Introduction : Le syndrome d’apnées obstructives du sommeil (SAOS) est un problème de santé publique fréquent. La gestion par pression positive continue (TPPC) est la référence, mais de nombreuses personnes le refusent ou ne s’y adaptent jamais. Ainsi, les orthèses d’avancée mandibulaire (OAM) titrables gagnent en popularité car elles apportent des solutions concrètes et bien souvent durables. L’approche myofonctionelle, soit d’offrir des activités linguales, est une piste complémentaire qui pourrait améliorer la gestion du SAOS. C’est dans ce but que nous avons observé la combinaison de ces deux éléments par la réalisation d’une OAM active (OAMA). En effet, le repositionnement actif de la mandibule en position avancée pourrait bien atténuer certains effets indésirables de l’OAM conventionnelle. Objectifs : Comparer, dans un environnement de soins courants, l’efficacité de l’OAMA à une OAM conventionnelle titrable chez des patients adultes atteints d’un SAOS sévère qui refusent ou sont intolérants au TPPC. L’évaluation se fera notamment par le taux de réponse globale qui inclut l’évolution de l’index d’apnée-hypopnée (IAH) et l’observance. Méthodologie : 18 participants complétèrent la totalité de l’étude, 8 dans le groupe OAM et 10 dans le groupe OAMA. Après avoir rempli des questionnaires, ils ont été invité à un examen dentaire, articulaire et à une première polysomnographie (PSG). Tous ont reçu le traitement par orthèse. Après minimum 3 mois de port, une nouvelle série de questionnaires a été remplie, un nouvel examen clinique a été réalisé ainsi qu’une seconde PSG. Résultats : L’IAH (p<0,001), le temps passé avec une saturation pulsée en dioxygène supérieure à 90% (p=0,002), l’index de désaturation (p=0,004) et le nombre de micro-éveil (p=0,007) ont significativement diminué dans les 2 groupes, sans différence significative entre les groupes. L’ensemble des résultats des questionnaires ont mis en évidence une amélioration significative entre le début et la fin de l’étude pour les 2 groupes sans toutefois de différence significative entre les deux types d’orthèses pour les variables sur la somnolence, la fatigue et les fonctions usuelles ou la qualité du sommeil Toutefois il y a significativement plus de salivation rapportée avec l’OAMA, plus de temps en éveil lors du sommeil et une tendance vers un port moins long au cours de la nuit. Une qualité du sommeil qui se normalise moins qu’avec l’OAM conventionnelle à aussi été notée. De façon subjective de par les rapports patients, à court terme, moins de claquements aux articulations temporo-mandibulaires (ATM) (p=0,05) et moins de changements d’occlusion (p=0,05) ont été rapportés par le groupe OAMA par rapport au groupe OAM. Enfin le taux de réponse globale ne différait pas de façon significative entre les groupes (p=0,64). Conclusion : L’OAMA est une option de traitement équipotente pour les index de sommeil lorsqu’on la compare à une OAM titrable conventionnelle. Bien que l’OAMA engendre moins de claquements au niveau des ATM et de modifications occlusales à court terme, il est essentiel, par une étude à plus grande taille, de confirmer si les tendances à moins bien dormir et à ne pas utiliser l’OAMA pour une durée semblable à l’OAM peut s’expliquer. / Introduction: Obstructive sleep apnea syndrome (OSAS) is a common public health issue. Management with continuous positive airway pressure (CPAP) is the gold standard, but many people are unable to cope with it or refuse it. So, titratable mandibular advancement devices (MADs) are gaining in popularity, because they provide real long-term solutions. The myofunctional approach, which involves lingual exercises, is an additional measure that could improve OSAS management. To this end, we have observed the association of these two elements by creating an active MAD (AMAD). Indeed, actively repositioning the mandible in the advanced position may well mitigate some of the adverse effects of conventional MADs. Objectives: To compare the efficacy of AMADs in a routine care environment with conventional titratable MADs in adult patients with severe OSAS who do not want or do not tolerate CPAP therapy. The evaluation will focus on the overall response rate, which includes changes in apnea-hypopnea index (AHI) and compliance. Methodology: 18 participants completed the entire study, 8 in the MAD group and 10 in the AMAD group. After completing a series of questionnaires, they were asked to undergo a dental and temporomandibular joint (TMJ) examination, and their first polysomnography (PSG). They all received the treatment. After the patients had used it for at least 3 months, another series of questionnaires was completed, and another clinical examination and a second PSG were carried out. Results: AHI (p <0.001), time spent with SpO2>90 (p = 0.002), desaturation index (p = 0.004) and number of micro-arousals (p = 0.007) significantly decreased in both groups, with no significant difference between groups. The overall results of the questionnaires showed a significant improvement between the beginning and the end of the study for both groups with no significant difference between the groups for drowsiness, fatigue, normal activities and sleep quality variables. However, a much higher salivation rate was reported with the AMAD, as well as longer wake times during sleep periods and a tendency for the device to be worn for less time during the night. It was also observed that sleep quality does not normalize as much as with conventional MADs. Subjectively, patients in the AMAD group reported fewer TMJ clicks (p = 0.05) and fewer occlusion changes (p = 0.05) in the short term, compared to the MAD group. Finally, there were no significant differences between the groups in the overall response rate (p = 0.64). Conclusion: AMAD is an equipotent treatment option, based on sleep indexes, when compared to conventional titratable MADs. While AMADs produce subjectively less TMJ clicking and occlusal changes in the short term, it is essential to conduct a large-scale study to confirm whether the tendencies to not sleep as well and to use AMADs for shorter periods than MADs can be explained.

Le syndrome d’apnées obstructives du sommeil (SAOS) est un problème de santé publique majeur qui est considéré comme un facteur indépendant de risque de survenue d’un infarctus du myocarde (IM). Les altérations cardiovasculaires associées au SAOS sont principalement dues à l’hypoxie intermittente (HI) chronique. En particulier, l’HI induit l’activation du facteur de transcription hypoxia-inducible factor-1 (HIF-1), susceptible d’être impliqué dans la vulnérabilité accrue du myocarde à l’ischémie-reperfusion. L’objectif de cette thèse était d’étudier le rôle de HIF-1 dans les mécanismes induits par l’HI et impliqués dans l’augmentation de la taille de l’infarctus suite à une ischémie-reperfusion. Ces travaux ont mis en évidence deux nouveaux effets délétères de l’HI, à savoir l’induction d’un stress du réticulum endoplasmique (RE) et d’altérations mitochondriales. A travers, l’inhibition génétique et/ou pharmacologique de HIF-1, nous avons montré que HIF-1 apparaît comme un acteur primordial dans l’ensemble des mécanismes délétères de l’HI, incluant ceux découverts lors de cette thèse. De plus, HIF-1 joue un rôle majeur dans l’augmentation de la taille de l’IM induite par l’HI chronique. Parallèlement, son activation myocardique est corrélée à l’index d’apnées-hypopnées chez des patients apnéiques atteints d’une maladie coronarienne (comparativement aux non-apnéiques). Par conséquent, l’activation de HIF-1 pourrait être utilisée comme marqueur diagnostic du SAOS chez les patients à risque cardiovasculaire. HIF-1 pourrait également représenter une cible pour le développement de nouvelles thérapies complémentaires ou substitutives aux traitements actuels. / Obstructive sleep apnea syndrome (OSAS) is a major public health problem that is considered an independent risk factor for the occurrence of myocardial infarction (MI). The cardiovascular alterations associated with OSA are mainly due to the chronic intermittent hypoxia (IH). In particular, activation by IH, the hypoxia-inducible factor-1 (HIF-1) transcription factor likely contributes to enhance myocardial vulnerability to ischemia-reperfusion injury. The aim of this thesis was to study the role of HIF-1 in the mechanisms involved in the increase in MI induced by chronic IH. This work has highlighted two new deleterious consequences of IH exposure, namely endoplasmic reticulum (ER) stress and mitochondrial alterations. Through genetic and/or pharmacological inhibition of HIF-1, we have shown that HIF-1 appears to be a primordial actor in all the deleterious mechanisms of IH, including those discovered during this thesis. HIF-1 also appears to play a major role in the IH-induced increase in MI size. In parallel, its myocardial activation is correlated with the apnea-hypopnea index in apnoeic, compared to non-apnoeic, patients with coronary heart disease. Therefore, HIF-1 activation could serve as a diagnostic marker of OSA in patients with cardiovascular risk. HIF 1 could also be a target for new therapeutic approaches, in complement or replacement of standard treatments.

A Síndrome da Apneia Obstrutiva do Sono (SAOS) é caracterizada por episódios repetitivos de obstrução da Via Aérea Superior (VAS) e sua patogênese está relacionada a anormalidades anatômicas da VAS. Algumas alterações esqueléticas da face favorecem a perda de permeabilidade da VAS, incluindo a inclinação do plano oclusal maior que a norma. A Cirurgia de Avanço Maxilomandibular (CAMM) já teve sua eficácia comprovada no tratamento da SAOS. O objetivo deste trabalho foi avaliar a influência da rotação anti-horária do plano oclusal na CAMM para tratamento de indivíduos portadores da SAOS e quantificar as alterações morfométricas produzidas na VAS e seus efeitos na SAOS. O método adotado foi o ensaio clínico prospectivo, com uma amostra composta por 38 participantes, sendo 23 homens (60,5%) e 15 mulheres (39,5%) com idades entre 21,7 e 55,4 anos (37,4 ± 9,2). Os indivíduos foram divididos em dois grupos: CAMM com rotação do plano oclusal CR (n=19) e CAMM sem rotação do plano oclusal SR (n=19). Todos os participantes realizaram uma tomografia computadorizada (TC) da VAS e polissonografia de noite toda, no pré e pós-operatório. No Grupo CR, a relação da influência da rotação anti-horária do plano oclusal no movimento do ponto B no eixo X mostrou forte correlação (r=0,78). A regressão linear foi estatisticamente significante (p<0,0001) e mostrou proporção de 0,71mm de avanço para cada grau de rotação anti-horária do ângulo do plano oclusal. A avaliação dos índices polissonográficos mostrou diferença na condição tempo pré e pós-cirúrgico, porém não houve diferença estatística entre os grupos. O volume total aumentou 44,7% no Grupo CR e 30,3% no Grupo SR. O volume retropalatal e volume retrolingual aumentaram 49% e 40,9% no Grupo CR e 42,9% e 15,2% no Grupo SR, respectivamente. A menor área axial no Grupo CR aumentou 91,7% na região RP e 97,4% na região RL; no Grupo SR, o aumento foi de 76,4% e 31%, respectivamente. A altura da via aérea diminuiu 5,9% e 2,6% nos grupos CR e SR, respectivamente. O Grupo CR, com rotação anti-horária do plano oclusal na CAMM, obteve melhores resultados em relação ao Grupo SR em todos os parâmetros morfométricos analisados: volume, área e medidas lineares na faringe, principalmente na região retrolingual. No sentido sagital, a cada grau de rotaçãoanti-horária do plano oclusal ocorreu a projeção de 0,71mm da mandíbula, justificando a maior abertura da região retrolingual da faringe, bem como uma maior redução do IAH, IA e IH / Obstructive Sleep Apnea Syndrome (OSAS) is characterized by repetitive episodes of upper airway (UAW) obstruction, and its pathogenesis is related to anatomical abnormalities of the UAW. Some skeletal changes in the face favor the loss of UAW permeability, including inclination of the occlusal plane greater than the norm. Maxillomandibular Advancement Surgery (MMAS) has already proven its efficacy in the treatment of OSAS. The objective of this study was to evaluate the influence of the counterclockwise rotation of the occlusal plane in the MMAS for treatment of individuals with OSAS, and to quantify the morphometric changes produced in the UAW and its effects on OSAS. The method used was the prospective clinical trial, with a sample composed of 38 participants, of which 23 were men (60.5%) and 15 were women (39.5%), between 21.7 and 55.4 years of age (37.4% ± 9.2). The individuals were divided into two groups: MMAS with rotation of the occlusal plane CR (n=19) and MMAS without rotation of the occlusal plane SR (n=19). All par-ticipants performed a UAW computed tomography (CT) and all-night polysomnography, pre and postoperatively. In the CR group, the relation of the influence of the counterclockwise rotation of the occlusal plane on the movement of point B on the X axis showed a strong correlation (r=0.78). The linear regression was statistically significant (p<0.0001) and showed a proportion of 0.71 mm of advance for each degree of counterclockwise rotation of the angle of the occlusal plane. The evaluation of polysomnographic indices showed a difference in pre and postsurgical time, but there was no statistical difference between the groups. The total volume increased 44.7% in the CR group and 30.3% in the SR group. The retropalatal (RP) volume and retrolingual (RL) volume increased 49% and 40.9% in the CR group and 42.9% and 15.2% in the SR group, respectively. The smaller axial area in the CR group increased 91.7% in the RP region and 97.4% in the RL region; in the SR group the increase was 76.4% and 31%, respectively. The airway height decreased 5.9% and 2.6% in the CR and SR groups, respectively. The CR group obtained better results in relation to the SR group in all the morphometric parameters analyzed: volume, area and linear measurements in the pharynx, mainly in the RL region. In the sagittal sense, at each degree of counterclockwise rotation of the occlusal plane, the projection of 0.71 mm of themandible occurred, justifying the greater opening of the RL region of the pharynx, as well as a greater reduction of AHI, IA and HI

Made available in DSpace on 2016-01-26T12:51:37Z (GMT). No. of bitstreams: 1 nelsoncolombini_tese.pdf: 1052278 bytes, checksum: 65caf5c2304f80f9167fa51d736325f5 (MD5) Previous issue date: 2010-03-22 / To describe the results obtained by the Maxillo Mandibular Advancement (MMA), associated to a glossectomy of Medium Line (GML) to CO2 Laser in the surgical treatment of Obstructive Sleep Apnea-Hypoapnea Syndrome (ASOSH), from moderate to severe, with adequate analysis of macroscstruture e microstructure of the sleep. Casuistics and Method: In the period from February 2005 to December 2008, 22 sequencial patients with ASOSH, from moderate to severe, with or without maxillary mandibular bone alterations, were selected. These patients were submitted to MMP plus GML using a CO2 laser. All patients underwent clinical, polissonographic and cephalometric evaluations. The polissonographic parameters used were: IAH, MD, Minimum SAT O2% < measured in minutes, sleep stages N1, N2, N3 and REM, preoperative and postoperative. The cephalometric parameters used were: SNA, SNB, PAS, PP2 PP2, preoperative and postoperative. Results: Evaluation of eventual differences in the preoperative and postoperative moments were investigated with the appropriate statistical tools. The surgical treatment proved to be effective in 8, out of 22 of the cases (36.36%), according to international criteria of normality. On the other hand, in these patients the IAH was not the best parameter to evaluate the therapeutic success. The MD (68.18% of improvement), stage N3 (59.09% of improvement) and Minimum SAT O2% < 90 measured in minutes (81.81% of improvement) demonstrated that they were the best instruments for characterizing the laboratorial control of the disease. Discussion: The MMA has expanded the dimensions of the pharynx and the hypopharynx. The GLM was associated in order to maximize the VAS, improve the stability of the dental occlusion, as well as the function of the temporomandibular joint, reducing the morbidity of the procedure. A postoperative evaluation with polysomnography showed improvements of the parameters in both macro and microarchitecture of the sleep (in relation to preoperative findings), besides proving that the IAH is not the best parameter for a postoperative evaluation (this applies to the patients of this series). Conclusions: The surgical treatment performed with MMA, associated to the GLM with CO2 laser was effective to treat patients with from ASOSH : - The improvement using the most accepted parameter by the international community (IAH < 5/ hour) was 8 out of the 22 (36.36%); - The IAH was not the best instrument to evaluate the control of the disease; - Were MD, stage N3 and Minimum SAT O2% < 90 measured in minutes showed that they are good indicators of the control of the disease (postoperative moment); - The Minimum SAT O2% < 90 measured in minutes was the best parameter in the evaluation of the surgical treatment (18/22 or 81.81%). / Descrever os resultados obtidos pelo Avanço Maxilo- Mandibular (AMM) associados à Glossectomia de Linha Média (GLM) a Laser CO2 no tratamento cirúrgico da Síndrome da Apnéia/Hipopnéia Obstrutiva do Sono (SAHOS) moderada e severa, usando instrumentos estatísticos que avaliem a arquiquetura do sono quanto à macro e micro estrutura para adequada e real avaliação dos resultados obtidos pelo tratamento proposto. Casuística e Método: No período de fevereiro de 2005 a dezembro de 2008 foram selecionados 22 pacientes seqüenciais portadores de SAHOS moderada e severa, com ou sem alterações esqueléticas maxilo-mandibulares. Estes pacientes foram submetidos à AMM, mais GLM com laser de CO2. Todos pacientes tiveram avaliação clínica, polissonográfica e cefalométrica. Os parâmetros polissonográficos utilizados foram: IAH, MD, SAT O2 % Mínima < 90 medida em minutos, estágios do sono N1, N2, N3 e REM, pré e pósoperatório. Os parâmetros cefalométricos utilizados foram: SNA, SNB, PAS, PP2 PP2 pré e pós-operatório. Resultados: Avaliação de eventuais diferenças nos momentos pré e pós-operatório foram investigadas com ferramenta estatística apropriada. O tratamento cirúrgico mostrou-se eficaz em 8/22 (36,36%) dos casos, segundo critérios internacionais de normalidade. Por outro lado nestes pacientes o IAH não foi o melhor parâmetro para avaliar sucesso terapêutico. MD (68,18% melhora), estágio N3 (59,09% de melhora) e SAT O2% Mínima < 90 medida em minutos (81,81% de melhora) mostraram-se melhores instrumentos para caracterizar controle laboratorial da enfermidade.Discussão: O AMM ampliou as dimensões da faringe e hipofaringe. A GLM foi associada para maximizar a VAS, aumentar a estabilidade da oclusão dentária e função da articulação têmporo-mandibular, reduzindo a morbidade do procedimento. Avaliação pós-operatória com polissonografia demonstrou melhora de parâmetros de macro e micro-arquitetura do sono (em relação aos achados pré-operatórios), além de comprovar não ser o IAH o melhor parâmetro para avaliação pós-operatória (isto para os pacientes desta série). Conclusões: O tratamento cirúrgico com AMM associado à GLM com laser de CO2 foi eficaz para tratar pacientes com SAHOS: A melhora utilizando o parâmetro mais aceito pela comunidade internacional (IAH < 5/hora) foi de 8/22 (36,36%); IAH não foi o melhor instrumento para avaliação do controle da enfermidade; MD, estágio N3 e SAT O2% Mínima < 90 medida em minutos mostraram-se bons indicadores de controle da enfermidade (momento pósoperatório); SAT O2% Mínima < 90 medida em minutos foi o melhor parâmetro na avaliação do tratamento cirúrgico (18/22 ou 81,81%).