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.

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.

Introdução: Embora a fisiopatogenia da rinossinusite crônica (RSC) ainda não esteja totalmente elucidada, em virtude da sua heterogeneidade e multifatorialidade, existe um crescente corpo de evidências apontando que as bactérias exerçam um papel significativo na gênese ou perpetuação da inflamação crônica. Uma das possíveis formas de atuação são os biofilmes bacterianos, comumente encontrados em pacientes com RSC e que estão relacionados com má evolução clínica. Ainda, existem evidências de que algumas espécies bacterianas, especialmente o Staphylococcus aureus (S. aureus), são capazes de invadir as células epiteliais e permanecerem viáveis em seu interior. Por fim, tem se demonstrado que pacientes RSC com pólipo nasal (RSCcPN) revelam alta associação com a presença de superantígenos estafilocócicos na mucosa respiratória, responsáveis pela estimulação acentuada de respostas inflamatórias locais. Apesar de essas diferentes formas bacterianas estarem bem descritas na RSC, não se sabe ainda com clareza como elas estão associadas nesses indivíduos. Objetivos: Avaliar a associação entre a presença de biofilmes, bactérias intracelulares e superantígenos estafilocócicos em pacientes com RSC (com e sem pólipo nasal), comparados com o grupo controle. Casuística e Métodos: Avaliou-se a prevalência de biofilmes bacterianos, bactérias intracelulares e presença de superantígenos bacterianos em indivíduos com RSCcPN, sem pólipo nasal (RSCsPN) e controles, analisando a associação de distribuição de prevalência desses diferentes grupos (teste exato de Fisher, nível de significância quando p<0,05). Os biofilmes foram definidos por características morfológicas à microscopia eletrônica de varredura (MEV), as bactérias intracelulares foram analisadas por microscopia eletrônica de transmissão (MET) e hibridização fluorescente in situ (FISH) para S. aureus, e superantígenos de S. aureus A-E foram quantificados pela técnica de ELISA (Enzime Linked Imunosorbent Assay). Foram incluídos 90 indivíduos, divididos em três grupos: 1) 38 pacientes com RSCcPN, 2) 26 com RSCsPN e 3) 26 controles. Resultados: Quarenta e dois por cento dos pacientes com RSCcPN (16/38), assim como os com RSCsPN (11/26) apresentaram amostras positivas para biofilmes bacterianos, mas não observou essa positividade no grupo controle (0/26). A análise para bactérias intracelulares demonstrou a presença em 31,5% de pacientes com RSCcPN (12/38), 19,2% em RSCsPN (5/26) e 0% nos controles (0/26). No estudo por FISH, 58% dos pacientes com RSCcPN (18/31) apresentaram positividade para S. aureus intracelular, seguido de 54% nos com RSCsPN (13/24) e em nenhum caso dos 24 analisados do grupo controle. Na avaliação por ELISA, apenas um paciente com RSCcPN foi positivo para a presença de superantígenos estafilocócicos. A avaliação da associação de biofilme bacteriano na superfície mucosa à MEV com bactéria intracelular à MET e com S. aureus intracelular por FISH nos dois diferentes grupos de RSC com e sem pólipo nasal, não mostrou diferença estatisticamente significativa. Conclusão: Foi observada uma maior prevalêcia de biofilmes e bactérias intracelulares em indivíduos com RSC com ou sem pólipo nasal, comparado a Resumo controles. Não houve diferença significativa dentre os grupos de RSC, com e sem pólipo nasal para a presença de biofilmes e bactérias intracelulares. Não houve associação entre a presença de biofilme e bactéria intracelular em pacientes com RSC. Os achados do presente estudo indicam que tanto biofilmes na superfície mucosa quanto microrganismos intracelulares podem estar envolvidos na fisiopatogenia da RSC. / Introduction: Although the pathophysiology of chronic rhinosinusitis (CRS) has not yet been fully elucidated, due to its heterogeneity and multifactorial etiology, there is a growing body of evidence that bacteria play a significant role in the genesis or perpetuation of chronic inflammation. One of the possible forms of acting are bacterial biofilms, which are commonly found in patients with CRS, and are associated with poor clinical outcomes in these patients. In addition to biofilms, there are some evidence pointing out that some bacterial species, especially Staphylococcus aureus (S. aureus), are able to invade into epithelial cells and remain viable intracellulary. Finally, it has been demonstrated that patients with CRS with nasal polyps (CRSwNP) have a high association with the presence of staphylococcal superantigens in the respiratory mucosa, responsible for the stimulation of marked local inflammatory responses. Although these different bacterial forms are well described in CRS, it is still unclear how they are associated in these individuals. Objectives: To evaluate the correlation between the presence of biofilms, intracellular bacteria expression and S. aureus superantigens in CRS patients (with and without nasal polyposis) compared to a control group. Casuistic and Methods: We evaluated the prevalence of bacterial biofilms, intracellular bacteria and the presence of bacterial superantigens in individuals with CRSwNP, without nasal polyp (CRSsNP) and controls, evaluating the association of prevalence distribution of these different groups (Fisher exact test, level of significance set at p<0.05). The biofilms were defined by morphological characteristics by scanning electron microscopy, intracellular bacteria were analyzed by transmission electron microscopy and fluorescence in situ hybridization (FISH) for S. aureus, and S. aureus A-E superantigens were quantified by ELISA. Ninety individuals were included, divided into 38 patients with CRSwNP, 26 patients with CRSsNP and 26 control patients. Results: 42% of patients with CRSwNP (16/38) as well as those with CRSsNP (11/26) presented positive samples for bacterial biofilms, while none of the control patients (0/26) had positive samples. The analysis for intracellular bacteria showed the presence in 31.5% of patients with CRSwNP (12/38), 19.2% in CRSsNP (5/26) and 0% in control patients (0/26). In the FISH study, 58% of patients with CRSwNP (18/31) presented intracellular S. aureus positivity, followed by 54% in patients with CRSsNP (13/24) and in none of the 24 analyzed in the control group. In the ELISA evaluation, only one patient with CRSwNP was positive for the presence of staphylococcal superantigens. The evaluation of the association of bacterial biofilm on the mucosal surface (SEM) with intracellular bacteria (MET) and with intracellular S. aureus by FISH in the two different groups of CRS (with and without nasal polyps) did not show a statistically significant difference. Conclusion: We found a higher prevalence of biofilms and intracellular bacteria in individuals with CRS, either with and without nasal polyps. There was no significant difference between the groups of CRS, with and without nasal polyp, for the presence of biofilms or intracellular bacteria. There was no significant diference on the association of biofilms and intracellular bacteria on pacientes with CRS. Our data indicate that both biofilms on the mucosal surface and intracellular microorganisms may be involved in the pathophysiology of CRS.

Objective: 1) Systematic review on the accuracy of Chronic Rhinosinusitis (CRS) identification in administrative databases; 2) Develop an administrative data algorithm to identify CRS patients who have endoscopic sinus surgery (ESS). Methods: A chart review was performed for all ESS surgical encounters at The Ottawa Hospital from 2011-12. Cases were defined as encounters in which ESS for performed for Otolaryngologist-diagnosed CRS. An algorithm to identify patients who underwent ESS for CRS was developed using diagnostic and procedural codes within health administrative data. This algorithm was internally validated. Results: Only three studies meeting inclusion criteria were identified in the systematic review and showed inaccurate CRS identification. The final algorithm using administrative and chart review data found that encounters having at least one CRS diagnostic code and one ESS procedural code had excellent accuracy for identifying ESS: sensitivity 96.0% sensitivity, specificity 100%, and positive predictive value 95.4%. Internal validation showed similar accuracy. Conclusion: Most published AD studies examining CRS do not consider the accuracy of case identification. We identified a simple algorithm based on administrative database codes accurately identified ESS-CRS encounters.

Background Chronic rhinosinusitis is an inflammatory condition of the nose and paranasal sinuses lasting more than 12 weeks. The common treatment is intranasal corticosteroids but if this treatment fails in relieving symptoms endoscopic sinus surgery (ESS) is considered - a common procedure in the Otolaryngology department in Örebro county. ESS can be assisted by image guided navigation (IGN).In a quality ensuring purpose, this study aimed to investigate the frequency and characteristics of post-operative complications after ESS and examining possible risk factors for complications. Methods Retrospective chart review study. The post-operative complication rate after ESS was calculated. Bivariate analysis was used to find potential factors associated with post-operative complications. The variables of significance were used in multivariate analysis. Result Out of 131 patients; 52 (39.7%) had any post-operative complication. 21 had major – and 35 had minor complications. Local infection was the most common complication. IGN was associated with an increased risk of complications, both minor (OR 2.4, 95% CI 1.0-5.6) and overall (OR 2.7, 95% CI 1.3-5.8). Extensive surgery was associated with an increased risk of complications, both major (OR 2.6, 95% CI 1.0-6.9) and overall (OR 2.2, 95% CI 1.0-4.6). Male sex was associated with increased risk of major complications (OR 2.3, 95% CI 1.2-15.5). Conclusion The complication rate is comparable to other studies with similar definition of complications. IGN assistance, extensive surgery and male sex were associated with an increased risk of complications. Further research should be performed before drawing conclusions determining why they increase the risk.

In der vorliegenden Arbeit wurde Gewebe aus den Nasennebenhöhlen von Patienten mit Nasenpolypen untersucht. Außerdem wurden Zusammenhänge zwischen den Zellpopulationen und den Angaben zu allergischen Erkrankungen und wiederholtem Auftreten der Polypen analysiert. Es fand sich eine interindividuell unterschiedlich starke Infiltration mit eosinophilen Granulozyten. Es konnten keine Unterschiede in der prozentualen Verteilung von eosinophilen Granulozyten im Polypengewebe bei allergischen/ nichtallergischen Patienten oder Patienten mit/ ohne Rezidiv nachgewiesen werden. Die Untersuchungen erfolgten mit dem Laser Scanning Zytometer (LSC), das mit der Standardmethode, der Begutachtung mittels Lichtmikroskop, verglichen wurde. Mit der beschriebenen Methode erfolgte die Untersuchung von Polypengewebe nach einem speziell für diese Anwendung entwickelten Protokoll. Die Ergebnisse korrelierten gut mit den Ergebnissen der Lichtmikroskopie. Aufgrund der Weiterentwicklung des LSC und der ständig wachsenden Anzahl der Nachweismöglichkeiten der an der Polyposis nasi beteiligten Zytokine stellt das LSC eine ideale Methode für die Erforschung der Pathogenese von chronischen Entzündungen der Nasennebenhöhlen dar.

In der vorliegenden Arbeit wurde Gewebe aus den Nasennebenhöhlen von Patienten mit Nasenpolypen untersucht. Außerdem wurden Zusammenhänge zwischen den Zellpopulationen und den Angaben zu allergischen Erkrankungen und wiederholtem Auftreten der Polypen analysiert. Es fand sich eine interindividuell unterschiedlich starke Infiltration mit eosinophilen Granulozyten. Es konnten keine Unterschiede in der prozentualen Verteilung von eosinophilen Granulozyten im Polypengewebe bei allergischen/ nichtallergischen Patienten oder Patienten mit/ ohne Rezidiv nachgewiesen werden. Die Untersuchungen erfolgten mit dem Laser Scanning Zytometer (LSC), das mit der Standardmethode, der Begutachtung mittels Lichtmikroskop, verglichen wurde. Mit der beschriebenen Methode erfolgte die Untersuchung von Polypengewebe nach einem speziell für diese Anwendung entwickelten Protokoll. Die Ergebnisse korrelierten gut mit den Ergebnissen der Lichtmikroskopie. Aufgrund der Weiterentwicklung des LSC und der ständig wachsenden Anzahl der Nachweismöglichkeiten der an der Polyposis nasi beteiligten Zytokine stellt das LSC eine ideale Methode für die Erforschung der Pathogenese von chronischen Entzündungen der Nasennebenhöhlen dar.

Objective: Allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP) are of high importance in otorhinolaryngology. Some of their symptoms are related to changes in the nasal trigeminal sensitivity. The aim of this study was to compare nasal trigeminal sensitivity in patients with AR, CRSwNP, and healthy controls (HC). - Methods: A total of 75 individuals participated (age 19–78 years; 34 AR, 10 CRSwNP and 31 HC). Olfactory function was determined using the extended Sniffin’ Sticks test battery. Trigeminal sensitivity was assessed with CO₂ detection thresholds.Trigeminal negative mucosal potentials (NMP) and EEG-derived event-related potentials (ERP) were recorded in response to selective olfactory (phenylethyl alcohol) and trigeminal (CO₂) stimuli using high-precision air-dilution olfactometry. - Results: In comparison to HC, AR patients had lower CO₂ thresholds, also reflected in shorter peak latencies in NMP and trigeminal ERP measurements. CRSwNP patients had a decreased sensitivity for trigeminal stimuli, also reflected in prolonged trigeminal ERP latencies, and reduced olfactory function compared to HC. - Conclusion: AR patients seemed to be more sensitive to trigeminal stimuli than CRSwNP patients. Importantly, the differences could be shown on psychophysical and electrophysiological levels. The changes in trigeminal sensitivity appear to be present already at the level of the respiratory epithelium. The differences between the two groups may depend on the specific inflammatory changes accompanying each disorder, the degree of inflammatory activity, or duration of the inflammatory disorder. However, because the sample sizes are relatively small, these results need to be confirmed in the future studies with larger groups.

La rhinosinusite chronique (RSC) est une maladie inflammatoire des sinus suffisamment prévalente au Canada et pouvant avoir un impact significatif sur la qualité de vie des patients. Depuis plusieurs années, cette maladie complexe constitue un terrain fertile pour la recherche scientifique. Bien qu’elle soit bien comprise au niveau syndromique, plusieurs mystères persistent quant aux mécanismes physiopathologiques sous-jacents. Ces questionnements pourraient potentiellement expliquer les différences cliniques observées, particulièrement dans les réponses thérapeutiques. Considérant les lacunes persistantes dans la compréhension entière de la maladie, le présent mémoire tente de faire le point sur les endotypes épithéliaux ainsi que sur le pathobiome de la RSC. Dans un premier temps, l’analyse transcriptomique de cellules épithéliales cultivées en laboratoire de patients avec RSC a permis d’identifier deux groupes distincts en termes de marqueurs inflammatoires et de signature épithéliale. Ceci laisse supposer que ces mécanismes physiopathologiques seraient grandement impliqués dans la maladie. Dans un deuxième temps, et dans un objectif exploratoire et de faisabilité, le séquençage d’échantillons de RSC a permis de détecter la présence de virus, laissant présager que ceux-ci pourraient avoir un rôle dans la physiopathologie de la maladie et combler les mystères résiduels dans sa compréhension globale. En conclusion, les endotypes déterminés par le profil d’expression génique permettraient une meilleure classification de la RSC et une meilleure personnalisation des thérapies. De plus, la présence tangible de virus dans la RSC est certainement prometteuse et ouvre une grande porte de recherche. Toutefois, d’autres études seront nécessaires pour mieux caractériser leur nature et leur rôle. / Chronic rhinosinusitis (CRS) is a complex inflammatory disease of the sinuses that is prevalent in Canada and that can significantly affect patients’ quality of life. For several years now, this heterogenous disease have been in the scope of many scientific research. While CRS is clinically well understood, much remains unknown concerning the underlying pathophysiological mechanisms. This could potentially explain the notable clinical differences observed between patients, especially in terms of therapeutic responses. In hope of bridging the gaps in understanding CRS, the present thesis aims to discuss epithelial endotypes as well as the feasibility and potential role of viruses in CRS. Firstly, gene expression profiling revealed two distinct clusters of CRS patients: a group with severe non-Type 2 inflammation and epithelial dysfunction, and a group characterised by moderate non-Type 2 inflammation and epithelial dysfunction. This highlights that these two different mechanisms are involved in the development of CRS. Secondly, and with an exploratory intent, next-generation sequencing and transcriptomic assembly of CRS samples have confirmed the presence of viruses, suggesting that viruses are present in CRS and could possibly play a role in the pathogenesis of this disease, potentially addressing the shortcomings in CRS. To summarize, epithelial endotypes identified by gene expression profiling could aid in better classifying CRS to provide a tailored therapeutic option. The presence of viruses in CRS samples unfolds an interesting chapter in this field. However, larger populations will be required to better characterize the nature of these viruses and to assess their intrinsic role in CRS.

Introdução: O estudo dos fatores clínicos associados ao prognóstico da rinossinusite crônica (rsc), seja associada à polipose nasossinusal (RSCcPN) ou não (RSCsPN), ainda é pouco abordado a longo prazo. Objetivo: Avaliar pacientes submetidos à ESS (cirurgia endoscópica nasal, do inglês endoscopic sinus surgery) para o tratamento de RSC no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo, entre 1996 e 2006, e correlacionar a recidiva em longo prazo com parâmetros como a extensão da doença, atopia, tabagismo, asma, eosinofilia e doença respiratória exacerbada pela aspirina (DREA). Métodos: Duzentos e um pacientes foram seguidos por um período médio de 12 anos. Os dados clínicos foram levantados, assim como exames de endoscopia nasal, Tomografia Computadorizada (TC), exames séricos, prick test e prova de função pulmonar. O tempo de seguimento pós-operatório foi analisado, sendo considerado fator de mau prognóstico a indicação de novo procedimento cirúrgico. Foi realizada comparação entre os fatores pela curva de Kaplan-Meyer, e pós-teste de Log-rank. Resultados e Discussão: Pacientes com RSCcPN tiveram chance de nova cirurgia três vezes maior do que aqueles sem pólipos nasais, no período seguido. Entre os pacientes com RSCsPN, apenas a asma foi um fator de pior prognóstico significativo, levando à chance de cirurgia 5,5 vezes maior do que os não-asmáticos. Já entre os pacientes com RSCcPN, aqueles com recidiva apresentaram maior extensão da doença à TC antes da primeira cirurgia. Foram ainda considerados fatores significativamente de pior prognóstico nos pacientes com RSCcPN: asma (odds ratio [OR] de 3,2); atopia a fungos (OR de 1,9); eosinofilia periférica (considerada como >500/µL, levando a OR de 1,9); e intolerância ao Ácido Acetil Salicílico (AAS) (DREA, apresentando OR de 2,5). Conclusões: Concluiu-se que a presença de pólipos per se é fator de pior prognóstico, aumentando em três vezes a chance de recorrência cirúrgica. Entre os pacientes com RSCsPN, apenas a asma influenciou o prognóstico. Já naqueles com RSCcPN, a asma, eosinofilia periférica, atopia a fungos e DREA aumentaram significativamente a probabilidade de nova intervenção cirúrgica. / Introduction: The analysis of prognostic factors associated with the recurrence of chronic rhinosinusitis (CRS), either with nasal polyps (CRSwNP) or without (CRSsNP), is still poorly discussed in the literature. Objective: To evaluate the patients that underwent endoscopic sinus surgery (ESS) due to CRS in Clinics Hospital of Ribeirão Preto Medical School, University of São Paulo, between 1996 and 2006, and to correlate the long-term recurrence to clinical factors, such as extensiveness of the disease, atopy, smoking habits, eosinophilia, and Aspirinexacerbated respiratory disease (AERD). Methods: We collected data of 201 patients, who were followed during an average period of 12 years. Clinical data collected were: extensiveness of the disease at endoscopy and at CT scans, prick test, blood exams, and pulmonary function. The follow-up period after surgery was assessed, and the indication of a new surgical procedure was considered as a poor prognostic factor. Comparison between factors was performed by Kaplan-Meyer curve, with Log-rank post-test. Results and discussion: CRSwNP patients were 3 times more likely to need a revisional surgery than CRSsNP during the follow-up period. Only asthma was a significant prognostic factor in patients with CRSsNP, leading to 5.5 times higher chance of recurrence than non-asthmatic patients. Among patients with CRSwNP, patients with recurrence presented, prior to surgery, higher CT scan extension of the disease. Other factors that influenced the prognosis on CRSwNP were: asthma (odds ratio [OR]: 3.2); atopy for fungi (OR: 1.9); peripheral eosinophilia (considered as >500/?L, leading to an OR: 1.9); and ASA intolerance (AERD; OR: 2.5). Conclusions: The presence of polyps were related to poor prognosis per se, leading to a higher chance of surgical recurrence. Among patients with CRSsNP, only asthma influenced the prognosis. Among the patients with CRSwNP, asthma, peripheral eosinophilia, fungi atopy, and AERD significantly increased the likelihood of further surgical intervention.