The effects of inhaled air pollution particles on lung clearance mechanisms is an important factor in understanding how the mammalian lung deals with such pollutants and, as such, how exposure to these pollutants can be regulated. The nanoparticle(diameter S lOOnm) and transition metal components of PMIO (particulate matter with a diameter less than lO~m) have been implicated as playing major roles in the impairment of alveolar macrophage function and the subsequent retention of particles in the respiratory system. The aim of this study was to investigate the effects of components of PMIO on macrophage functions both directly, by examining macrophage phagocytosis and migration, and indirectly, by studying peripheral factors affecting macrophagefunction such as recruitment by type II cells and complement based mechanisms. We hypothesised that the alveolar epithelial type II cell line would release leukocyte chemoattractants in response to particle exposure and that this could be measured by use of a macrophage migration assay. A sub-toxic dose (125 ~g/ml)of surrogate air pollutionparticles (fine and nanoparticle carbon black and titanium dioxide) was established by measuring LOH release from a murine alveolar macrophage cell line (1774.2) and an alveolar epithelial type II cell line (L-2) in response to particle exposure. Optimisation ofa chemotaxis assay and measurement of macrophage migration towards conditioned medium obtained from the particle-exposed type II cells was conducted and it was determined that carbon black nanoparticles induced type II cells to secrete a chemoattractant that resulted in significant increases in macrophage migration compared to the negative control. This was in contrast to other particle types tested in this study which did not induce any increases in macrophage migration. It was also hypothesised that complement proteins could be involved in macrophage recruitment to sites of particle deposition and, as such, the migration of macrophages towards particle exposed blood serum was examined in vitro. Foetal bovine serum (FBS) was exposed to fine and nanoparticle caroon black and titanium dioxide (l-Smg/ml) for 2 hours. It was found, in accord with the previous study involving type II cells, that carbon black nanoparticles could activate the generation of chemotactic factors in serum that could subsequently induce significant increases (p < 0.001) in macrophage migration when serum was diluted to 10% using serum-free RPMI 1640 culture medium. This effect could be ameliorated by co-incubating the particle-treated serum in the presence of the antioxidant Trolox suggesting that oxidative stress played a role in the generation of the chemoattractant molecules. However, incubation of the serum with a pure oxidant at a range of doses did not result in the generation of chemotactic molecules suggesting that another factor could be involved in the chemoattractant generation. Further investigation to determine the exact molecular mechanism behind the chemoattractant generation is warranted. In contrast to the previous studies, we have also found evidence that components of PM₁₀ can cause decreased efficacy of macrophage clearance mechanisms in vivo and in vitro. It was hypothesised that PM₁₀ instillation would result in a decrease in macrophage phagocytic potential and an increase in chemotactic potential ex vivo. Rats were instilled with 125 and 250μg of PM₁₀ collected from North Kensington, London or sterile saline (negative control). Post-instillation (18 hours), significantly elevated concentrations of TNFa were detected in the BAL fluid together with a significant increase in the number of BAL neutrophils. Phagocytosis and chemotaxis assays conducted with BAL macrophages ex vivo showed that macrophage migration towards a positive chemoattractant, Zymosan Activated Serum (ZAS), was significantly lower than the macrophages obtained from the negative control rats. Macrophage phagocytosis of latex beads ex vivo was also found to be significantly decreased when PM₁₀ was visible inside the cell. An in vitro study where a macrophage cell line (J774.Al) was exposed to a low dose of nanoparticle carbon black (31.25μg) together with varying concentrations (100μM - 100nM) of zinc chloride (ZnCl₂) was also conducted. Exposure of macrophages to nanoparticle carbon black and zinc chloride alone induced a decrease in macrophage phagocytosis. It was found that when macrophages were co-exposed to nanoparticle carbon black and ZnCl₂, there was an additive decrease in macrophage phagocytic potential. The results contained within this manuscript demonstrate that the components of PM₁₀ can induce adverse effects on specific aspects of macrophage clearance mechanisms, but that nanoparticles can also stimulate the production of chemoattractants to aid in the recruitment of phagocytes and subsequent particle clearance. Although a contrary relationship appears to exist between these findings, the recruitment of leukocytes in response to particulate exposure is a mechanism that supports particle clearance. However, the retardation of phagocytic and chemotactic mechanisms in particle exposed macrophages may help to explain the increased toxicity, inflammation and retention time observed with nanoparticle inhalation.

Made available in DSpace on 2016-12-06T17:07:09Z (GMT). No. of bitstreams: 1 Dissertacao Juliana Completa.pdf: 511459 bytes, checksum: 3285c75fc92aa665e5c911151417275b (MD5) Previous issue date: 2006-07-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The proposal of this research was to verify the effect of the physical exercise in patients with different levels of COPD, submitted to a Pulmonary program of long duration. It was characterized for a research of the descriptive and analytical type, where the collection of the data was made through the handbook revision of a data base, in a sample of 40 patients. As results were gotten that in relation the changeable tolerance to the exercise, in the different levels of COPD, affirms that had a predominance of bigger effect of the physical exercise in the group of light and moderate level. For the variable ardiovascular alterations, one concludes, that it had a predominance of improvement in the groups moderate and serious. In relation the changeable subjective sensation of breathless between the COPD levels, had a predominance of the groups light and moderate in the improvement of the effect of the physical exercise. For the changeable subjective sensation of pain in lower extremity, a predominance of improvement in the group of moderate level of the illness was observed. How much the changeable respiratory muscle force, can be noticed a predominance of improvement in the group of patients of serious level. With the displayed one, it can be concluded through these analyses, that when analyzed under the optics of the statistics, all the three groups had presented improvement on the effect of the supervised physical training enter the groups of carriers of COPD, characterized for improvement the tolerance to the physical exercise, improve of the cardiovascular conditioning, reduction of the subjective sensation of breathless and pain in lower extremity and improve of the respiratory muscle force, of similar form. / A proposta desta pesquisa foi verificar os efeitos do exercício físico em pacientes com diferentes níveis de DPOC, submetidos a um programa de Reabilitação Pulmonar de longa duração. Caracterizou-se por uma pesquisa do tipo descritiva e analítica, onde a coleta dos dados foi feita através da revisão de prontuário de um banco de dados, numa amostra de 40 pacientes. Como resultados obteve-se que em relação a variável tolerância ao exercício, nos diferentes níveis de DPOC, afirma-se que houve uma predominância de maior efeito do exercício físico no grupo de nível leve e moderado. Para a variável alterações cardiovasculares, conclui-se, que houve um predomínio de melhora nos grupos moderado e grave. Em relação a variável sensação subjetiva de dispnéia entre os níveis de DPOC, houve uma predominância dos grupos leve e moderado na melhora dos efeitos do exercício físico. Para a variável sensação subjetiva de dor em membros inferiores, observou-se um predomínio de melhora no grupo de nível moderado da doença. Quanto a variável força muscular respiratória, pode-se notar um predomínio de melhora no grupo de pacientes de nível grave. Com o exposto, pode-se concluir através destas análises, que quando analisada sob a ótica da estatística, todos os três grupos apresentaram melhora sobre os efeitos do treinamento físico supervisionado entre os grupos de portadores de DPOC, caracterizadas por melhora a tolerância ao exercício físico, melhora do condicionamento cardiovascular, diminuição da sensação subjetiva de dispnéia e dor em membros inferiores e melhora da força muscular respiratória, de forma semelhante.

O objetivo desse estudo foi avaliar o comprometimento de pequenas vias aéreas na Fibrose Pulmonar Idiopática (FPI) analisando curvas Pressão- Volume (PV) do sistema respiratório. Coletamos curvas PV de doze pacientes antes da biopsia pulmonar, que confirmou FPI em sete pacientes e Pneumonite de Hipersensibilidade em cinco. Todas as curvas foram ajustadas com modelo sigmóide, V = a + b / (1 + e -(P-c/d)), e exponencial V = A - B . e -k.P (aplicado apenas à parte superior). O modelo exponencial, apesar do bom ajuste à parte superior, não representou a parte inicial da curva, gerando parâmetros sem significado. O modelo sigmóide ajustou bem toda a curva e gerou parâmetros com significado fisiológico, que sugerem a presença de colapso de pequenas vias aéreas na FPI. / The objective of this study was to evaluate small airways compromise in Idiopathic Pulmonary Fibrosis (IPF) using pressure-volume (PV) curves of the respiratory system. We collected PV curves from twelve patients before lung biopsy, which confirmed IPF in seven patients and Hipersensitivity Pneumonia in five. All curves were fitted with a sigmoid model, V = a + b / (1 + e -(P-c/d)), and an exponential model, V = A - B . e -k.P (applied only to the superior part of the curve). The exponential model, despite having a good fit to the superior part of the curve, did not represent the initial part, and yielded parameters with no physiological meaning. The sigmoid model had a good fit to the entire curve and yielded parameters with physiological meaning, suggesting the presence of small airways collapse in IPF.

Introdução: Poucos estudos têm sido direcionados às mudanças histopatológicas nas pequenas vias áreas e seu possível papel no processo de remodelamento, nas pneumonias intersticiais idiopáticas. Objetivos: Estudar aspectos morfológicos, morfométricos e de imunohistoquímica das pequenas via aéreas na Fibrose Pulmonar Idiopática/ Pneumonia Intersticial Usual (FPI/ UIP) e Pneumonia Intersticial Não-específica (NSIP). Métodos: Foram estudadas as pequenas vias aéreas em biópsias pulmonares de 29 pacientes com FPI/ UIP e 08 com NSIP. As biópsias foram comparadas com 13 pacientes com Bronquiolite Constritiva Crônica (BC) - como controle positivo - e 10 pulmões controles normais de autópsia. Foram analisados semi e quantitativamente aspectos arquiteturais, inflamatórios, estruturais das vias aéreas, além da expressão de TGF-&#946;, MMP -2, -7, -9, e seus inibidores (TIMP-1, -2). Resultados: Comparados com os controles, pacientes com FPI/ UIP, NSIP e BC apresentaram inflamação bronquiolar, inflamação e fibrose peribronquiolar aumentadas e áreas luminais diminuídas. Pacientes com FPI/ UIP tiveram paredes das vias aéreas mais espessadas, devido ao aumento de todos os compartimentos. Pacientes com NSIP apresentaram área do epitélio aumentada, enquanto pacientes com BC tiveram maior lâmina própria. Todos os grupos estudados demonstraram expressão epitelial bronquiolar aumentada de MMP-7 e -9 comparados ao controle. Conclusão: As pequenas vias aéreas são patologicamente alteradas e podem fazer parte do processo de remodelamento nas pneumonias intersticiais idiopáticas. / Background: Few studies have addressed small airway (SA) histopathological changes, and their possible role in the remodeling process, in idiopathic interstitial pneumonias. Objectives: To study morphological, morphometrical and immunohistochemical features of SA in Idiopathic Pulmonary Fibrosis (Usual Interstitial Pneumonia - UIP) and Non-Specific Interstitial Pneumonia (NSIP). Methods: We analyzed SA pathology in lung biopsies of 29 patients with UIP and of 8 with NSIP. Biopsies were compared with lung tissue of 13 patients with Constrictive Bronchiolitis (CB) - as a positive control - and 10 normal autopsied control lungs. We analyzed, semi-quantitatively, SA structure, inflammation, architectural features and the bronchiolar epithelial immunohistochemical expression of TGF-&#946;, MMP -2, -7, -9, and their tissue inhibitors (TIMP-1, -2). Results: Compared to controls, patients with UIP, NSIP and CB presented increased bronchiolar inflammation, peribronchiolar inflammation and fibrosis and decreased luminal areas. UIP patients had thicker walls, due to an increase in most airway compartments. NSIP patients presented increased epithelial areas, whereas patients with CB had larger inner wall areas. All of the groups studied presented increased bronchiolar expression of MMP-7 and MMP-9, compared to the controls. Conclusion: We conclude that SA are pathologically altered and may take part in the lung remodeling process in idiopathic interstitial pneumonias.

No description available.

Introdução: A doença pulmonar na fibrose cística (FC) é obstrutiva e supurativa, caracterizada por exacerbações recorrentes dos sintomas respiratórios e pela deterioração progressiva da função pulmonar. A gravidade da doença pulmonar é mensurada pelo volume expiratório forçado no primeiro segundo (VEF1), obtido através da espirometria. O VEF1 é um preditor de mortalidade bem documentado na literatura, utilizado como desfecho em ensaios clínicos e como parâmetro para indicar e monitorizar respostas terapêuticas. O objetivo do estudo foi avaliar o impacto da realização da espirometria em todas as consultas médicas na frequência das intervenções clínicas e na função pulmonar dos pacientes com FC. Métodos: Pacientes com diagnóstico de FC em acompanhamento em centro de referência, com idade entre 5-18 anos, realizaram uma espirometria antes de cada consulta médica durante o período de um ano (2014). Os dados coletados durante o seguimento foram comparados com o período de 24 meses anteriores ao estudo, período no qual os pacientes realizavam rotineiramente apenas uma espirometria a cada seis meses. Os principais desfechos avaliados foram diagnóstico de exacerbação pulmonar, frequência de introdução de novas terapias de uso crônico, encaminhamento ao ambulatório de transplante pulmonar e média do VEF1 basal. A utilização da espirometria para tomada de decisão clínica foi referida pelo médico assistente através de questionário. Resultados: Participaram do estudo 80 pacientes (idade média 12,1 anos e 61,3% do sexo masculino), tendo sido realizadas 418 consultas durante o ano de seguimento (5,2 consultas por paciente/ano). Exacerbações pulmonares foram diagnosticadas em 27,5% das consultas, com taxa de 1,44 exacerbações pulmonares por paciente/ano, frequência significativamente maior quando comparada com os anos 2012 (p=0,001) e 2013 (p=0,05). A espirometria foi útil para diagnóstico de exacerbação pulmonar em 83,5% das vezes, e em 21,9% destes casos o diagnóstico de exacerbação foi feito exclusivamente pelo parâmetro do declínio agudo do VEF1. Terapias de uso crônico foram introduzidas 0,4 vezes por paciente/ano, sem diferença estatisticamente significante com os períodos anteriores. A espirometria foi útil em 83,9% das vezes em que se iniciou uma nova terapia. Foram realizados três encaminhamentos para o serviço de transplante pulmonar, sem diferença estatística com os períodos anteriores. A média do VEF1 basal da amostra foi de 80% do previsto (DP+28,2), sem diferença significativa com os valores observados nos anos anteriores 78,1% em 2013 (p=0,27); e 76,7% em 2012 (p=0,7), indicando tendência para manutenção da função pulmonar destes pacientes. Conclusão: O estudo evidencia um impacto significativo da realização da espirometria rotineira em todas as consultas médicas no aumento do reconhecimento e tratamento de exacerbações pulmonares, com potenciais benefícios na função pulmonar destes pacientes / Background: Pulmonary disease in cystic fibrosis (CF) is obstructive and suppurative, characterized by recurrent exacerbations of respiratory symptoms and progressive deterioration of lung function. The severity of lung disease is measured by forced expiratory volume in the first second (FEV1), obtained through spirometry. FEV1 is a well documented predictor of mortality in the literature, used as an endpoint in clinical trials and as a parameter for indicating and monitoring therapeutic responses. The aim of the study was to evaluate the impact of performing spirometry during routine medical visits on the frequency of clinical interventions and lung function in CF patients. Methods: Patients with a diagnosis of CF in follow-up at the reference center, aged 5-18 years, underwent spirometry before each clinical visit during a one-year period (2014). Data collected during follow-up were compared with the 24-month period prior to the study, during which patients routinely performed only one spirometry every six months. The outcomes included diagnosis of pulmonary exacerbation, frequency of introduction of new therapies for chronic use, referral for pulmonary transplantation, mean baseline FEV1. The use of spirometry for clinical decision making was reported by the attending physician by questionnaire. Results: 80 patients (mean age 12.1 years and 61.3% males) participated in the study, and 418 visits were performed during the year of follow-up (5.2 visits per patient/year). Pulmonary exacerbations were diagnosed in 27.5% of the consultations, with a rate of 1.44 pulmonary exacerbations per patient/year, significantly higher than the year of 2012 (p = 0.001) and 2013 (p = 0.05). Spirometry was useful for diagnosis of pulmonary exacerbation in 83.5% of the time, and in 21.9% of these cases the diagnosis of exacerbation was made exclusively by the parameter of the acute decline of FEV1. Chronic use therapies were introduced 0.4 times per patient/year, with no statistically significant difference with previous periods. Spirometry was useful in 83.9% of the times a new therapy was started. Three referrals were made for pulmonary transplantation, with no statistical difference with previous periods. The mean baseline FEV1 of the sample was 80% predicted (SD+28.2), compared to 78.1% in 2013 (p=0.27); and 76.7% in 2012 (p=0.7), indicating a tendency for stabilization of the pulmonary function of these patients. Conclusion: The study evidences a significant impact of routine spirometry during routine encounters of CF patients in the increase of diagnosis and treatment of pulmonary exacerbations, with potential benefits for the pulmonary function of these patients

Introduction Les mécanismes sous-jacents à la relation entre la fonction ventilatoire et l’incidence de pathologies cardiovasculaires restent incertains. Le syndrome métabolique, cluster des principaux facteurs de risque cardiovasculaire dont l’obésité abdominale, pourrait jouer un rôle dans cette relation. Le lien entre le syndrome métabolique et la fonction ventilatoire est méconnu. Parallèlement, peu de données ont été publiées sur la relation entre l’obésité abdominale et le risque d’asthme. De nombreuses études ont rapporté une relation positive entre l’indice de masse corporelle (IMC) et l’incidence de l’asthme en particulier chez la femme. L’IMC est un indice global qui ne permet pas de distinguer la masse maigre de la masse grasse ni d’estimer la distribution régionale de l’adiposité. L’adiposité, en particulier abdominale, tend à augmenter avec l’âge au détriment de la masse maigre. Chez le sujet âgé, bien que fréquent et souvent sévère, l’asthme reste peu étudié.Matériel et Méthodes La relation entre le syndrome métabolique et la fonction ventilatoire (Volume Expiratoire Maximal Seconde, Capacité Vitale Forcée) a été étudiée à partir des données de 121965 sujets ayant bénéficié d’un examen périodique de santé au centre IPC à Paris entre 1999 et 2006. Une analyse en composantes principales a permis d’évaluer la part respective de chacun des paramètres du syndrome dans cette relation. Puis, l’étude du déclin de la fonction ventilatoire (VEMS) et de son lien avec l’adiposité abdominale a été conduite chez près de 10000 sujets du centre IPC réexaminés à 5 ans. Enfin, la relation entre l’adiposité abdominale et la prévalence et l’incidence de l’asthme a été analysée au sein de la cohorte des 3 Cités chez 7643sujets âgés de 65 ans et plus. Principaux résultats Le syndrome métabolique était associé à l’altération de la fonction ventilatoire (Odds Ratio ajusté, Intervalle de Confiance à 95%=1,28 [1,20-1,37] et ORa=1,41 [1,31-1,51], respectivement pour le VEMS et la CVF<Limite Inférieure de la Normale). Cette association reposait essentiellement sur la présence de l’obésité abdominale indépendamment entre autres de l’IMC et du statut tabagique chez l’homme comme chez la femme. Un déclin accéléré de la fonction ventilatoire était associé au gain d’adiposité abdominale (∆VEMS= -24,6 ; -29,0 ; -36,2 ml/an pour un tour de taille « diminué », « stable » et « augmenté », respectivement). Un risque augmenté d’asthme était associé au surpoids abdominal et à l’obésité abdominale dans les deux sexes (ORa, IC95%=1,30 [1,02-1,65] et 1,76 [1,31-2,36], respectivement). Conclusion Ces résultats apportent des arguments en faveur du rôle de l’obésité abdominale dans le développement des pathologies respiratoires chroniques. Nos résultats suggèrent que la mesure de la fonction ventilatoire pourrait aider à identifier les sujets à haut risque cardiométabolique. / Introduction The mechanisms underlying the relationship between lung function and the incidence of cardiovascular disease remain uncertain. Metabolic syndrome, a cluster of major cardiovascular risk factors including abdominal obesity, may play a role in this relationship. Data on the association between lung function and metabolic syndrome are sparse. Few data have been published on the relationship between abdominal obesity and the risk of asthma. Many studies have reported a positive relationship between body mass index (BMI) and the incidence of asthma particularly in women. BMI is a crude measure of obesity that does not discriminate between muscle and adipose tissue mass or estimate regional adiposity. Adiposity, and particularly visceral fat mass, tends to increase with aging at the expense of muscle mass and these changes in body composition make BMI an inadequate body fatness indicator. In the elderly, although frequent and often severe, asthma remains poorly studied.Materials and MethodsFirst, the relationship between metabolic syndrome and lung function (Forced expiratory volume in one second, Forced Vital Capacity) was studied using data from 121,965 patients who had a health examination at the Paris Investigations Préventives et Cliniques center between 1999 and 2006. A principal component analysis was used to investigate the differential associations between lung function and specific components of metabolic syndrome. Second, the study of lung function (FEV1) decline and its relationship with abdominal fat was conducted among nearly 10,000 subjects followed 5 years later at the IPC center. Third, the relationship between abdominal adiposity and prevalence and incidence of asthma was analyzed within the 3 Cities cohort study including 7,643 subjects aged 65 and over.Main resultsMetabolic syndrome was associated with impaired lung function (Adjusted Odds Ratio, 95% Confidence Interval=1.28 [1.20-1.37] et ORa=1.41 [1.31-1.51], for FEV1 and FVC<Lower Limit of Normal, respectively). This association was mainly due on the presence of abdominal obesity independently of BMI and smoking status in men as in women. An accelerated decline in lung function was associated with abdominal fat gain (∆VEMS= -24.6 ; -29.0 ; -36.2 ml/year for waist circumference « decreased», « stable » et « increased », respectively). An increased risk of asthma was associated with abdominal overweight and abdominal obesity in both sexes (ORa, IC95%=1.30 [1.02-1.65] and 1.76 [1.31-2.36], respectively).ConclusionThese results provide arguments for the role of abdominal obesity in the development of chronic lung diseases. Measurement of lung function may help to identify patients at cardiometabolic high risk.

Por serem as manifestações pulmonares de etiologia infecciosas muito freqüentes e potencialmente graves nas crianças com aids, o diagnóstico deve ser precoce para uma rápida e efetiva intervenção terapêutica. A proteína C reativa (PCR), um dos marcadores das provas de fase aguda, tem sido usada na prática clínica como um recurso diagnóstico na diferenciação entre patologias sistêmicas de etiologia viral e bacteriana, bem como na monitorização da eficácia da terapêutica antimicrobiana frente a uma infecção. Apesar da proteína C reativa ser um exame inespecífico e poder estar aumentada em diferentes situações clínicas (infecções sistêmicas, doenças inflamatórias e neoplásicas, isquemias, queimaduras), a infecção bacteriana é a causa mais freqüente para o seu aumento. A PCR eleva-se rapidamente após a injúria tecidual, atingindo valores 10 a 1000 vezes superiores a seu nível basal: em virtude de sua curta meia vida, retorna em pouco tempo aos valores prévios após o fim da agressão. Com o objetivo de encontrar um método laboratorial auxiliar para as infecções pulmonares nas crianças com infecção pelo HIV foi estudada a proteína C reativa, pela técnica de nefelometria, em dois momentos distintos: na ausência de quadro infeccioso concomitante (grupo 1) e na vigência de pneumonia aguda (grupo 2). O grupo 1 envolveu o estudo de 66 crianças com infecção pelo HIV, resultando em 84 amostras de PCR coletadas na ausência de quadro infeccioso concomitante.No grupo 2 foram analisadas 6 crianças com infecção pelo HIV com 9 episódios de pneumonia aguda. As crianças com infecção pelo HIV foram classificadas de acordo com as categorias clínicas e imunológicas da classificação do CDC para infecção pelo HIV em crianças. Dentre as 66 crianças incluídas no grupo 1, 6 pertenciam à categoria N, 11 à categoria A, 27 à categoria B e 22 à categoria C. Das 84 amostras de PCR coletadas no grupo 1, 76 (90,48%) encontravam-se abaixo de 5 mg/l, 7 amostras entre 5 a 20 mg /l e, apenas 1 amostra entre 20 a 40 mg/l (1,15%). No grupo 2, todas as crianças eram pertencentes às categorias B3 (1/6) ou C3 (5/6), refletindo um estágio mais avançado da doença. Das 9 amostras de PCR, 6 apresentavam valores maiores que 40 mg/l, 1 entre 20 e 40 mg/l e as 2 amostras restantes, entre 5 e 20 mg/l. Os dados sugerem portanto que a infecção pelo HIV por si só não é acompanhada de aumento da PCR, bem como não existe relação com a classificação imunológica em que o paciente se encontre. Pacientes com infecção pelo HIV na vigência de pneumonia aguda apresentam níveis aumentados de PCR. Neste estudo, o ponto de corte que diferenciou os grupos 1 e 2 foi PCR = 28,9 mg/l com sensibilidade de 77,8% e especificidade de 100% (IC 95%) / As pulmonary infection is a common and potentially serious condition in HIV-infected children, effectiveness of treatment of this kind of affection depends to a large extent on the promptness of accurate diagnosis. The C-Reactive Protein (CRP), a reasonably well-established acute phase marker, has long been used to differentiate bacterial from viral infections. Despite its lack of specifity, that is, the fact that other conditions like inflammatory diseases, neoplasms, ischemia and burns may also increase CRP levels, Bacterial infections are the most frequent cause of increased CRP found in daily clinical practice. Shortly after any tissular injury, CRP increases considerably, reaching up to 10-1000 times its previous levels. Due to its short half-life, its decrease after the end of the affection is quick as well. This study aimed at evaluating the CRP (assessed by nephelometry) as an auxiliary tool to diagnose pulmonary infection in HIV-infected children. Two groups of patients were considered in this study: group 1 was constituted by 66 HIV-infected children with no clinical signs of concomitant infection (amounting to 84 CRP samples) and group 2 was constituted by 6 HIV-infected children with pneumonia (amounting to 9 CRP samples). All the subjects were assigned to categories according to the pediatric HIV classification system (CDC, 1994). Among the 66 children from group 1, 6 were assigned to categories N, 11 to A, 27 to B and 22 to C. Regarding the levels of CRP in group 1 it was found: 76 samples (90.48%) < 5 mg/l, 7 (8.33%) in the range between 5 and 20 mg/l and 1 sample between 20 and 40 mg/l. In the group 2, all the children were assigned either to category B3 (1/6) or C3 (5/6) and the CRP level distribution was the following: 6 (6/9) > 40 mg/l, 1 (1/6) between 20 and 40 mg/l and 2 (2/6) between 5 and 20 mg/l. These results suggest that 1.HIV infection by itself does not increase the levels of CRP, regardless the immunologic classification of the patient; 2.HIV-infected children with pneumonia present increased levels of CRP 3.In this study, the cut-off point to differentiate groups 1 and 2 was 28,9 mg/l, with sensitivity of 77,8% and specificity of 100% (p < 0.05)

INTRODUÇÃO: A inflamação desempenha um papel central no desenvolvimento da asma, que é considerada uma doença alérgica com um perfil inflamatório clássico Th2. No entanto, as citocinas de perfil IL-17 tem sido estudadas para melhor compreender sua participação na fisiopatologia desta doença. Pacientes asmáticos graves apresentam exacerbações freqüentes, sendo a causa infecciosa um dos principais desencadeantes e que podem perpetuar as respostas inflamatórias. A resposta Th17 pode estar claramente associada a esses eventos. OBJETIVO: Este estudo avaliou os efeitos da terapia com anticorpo monoclonal anti-IL-17 nas alterações presentes nos septos alveolares em um modelo experimental de inflamação pulmonar alérgica crônica exacerbado por LPS. MÉTODOS: Foram utilizados 60 camundongos macho da espécie BALB/c, sendo sensibilizados com ovoalbumina intraperitoneal e repetidamente expostos à inalação com ovoalbumina, seguidos por tratamento com ou sem anti-IL-17. Vinte e quatro horas antes do final do protocolo experimental de 29 dias, dois grupos receberam LPS intratraqueal (0,1 mg/ml, sendo os grupos OVA-LPS e OVA-LPS anti-IL-17). Posteriormente, avaliamos o fluido do lavado broncoalveolar (FLBA), por morfometria quantificamos o recrutamento das células apresentadoras de antígenos (FOXP3 e células dendríticas), de eosinófilos, a expressão celular de citocinas próinflamatórias (TNF-alfa, IL-2, IL-4, IL-5, IL-6, IL13 e IL-17), anti-inflamatórias (IL-10), quimiocina (TARC), além da quantificação de IL-6 por RT-PCR. Avaliamos também elementos da matriz extracelular (fibras colágenas tipo I e III, MMP-9, MMP-12, TIMP-1, TGF-beta, actina, decorina, lumicam, biglicano, fibronectina e integrina), edema dos septos alveolares, resposta das vias de estresse oxidativo através dos marcadores iNOS e 8-iso-PGF2alfa e as vias sinalizadoras NF-kB e Rho quinase, além da avaliação do diâmetro alveolar médio. RESULTADOS: Os animais do grupo OVA-LPS apresentaram uma potencialização de todas as respostas (p < 0,05) comparativamente ao grupo OVA, exceto para: expressão de IL-17, TNF-alfa, NF-kB, TIMP-1 e na fração de volume de fibras colágenas tipo I, decorina, lumicam e actina. No grupo OVA-anti-IL17 houve atenuação de todos os parâmetros quando comparado ao grupo OVA (p < 0,05). Nos animais do modelo de inflamação alérgica crônica exacerbado pelo LPS e tratado com anti-IL-17 (grupo OVA-LPS anti-IL-17) houve diminuição comparativamente ao grupo OVA-LPS dos seguintes parâmetros: número de células totais do lavado broncoalveolar, de células positivas para FOXP3 e células dendríticas, número de CD4+ e CD8+, de células positivas para IL-10 anti-inflamatória e citocinas pró-inflamatórias (TNF-alfa, IL-2, IL-4, IL-5, IL-6, IL-13 e IL-17); quimiocinas (TARC), expressão gênica de IL-6, edema nos septos alveolares; elementos da matriz extracelular (fração de volume de fibras colágenas tipo I e III, actina, decorina, biglicano, lumicam, fibronectina, integrina e expressão de células positivas para TGF-beta, MMP-9, MMP-12 e TIMP-1), da resposta das vias de estresse oxidativo: (células positivas para iNOS e fração de volume de isoprostano PGF-2alfa; da expressão celular de NF-kB, e das proteínas Rho quinase 1 e 2 (p < 0,05). Não houve diferenças no diâmetro alveolar médio entre todos os grupos experimentais. CONCLUSÃO: Esses dados sugerem que a inibição da IL-17 pode ser uma via terapêutica promissora para o tratamento da inflamação alérgica crônica, mesmo durante uma exacerbação e pode contribuir para o controle da inflamação Th1/ Th2/Th17, da expressão de quimiocinas, do remodelamento da matriz extracelular e do estresse oxidativo. As vias sinalizadoras de NF-kB e Rho-quinase estão envolvidas no controle dessas respostas neste modelo de inflamação alérgica crônica exacerbado pelo LPS / INTRODUCTION: Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, IL-17 profile cytokines have been studied to better understand their involvement in the pathophysiology of this disease. Severe asthmatic patients have frequent exacerbations, the infectious cause being one of the main triggers and that can perpetuate the inflammatory responses. The Th17 response may be clearly associated with these events. OBJECTIVE: This study evaluates the effects of anti-IL-17 monoclonal antibody therapy on alveolar septa in an experimental model of chronic allergic lung inflammation of asthma exacerbated by LPS. METHODS: Sixty male BALB / c mice were used, being sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours before the end of the 29-day experimental protocol, two groups received intratracheal LPS (0.1 mg / ml, OVA-LPS and anti-IL-17 OVA-LPS groups). Afterwards, we evaluated bronchoalveolar lavage fluid (BALF), by morphometry we quantified the recruitment of antigen-presenting cells (FOXP3 and dendritic cells), eosinophils, the cellular expression of proinflammatory cytokines (TNF-alpha, IL-2, IL IL-5, IL-6, IL-13 and IL-17), anti-inflammatory cytokines (IL-10), chemokine (TARC), and quantification of IL6 by RT-PCR. We also evaluated elements of the extracellular matrix (collagen fibers type I and III, MMP-9, MMP-12, TIMP-1, TGF-beta, actin, decorin, lumicam, biglican and fibronectin), alveolar septum edema, oxidative stress through the marker iNOS and 8-iso-PGF2? and the signaling pathways NF-kB and Rho kinase. In addition, we evaluated of the mean alveolar diameter. RESULTS: The animals of the OVA-LPS group presented a potentiation of the all responses compared to OVA (p < 0.05), except for: expression of IL-17, TNFalpha, NF-kB, TIMP-1 and in the volume fraction of type I collagen fibers, decorin, lumicam and actin. Treatment with anti-IL-17 (OVA-anti-IL17 group) attenuated all parameters compared to OVA group (p < 0.05). The animals of the chronic allergic inflammation model exacerbated by LPS and treated with anti-IL-17 (OVA-LPS anti-IL-17 group) had a decreased of the following parameters compared to OVA-LPS: total bronchoalveolar lavage cells number, FOXP3 and dendritic positive cells, CD4 + and CD8 + numbers, of cells positive for IL-10 antiinflammatory, and pro-inflammatory cytokines (TNF-alfa, IL-2, IL-4, IL-5, IL-6, IL- 13 and IL-17); chemokine (TARC), genic expression IL6; edema in the alveolar septum; extracellular matrix elements (volume fraction of collagen fibers type I and III, actin, decorin, biglican, lumicam, fibronectin, and expression of TGF-beta, MMP-9, MMP-12 and TIMP-1 positive cells) of the oxidative stress pathways response (iNOS positive cells and isoprostane volume fraction 8-isoPGF-2alfa) NFkB and Rho kinase 1 and 2 positive cells (p < 0.05). There were no differences in mean alveolar diameter among all experimental groups. CONCLUSION: These data suggest that inhibition of IL-17 may be a promising therapeutic pathway for the treatment of chronic allergic inflammation, even during an exacerbation, and may contribute to the control of Th1 / Th2 / Th17 inflammation, chemokine expression, extracellular matrix remodeling and oxidative stress. Signaling pathways of NF-kB and Rho-kinase are involved in the control of these responses in this model of chronic allergic inflammation exacerbated by LPS

INTRODUÇÃO: A pneumonite de hipersensibilidade (PH) é uma doença intersticial causada pela inalação de antígenos orgânicos específicos ou substâncias de baixo peso molecular em indivíduos geneticamente suscetíveis. A PH crônica representa seu estágio final, na qual a exposição antigênica prolongada leva à fibrose. Na PH crônica, o envolvimento das pequenas vias aéreas (PVA) é proeminente; entretanto, uma avaliação detalhada através de métodos funcionais e de avaliação quantitativa e automatizada pela tomografia computadorizada (TC) não foi realizada previamente. MÉTODOS: estudo transversal de 28 pacientes com PH crônica, com avaliação através de provas de função pulmonar (PFPs); oscilometria forçada (FOT); análise automatizada do volume pulmonar através da TC, incluindo quantificação de aprisionamento aéreo; e teste cardiopulmonar de exercício (TCPE) incremental em cicloergômetro para avaliar performance ao exercício, incluindo medidas seriadas da capacidade inspiratória e hiperinsuflação dinâmica (HD). Foram incluídos pacientes entre 18 a 75 anos, com diagnóstico confirmado pela combinação de achados tomográficos, exposição antigênica e biópsia compatível e/ou LBA com linfocitose. Foram excluídos pacientes com CVF e/ou VEF1 < 30% predito, tabagismo > 20 anos-maço, uso de oxigênio suplementar; diagnóstico prévio de asma ou DPOC, diagnóstico de hipertensão arterial pulmonar ou impossibilidade de realizar TCPE. Os dados foram comparados com controles saudáveis. RESULTADOS: 28 pacientes (16 mulheres; idade média 56 +- 11 anos; CVF 57 +- 17% predito) foram avaliados, e todos apresentavam padrão ventilatório restritivo sem resposta broncodilatadora. Na FOT, 4 pacientes apresentaram resistência aumentada a 5 Hz (R5), enquanto todos apresentaram baixa reactância (X5), sendo que nenhum apresentou resposta broncodilatadora significativa. Pacientes com PH crônica tiveram menor capacidade de exercício com menor O2 de pico, diminuição da reserva ventilatória, hiperventilação, dessaturação de oxigênio e escores de dispneia (Borg) aumentados quando comparado aos controles. A prevalência de HD foi encontrada em apenas 18% da coorte. Ao comparar pacientes com PH crônica com O2 normal e baixo (< 84% predito, LIN), o último grupo apresentou maior hiperventilação (slope E/CO2), um menor volume corrente e menores escores de capacidade física na avaliação do questionário de qualidade de vida (SF-36). A análise da curva ROC mostrou que volumes pulmonares reduzidos (CVF%, CPT% e DLCO%) foram preditores de baixa capacidade ao exercício. Na TC, a PH crônica teve aumento de áreas com alta densidade em unidades Hounsfield, inferindo maior extensão de opacidades em vidro fosco e fibrose em relação aos controles saudáveis. A extensão das áreas de atenuação reduzida (AAR) e aprisionamento aéreo em relação ao volume pulmonar total é pequena, e não se correlaciona com índices funcionais obstrutivos; entretanto, pacientes com maior percentual dessas áreas apresentam menos fibrose e função pulmonar mais preservada. CONCLUSÃO: a PH crônica se caracterizou por um acometimento eminentemente restritivo, e não de obstrução de vias aéreas, nos diferentes métodos diagnósticos aplicados. A redução da capacidade de exercício foi prevalente devido à limitação ventilatória e de troca gasosa, a exemplo de outras doenças intersticiais pulmonares, e não pela HD. Redução dos volumes pulmonares foram bons preditores das respostas ventilatórias durante o exercício / INTRODUCTION: Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by the inhalation of specific organic antigens or low molecular weight substances in genetically susceptible individuals. Chronic HP represents its final stage, in which prolonged antigenic exposure causes fibrosis. In chronic HP, small airway involvement is prominent; however, a detailed characterization through functional evaluation and through automatic quantitative evaluation of computed tomography (CT) has not been previously assessed. METHODS: Cross-sectional study with 28 chronic HP patients, with evaluation by pulmonary function tests (PFTs), forced oscillometry (FOT), automated lung volume analysis through CT, including quantification of air trapping (AT); and incremental cardiopulmonary exercise testing (CPET) on a cycle ergometer to evaluate exercise performance, including serial measurements of inspiratory capacity to establish dynamic hyperinflation (DH). Inclusion criteria: patients aged 18 to 75 years, with a chronic HP diagnosis confirmed by the combination of CT findings, known antigenic exposure and compatible biopsy and / or BAL with lymphocytosis. Exclusion criteria: FVC and / or FEV1 < 30% predicted, smoking > 20 pack-years, supplemental oxygen use; previous diagnosis of asthma or COPD; pulmonary arterial hypertension, or medical conditions that could interfere with CPET. Data were compared with healthy controls. RESULTS: All patients (16 women; mean age 56 +- 11 years; FVC 57 +- 17% predicted) had restrictive ventilatory pattern without bronchodilator response. In FOT, 4 patients had increased resistance at 5 Hz (R5), all patients presented low reactance (X5) values, and none presented a significant bronchodilator response. Chronic HP patients had reduced exercise performance with lower peak V?O2, diminished breathing reserve, hyperventilation, oxygen desaturation and augmented Borg dyspnea scores when compared with controls. The prevalence of DH was only found in 18% of patients. When comparing chronic HP patients with normal and low peak VO2 (< 84%predicted, LLN), the later exhibited higher hyperventilation (VE/VCO2 slope), lower tidal volumes, and poorer physical functioning scores on Short-form-36 health survey. ROC curve analysis showed that reduced lung volumes (FVC%, TLC% and DLCO%) were high predictors of poor exercise capacity. On CT, chronic HP is characterized by increased pulmonary densities (Hounsfield Units) inferring the extension of ground glass opacities and fibrosis when compared with healthy subjects. The extension of low attenuation areas (LAA) and AT in relation to the hole lung volume is low and does not correlate with PFT indexes of obstruction; however, patients with greater extension of these areas had less fibrosis and more preserved PFTs. CONCLUSIONS: Chronic HP was characterized by an imminently restrictive lung disorder, and not by airway obstruction, according to the different diagnostic methods applied in this study. Reduction of exercise capacity was prevalent due to ventilatory and gas exchange limitation, similarly to other fibrotic interstitial lung diseases, rather than due to DH. Reduced lung volumes were good predictors of ventilatory responses during exercise