Orientador: Ricardo de Lima Zollner / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T16:04:12Z (GMT). No. of bitstreams: 1 Vilella_LuizFelipeNoraRosa_M.pdf: 1382640 bytes, checksum: d0c8bc891d04399e182ad18470fe85b2 (MD5) Previous issue date: 2013 / Resumo: As vias aéreas superiores e inferiores constituem um sistema integrado, cuja interação é evidente na presença das doenças alérgicas, incluindo a rinite alérgica, que é co-morbidade relevante para o desenvolvimento da asma. Mecanismos já consolidados estão envolvidos, contudo o reflexo naso-brônquico, que consiste em um reflexo neural originado nas vias aéreas superiores causando impacto nas vias aéreas inferiores por meio da inflamação neurogênica foi sugerido em estudos experimentais. Evidências da presença deste reflexo em humanos baseiam-se em diferentes métodos que demonstraram prejuízo na função pulmonar após estimulação nasal, porém o monitoramento objetivo da permeabilidade nasal pela rinometria acústica associado ao estudo da função pulmonar por meio da espirometria, possibilita acessar respostas agudas nas vias aéreas após estimulação nasal, representando uma ferramenta promissora na investigação do reflexo naso-brônquico. Portanto, o objetivo deste estudo foi avaliar alterações na função pulmonar após provocação nasal, visando identificar o reflexo naso-brônquico na rinite alérgica isolada. 33 voluntários com rinite alérgica persistente moderada/grave (grupo experimento) e 10 saudáveis (grupo controle) foram submetidos a avaliação inicial e protocolo de investigação composto por espirometria e rinometria acústica basais, seguidas por teste de provocação nasal com concentrações crescentes de histamina; após aplicação de cada concentração a rinometria acústica era novamente realizada passados 1, 4, 8 e 12 minutos, sendo considerada provocação positiva após 20% de obstrução em AST-2, determinando o PN20; por fim, imediatamente nova espirometria era realizada. Ao comparar os dados de função pulmonar antes e após provocação nasal, foi observada diferença significativa no grupo rinite para VEF1 (p=0,002), CVF (p=0,005) e PFE (p=0,005), entretanto não houve variação significativa para nenhum dos parâmetros analisados no grupo controle. O reflexo naso-brônquico foi identificado a partir da variação do VEF1, após a provocação nasal no grupo controle (média acrescida de dois desvios padrões), logo 18,2% dos indivíduos com rinite apresentaram reflexo naso-brônquico (queda > 3% em VEF1). Além disso, para estes verificamos correlação positiva entre as alterações observadas em VEF1 e FEF25-75% (p=0,002 / r=0,97), sugerindo envolvimento das vias aéreas de pequeno calibre. Considerando as vias aéreas superiores, o protocolo proposto demonstrou respostas similares nos dois grupos, sem diferença significativa entre os mesmos para dose de histamina (p=0,98), tempo para atingir PN20 (p=0,97) e porcentagem de obstrução nasal (p=0,97). As alterações observadas na função pulmonar após provocação nasal sugerem a presença do reflexo naso-brônquico no paciente com rinite alérgica persistente moderada/grave. O protocolo proposto apresentou reprodutibilidade, sem intercorrências e, diante dos resultados obtidos, propomos que deva ser pensado na prática clinica com objetivo de aperfeiçoar o diagnóstico da presença do reflexo naso-brônquico, relevante para os pacientes com hiperreatividade brônquica / Abstract: Upper and lower airways consists an integrated system and their interaction becomes evident in allergic diseases, highlighting allergic rhinitis, which is co morbidity to asthma onset. Consolidated paths are involved in this crosstalk, however the nasobronchial reflex, that represents a neural reflex originated in upper airways that causes lower airways impairments was suggested in experimental studies. Evidences for the presence of this reflex in humans are based in different methods that have demonstrated impaired pulmonary function after nasal challenge, although, utilizing objective monitoring of nasal patency by acoustic rhinometry in association with pulmonary function evaluation provided by spirometry, it is possible to access acute airways responses after nasal provocations, representing to be promising tools in nasobronchial reflex investigation. Thus, the aim of this study was to evaluate changes in pulmonary function after nasal provocation, looking for nasobronchial reflex identification in subjects with isolated allergic rhinitis. 33 subjects with persistent moderate/severe allergic rhinitis and 10 healthy subjects underwent screening evaluation and investigation protocol consisting in baseline spirometric and acoustic rhinometry measurements, followed by histamine nasal provocation in increasing concentrations; after each histamine application, comparative acoustic rhinometry measurements were performed passed 1, 4, 8 and 12 minutes and positive provocation was considered after reached 20% of obstruction in MCA-2, determining the NPT20; finally, another spirometry was performed immediately NPT20 was reached. Comparing the pulmonary function before and after provocation in the rhinitis group, it was observed significant difference for FEV1 (p=0,002), FVC (p=0,005) and PEF (p=0,005), however in the same comparison for the control group no significant difference could be found for any of the analyzed parameters. Nasobronchial reflex was identified based on VEF1 percentage of variation after nasal provocation in control group (mean plus two standard deviations), 18,2% of rhinitis group presented nasobronchial reflex (> 3% fall in FEV1). Furthermore, for these ones we could verify positive correlation between VEF1 and FEF25-75% impairments (p=0,002/r=0,97), suggesting distal lower airways involvement. Considering upper airways, the proposed protocol demonstrated similar reactions in the two groups, with no significant differences between them for histamine dose (p=0,98), time to reach NPT20 (p=0,97) and percentage of nasal obstruction (p=0,97). Concluding, spirometric impairments showed here suggest the presence of nasobronchial reflex in patients with persistent moderate/severe allergic rhinitis. The proposed protocol proved to be reproducible, without intercurrences and, regarding results showed here, we propose that it should be thought in clinical practice, in order to improve the diagnosis of the presence of nasobronchial reflex, relevant to patients with bronchial hyperreactivity / Mestrado / Clinica Medica / Mestre em Clinica Medica

Orientador: Ricardo de Lima Zollner / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-24T18:58:24Z (GMT). No. of bitstreams: 1 ZanellatoFabbri_Natalia_D.pdf: 35087770 bytes, checksum: d1d79dc3e2bc0a5a2a05b4261a363a74 (MD5) Previous issue date: 2014 / Resumo: Apesar das diversas terapias disponíveis para o tratamento da rinite alérgica (RA), muitos pacientes não obtêm alívio dos sintomas com uso de um único fármaco e apresentam frequentemente queixa da manutenção dos sintomas mesmo sob tratamento. Estudos clínicos aleatorizados compararam a eficácia de anti-histamínicos e corticoides intranasais, isolados e associados e demonstraram que as terapias com drogas combinadas apresentam melhores resultados. A RA é um fator de risco para o desenvolvimento de obstrução de VAI e estudos clínicos com pacientes asmáticos demostraram redução da responsividade brônquica e sintomas de asma apenas com tratamento tópico nasal. O objetivo do presente estudo foi avaliar (1) o efeito do tratamento tópico nasal com azelastina (AZE), budesonida (BUD) e combinação AZE/BUD na obstrução nasal e sintomas de RA; (2) o efeito do estímulo nasal inespecífico com histamina na função pulmonar; e (3) o efeito dos tratamentos tópicos nasais na função pulmonar de pacientes com RA. O desenho do presente trabalho foi aleatorizado, cruzado e cego composto por 3 tratamentos. 28 pacientes participaram do estudo, com tratamento tópico nasal de 30 dias e intervalo de 7 dias entre os tratamentos. Os pacientes foram submetidos ao protocolo de TPN com histamina, avaliado por escore de sintomas, rinometria acústica e espirometria. Nossos resultados mostraram que a terapia com AZE/BUD é mais efetiva na prevenção da obstrução nasal e sintomas da RA comparada ao tratamento com as drogas isoladas. Além disso, encontramos indivíduos com alterações na função pulmonar após estímulo nasal inespecífico e controle destas alterações após tratamento tópico nasal, sugerindo influência positiva do tratamento nasal na função pulmonar de indivíduos com hiperreatividade brônquica / Abstract: Despite the several therapies available for the treatment of allergic rhinitis (AR) many patients do not get relief of symptoms using a single drug and often have the maintenance of symptoms even under treatment. Randomized clinical trials comparing the efficacy of antihistamines and intranasal corticosteroids, isolated and associates, show that the combination drug therapies have better outcomes. The AR is a risk factor for the development of obstruction in lower airways and clinical studies with asthmatic patients demonstrated reduction of bronchial hyperresponsiveness and asthma symptoms after just nasal topical treatment. The aim of this study was to evaluate (1) the effect of treatment with topical nasal azelastine (AZE), budesonide (BUD) and combined drugs (AZE/BUD) in nasal obstruction and symptoms of RA; (2) the effect of non-specific nasal challenge with histamine in lung function; and (3) the effect of topical nasal treatment on lung function in patients with RA. The design of this study was randomized, crossover and blind consisting of 3 periods of treatment with nasal sprays. 28 patients participated in the study, composed for 3 periods of treatment (30 days) and 7-day interval between treatments. Patients underwent protocol nasal provocation test with histamine assessed by symptom scores, acoustic rhinometry and spirometry. Our results showed that therapy with AZE/BUD is more effective in preventing nasal obstruction and symptoms of RA compared to treatment with drugs isolated. Furthermore, we find individuals with changes in pulmonary function after nonspecific nasal stimulation and control of these changes after nasal topical treatment, suggesting a positive influence of nasal treatment on lung function in subjects with bronchial hyperreactivity / Doutorado / Clinica Medica / Doutora em Clínica Médica

L’obstruction nasale chronique (ONC) est un symptôme banal qui révèle de nombreuses pathologies rhinologiques ostéo-cartilagineuses et/ou muqueuses. Les explorations de l’ONC aident à la démarche diagnostique et permettent d’évaluer le retentissement de l’ONC sur la muqueuse nasale.Afin de répondre aux problèmes que je rencontre dans ma pratique clinique en rhinologie, j’ai orienté mes travaux de recherche vers le développement de nouveaux outils d’exploration des pathologies nasales obstructives :1. A l’échelle tissulaire, dans le cadre des rhinites chroniques, en particulier le dysfonctionnement nasal neurovégétatif qui restait un diagnostic d’élimination. J’ai montré que la compliance nasale, mesurée par rhinométrie acoustique, est perturbée dans les deux causes les plus fréquentes de rhinite chronique, d’une part, et est utile au diagnostic de dysfonctionnement nasal neurovégétatif, d’autre part.2. A l’échelle cellulaire, en m’intéressant à la cellule ciliée de l’épithélium respiratoire. J’ai étudié les avantages et les limites de l’étude ciliaire par microscopie électronique à transmission pour le diagnostic de dyskinésie ciliaire primitive. A l’aide de la vidéomicroscopie numérique à haute vitesse, j’ai développé des paramètres objectifs permettant de caractériser précisément le battement ciliaire. J’ai montré que ces paramètres étaient utiles pour le diagnostic de dyskinésie ciliaire primitive, pour étudier les cils respiratoires au cours de l’amaurose congénitale de Leber ou pour étudier le rôle de la protéine BUG22 dans le battement ciliaire de la paramécie. / Chronic nasal obstruction (CNO) is a common symptom and corresponds to diseases affecting bones, cartilages and/or mucosa of the nose. Objective monitoring of nasal patency is useful for identifying the etiology of CNO and for evaluating its effects on the mucosa.My research is guided by the numerous challenges encountered through my clinical practice of rhinology. I have developed new objective tools for exploring obstructive nasal diseases:1. At tissue level, I focused on chronic rhinitis, especially the neurovegetative nasal dysfunction which remained a diagnosis of exclusion so far. Using acoustic rhinometry, I have shown that the nasal compliance was abnormal in the two most common causes of chronic rhinitis and was a useful measure for the diagnosis of neurovegetative nasal dysfunction.2. At cell level, I focused on the ciliated cell of the respiratory epithelium. I studied the advantages and limits of transmission electron microscopy analysis of cilia for the diagnosis of primary ciliary dyskinesia. Using digital high-speed videomicroscopy, I have established objective parameters that precisely characterize ciliary beating. I have shown that these parameters were useful for diagnosing primary ciliary dyskinesia, for studying respiratory cilia of patients affected by Leber congenital amaurosis or for studying the role of BUG22 protein in ciliary beating of paramecia.

Untersuchung zur Wirkung von intranasal verabreichtem Xylometazolin bei brachy- und normozephalen Hunden: Impuls-Oszillometrie und akustische Rhinometrie P. Franco, J. P. Hueber, G. U. Oechtering Klinik für Kleintiere, Arbeitsgruppe Brachyzephalie, Universität Leipzig Einleitung: Die zuchtbedingte Verkürzung des Gesichtsschädels brachy - zephaler Hunderassen hat zu einer Reihe klinisch relevanter morphologischer und physiologischer Veränderungen geführt. Hierzu zählen stenotische Naseneingänge, eine durch fehlgebildete Conchen obstruierte Nasenhöhle sowie ein verdicktes und verlängertes Gaumensegel. Diese Einengung der oberen Atemwege führt zu Atemnot und ausgeprägter Belastungsintoleranz, was als Brachyzephales Atemnotsyndrom (BAS) bezeichnet wird. Xylometazolin ist ein für den Menschen zugelassenes Alpha-Sympathomime - tikum. Topische und systemische Sympathomimetika werden beim Menschen zur Behandlung nasaler Kongestionen zum Abschwellen der Nasenschleimhaut eingesetzt. Zielstellung: Ausgehend von der Hypothese, dass Xylometazolin auch bei Hunden zu einem Abschwellen der Nasenschleimhaut führt und dass die Morphologie der Nasenmuscheln sich zwischen den zwei Zielgruppen unterscheidet, sollte der intranasale Strömungswiderstand bei brachy- und normozephalen Hunden vor und nach Xylometazolingabe mit Impuls- Oszillometrie untersucht werden. Zusätzlich wurden in der Beaglegruppe mit akustischer Rhinometrie das Nasenhöhlenvolumen und die minimale Querschnittsfläche bestimmt. Methodik: Die Messungen erfolgten nach dem Prinzip der Impuls-Oszillometrie (IOS) und akustischer Rhinometrie. In einer prospektiven klini - schen Studie wurden 10 brachyzephale Hunde (5 Möpse, 5 Französische Bulldoggen) und 6 Beagles untersucht. Bei den anästhesierten, spontan atmenden Tieren wurde der intranasale Strömungswiderstand mit Impuls- Oszillometrie unmittelbar vor und 30 Minuten nach intranasal verabreichtem Xylometazolin gemessen. Messungen mit akustischer Rhinometrie erfolgten zusätzlich vor und nach Xylometazolingabe. Bei allen Tieren wurden die oberen Atemwege endoskopisch und computertomographisch untersucht. Ergebnisse: Der aus drei Messungen gemittelte intranasale Strömungswiderstand bei Patienten mit BAS betrug vor Xylometazolingabe 0,87 ± 0,097 kPa/(L/s). Nach Xylometazolingabe reduzierte sich der intranasale Strömungswiderstand um etwa 48% auf 0,42 ± 0,55 kPa/(L/s). Vergleich - bare Ergebnisse ermittelten wir in der Beaglegruppe. Nach Xylometazolingabe ergab sich bei den Beagles eine Zunahme des Nasenvolumens und der minimalen Querschnittsfläche. Schlussfolgerungen: Wir konnten erstmals zeigen, dass Xylometazolin auch bei Hunden zum Abschwellen der Nasenschleimhaut führt und sich das Abschwellverhalten zwischen brachy- und normozephalen Hunden kaum voneinander unterscheidet. A13 Abstracts 18. Jahrestagung der DVG-FG InnLab © Schattauer 2010 Tierärztliche Praxis Kleintiere 1/2010