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

Mast cells play a critical role in both acute and chronic inflammation and mature in peripheral tissues from bone marrow-derived progenitors that circulate in the blood as immature precursors. Mast cell progenitors are likely to encounter the serum-borne bioactive sphingolipid metabolite, sphingosine-1-phosphate (S1P), during migration to target tissues. Mast cells developed from human cord blood-derived progenitors cultured with stem cell factor (SCF) alone express intragranular tryptase (MCT), the phenotype predominant in the lung. S1P accelerated the development of cord blood-derived mast cells (CB-MCs) and strikingly increased the numbers of mast cells expressing chymase. These mast cells have functional FcepsilonRI, and similar to skin mast cells that express both tryptase and chymase (MCTC), also express CD88, the receptor for C5a, and are activated by anaphylatoxin C5a and the secretagogue compound 48/80. S1P induced release of IL-6, a cytokine known to promote development of functionally mature MCTC, from cord blood cultures containing adherent macrophages, and from highly purified macrophages, but not from macrophage-depleted CB-MCs. In contrast, S1P stimulated secretion of the chemokine, monocyte chemoattractant protein 1 (MCP-1/CCL2), from these macrophage-depleted and purified CB-MCs.

Objetivos: descrever as características dos lactentes com Sequência de Robin (SR) atendidos no Hospital de Reabilitação de Anomalias Craniofaciais da Universidade de São Paulo (HRAC-USP) e identificar as variáveis associadas a um protocolo terapêutico: documentar as síndromes associadas; verificar o tipo de obstrução respiratória, os sintomas clínicos e intervenções terapêuticas; verificar a ocorrência de disfagia, complicações, comorbidades e óbitos. Material e Métodos: Foram avaliados retrospectivamente 223 lactentes com SR, menores de um ano de idade, internados no HRAC-USP no período de julho de 2003 a junho de 2008. Resultados: 52% dos lactentes eram do sexo masculino, 121 (54%) apresentavam provável Sequência de Robin isolada (SRI) e102 (46%) apresentavam Sequência de Robin associada à síndrome ou associada a outras anomalias (SRS). As síndromes mais freqüentes foram síndrome de Stickler e síndrome de Moebius. 45% dos lactentes internaram antes de um mês de idade e o tempo médio de hospitalização foi de 20 dias. O tipo de obstrução respiratória mais freqüente, diagnosticado pela nasofaringoscopia, foi tipo 1, presente em 68% dos casos. A maioria dos lactentes (81%) foi tratada conservadoramente e a intubação nasofaríngea foi o tratamento mais utilizado (48%). A traqueostomia foi realizada em 19% dos lactentes e destes a maioria era do grupo SRS. A quase totalidade dos lactentes apresentava disfagia, a qual foi mais grave nos que apresentavam obstrução tipo 3 e 4, nos submetidos à traqueostomia e nos do grupo SRS. A gastrostomia foi realizada em 25% dos lactentes e a doença de refluxo gastroesofágico ocorreu em 54% do total de lactentes estudados. A complicação mais freqüente foi pneumonia e a mortalidade foi 5,38%, sendo que todos os pacientes que evoluíram para óbito eram sindrômicos. Conclusões: A maioria dos lactentes com SR pode ser tratada conservadoramente e a intubação nasofaríngea foi o método mais empregado. As dificuldades alimentares foram universais e relacionadas ao grau de obstrução respiratória. / Objectives: to describe the characteristics of infants with Robin Sequence (SR) treated at the Hospital for Rehabilitation of Craniofacial Anomalies - University of São Paulo (HRAC-USP) and identify the variables associated with a therapeutic protocol; record the associated syndromes; verify the type of respiratory obstruction, clinical symptoms and therapeutic interventions; and to verify the occurrence of dysphagia, complications, comorbities and death. Material and Methods: A total of 223 infants with SR were retrospectively evaluated, all younger than one month of age, hospitalized at HRAC-USP in the period July 2003 to June 2008. Results: 52% of the infants were males, 121 (54%) presented probable Isolated Robin Sequence (SRI) and 102 (46%) exhibited Robin Sequence with associated syndrome or anomalies (SRS). The most frequent syndromes were Stickler syndrome and Moebius syndrome. Among the infants, 45% were hospitalized before one month of age and the mean time of hospitalization was 20 days. The most frequent respiratory obstruction diagnosed through nasopharyngoscopy was type 1, present in 68% of cases. Most of the infants were treated conventionally and nasopharyngeal intubation was the most used procedure (48%). Tracheostomy was performed in only 19% of infants, most of whom were syndromic. Nearly all infants presented dysphagia, which was more severe in infants with obstruction type 3 and type 4, submitted to tracheostomy, and in the SRS group. Gastrostomy was performed in 25% of infants and gastroesophageal reflux occurred in 54% of SR infants. The most frequent complication was pneumonia and the mortality rate was 5.38%; all cases of death occurred among syndromic children. Conclusions: Most of the SR infants were treated conventionally and nasopharyngeal intubation was the most used procedure. Feeding difficulties were universal and related to the degree of respiratory obstruction.

INTRODUÇÃO: A sonoendoscopia é um método propedêutico útil para identificação do sítio de colapso da via aérea superior (VAS) nos pacientes que apresentam Síndrome da Apneia Obstrutiva do Sono (SAOS). Atualmente tem sido realizada durante sono induzido por drogas, principalmente pelo propofol, sedativo que pode interferir na colapsabilidade das VAS. Nós formulamos a hipótese de que o propofol pode aumentar a colapsabilidade da VAS durante a realização da sonoendoscopia. Os objetivos desse estudo foram avaliar se o uso do propofol para a realização de sonoendoscopia aumenta o número de estruturas envolvidas no colapso da via aérea superior e avaliar seu efeito na colapsabilidade da faringe e no drive respiratório durante o exame. MÉTODOS: Vinte e um pacientes apneicos foram submetidos a polissonografia e a duas sonoendoscopias durante sono natural e durante sono induzido por propofol na mesma semana. Durante sono natural o paciente estava monitorado com polissonografia em tempo real e foi administrado hemitartarato de zolpidem 10mg para indução do sono e melhor tolerância ao exame. O propofol foi administrado segundo infusão alvo controlada, com concentração alvo inicial de 1,5ug/ml e aumentos de 0,1-0,2 ug/mL até sedação adequada (nível do monitor BIS 50-70 e escala de sedação de Ramsay nível 5). Os dados endoscópicos foram classificados segundo a classificação de VOTE modificada. Os pacientes foram monitorados com sensores de fluxo e de pressão faríngea e os dados de Pico de Fluxo Inspiratório (PFI), Dependência de Esforço Negativo (DEN) e Driving Pressure (DP) foram analisados. RESULTADOS: O índice de Apneia-hipopneia médio de nossa amostra foi de 43,7 eventos/hora. A presença do colapso das VAS e de sua configuração durante sono natural e durante sono induzido por propofol foram semelhantes em todos os sítios da VAS: palato (p=0,13), orofaringe (p=1,00), língua (p=1,00) e epiglote (p=0,25). O uso do propofol não aumentou a quantidade de estruturas faríngeas colapsadas (p=0,45). Observou-se forte concordância entre o colapso da região de base de língua nos dois métodos (k=0,829); concordância substancial para as regiões do palato e epiglote (k=0,685 e 640 respectivamente), e uma concordância moderada para a região da orofaringe (k=0,417). A colapsabilidade da faringe avaliada pelo PFI e pela DEN foi semelhante nos dois exames (p=0,65 e p=0,22 respectivamente). O propofol não alterou o drive respiratório avaliado pelo DP (p=0,37). CONCLUSÃO: O uso do propofol não alterou a colapsabilidade da VAS durante a realização da sonoendoscopia quando comparado com o exame durante sono natural / INTRODUCTION:sleep endoscopy is a useful method for identifying the obstruction sites in the upper airways in patients with obstructive sleep apnea syndrome (OSAS). Currently it has been performed using sedatives (druginduced sleep endoscopy - DISE), mainly with propofol. This sedative increases the collapsibility of the upper airway. Here we tested the hypothesis that propofol may increase the upper airway collapsibility during DISE. METHODS: twentyone apneic patients underwent polysomnography and sleep endoscopy during natural sleep and during DISE with propofol. Real time polysomnography was performed during natural sleep. Each patient was given 10 mg of Zolpidem hemitartrate prior to the examination to help sleep induction and to allow better tolerance. During DISE we used a propofol target-controlled infusion and the initial target effect site concentration was set at 1,5 ug/mL. This was adjusted by 0,1-0,2 ug/mL titrated up to adequate sedation (Bispectral index - BIS - monitor level between 50-70 and Ramsay sedation scale level 5). The endoscopic results were classified according to the modified VOTE classification. Patients were monitored with an airflow and a pharyngeal pressure sensors. The airway collapsibility was also assessed by the peakflow and the negative effort Dependence (NED). The respiratory drive was evaluated by the driving pressure (DP). RESULTS: diagnostic sleep studies demonstrated a mean apneahypopnea index of 43,7 events/hour. The number of collapsed UA structures observed during natural sleep were similar to those observed during DISE with propofol (p=0,45). Also, the frequencies and the configuration of the airway collapse observed during natural sleep and during DISE were similar in all sites of obstruction: palate (p=0,13), oropharynx (p=1,00), tongue (p=1,00) and epiglottis (p=0,25). The correlation of the endoscopic results was strong for the tongue (u value 0,829), substatial for the velum and epiglotis (k values 0,68 and 0,64 respectively) and moderate for the oropharynx (k value 0,42). The peakflow and the NED evaluations (p=0,65 and p=0,22 respectively) revealed a similar collapsibility in both situations. Propofol didn`t impair the respiratory drive, assessed by the DP values (p=0,37). CONCLUSION: The use of propofol during DISE had no effect on the upper airway collapsibility when compared to sleep endoscopy during natural sleep

Introdução: Dependendo da magnitude da má oclusão de Classe III, esta é uma alteração difícil de ser tratada apenas com a correção ortodôntica. Tanto as cirurgias de recuo mandibular quanto as bimaxilares promovem uma melhora na oclusão, na função mastigatória e na estética facial, ao corrigirem as posições da mandíbula e/ou maxila, mas um importante aspecto da cirurgia ortognática, que não pode ser negligenciado, são os efeitos que os movimentos esqueléticos das bases ósseas podem provocar na região das vias aéreas, ao alterar a posição do osso hióide e da língua. O estreitamento das vias aéreas superiores (VAS) pode comprometer o sono dos pacientes submetidos à correção cirúrgica e predispor ao desenvolvimento da apneia/hipopneia obstrutiva do sono (AOS). Objetivos: O presente trabalho tem como objetivo avaliar as alterações de volume e área axial mínima do espaço aéreo faringeo em pacientes com má oclusão de Classe III esquelética, submetidos à cirurgia ortognática bimaxilar, pela técnica de osteotomia Le Fort I da maxila e osteotomia sagital bilateral da mandíbula. Material e Métodos: As avaliações foram feitas em tomografias computadorizadas Cone-beam, utilizando-se o Programa Dolphin Imaging 11.7. As tomografias de 50 pacientes, de ambos os sexos, com média de idade de 33,40 (± 9,38) anos, foram analisadas nos períodos pré e pósoperatório e as medidas de volume e área axial mínima foram mensuradas. Foi utilizado o teste t pareado e os testes foram realizados utilizando-se o programa Statistica 7.0, adotando-se um nível de significância de 5%. Resultados: ao calcular o erro do método, não foram encontrados erros casuais e nem sistemáticos (p> 0,05 em todas as medidas). As cirurgias bimaxilares para correção da Classe III esquelética promoveram um aumento de 16,68% (±22,61) no volume e 23,58% (± 31,46) na área axial mínima. Conclusões: Mesmo que os efeitos da cirurgia de avanço maxilar e recuo mandibular sobre as vias aéreas não sejam completamente previsíveis, podemos observar que a maioria dos pacientes não apresentaram prejuízos na anatomia faringeana que resulte em diminuição do volume aéreo e área axial mínima, predispondo-o ao desenvolvimento da AOS. / Introduction: Depending on the extend of Class III malocclusion, it becomes difficult to be treated only with orthodontic correction. Both mandibular setback surgery as bimaxillary surgery, promote an improvement in occlusion, masticatory function and facial aesthetics, correcting the position of the mandible and/or maxilla. But an important aspect of orthognathic surgery that cant be overlooked, are the effects that the skeletal movements of the bone bases causes in the airway space, since they change the position of the hyoid bone and tongue. The narrowing of the pharingeal airway space (PAS) may impair the patient\'s sleep and predispose to the development of obstructive sleep apnea (OSA). Purpose: This study aims to evaluate surgical changes in the airway volume and minimal cross-sectional area in the pharyngeal airway space (PAS) in patients with skeletal Class III malocclusion, submitted to bimaxillary surgery, using a Le Fort I maxillary osteotomy and bilateral sagittal split ramus osteotomy technique. Material and Methods: The evaluations were made through Cone-beam computed tomography (CBCT), using Dolphin Imaging program version 11.7. The CT scans of 50 patients of both genders, with a mean age of 33.40 (± 9.38), were analyzed pre and postoperatively and volume and minimum axial area were measured. Paired t test was used and tests were performed using Statistica 7.0 software, adopting a 5% significance level. Results: Method error were done and no random or systematic errors were found (p> 0.05 for all measures). Bimaxillary surgery for skeletal Class III correction promoted an increase of 16.68% (± 22.61) in volume and 23.58% (± 31.46) at the minimum axial area. Conclusion: Even if the effects of the maxillary advancement and mandibular setback surgery on the airway are not completely predictable, we observed that most patients didnt have pharyngeal airway anatomy damage, that could result decreased on airway volume and minimum axial area predisposing to OSA development.

Bakgrund Ambulanssjuksköterskans hantering av luftvägen och ventilering vid hjärtstopp är av stor vikt för att en patient ska kunna återupplivas. Många hjälpmedel finns för att underlätta detta arbete, men prehospitalt finns det åtskilliga faktorer att ta hänsyn till som inte existerar på sjukhus och som kan inverka på ambulanssjuksköterskans val av metod för ventilering. Syfte Att undersöka vilka faktorer som påverkar ambulanssjuksköterskans val av metod för ventilering vid hjärtstopp. Metod En kvalitativ design användes med semistrukturerade intervjuer. Åtta intervjuer med specialistsjuksköterskor inom intensivvård och ambulanssjukvård genomfördes. Kvalitativ innehållsanalys användes för att analysera materialet.  Resultat Dataanalysen resulterade i fyra kategorier med tillhörande underkategorier. I kategorin Tiden prioriterades snabb ventilering för patienten samtidigt som avståndet till sjukhus också påverkade val av metod. Patienten och dennes förutsättningar är en kategori där bakomliggande orsaker till hjärtstoppet, patientens anatomiska förutsättningar samt om hjärtstoppet avslutades på plats eller inte påverkade ambulanssjuksköterskans metodval. Tredje kategorin var resurser som påverkade metodvalet genom att antalet enheter på plats och deras kompetens och erfarenhet hade en inverkan på metodval. Den fjärde kategorin användarvänlighet handlar om miljöfaktorer som påverkade metodvalet samt transport av patienten där avancerade metoder föredrogs för att underlätta förflyttningen. Slutsats Många av dessa faktorer är sådant som inte är något problem på sjukhus men som ambulanssjuksköterskan behöver vara medveten om. Vissa av faktorerna kan avhjälpas av verksamheten med ökad utbildning och modern utrustning men andra faktorer är sådant som ambulanssjuksköterskan behöver vara redo för att hantera. / Background Airway management is of great importance to the resuscitation in patients with cardiac arrest. There are a lot of tools to alleviate this task, but there are several factors to consider in out-of-hospital cardiac arrest, that doesn't exists within the hospital walls, that may influence the ambulance nurse method for managing the ventilation. Aim To study witch factors that influence the ambulance nurse choice of method to ventilate an out-of-hospital cardiac arrest. Methods A qualitative design was used with semi-structured interviews. Eight interviews were conducted with nursing specialists within intensive- and prehospital care. Qualitative content analysis was used to analyze the collected data. Results Data analysis resulted in four categories with associated under-categories. In the category Time distance to hospital had an effect on the choice of ventilation and fast ventilation was prioritized. The Patient was a category where the cause of the cardiac arrest, the patient anatomy and if the resuscitation was terminated on the spot or not was identified to have an impact on the method of airway management. The third category was Resources that influenced the airway approach was the amount of units on the scene and their competence and experience. The fourth category was ease-of-use where environment had an influence on airway management as well as the transportation of the patient. Conclusion Even though these factors often are a none-issue in the hospital it's vital to the ambulance nurse to be aware of these. Some factors can be alleviated by the agency with increased education and modern equipment but other factors are just something the ambulance nurse needs to be aware of and able to handle.

Die Ergebnisse der Arbeit weisen mehrfach auf eine defizitäre IL-10 Produktion in Alveolarmakrophagen von Asthmatikern hin. Die reduzierte IL-10 Expression auf Protein- und Genebene korrelierte mit einer erhöhten Produktion proinflammatorischer Zytokine (TNF-?, MIP1-?, GM-CSF). Diese Beobachtung impliziert einen Defekt in der IL-10 Synthese, der in einer verstärkten und prolongierten pulmonalen Entzündungsantwort resultiert. Daraus läßt sich schlußfolgern, dass beim Asthma bronchiale eine Dysbalance zwischen pro- und antiinflammatorischen Zytokinen pathogenetisch von Bedeutung ist. Die verringerte Sensitivität von Alveolarmakrophagen auf die inhibitorischen Effekte von exogenem IL-10 im Vergleich zu Blutmonozyten ist durch Unterschiede in den Mechanismen der Signaltransduktion bedingt (37, 54). Der Nachweis der Expression von proinflammatorischen Zytokinen in Bronchialmyozyten (RANTES, IL-8) führte zu einer Neubewertung dieser Zellen als Immuneffektorzellen in der Pathogenese des Asthma bronchiale. Neben der Kontraktilität sind Myozyten auch aktiv an der Aufrechterhaltung der Atemwegsentzündung beteiligt. Die inhibitorischen Effekte von IL-10 und IL-13 auf die Synthese proinflammatorischer Chemokine (RANTES, IL-8, MIP-1() in migrierten Entzündungszellen und residenten Bronchialmyozyten konnten in verschiedenen Arbeiten gut dokumentiert werden. Die Vielzahl antiinflammatorischer Effekte von IL-10, die sich auf unterschiedliche Zellsysteme wie Monozyten, Makrophagen und Bronchialmyozyten erstrecken, unterstreicht die pathogenetische Bedeutung dieses Zytokins. Der molekulare Mechanismus, welcher die IL-10 Wirkung vermittelt, ist derzeit noch nicht vollständig aufgeklärt. Angenommen wird eine rezeptorvermittelte Inhibition von Transkriptionsfaktoren des Stat Systems und NF-(B (76). Zukünftige molekularbiologische und klinische Studien sind jedoch notwendig, um den Kenntnisstand der Effekte antiinflammatorischer Zytokine zu vertiefen, und die Gabe von rekombinantem IL-10 als möglichen Ansatz zur Therapie chronisch entzündlicher Lungenerkrankungen zu evaluieren (81). / The results of this present thesis show a deficiency of IL-10 production in alveolar macrophages in asthma. The reduced IL-10 expression on protein and m-RNA level correlated with an increased production of pro-inflammatory cytokines such as TNF-(, MIP1- ( and GM-CSF. These observations implicate an impaired IL-10 synthesis in asthma with a subsequent prolongation of the inflammatory response. This leads to the conclusion that a dysbalance between pro- and anti-inflammatory cytokines is present in asthma and may be therefore of pathogenetic importance. The reduced sensitivity of alveolar macrophages to the inhibitory effects of exogenous IL-10 compared to peripheral blood monocytes may be caused by different signal transduction mechanisms. The expression of the proinflammatory cytokines RANTES and IL-8 in cultured human airway smooth muscle cells led to the conclusion that airway smooth muscle cells may act beside their contractile function as immunomodulatory cells in the pathogenesis of asthma. The inhibitory effects of IL-10 and IL-13 on the synthesis of proinflammatory cytokines (RANTES, IL-8, MIP1-() in immigrated inflammatory cells and resident cells such as airway smooth muscle cells have been shown in several publications that are part of the present thesis. The numerous antiinflammatory effects of IL-10 on different inflammatory cell systems such as monocytes/macrophages and smooth muscle cells underline the pathogenetic importance of this cytokine. The molecular mechanisms that mediate the IL-10 effects involve the transcription factors NF-(B and the Stat-System. Future studies are needed to determine the molecular mechanisms of the anti-inflammatory effects of IL-10 and IL-13 more deeply and to evaluate their application for the therapy of chronic inflammatory pulmonary diseases.

Obstructive sleep apnoea/hypopnoea syndrome (OSAHS) is characterised by repeated cycles of upper airway obstruction during sleep, leading to diurnal symptoms. Individuals with Down syndrome (DS) are predisposed to this as the DS phenotype overlaps with OSAHS risk factors. Around 2-4% of the general adult population and 55% of children with DS have OSAHS but, to date, no large-scale study has assessed OSAHS prevalence or efficacy of treatment in DS adults. This study aimed to: 1) Systematically assess subjective and objective OSAHS prevalence; 2) Assess the effectiveness of continuous positive airway pressure (CPAP) in an adult DS population. Standard questionnaires including pictorial Epworth Sleepiness Scale (pESS) and Developmental Behaviour Checklist for Adults (DBC-A) were sent to UK adults aged ≥16yr with DS and their caregivers. All questionnaire responders were invited to undergo home polygraphy. Symptomatic adults with DS with ≥10 apnoeas/hypopnoeas per hour in bed (AH) on home polygraphy were invited to participate in a prospective randomised controlled trial (RCT) of CPAP v. lifestyle advice, with review at 1, 3, 6 and 12m. Participants in the lifestyle arm were offered CPAP at 1m. Standard measurements of sleepiness, behaviour, cognitive function and general health were undertaken. Standard statistical analyses were conducted, with significance set at p < 0.001 to control for multiple testing. Of 5270 questionnaires sent, 1105 responses were valid (21%). Responders (55% males) were overweight/obese young adults: mean BMI 29.0±6.8kg/m2; mean age 28±9 years. Women had a higher BMI (p < 0.0001), but collar size was greater in men (p < 0.0001). Mean pESS scores were broadly within the normal range (7±5/24). No significant gender differences in OSAHS symptoms were noted. Individuals with probable OSAHS had higher pESS and DBC-A scores, and significantly more symptoms of OSAHS. Subjective OSAHS prevalence was estimated at 35%. Of the 790 individuals invited, 149 underwent polygraphy, with 134 valid studies obtained: mean AH 21.8(10.9-42.7); mean oximetry desaturation index (ODI) 6.6(2.3-20.0). No significant gender differences were observed. Forty-two percent of participants met standard clinical diagnostic criteria for OSAHS. Twenty-eight eligible adults with DS (19 male) were randomised: age 28±9yr; BMI 31.5±7.9kg/m2; AH 28.6(14.8-47.9); ODI 7.3(1.8-21.9); pESS 11±6/24. Groups did not differ significantly at baseline. By 12m, 4 participants had withdrawn (all remaining participants on CPAP). The pESS (p=0.001), DBC-A Disruptive (p < 0.0001) and Kaufmann Brief Intelligence Test verbal subscale (p=0.001) scores improved significantly. This first large study of OSAHS prevalence in the adult DS population estimates a prevalence of 35-42% - around 10 times higher than in the general adult population. Sustained, significant improvements in sleepiness, cognitive function and behavioural/emotional outcomes with CPAP use over a 12m period were demonstrated during this first RCT of CPAP in adults with DS. A larger trial of CPAP in this population is warranted.

A pressão positiva contínua nas vias aéreas(CPAP) é a forma mais simples de ventilação não invasiva. O objetivo deste estudo é comparar o desempenho de dois modelos de gerador de fluxo com um ventilador projetado especificamente para ventilação não invasiva no modo CPAP, através de um modelo mecânico de pulmão e em voluntários sadios, em três diferentes alimentações de pressão e em CPAP de 5, 10 e 15 cm H2O. Conclui-se que os geradores de fluxo têm capacidade similar ao ventilador específico para manter o nível de CPAP, se ajustados para sua melhor pressão de alimentação, que foi ao redor de 100 L/min / Continuous positive airway pressure (CPAP) is the simplest form of noninvasive ventilation. Mechanical ventilators designed to invasive ventilation, ventilators specifically designed to noninvasive ventilation (NIV-Ventilator) and continuous flow generators can provide CPAP. The objectives of this study is compare the performance of two continuous flow generators with a ventilator designed to NIV to deliver continuous positive airway pressure (CPAP) and compare flow generators using different oxygen pressure supplies in lung model and healthy subjects, in CPAP of 5, 10 and 15 cm H2O. It was observed that flow generators had similar performance to noninvasive ventilator if they were adjust in their best output flow, that was around 100 L/min

A prevalência mundial de asma na infância é alta. Alterações estruturais das vias aéreas são observadas na asma, e podem ocorrer precocemente na infância. Este estudo tem como objetivo comparar os resultados de um modelo de sensibilização alérgica, em camundongos de diferentes idades. Para tanto foram utilizados camundongos Balb/C pré-desmamados, jovens e adultos. O grupo de animais pré desmamados foram divididos em outros dois grupos (18D 18D1), sendo que ambos foram sensibilizados com duas injeções intraperitoneal (i.p.) de 10 g ovalbumina (OVA) no 5º e 7º dia de vida. Após, o primeiro grupo de camundongos pré desmamados foram submetidos a 01 (um) desafio, este consistente em receberem inalações por 3 dias consecutivos, a 3% de OVA, por 10 minutos, nos dias 14, 15 e 16. O segundo grupo de camundongos pré desmamados foram submetidos 02 (dois) desafios, estes nos dias 09, 10 e 11; e 14, 15 e 16 dias de vida. O grupo de camundongos jovens (40D) receberam as mesmas inalações nos dias 22 a 24 e depois nos dias 36 a 38. Um quarto grupo de camundongos, denominados adultos (100D), foram sensibilizados com 10 g OVA i.p. nos dias 60 e 62 de vida; e também recebendo inalações por 3 dias consecutivos a 3% de OVA, por 10 minutos, nos dias 77 a 79 de vida, repetindo o procedimento nos dias 96, 97 e 98, sendo que os animais em todos os xiii grupos foram sacrificados 48hs após a última inalação. Todos os grupos possuíam um grupo controle respectivo, mesmo protocolo, mas ao invés de OVA, recebiam apenas solução salina. Observamos que os animais sensibilizados, quando comparados entre si, não apresentavam diferença quanto à densidade de células de eosinófilos (p = 0,052). A densidade de células TCD3+ foi maior nos camundongos adultos e no grupo de animais pré desmamados com dois desafios (p<0,001), não havendo diferença nos demais grupos (p=1,000). Foi possível observar também uma maior expressão de IL-5 nas vias aéreas quando comparados os grupos OVA de 18 dias de vida (18D e 18D1) com os seus controles (p=0,017). Todavia não houve esta diferença de IL-5 nos grupos jovens e adultos. Entre os grupos controles, a expressão de IL-5 foi menor nos grupos de 18 dias de vida (18D e 18D1) em relação aos animais dos grupos de 40 e 100 dias de vida (40D e 100D - p<0,001). Verificamos ainda que o grupo de animais pré desmamados com um desafio (p = 0,003) e os camundongos adultos (p = 0,006) apresentaram aumento da expressão de TGF- nas vias aéreas, quando comparados aos seus respectivos controles; e que os camundongos do grupo pré desmamado com um ou dois desafios apresentaram maior expressão de PAS no epitélio bronquiolar, quando comparado aos camundongos jovens e adultos (18D e 18D1 - p=0,007 e 40D e 100D - p=0,073). Entre os camundongos sensibilizados, o grupo pré desmamado com um único desafio, apresentou menor fração de área de colágeno comparado ao grupo de camundongos pré desmamados que receberam dois desafios (p<0,001), não havendo outras diferenças entre os grupos. xiv Camundongos jovens e adultos apresentaram um aumento de espessura do músculo liso da via aérea (MLB) quando comparados a seus respectivos controles (p = 0,048). Desta forma, foi possível demonstrar que os camundongos pré desmamados podem desenvolver alterações inflamatórias e estruturais nas vias aéreas, porém apresentam características diferentes das alterações observadas em animais com maior idade. Por fim, conclui-se que o presente estudo proporciona resultado e forma a ser utilizado como base para um estudo experimental, seja para verificar o resultado de medicamentos, seja para um estudo comparativo em crianças, jovens e adultos com asma, a fim de se verificar as diferenças apresentadas; e assim, auxiliar na adequada conduta clínica para prevenção ou combate dessa doença / The prevalence of childhood asthma is high worldwide. Recent data indicate that asthma structural changes occur early in childhood, and that structure alterations occur early in life. In this study we have aimed to compare a model of allergic sensitization in infantile, juvenile and adult mice. BALB/c mice at different ages were sensitized with two intraperitoneal injections (i.p.) of 10 g ovalbumin (OVA) at day 05 and 07 and received 3 daily inhalations of 3% OVA for 10 min on days 14 to 16 and 09 to 11 - 14 to 16 the infantile groups (18d - 18d1).The juvenile mice (40d) at days 22 to 24 - 36 to 38 and adult mice (100d) were sensitized with 3% OVA i.p. at day 60 and 62 and received 2x 3 daily inhalations at days 77-79 and at day 96-98, being euthanized 48h later. Control groups received saline using the same protocols. The OVA treated animals were compared among each other there were no differences regarding eosinophil cell density (p= 0.052). The density of T CD3+ cells was higher in the adult mice and in the infantile group with two challenges in relation to 18D e 40D (p=0.000), but without differences between the former groups (p= 1.000). When OVA groups were compared to the respective controls, infantile groups presented increased IL-5 expression in the airways (p=0.017), no differences were observed in the juvenile and adult mice. Among controls, IL-5 expression was lower in the infantile groups in relation to the juvenile and adult mice (p<0.001). The infantile group (p=0.003) with one challenge and the adult mice (p=0.006) presented increased TGF- expression in the airways when compared to their respective controls. Infantile mice with one or two challenges presented more PAS positivity in the bronchiolar epithelium than the juvenile and adult mice (p=0.007 and p=0.073). Among the OVA mice, infantile mice with one xvi challenge presented lower collagen area fraction than the group of infantile mice that received two challenges (p=0.000), without further differences among groups. Juvenile and adult mice had increased ASM thickness when compared to their age related controls (p=0.48). In summary, we have shown that infantile mice develop inflammatory and structural alterations in the airways, but that are partially different from those developed in older animals. Understanding the phenotypic differences in children vs adult asthma is very important to treat disease adequately and to manage prevention of severity