Schnarchgeräusche treten als Symptom bei schlafbezogenen Atemstörungen auf. Hierbei wird vermutet, dass bei unterschiedlichen Atemstörungen verschiedenartige Schnarchgeräusche entstehen. Ein Zusammenhang zwischen Schnarchgeräuschen und klinischen, HNO-ärztlichen Untersuchungsbefunden wird ebenso diskutiert. Ziel der Arbeit war es, klinische und polysomnographische Befunde mit den analysierten Schnarchgeräuschen zu korrelieren, um Aussagen über die Schwere einer schlafbezo-genen Atemstörung und über die pathologischen Befunde des oberen Respirations-traktes auf Grund einer Frequenzanalyse der Schnarchgeräusche machen zu können. An der Studie nahmen 58 Patienten mit Verdacht auf schlafbezogene Atemstörung teil (8 weibliche und 50 männliche Patienten). Diese Patienten wurden im Rahmen einer HNO-ärztlichen Untersuchung auf anatomische und pathologische Verhältnisse der oberen Luft- und Speisewege untersucht. Hierbei wurden im speziellen die Tonsillen, die Uvula, das Velum, die Nasenmuscheln und die Pharynxlängsfalten auf Hyperplasien untersucht. Zudem wurde das Septum und die Zunge zur mandibulären Okklusions-ebene, klassifiziert durch den Malampatti-Index, auf Fehlstellungen in Augenschein genommen. Die Inspektion der oberen Luft- und Speisewege am wachen Patienten ist als eine statische Untersuchung zu werten. Die Patienten wurden im Schlaflabor polysomnographisch untersucht und die Schnarch-geräusche simultan aufgezeichnet. Durch die Fast-Fourier Analyse wurden die Frequenz-intensitätsmaxima der Schnarchgeräusche ermittelt. Die Ergebnisse der klinischen Untersuchung wurden mit den Intensitätsmaxima der einzelnen Schnarchgeräuschen der jeweiligen Patienten korreliert. Zudem wurden die polysomnographischen Untersuchungsergebnisse mit den Frequenzen der beiden Intensitätsmaxima in einer statistischen Auswertung miteinander verglichen. In der vorliegenden Studie zeigt sich, dass keine Korrelation zwischen den einzelnen klinischen Untersuchungsergebnissen und der Schnarchfrequenz der einzelnen Patienten besteht. Mit Hilfe der Frequenzanalyse in Zusammenhang mit der polysomnographischen Untersuchung konnten Rückschlüsse auf die Schwere der schlafbezogenen Atemstörungen gezogen werden. Es zeigte sich, dass ein Zusammenhang zwischen den Intensitätsmaxima der Frequenzanalyse und dem AHI der Patienten besteht. Je höher die Frequenz der Intensitätsmaxima war, desto höher war der Anstieg des AHI. Von diesem Ergebnis ausgehend wird gezeigt, dass bei Patienten mit OSAS bei einem AHI>15 die Schnarchfrequenz zwischen 2000 und 5000 Hz liegt. Je größer die schlafbezogene Atemstörung ist, desto hochfrequenter sind die Schnarchgeräusche. Zudem konnten auch schlafbezogene Atemstörungen bei Patienten, bei denen der AHI<15 und die Schnarchfrequenz größer als 1000 Hz war, mit Hilfe der Frequenz-analyse einem potentiellen UARS zugeschrieben werden. Patienten mit tieffrequenten Schnarchgeräuschen und einem niedrigen AHI werden in die Kategorie primäres Schnarchen eingeordnet. Das Ausmaß einer schlafbezogenen Atemstörung kann mit Hilfe der Frequenzanalyse der Schnarchgeräusche bestimmt werden. Die Frequenzanalyse von Schnarchgeräuschen stellt eine leicht durchzuführende, nicht-invasive Methode zur Topodiagnostik von Schnarchen dar und könnte im diagnostischen Procedere bei schlafbezogenen Atmenstörungen möglicherweise in Zukunft einen festen Platz einnehmen.

Os softwares de avaliação em três dimensões revolucionaram os planejamentos da cirurgia ortognática. Com eles é possível realizar desde simulações dos movimentos cirúrgicos, até avaliação das vias aéreas superiores (VAS) em volume e área, o que não era possível nas radiografias bidimensionais. Muitos pacientes recorrem à cirurgia ortognática com finalidade de melhorar a oclusão e a estética. Dependendo da movimentação cirúrgica, o espaço aéreo pode aumentar ou diminuir. O presente trabalho tem como objetivo avaliar as alterações de área e de volume do espaço aéreo faríngeo em pacientes submetidos à cirurgia ortognática de avanço bimaxilar. Foi realizada a análise da área axial mínima e do volume aéreo superior pré-operatório (T0) e pós-operatório (T1) de 50 pacientes, sendo 17 do sexo masculino e 33 do sexo feminino, com média de idade de 36,6 (±12,1) anos. As avaliações foram feitas através de tomografia computadorizada de feixe cônico, utilizando o Programa Nemoceph 3DOS. Foi utilizado o teste ´´t`` pareado para comparar os dados pré e pós-operatórios de volume e o teste de Wilcoxon para comparar os dados pré e pós-operatório de área axial mínima. Todos os testes foram realizados com o programa Statistica, adotando um nível de significância de 5%. No estudo do erro do método, não houve erro casual nem sistemático entre a primeira e a segunda aferição das variáveis (p > 0,05 em todas as medidas). A cirurgia de avanço bimaxilar apresentou uma média de 70,46% (59,38) de aumento volumétrico e uma mediana de 61,27% de aumento na área axial mínima, onde a mesma variou de -22,50% à 659,06%. Com este trabalho, conclui-se que o avanço bimaxilar proporciona um aumento significativo de volume e área axial mínima das vias aéreas superiores, porém este ganho não é homogêneo em todos os pacientes. / Software in three dimensions has come to revolutionize the orthognathic surgery planning. With them it is possible to perform from simulations of the surgical movements, until evaluation of the upper airways in volume and area, which wasnt possible in two dimensions software. Many patients resort to orthognathic surgery in order to improve occlusion and facial profile. Depending of the surgical movements, the airway space may increase or decrease. The aim of the study is to evaluate the changes in the area and volume of the pharyngeal airway space in patients submitted to bimaxillary advancement in orthognathic surgery. It was analyzed the minimum axial area and the volume of the pharyngeal airway space preoperative (T0) and postoperative (T1) air volumes of 50 patients, which 17 were male and 33 were female, with a mean age of 36.6 (± 12.1) years. The evaluations were done using Cone-beam computed tomography in Nemoceph 3D-OS Program. It was used the paired t test to compare the pre and postoperative volume data and the Wilcoxon test to compare the pre and postoperative data of the minimal axial area. All the tests were performed with the Statistica program, adopting a level of significance of 5%. In the study of the method error, there was no casual or systematic error between the first and second measurements of the variables (p> 0.05 in all measurements). The bimaxillary advancement surgery presented a mean of 70.46% (59.38) of volumetric increase and a median increase of 61.27% in the minimum axial area, that varied from -22.50% to 659.06%. In this study, it was concluded that bimaxillary advancement provides a significant increase in volume and minimum axial area of the upper airways, but the increase it isnt homogeneous in all patients.

A fibrose cística (FC) é uma doença genética irreversível, mas os avanços no tratamento têm aumentado a expectativa de vida dos pacientes. O acometimento das vias aéreas superiores, principalmente por alteraçõesdos seios paranasais aos exames de imagem, é prevalente nestes pacientes, embora muitos apresentem poucos sintomas. Poucos trabalhos abordam as características e o manejo das doenças nasossinusais em pacientes adultos com FC. O acometimento nasossinusal, além de ter provável influência nas exacerbações pulmonares, pode afetar negativamente a qualidade de vida.Objetivos:(1) Identificar as características e o grau de acometimento das vias aéreas superiores;(2) Estabelecer associações com as manifestações clínicas e determinar preditores na pontuação do questionário SNOT-22.Métodos: A metodologia adotada para a presenteteseconsistiu na elaboração de três artigos: (1) Artigo original de revisão sistemática sobre achados tomográficos de seios paranasais em pacientes com FC; (2) Artigo de revisão narrativa sobre diagnóstico e tratamento da rinossinusite crônica (RSC) em pacientes com FC; e (3) Artigo original de estudo transversal e prospectivo sobre manifestações nasossinusais e avaliação da qualidade de vida pelo questionário SNOT-22 em pacientes adultos com FC. A revisão da literatura fundamentou-se na busca por artigos com as evidências mais recentes sobre o assunto nos bancos de dados Medline, Embase, Web of Science, Lilacs, Scielo e Cochrane. O estudo transversal consistiu na avaliação de pacientes adultos com FC clinicamente estáveis, sendo submetidos a avaliação clínica, exames de função pulmonar, endoscopia nasal e tomografia computadorizada de seios da face. Todos os pacientes responderam o questionário SNOT-22.Resultados: A literatura relata que os achados tomográficos mais comuns nos pacientes com FC são a opacificação dos seios paranasais, a presença de hipoplasia ou aplasia dos seios frontal e esfenoidal, o subdesenvolvimento pansinusal e a medialização da parede nasal lateral. Quando sintomática, a RSC com pólipos nasais pode afetar a qualidade de vida e desencadear as exacerbações pulmonares, já que os seios paranasais podem ser colonizados por bactérias patogênicas, principalmente a Pseudomonas aeruginosa. Esta bactéria tem papel crucial na morbidade e mortalidade após o transplante pulmonar em pacientes com FC. Embora o tratamento clínico das vias aéreas superiores seja indicado no manejo inicial, a indicação é muitas vezes extrapolada de estudos sobre RSC na população geral. No estudo original da tese, uma idade média maior, idade de diagnóstico mais tardio, sintomas de rinite crônica e critérios clínicos para rinossinusite foram mais observados em pacientes com pontuação maior no SNOT-22. Na análise de regressão múltipla, houve associação positiva da idade e presença de P. aeruginosa no escarro com a pontuação no SNOT-22.Em concordância com a literatura, o estudo também revelou uma alta prevalência de alterações tomográficas, sendo a aplasia/hipoplasia do seio esfenoidal o achado mais frequente.Conclusão:Apesar dasinúmeras alterações tomográficas, os pacientes relatam pouca intensidade dos sintomas nasossinusais. A idade e a presença da P. aeruginosa foram fatores associados a maior pontuação no SNOT-22. Mais estudos são necessários para compreender melhor o acometimento das vias aéreas superiores e melhorar o manejo da RSC na FC, a fim de preservar a função pulmonar, mas evitandoa indicação de procedimentos invasivos e a exposição radiológica desnecessária. / Cystic fibrosis (CF) is an irreversible genetic disease, but advances in treatment have increased the life expectancy of patients. Involvement of upper airways, especially by pathological changes in sinus imaging, is prevalent in these patients, although few exhibit symptoms. There are few studies about characteristics and management of sinonasal diseases in adult CF patients. Sinonasal involvement may initiate pulmonary exacerbations and negatively affect quality of life. Objectives: To identify characteristics and degree of involvement of upper airways, establishing associations with clinical manifestations and determine predictors in SNOT-22 questionnaire score. Methods: The methodology adopted for this thesis included the elaboration of three articles: (1) original systematic review article aboutparanasal sinuses CT findings in CF patients; (2) narrative review article about diagnosis and treatment of chronic rhinosinusitis (CRS) in CF patients; and (3) original article about crosssectional prospective study of sinonasal manifestations and assessment of quality of life by SNOT-22 questionnaire in adult CF patients. The literature review was based on search of articles with the latest evidence on the subject in databases Medline, Embase, Web of Science, Lilacs, Scielo and Cochrane. The cross-sectional study consisted in evaluation of adult CF patients clinically stable. They underwent clinical evaluation, pulmonary function tests, nasal endoscopy and paranasal sinuses CT scan. All patients answered SNOT-22 questionnaire. Results:Literature reports that the most common CT findings in CF patients areparanasal sinuses opacification, presence of sphenoid and frontal sinuses hypoplasia or aplasia, pansinusal underdevelopment and medial bulging oflateral nasal wall. When symptomatic, CRS with nasal polyps can affect quality of life and trigger pulmonary exacerbations. It is explained since paranasal sinuses may be colonized by pathogenic bacteria, especially Pseudomonas aeruginosa. This bacterium plays a crucial role in morbidity and mortality after lung transplantation in CF patients. Clinical treatment of upper airways is indicated as first management, but this indication is often extrapolated from studies on CRS in general population. In the original study, a high average age, age of later diagnosis, symptoms of chronic rhinitis and clinical criteria for rhinosinusitis were more frequently observed in patients with high SNOT-22 scores. In multiple regression analysis, there was a positive association between age and the presence of P. aeruginosa in sputum with the SNOT-22 score. According to literature, this study also revealed a high prevalence of tomographic alterations.Sphenoid sinus aplasia or hypoplasia was the most common finding. Conclusion: Despite CT findings, patients report little intensity of sinonasal symptoms. Age and presence of P. aeruginosa were associated with higher SNOT-22 scores. The most important is to preserve lung function, but avoinding unnecessary invasive procedures and radiation exposure. More studies are needed to better understand the involvement of upper airways and improve management of CRS in CF.

L'air que nous respirons au travers des voies aériennes supérieures est essentiel pour la vie et pour la communication orale. Dans les études de production de parole humaine, l'écoulement d'air est en général extrêmement simplifié. Or cet écoulement est complexe car turbulent et fortement sensible aux conditions limites. Dans le cas de la production de fricatives non voisées, une description plus fine de l'écoulement s'avère nécessaire pour pouvoir modéliser correctement les mécanismes aéroacoustiques sous-jacents. A l'aide d'expériences in-vitro et de simulations numériques, l'objectif de cette thèse est de contribuer à la modélisation et la caractérisation aéroacoustique d'écoulements dans des configurations de type canal avec obstacle(s), avec application à la production de fricatives non voisées. Une attention toute particulière est portée à l'influence des conditions limites et à la turbulence. / Airflow through the human upper airways is essential for life and for oral communication. In studies dealing with human speech production, airflow is mostly severely simplified. Nevertheless, this airflow is complex owing to turbulence and extreme sensitivity to boundary conditions. Recently, deeper attention has been given to characterize the airflow in the case of unvoiced fricative production and the necessity of obtaining a more detailed flow description has been outlined. With the aid of in-vitro experiments and numerical simulations, the aim of the current PhD research is to contribute to the aeroacoustic modeling and characterization of airflows through various configurations of ducts with obstacle(s), relevant for unvoiced fricative speech production. Special interest is given to the influence of boundary conditions and to turbulence.

A fibrose cística (FC) é uma doença genética irreversível, mas os avanços no tratamento têm aumentado a expectativa de vida dos pacientes. O acometimento das vias aéreas superiores, principalmente por alteraçõesdos seios paranasais aos exames de imagem, é prevalente nestes pacientes, embora muitos apresentem poucos sintomas. Poucos trabalhos abordam as características e o manejo das doenças nasossinusais em pacientes adultos com FC. O acometimento nasossinusal, além de ter provável influência nas exacerbações pulmonares, pode afetar negativamente a qualidade de vida.Objetivos:(1) Identificar as características e o grau de acometimento das vias aéreas superiores;(2) Estabelecer associações com as manifestações clínicas e determinar preditores na pontuação do questionário SNOT-22.Métodos: A metodologia adotada para a presenteteseconsistiu na elaboração de três artigos: (1) Artigo original de revisão sistemática sobre achados tomográficos de seios paranasais em pacientes com FC; (2) Artigo de revisão narrativa sobre diagnóstico e tratamento da rinossinusite crônica (RSC) em pacientes com FC; e (3) Artigo original de estudo transversal e prospectivo sobre manifestações nasossinusais e avaliação da qualidade de vida pelo questionário SNOT-22 em pacientes adultos com FC. A revisão da literatura fundamentou-se na busca por artigos com as evidências mais recentes sobre o assunto nos bancos de dados Medline, Embase, Web of Science, Lilacs, Scielo e Cochrane. O estudo transversal consistiu na avaliação de pacientes adultos com FC clinicamente estáveis, sendo submetidos a avaliação clínica, exames de função pulmonar, endoscopia nasal e tomografia computadorizada de seios da face. Todos os pacientes responderam o questionário SNOT-22.Resultados: A literatura relata que os achados tomográficos mais comuns nos pacientes com FC são a opacificação dos seios paranasais, a presença de hipoplasia ou aplasia dos seios frontal e esfenoidal, o subdesenvolvimento pansinusal e a medialização da parede nasal lateral. Quando sintomática, a RSC com pólipos nasais pode afetar a qualidade de vida e desencadear as exacerbações pulmonares, já que os seios paranasais podem ser colonizados por bactérias patogênicas, principalmente a Pseudomonas aeruginosa. Esta bactéria tem papel crucial na morbidade e mortalidade após o transplante pulmonar em pacientes com FC. Embora o tratamento clínico das vias aéreas superiores seja indicado no manejo inicial, a indicação é muitas vezes extrapolada de estudos sobre RSC na população geral. No estudo original da tese, uma idade média maior, idade de diagnóstico mais tardio, sintomas de rinite crônica e critérios clínicos para rinossinusite foram mais observados em pacientes com pontuação maior no SNOT-22. Na análise de regressão múltipla, houve associação positiva da idade e presença de P. aeruginosa no escarro com a pontuação no SNOT-22.Em concordância com a literatura, o estudo também revelou uma alta prevalência de alterações tomográficas, sendo a aplasia/hipoplasia do seio esfenoidal o achado mais frequente.Conclusão:Apesar dasinúmeras alterações tomográficas, os pacientes relatam pouca intensidade dos sintomas nasossinusais. A idade e a presença da P. aeruginosa foram fatores associados a maior pontuação no SNOT-22. Mais estudos são necessários para compreender melhor o acometimento das vias aéreas superiores e melhorar o manejo da RSC na FC, a fim de preservar a função pulmonar, mas evitandoa indicação de procedimentos invasivos e a exposição radiológica desnecessária. / Cystic fibrosis (CF) is an irreversible genetic disease, but advances in treatment have increased the life expectancy of patients. Involvement of upper airways, especially by pathological changes in sinus imaging, is prevalent in these patients, although few exhibit symptoms. There are few studies about characteristics and management of sinonasal diseases in adult CF patients. Sinonasal involvement may initiate pulmonary exacerbations and negatively affect quality of life. Objectives: To identify characteristics and degree of involvement of upper airways, establishing associations with clinical manifestations and determine predictors in SNOT-22 questionnaire score. Methods: The methodology adopted for this thesis included the elaboration of three articles: (1) original systematic review article aboutparanasal sinuses CT findings in CF patients; (2) narrative review article about diagnosis and treatment of chronic rhinosinusitis (CRS) in CF patients; and (3) original article about crosssectional prospective study of sinonasal manifestations and assessment of quality of life by SNOT-22 questionnaire in adult CF patients. The literature review was based on search of articles with the latest evidence on the subject in databases Medline, Embase, Web of Science, Lilacs, Scielo and Cochrane. The cross-sectional study consisted in evaluation of adult CF patients clinically stable. They underwent clinical evaluation, pulmonary function tests, nasal endoscopy and paranasal sinuses CT scan. All patients answered SNOT-22 questionnaire. Results:Literature reports that the most common CT findings in CF patients areparanasal sinuses opacification, presence of sphenoid and frontal sinuses hypoplasia or aplasia, pansinusal underdevelopment and medial bulging oflateral nasal wall. When symptomatic, CRS with nasal polyps can affect quality of life and trigger pulmonary exacerbations. It is explained since paranasal sinuses may be colonized by pathogenic bacteria, especially Pseudomonas aeruginosa. This bacterium plays a crucial role in morbidity and mortality after lung transplantation in CF patients. Clinical treatment of upper airways is indicated as first management, but this indication is often extrapolated from studies on CRS in general population. In the original study, a high average age, age of later diagnosis, symptoms of chronic rhinitis and clinical criteria for rhinosinusitis were more frequently observed in patients with high SNOT-22 scores. In multiple regression analysis, there was a positive association between age and the presence of P. aeruginosa in sputum with the SNOT-22 score. According to literature, this study also revealed a high prevalence of tomographic alterations.Sphenoid sinus aplasia or hypoplasia was the most common finding. Conclusion: Despite CT findings, patients report little intensity of sinonasal symptoms. Age and presence of P. aeruginosa were associated with higher SNOT-22 scores. The most important is to preserve lung function, but avoinding unnecessary invasive procedures and radiation exposure. More studies are needed to better understand the involvement of upper airways and improve management of CRS in CF.

Os softwares de avaliação em três dimensões revolucionaram os planejamentos da cirurgia ortognática. Com eles é possível realizar desde simulações dos movimentos cirúrgicos, até avaliação das vias aéreas superiores (VAS) em volume e área, o que não era possível nas radiografias bidimensionais. Muitos pacientes recorrem à cirurgia ortognática com finalidade de melhorar a oclusão e a estética. Dependendo da movimentação cirúrgica, o espaço aéreo pode aumentar ou diminuir. O presente trabalho tem como objetivo avaliar as alterações de área e de volume do espaço aéreo faríngeo em pacientes submetidos à cirurgia ortognática de avanço bimaxilar. Foi realizada a análise da área axial mínima e do volume aéreo superior pré-operatório (T0) e pós-operatório (T1) de 50 pacientes, sendo 17 do sexo masculino e 33 do sexo feminino, com média de idade de 36,6 (±12,1) anos. As avaliações foram feitas através de tomografia computadorizada de feixe cônico, utilizando o Programa Nemoceph 3DOS. Foi utilizado o teste ´´t`` pareado para comparar os dados pré e pós-operatórios de volume e o teste de Wilcoxon para comparar os dados pré e pós-operatório de área axial mínima. Todos os testes foram realizados com o programa Statistica, adotando um nível de significância de 5%. No estudo do erro do método, não houve erro casual nem sistemático entre a primeira e a segunda aferição das variáveis (p > 0,05 em todas as medidas). A cirurgia de avanço bimaxilar apresentou uma média de 70,46% (59,38) de aumento volumétrico e uma mediana de 61,27% de aumento na área axial mínima, onde a mesma variou de -22,50% à 659,06%. Com este trabalho, conclui-se que o avanço bimaxilar proporciona um aumento significativo de volume e área axial mínima das vias aéreas superiores, porém este ganho não é homogêneo em todos os pacientes. / Software in three dimensions has come to revolutionize the orthognathic surgery planning. With them it is possible to perform from simulations of the surgical movements, until evaluation of the upper airways in volume and area, which wasnt possible in two dimensions software. Many patients resort to orthognathic surgery in order to improve occlusion and facial profile. Depending of the surgical movements, the airway space may increase or decrease. The aim of the study is to evaluate the changes in the area and volume of the pharyngeal airway space in patients submitted to bimaxillary advancement in orthognathic surgery. It was analyzed the minimum axial area and the volume of the pharyngeal airway space preoperative (T0) and postoperative (T1) air volumes of 50 patients, which 17 were male and 33 were female, with a mean age of 36.6 (± 12.1) years. The evaluations were done using Cone-beam computed tomography in Nemoceph 3D-OS Program. It was used the paired t test to compare the pre and postoperative volume data and the Wilcoxon test to compare the pre and postoperative data of the minimal axial area. All the tests were performed with the Statistica program, adopting a level of significance of 5%. In the study of the method error, there was no casual or systematic error between the first and second measurements of the variables (p> 0.05 in all measurements). The bimaxillary advancement surgery presented a mean of 70.46% (59.38) of volumetric increase and a median increase of 61.27% in the minimum axial area, that varied from -22.50% to 659.06%. In this study, it was concluded that bimaxillary advancement provides a significant increase in volume and minimum axial area of the upper airways, but the increase it isnt homogeneous in all patients.

A fibrose cística (FC) é uma doença genética irreversível, mas os avanços no tratamento têm aumentado a expectativa de vida dos pacientes. O acometimento das vias aéreas superiores, principalmente por alteraçõesdos seios paranasais aos exames de imagem, é prevalente nestes pacientes, embora muitos apresentem poucos sintomas. Poucos trabalhos abordam as características e o manejo das doenças nasossinusais em pacientes adultos com FC. O acometimento nasossinusal, além de ter provável influência nas exacerbações pulmonares, pode afetar negativamente a qualidade de vida.Objetivos:(1) Identificar as características e o grau de acometimento das vias aéreas superiores;(2) Estabelecer associações com as manifestações clínicas e determinar preditores na pontuação do questionário SNOT-22.Métodos: A metodologia adotada para a presenteteseconsistiu na elaboração de três artigos: (1) Artigo original de revisão sistemática sobre achados tomográficos de seios paranasais em pacientes com FC; (2) Artigo de revisão narrativa sobre diagnóstico e tratamento da rinossinusite crônica (RSC) em pacientes com FC; e (3) Artigo original de estudo transversal e prospectivo sobre manifestações nasossinusais e avaliação da qualidade de vida pelo questionário SNOT-22 em pacientes adultos com FC. A revisão da literatura fundamentou-se na busca por artigos com as evidências mais recentes sobre o assunto nos bancos de dados Medline, Embase, Web of Science, Lilacs, Scielo e Cochrane. O estudo transversal consistiu na avaliação de pacientes adultos com FC clinicamente estáveis, sendo submetidos a avaliação clínica, exames de função pulmonar, endoscopia nasal e tomografia computadorizada de seios da face. Todos os pacientes responderam o questionário SNOT-22.Resultados: A literatura relata que os achados tomográficos mais comuns nos pacientes com FC são a opacificação dos seios paranasais, a presença de hipoplasia ou aplasia dos seios frontal e esfenoidal, o subdesenvolvimento pansinusal e a medialização da parede nasal lateral. Quando sintomática, a RSC com pólipos nasais pode afetar a qualidade de vida e desencadear as exacerbações pulmonares, já que os seios paranasais podem ser colonizados por bactérias patogênicas, principalmente a Pseudomonas aeruginosa. Esta bactéria tem papel crucial na morbidade e mortalidade após o transplante pulmonar em pacientes com FC. Embora o tratamento clínico das vias aéreas superiores seja indicado no manejo inicial, a indicação é muitas vezes extrapolada de estudos sobre RSC na população geral. No estudo original da tese, uma idade média maior, idade de diagnóstico mais tardio, sintomas de rinite crônica e critérios clínicos para rinossinusite foram mais observados em pacientes com pontuação maior no SNOT-22. Na análise de regressão múltipla, houve associação positiva da idade e presença de P. aeruginosa no escarro com a pontuação no SNOT-22.Em concordância com a literatura, o estudo também revelou uma alta prevalência de alterações tomográficas, sendo a aplasia/hipoplasia do seio esfenoidal o achado mais frequente.Conclusão:Apesar dasinúmeras alterações tomográficas, os pacientes relatam pouca intensidade dos sintomas nasossinusais. A idade e a presença da P. aeruginosa foram fatores associados a maior pontuação no SNOT-22. Mais estudos são necessários para compreender melhor o acometimento das vias aéreas superiores e melhorar o manejo da RSC na FC, a fim de preservar a função pulmonar, mas evitandoa indicação de procedimentos invasivos e a exposição radiológica desnecessária. / Cystic fibrosis (CF) is an irreversible genetic disease, but advances in treatment have increased the life expectancy of patients. Involvement of upper airways, especially by pathological changes in sinus imaging, is prevalent in these patients, although few exhibit symptoms. There are few studies about characteristics and management of sinonasal diseases in adult CF patients. Sinonasal involvement may initiate pulmonary exacerbations and negatively affect quality of life. Objectives: To identify characteristics and degree of involvement of upper airways, establishing associations with clinical manifestations and determine predictors in SNOT-22 questionnaire score. Methods: The methodology adopted for this thesis included the elaboration of three articles: (1) original systematic review article aboutparanasal sinuses CT findings in CF patients; (2) narrative review article about diagnosis and treatment of chronic rhinosinusitis (CRS) in CF patients; and (3) original article about crosssectional prospective study of sinonasal manifestations and assessment of quality of life by SNOT-22 questionnaire in adult CF patients. The literature review was based on search of articles with the latest evidence on the subject in databases Medline, Embase, Web of Science, Lilacs, Scielo and Cochrane. The cross-sectional study consisted in evaluation of adult CF patients clinically stable. They underwent clinical evaluation, pulmonary function tests, nasal endoscopy and paranasal sinuses CT scan. All patients answered SNOT-22 questionnaire. Results:Literature reports that the most common CT findings in CF patients areparanasal sinuses opacification, presence of sphenoid and frontal sinuses hypoplasia or aplasia, pansinusal underdevelopment and medial bulging oflateral nasal wall. When symptomatic, CRS with nasal polyps can affect quality of life and trigger pulmonary exacerbations. It is explained since paranasal sinuses may be colonized by pathogenic bacteria, especially Pseudomonas aeruginosa. This bacterium plays a crucial role in morbidity and mortality after lung transplantation in CF patients. Clinical treatment of upper airways is indicated as first management, but this indication is often extrapolated from studies on CRS in general population. In the original study, a high average age, age of later diagnosis, symptoms of chronic rhinitis and clinical criteria for rhinosinusitis were more frequently observed in patients with high SNOT-22 scores. In multiple regression analysis, there was a positive association between age and the presence of P. aeruginosa in sputum with the SNOT-22 score. According to literature, this study also revealed a high prevalence of tomographic alterations.Sphenoid sinus aplasia or hypoplasia was the most common finding. Conclusion: Despite CT findings, patients report little intensity of sinonasal symptoms. Age and presence of P. aeruginosa were associated with higher SNOT-22 scores. The most important is to preserve lung function, but avoinding unnecessary invasive procedures and radiation exposure. More studies are needed to better understand the involvement of upper airways and improve management of CRS in CF.

La délivrance de médicaments lors de la mise en œuvre de thérapies inhalées est dépendante de nombreux facteurs. Parmi ceux-ci la morphologie des voies aériennes supérieures(VAS) et en particulier celle de la région glottique est déterminante dans les mécanismes de dépôt de particules par impaction inertielle. Dans le cadre de ce travail, il est examiné d’une part la dynamique glottique durant différentes modalités de respiration et d’autre part déterminé numériquement l’effet de ces mouvements et des conditions de respiration associées sur le dépôt des aérosols dans les VAS.Une étude clinique a été menée dans un premier temps sur un panel de 20 sujets sains (10 hommes et 10 femmes) au sein du service ORL de l’hôpital de la Timone à Marseille pour déterminer le mouvement glottique durant différentes tâches de ventilation allant d’une respiration normale avec moins de 20 cycles/min à une ventilation accélérée jusqu’à 90 cycles/min. L’acquisition des mouvements glottiques a été réalisée par imagerie numérique durant un examen de laryngoscopie avec mesure simultanée des débits associés aux différentes tâches de respiration.Les mesures expérimentales montrent que la géométrie glottique varie pendant la respiration en fonction de la tâche de respiration, du volume courant et de la fréquence respiratoire. Une étude statistique a permis d’isoler deux comportements types l’un où l’aire glottique demeure sensiblement constante durant la respiration et l’autre ou une variation de cette même aire est observée. Sur ce dernier groupe d’individus la variation d’aire maximale observée sur les hommes est de 26%, l’ouverture maximale étant atteinte durant la phase d’inspiration et l’aire minimale durant l’expiration.Ces résultats, ainsi que des données anatomiques, ont permis de construire un modèle géométrique idéalisé des VAS. Ce modèle reproduit fidèlement les principales singularités des voies extrathoraciques en apportant un grand soin à la description de la région glottique. Le transport et le dépôt d’aérosols dans ce modèle a été étudié en ayant recours à des simulations numériques3D de l’écoulement cyclique. Une étude paramétrique a permis d’évaluer l’influence sur le dépôt de l’écoulement cyclique, de la nature du gaz porteur (Air vs mélange d’hélium-oxygène), de la prise en compte de la dynamique glottique et de la taille des particules.Les résultats mettent principalement en évidence une nette diminution de la part extrathoracique du travail respiratoire lors de l’emploi du mélange He-O2 et un écoulement de type jet en aval de la glotte durant l’inspiration associé à une recirculation sous le plancher glottique. Le mécanisme de dépôt principal étant l’impaction inertielle (pour les tailles des particules 1 - 10μm)le zone principale de dépôt est situé dans l’oropahrynx, quelles que soient les conditions pendant inspiration. La fraction de dépôt augmente rapidement avec le diamètre des particules atteignant près de 80% pour les particules de 10μm et diminuer deux fois pour He-O2 en comparaison avec air.Finalement, la dynamique du dépôt ne varie pas de façon significative entre le modèle où la glotte est considérée comme statique et celle où elle est mobile. Donc, dans les conditions de respiration normal le mouvement de la glotte peut être négligé. / During inhaled therapies several factors limits the amount of drug delivered to the lungs. E.g. the upper airways morphology and in particular the glottis, defined by the vocal-fold aperture, causes upper airways to narrow in a minimal cross section, which is determinant on aerosol depo­ sition by inertial impaction. This thesis aims to (i) investigate evolution of the glottal area during breathing, and (ii) predict the effects of a dynamic glottis and realistic airflow conditions on the aerosol deposition in upper airways using three-dimensional simulations.First, a clinical study was conducted on 20 healthy volunteers (10 males and 10 females) to explore the glottal motion during several specifie slow (below 20 cycles/min) and rapid breathing tasks (up to 90 cycles/min). The breathing was investigated simultaneously for the glottal area variations using laryngoscopie video recordings and for airflow rate using oral flowmeter.The experimental measurements showed that the glottal geometry observed during a breathing cycle can be extremely variable depending on the respiratory phase, tidal volume, and breathing frequency. Testing the dynamic behaviour of the glottis during breathing, two groups of subjects were identified: one with relatively constant glottal area and other with significant variations. In average, the variations for the latter group of subjects was observed for males at 26% comparing maximale and minimal glottal opening during inspiration and expiration respectively.The results of the clinical study together with anatomical morphological data served to create a madel with idealised geometry of upper airways. This madel represents the major geometrical characteristics of upper airways with special interest in the glottal region. Transport and deposition of aerosols was studied using 3D numerical cyclic simulations and parametrical analysis allowed to evaluate the influence of the cyclic flow, glottal dynamics, type of carrier gas (air or helium-oxygen mixture) and particle size on the deposition of aerosols in the upper airways.The numerical simulations demonstrated significant decrease of respiration work with He-02 and jet-like flow with recirculation zone in the oro-pharynx and downstream the glottal plane. The principal deposition mechanism is inertial impaction (for the particle diameters 1 - lOiJ.m) with most significant deposition region in the oro-pharynx. Important parameters for deposition are the particle size and the nature of carrier gas. For He-02 the deposition reaches two times smaller values than for air and the fraction of deposited particles increases significantly with diameter, reaching 80% of deposited efficiency for 10 iJ.m particles. Finally, the CFD results demonstrated negligible differences in aerosol transport and deposition between different glottal characteristics. Therefore, in normal breathing conditions the glottal motion can be neglected

Dans les nouveaux protocoles thérapeutiques par voie inhalée, le dosage des particules actives reste un problème complexe qui dépend de trois principaux facteurs : leur taille, la dynamique des flux et les variations de calibre bronchique. La solution nécessite de disposer d'un modèle de distribution des gaz et aérosols administrés dans les poumons. Ventilation pulmonaire et effets du cycle respiratoire sur la dynamique des fluides deviennent deux enjeux clés de la pratique clinique.<br /><br />Dans ce contexte, le projet RNTS RMOD a pour objectif de développer un simulateur morpho-fonctionnel des voies respiratoires pour l'aide au diagnostic, au geste médico-chirurgical et à l'administration de médicaments par inhalation.<br /><br />Contribuant au projet RMOD, la recherche développée dans cette thèse propose une modélisation in-silico de la structure des voies aériennes supérieures (VAS) et proximales (VAP) à partir d'examens tomodensitométriques (TDM). L'investigation morphologique et la simulation fonctionnelle bénéficient alors de géométries 3D réelles, adaptées au patient et spécifiques des pathologies rencontrées.<br /><br />La modélisation développée fait coopérer des méthodes originales de segmentation, de construction de surface maillée et d'analyse morpho-fonctionnelle.<br /><br />La segmentation des VAP est obtenue par un schéma diffusif et agrégatif gouverné par un modèle markovien, dont l'initialisation repose sur l'opérateur de coût de connexion sous contrainte topographique. De cette segmentation, l'axe central de l'arbre bronchique est extrait de manière robuste et précise en combinant information de distance, propagation de fronts, et partition conditionnelle locale. Cet axe central est représenté sous forme d'une structure hiérarchique multivaluée synthétisant caractéristiques topologiques et géométriques de l'arbre bronchique. Une surface maillée est ensuite construite en appliquant une procédure de Marching Cubes adaptative, les paramètres des différents filtres mis en jeu étant automatiquement ajustés aux caractéristiques locales du réseau bronchique conditionnellement aux attributs de l'axe central.<br /><br />La segmentation des VAS repose sur une propagation markovienne exploitant les variations locales de densité. L'initialisation combine morphologie mathématique et information de contour afin de garantir la robustesse à la topologie. Une procédure de type triangulation de Delaunay restreinte à une surface fournit ensuite la représentation maillée des VAS. Il est établi que la topologie et la géométrie des structures complexes composant les VAS sont effectivement préservées.<br /><br />Pour permettre aux médecins de valider les modèles maillés ainsi construits, un environnement virtuel 3D convivial et interactif a été réalisé. En outre, la morphologie des voies aériennes exo- et endo-luminale est analysée de façon automatique à partir de simulations d'écoulement pour des géométries réelles.<br /><br />Enfin, une modélisation unifiée des VAP et VAS est obtenue pour la première fois. Elle démontre la pertinence des approches développées. Elle ouvre la voie à la construction de modèles in-silico complets de l'appareil respiratoire ainsi qu'aux études fonctionnelles prenant en compte les paramètres morphologiques susceptibles d'influer localement ou globalement sur la dynamique des écoulements.

Introduction : L’expansion palatine rapide assistée chirurgicalement (EPRAC) est une option de traitement privilégiée chez les patients ayant atteint la maturité squelettique et présentant une déficience transverse du maxillaire. L’effet bénéfique de l’EPRAC sur la fonction respiratoire est régulièrement mentionné, toutefois, encore peu d’études ont évalué son impact sur les voies aériennes supérieures. L’objectif de cette étude clinique prospective comparative consistait à évaluer les effets tridimensionnels de l’EPRAC sur la cavité nasale, le nasopharynx et l’oropharynx à l’aide de la tomodensitométrie. Méthodologie : L’échantillon était constitué de 14 patients (5 hommes, 9 femmes) dont l’âge moyen était de 23,0 ± 1,9 ans (16 ans 4 mois à 39 ans 7 mois). Tous ont été traités avec un appareil d’expansion de type Hyrax collé et l’expansion moyenne a été de 9,82 mm (7,5 - 12,0 mm). Tous ont eu une période de contention d’une année avant le début de tout autre traitement orthodontique. Une évaluation par tomodensitométrie volumique à faisceau conique a été réalisée aux temps T0 (initial), T1 (6 mois post-expansion) et T2 (1an post-expansion) et le volume des fosses nasales, du nasopharynx et de l’oropharynx ainsi que les dimensions de la zone de constriction maximale de l’oropharynx ont été mesurés sur les volumes tridimensionnels obtenus. Résultats : Les résultats radiologiques ont démontré une augmentation significative du volume des fosses nasales et du nasopharynx ainsi qu’une augmentation de la zone de constriction maximale de l’oropharynx à 6 mois post-expansion. Par la suite, une portion du gain enregistré pour ces trois paramètres était perdue à un an post-EPRAC sans toutefois retourner aux valeurs initiales. Aucun effet significatif sur le volume de l’oropharynx n’a été observé. De plus, aucune corrélation significative entre la quantité d’expansion réalisée et l’ensemble des données radiologiques n’a été observée. L’analyse de la corrélation intra-classe a démontré une excellente fiabilité intra-examinateur. Conclusions : L’EPRAC entraîne un changement significatif du volume de la cavité nasale et du nasopharynx. L’EPRAC ne modifie pas le volume de l’oropharynx, par contre, un effet significatif sur la zone de constriction maximale de l’oropharynx est noté. Les effets observés n’ont pas de corrélation avec le montant d’activation de la vis d’expansion. / Introduction: Surgically assisted rapid palatal expansion (SARPE) is a treatment of choice for patients who have reached skeletal maturity and present a maxillary transverse deficiency. It is often mentioned that SARPE has the benefit to improve respiratory function, however, only a few research projects have investigated the effects of SARPE on the upper airways. The objective of this clinical prospective comparative study was to evaluate the three-dimensional effects of SARPE on the nasal cavity, the nasopharynx and the oropharynx using computed tomography. Materials and Methods: The sample consisted of 14 subjects (5 males, 9 females) whose mean age was 23.0 ± 1.9 years (range: 16 y. 4 mo. to 39 y. 7 mo.). All patients were treated using a bonded Hyrax expander and the mean expansion was 9.82 mm (7.5-12.0 mm). A one-year retention period was undertaken before the beginning of any other orthodontic treatment. A cone-beam computed tomography (CBCT) evaluation was performed at T0 (initial), T1 (6 months post-expansion) and T2 (1 year post-expansion), and then the nasal cavity, nasopharyngeal and oropharyngeal volumes and the oropharyngeal minimal cross-sectional area were measured on the three-dimensional volumes that were obtained. Results: Radiological results have demonstrated a significant increase of the nasal and nasopharyngeal volumes and also an increase of the oropharyngeal minimal cross-sectional area at 6 months post-expansion. At one year post-SARPE, for these three parameters, a part of the gain was lost but did not return to the initial values. No significant effect on oropharyngeal volume was found. No significant correlation between expansion screw activation and radiological parameters were noted. Intra-class correlation analysis showed excellent intra-examiner reliability. Conclusions: SARPE causes significant changes of the nasal cavity and nasopharyngeal volumes. SARPE does not modify the oropharyngeal volume, but induces significant changes of the oropharyngeal minimal cross-sectional area. The observed effects do not have a correlation with the amount of expansion screw activation.