₂) was measured. Lung function tests were performed. A technique based on computed tomography was developed to study lung aeration during sleep.</p><p>Patients with OSA displayed a higher VRCO₂ in comparison to healthy subjects and snorers (p<0.01). Increased closing volume and reduced expiratory reserve volume (ERV) were found in patients with OSA (p<0.001). In a multiple regression analysis, ERV was an independent predictor of nocturnal apnea (R²=0.13; p=0.001) and desaturation frequency (R²=0.11; p<0.01). In both healthy subjects and OSA patients, lung aeration was reduced during sleep by 0.10 ml gas/g tissue in the dorsal lung region (p<0.05 and p<0.01). OSA patients had a significantly lower gas/tissue ratio in comparison to healthy subjects both awake (-23%; p<0.04) and during sleep (-25%; p<0.04). In a univariate analysis, functional residual capacity (FRC) correlated with the change in lung aeration from wakefulness to sleep (r=-0.78; p<0.001). In patients with OSA, ERV (r=-0.69; p<0.05) and sleep time (r=0.69; p<0.05) correlated with the fall in lung aeration. </p><p>In conclusion, patients with OSA display an increased ventilatory response to CO₂, reduced ERV and increased closing volume. ERV predicts nocturnal apnea and desaturation frequency to a similar extent as obesity. Lung aeration is reduced in the dorsal region during sleep and patients with OSA display a lower amount of gas in comparison to healthy subjects. Decrease in lung volumes, promoting airway closure, and loss of muscle tone contributed to the altered lung function during sleep.</p>

Obstructive sleep apnea (OSA) appears to affect up to 5% of the population. The extent to what pulmonary function awake and during sleep relates to obstructive breathing and hypoxemia during sleep in these patients is unclear. The aim of this study was to investigate respiratory function in patients with varying degree of snoring and OSA and to analyse regional lung aeration during sleep. In all, 35 healthy subjects and 90 patients with snoring and OSA were studied. The ventilatory response to CO2 (VRCO2) was measured. Lung function tests were performed. A technique based on computed tomography was developed to study lung aeration during sleep. Patients with OSA displayed a higher VRCO2 in comparison to healthy subjects and snorers (p&lt;0.01). Increased closing volume and reduced expiratory reserve volume (ERV) were found in patients with OSA (p&lt;0.001). In a multiple regression analysis, ERV was an independent predictor of nocturnal apnea (R2=0.13; p=0.001) and desaturation frequency (R2=0.11; p&lt;0.01). In both healthy subjects and OSA patients, lung aeration was reduced during sleep by 0.10 ml gas/g tissue in the dorsal lung region (p&lt;0.05 and p&lt;0.01). OSA patients had a significantly lower gas/tissue ratio in comparison to healthy subjects both awake (-23%; p&lt;0.04) and during sleep (-25%; p&lt;0.04). In a univariate analysis, functional residual capacity (FRC) correlated with the change in lung aeration from wakefulness to sleep (r=-0.78; p&lt;0.001). In patients with OSA, ERV (r=-0.69; p&lt;0.05) and sleep time (r=0.69; p&lt;0.05) correlated with the fall in lung aeration. In conclusion, patients with OSA display an increased ventilatory response to CO2, reduced ERV and increased closing volume. ERV predicts nocturnal apnea and desaturation frequency to a similar extent as obesity. Lung aeration is reduced in the dorsal region during sleep and patients with OSA display a lower amount of gas in comparison to healthy subjects. Decrease in lung volumes, promoting airway closure, and loss of muscle tone contributed to the altered lung function during sleep.

No description available.

Introduction: Les troubles respiratoires du sommeil (TRS), qui représentent une préoccupation croissante pour la santé, ont des effets significatifs sur la santé, le comportement et la performance académique chez l’enfant. Les malformations craniofaciales, l’hypertrophie adéno-amygdalienne et l'obésité, représentent des facteurs de risque importants dans le développement de cette condition. Les symptômes des TRS ont été étudiés dans une étude prospective chez les enfants et adolescents durant leur traitement orthodontique dans un milieu universitaire. Cette étude a cherché à décrire la prévalence et les facteurs de risque principaux des TRS, ainsi que l'impact des différentes interventions orthodontiques sur les symptômes TRS. Matériel et méthodes: dans une étude cohorte prospective, un groupe de 168 sujets âgés de 12 à 21 ans ont été soumis, quatre ans après la prise de données initiale, à un examen craniofacial en plus d'être administré des questionnaires qui ont recueilli des données sur la situation socio-démographique, le bruxisme et les troubles d’ATM, le sommeil et le comportement diurne, et les facteurs neuropsychologiques. Résultats: l'indice de masse corporelle a été augmenté mais est demeurée dans la même catégorie aux deux moments de l'enquête. Il ya eu une augmentation du serrement des dents et des symptômes de l'ATM, une diminution de la taille des amygdales, et une augmentation de la somnolence diurne. La prévalence des TRS n'a pas changé entre l’étude initiale et l’étude de suivi. Aucune intervention orthodontique s'est avérée avoir un effet cliniquement significatif sur les voies aériennes supérieures. Conclusions: la prévalence des symptômes TRS était constante par rapport aux valeurs de base pour la population étudiée, mais a augmenté si rapportée à la population générale. Les traitements orthodontiques ne montrent aucun effet sur les TRS. Mots-clés : apnée du sommeil, craniofacial, prévalence, ronflement, traitement orthodontique, voies aériennes supérieures / Introduction: Sleep-disordered breathing (SDB), a growing health concern, has significant effects on a child’s health, behaviour, and scholastic performance. Craniofacial malformations, along with adenotonsillar hypertrophy and obesity, represent important risk factors in the development of this condition. SDB symptoms in children and adolescents followed for orthodontic treatment in a university setting have been investigated in this prospective study. The aims of this study were to describe the prevalence and main risk factors of SDB and the impact of different orthodontic interventions on the SDB symptoms. Materials and methods: in a prospective cohort study, four years following an initial evaluation, a group of 168 subjects aged 12-21 years underwent a craniofacial examination in addition to being administered self-completed questionnaires that collected information on socio-demographic and psychosocial factors, bruxism and temporo-mandibular joint (TMJ) disorders, sleep and daytime behaviour, and neuropsychological factors. Results: Body mass index (BMI) was slightly increased but remained in the same category at the two time points of investigation. There was an increase in tooth clenching and TMJ symptoms, a decrease in tonsils’ size, and an increase in daytime sleepiness. Prevalence of SDB did not change between baseline and follow-up studies. No orthodontic treatment intervention proved to have any clinically significant impact on the upper airway. Conclusions: SDB symptoms prevalence was constant when compared to the baseline values for the studied population, but increased if reported to the general population. Regular orthodontic treatment didn’t show any effect on SDB symptoms. Keywords : craniofacial, orthodontic treatment, prevalence, sleep apnea, snoring, upper airway

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Diss. (sammanfattning) Linköping : Univ., 2004. / Härtill 4 uppsatser.

Fundação Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro / Introdução: a apneia obstrutiva do sono (AOS) é considerada um fator de risco para as doenças cardiovasculares. Os mecanismos responsáveis pelo desenvolvimento da aterosclerose potencializados pela AOS não são completamente conhecidos. Entretanto, existem evidências de que a AOS está associada com aumento no estresse oxidativo, elevação nos mediadores inflamatórios, resistência à insulina, ativação do sistema nervoso simpático, elevação da pressão arterial (PA) e a disfunção endotelial. Objetivo: avaliar a relação da AOS com a função endotelial, o estresse oxidativo, os biomarcadores inflamatórios, o perfil metabólico, a adiposidade corporal, a atividade simpática e a PA em indivíduos obesos. Métodos: estudo transversal envolvendo 53 pacientes obesos, com índice de massa corporal (IMC) &#8805; 30 e < 40 Kg/m2, sem distinção de raça e gênero, apresentando idade entre 20 e 55 anos. O estudo do sono foi realizado com o equipamento Watch-PAT 200, sendo feito o diagnóstico de AOS quando índice apneia-hipopneia (IAH) &#8805; 5 eventos/h. Todos os participantes foram submetidos à avaliação do (a): adiposidade corporal (peso, % gordura corporal e circunferências da cintura, quadril e pescoço); PA; atividade do sistema nervoso simpático (concentrações plasmáticas de catecolaminas); biomarcadores inflamatórios (proteína C reativa ultrassensível (PCR-us) e adiponectina); estresse oxidativo (malondialdeído); metabolismo glicídico (glicose, insulina e HOMA-IR) e lipídico (colesterol total e frações e triglicerídeos); e função endotelial (índice de hiperemia reativa (RHI) avaliado com o equipamento Endo-PAT 2000 e moléculas de adesão celular). A análise estatística foi realizada com o software STATA versão 10. Resultados: dos 53 pacientes avaliados 20 foram alocados no grupo sem AOS (grupo controle; GC) (IAH: 2,550,35 eventos/h) e 33 no grupo com AOS (GAOS) (IAH: 20,163,57 eventos/h). A faixa etária (39,61,48 vs. 32,52,09 anos) e o percentual de participantes do gênero masculino (61% vs. 25%) foram significativamente maiores no GAOS do que no GC (p=0,01). O GAOS em comparação o GC apresentou valores significativamente mais elevados de circunferência do pescoço (CP) (40,980,63 vs. 38,650,75 cm; p=0,02), glicemia (92,541,97 vs. 80,21,92 mg/dL; p=0,0001), PA sistólica (126,051,61 vs.118,16 1,86 mmHg; p=0,003) e noradrenalina (0,160,02 vs. 0,120,03 ng/mL; p=0,02). Após ajustes para fatores de confundimento, a glicose e a PCR-us foram significativamente mais elevadas no GAOS. Os 2 grupos apresentaram valores semelhantes de IMC, insulina, HOMA-IR, perfil lipídico, adiponectina, PA diastólica, adrenalina, dopamina, moléculas de adesão celular e malondialdeído. A função endotelial avaliada pelo RHI também foi semelhante nos 2 grupos (GAOS:1,850,2 vs. GC:1,980,1; p=0,31). Nas análises de correlação, considerando todos os participantes do estudo, o IAH apresentou associação positiva e significativa com CP e PCR-us após ajustes para fatores de confundimento. A saturação mínima de O2 se associou de forma negativa e significativa com a CP, os níveis séricos de insulina e o HOMA-IR, mesmo após ajustes para fatores de confundimento. Conclusões: o presente estudo sugere que em obesos a AOS está associada com valores mais elevados de glicemia e inflamação; o aumento do IAH apresenta associação significativa com a obesidade central e com a inflamação; e a queda na saturação de oxigênio se associa com resistência à insulina. / Introduction: obstructive sleep apnea (OSA) is considered a risk factor for cardiovascular disease. The mechanisms responsible for the development of atherosclerosis triggered by OSA are not completely known. However, there is evidence that OSA is associated with increased oxidative stress, higher levels of inflammatory mediators, insulin resistance, increased sympathetic nervous system activity, elevated blood pressure (BP) and endothelial dysfunction. Objective: to evaluate the relation of OSA with endothelial function, oxidative stress, inflammatory biomarkers, metabolic profile, body adiposity, sympathetic activity and BP in obese individuals. Methods: cross-sectional study involving 53 obese patients with body mass index (BMI) > 30 and < 40 kg/m2, without distinction of race and gender, aged between 20 and 55 years. The sleep study was performed with the equipment Watch-PAT200 and the diagnosis of OSA was made when apnea-hipopnea index (AHI) &#8805; 5 events/h. All participants underwent evaluation of: body adiposity (weight, % body fat and circumferences of waist, hip and neck); BP; sympathetic nervous system activity (plasma levels of catecholamines); inflammatory biomarkers (high sensible c-reactive protein (hs-CRP) and adiponectin); oxidative stress (malondialdehyde); metabolism of glucose (glucose, insulin and HOMA-IR) and lipids (total cholesterol and fractions and triglycerides); and endothelial function (reactive hyperemia index (RHI) evaluated by Endo-PAT 2000 and cellular adhesion molecules). Statistical analysis was performed with software STATA version 10. Results: of the 53 evaluated patients, 20 were included in the group without OSA (Control group; CG) (AHI: 2.550.35 events/h) and 33 in the group with OSA (OSAG) (IAH: 20.163.57 events/h). The mean age (39.61.48 vs. 32.52.09 years) and the percentage of male participants (61% vs. 25%) were significantly higher in OSAG than in CG (p=0.01). The OSAG compared the CG showed significantly higher values of neck circumference (NC) (40.980.63 vs. 38.650.75 cm, p=0.02), glucose (92.541.97 vs. 80.21.92 mg/dL, p=0.0001), systolic BP (126.051.61 vs. 118.161.86 mmHg, p=0.003) and noradrenaline (0.160.02 vs. 0.120.03 ng/mL, p=0.02). After adjustment for confounders, glucose and hs-CRP were significantly higher in OSAG. Both groups presented similar values of BMI, insulin, HOMA-IR, lipid profile, adiponectin, diastolic BP, adrenaline, dopamine, adhesion cellular molecules and malondialdehyde. Endothelial function evaluated by RHI was also similar in both groups (OSAG: 1.850.2 vs. CG: 1.980.1, p=0.31). In correlation analysis, considering the whole group of patients, AHI presented a positive and significant association with NC and hs-CRP after adjustments for confounders. The minimum oxygen saturation was associated negatively and significantly with NC, insulin and HOMA-IR even after adjustments for confounders. Conclusions: the present study suggests that in obese individuals, OSA is associated with higher values of glucose and inflammation; higher AHI presents significant association with central adiposity and with inflammation; and lower oxygen saturation is associated with insulin resistance.

Esta tese de doutorado aborda o assunto apneia do sono, especialmente a síndrome de apneia e hipopneia obstrutiva do sono (SAHOS) como principal motivo de investigação. Nosso estudo teve como objetivo estudar o mecanismo fisiológico de funcionamento da válvula expiratória nasal (nEPAP) denominada Provent. Trata-se de um dispositivo descartável utilizado em ambas as narinas e que permite a inspiração normal, porém oferece resistência à expiração, fazendo com que o próprio paciente gere uma determinada pressão expiratória nasal. Este mecanismo de atuação da válvula determina algum grau de modificação na via aérea superior e no pulmão. Embora já se saiba que este dispositivo é efetivo no tratamento de pacientes com SAHOS leve e moderada3 o seu mecanismo fisiológico de funcionamento ainda não está completamente entendido. Utilizamos um método de ressonância magnética para avaliar a via aérea superior e o pulmão de pacientes em utilização do Provent nasal. Estudamos dez pacientes, 7 homens e 3 mulheres, entre 30 e 62 anos, com diagnóstico clínico de SAHOS e confirmado pela polissonografia (IAH>5 ev/h). Realizamos então, em diferentes momentos, polissonografia diagnóstica, polissonografia em uso da válvula nasal e exame de imagem (ressonância magnética). A faringe e o pulmão foram inspecionados e medidos durante alguns ciclos respiratórios, com e sem a válvula nasal. Neste estudo, validamos o exame de Ressonância Magnética para a avaliação da área transversal da via aérea superior e da capacidade residual funcional durante a respiração através da válvula nasal. Com os nossos resultados reforçamos os achados anteriores da literatura referentes aos três possíveis mecanismos de funcionamento desta válvula nasal: hiperinflação pulmonar importante aumentando a tração na traqueia, uma tendência à dilatação da faringe durante a expiração que se mantém no início da inspiração reduzindo a colapsabilidade da faringe e, finalmente, hipoventilação e aumento de PCO2. Considerando estes resultados, podemos dizer que a pressão expiratória positiva nasal pode ser uma alternativa de tratamento da SAHOS. Os resultados deste estudo são apresentados sob a forma de artigo já publicado em revista internacional de alto impacto científico (Journal of Applied Physiology). Adicionalmente, na forma de apêndice, realizamos outro estudo objetivando estudar o comportamento da SAHOS na Doença de Parkinson e as alterações ocasionadas em marcadores periféricos de lesão neuronal, especificamente a proteína S100B e a Enolase. Os transtornos do sono, incluindo os distúrbios respiratórios, são frequentes nos pacientes com Doença de Parkinson (DP), e, estudos já realizados mostram que a proteína S100B pode estar aumentada tanto em pacientes com SAHOS1 como naqueles com Doença de Parkinson2, sugerindo a possibilidade de algum grau de dano neuronal nestes pacientes quando comparados com indivíduos normais. Estes achados serviram de motivação para o estudo das variáveis neurofisiológicas do sono e do comportamento de biomarcadores em pacientes com Parkinson e, supostamente, SAHOS concomitantemente. / The issue of this doctoral thesis is Obstructive Sleep Apnea (OSA). Our study intended to clarify the mechanism of action of nEPAP (Nasal Expiratory Positive Airway Pressure), delivered with a disposable device (Provent, Ventus Medical). It has been shown to improve sleep disordered breathing (SDB) in some subjects3, but how it works is still not completely understood. We studied 10 patients, 7 males and 3 females, age between 30 and 62 years old, with clinic OSA and confirmed by sleep study (IHA>5). Sleep studies were performed in different nights, a night for diagnostic of OSA and other night under nasal valve. We did use MRI (Magnetic Resonance Imaging) to see upper airway and lung in patients wearing Provent. The present study demonstrate that significant hyperinflation (an increase in end expiratory lung volume) occurs during breathing through the device. In addition, there may be some trend to dilate the UA during expiration, and this may carry over into inspiration, providing a second mechanism to reduce the tendency of the UA to collapse in patients with SDB. Finally, we were able to show significant hypoventilation and a rise in PCO2 during breathing through the nEPAP during wakefulness, which may persist into sleep. Results are presented in the format of a paper published in a international journal with high scientific impact (Journal of Applied Physiology). In addition, as appendix, we did perform other protocol intended to study OSA in the Parkinson Disease (PD) and correlation with detectable levels of S100B and NSE, biochemical markers of neuronal damage. Sleep breathing disorders are frequent in Parkinson Disease and there are some studies showing that S100B, a known biochemical marker of astrocyte damage, is increased in both SAOS and PD1 2, suggesting a possible neuronal damage while compared to controls. These findings were motivation to investigate biochemical markers and sleep in patients with Parkinson. Our results suggest that sleep disturbance in PD causes a worse sleep quality and leads to S100B elevation during the night. Probably PD patients are suffering some degree of brain damage during the night that trigger a S100B response.

L'hypoxie intermittente (HI), induite par les apnées du sommeil, conduit à des altérations de la sensibilité à l'insuline et de l'homéostasie glucidique mais les mécanismes impliqués restent mal connus. L'objectif de ce travail était d'étudier les effets et les mécanismes sous jacents d'une exposition chronique à l'HI sur l'homéostasie glucidique. L'HI induit une résistance à l'insuline à la fois systémique et tissulaire, ainsi qu'une amélioration de la tolérance au glucose associée à une activation de l'AMPK musculaire. L'HI cause également des altérations du foie et du tissu adipeux associées à un changement du pattern d'expression des gènes dans ces tissus et à un risque accru de développement de pathologies vasculaires comme l'athérosclérose. Enfin, la délétion de PHD1, une des protéines régulatrices de HIF-1, entraîne une résistance à l'insuline associée une stéatose hépatique, faisant de HIF-1 une cible potentielle impliquée dans les altérations metaboliques induites par l'HI. / Intermittent hypoxia (IH), induced by sleep apnea, leads to alterations in insulin sensitivity and glucose homeostasis but the mechanisms involved remains poorly understood. The objective of this work was to study the effects and the underlying mechanisms of chronic exposure to IH on glucose homeostasis. IH induces both systemic and tissue-specific insulin resistance , as well as improved glucose tolerance associated with an activation of muscle AMPK. IH also causes a change in the pattern of gene expression in liver and adipose tissue and an increased risk of vascular pathologies such as atherosclerosis development. Finally, the deletion of PHD1, a regulatory protein of HIF-1, leads to insulin resistance associated with hepatic steatosis, making HIF-1 a possible target involved in the metabolic changes induced by IH.