Objetivo: Avaliar a qualidade de vida (QV) nos pacientes com bronquiolite obliterante pós-infecciosa (BOPI) comparando os escores de qualidade de vida com os de crianças hígidas. Verificar as associações entre os escores de qualidade de vida e os dados de função pulmonar de crianças com BOPI. Descrever as características sociodemográficas e clínicas das crianças envolvidas no estudo. Avaliar as propriedades psicométricas do questionário através da confiabilidade e validade. Metodologia: Após o cumprimento das exigências éticas, os dados sobre qualidade de vida foram obtidos através do questionário genérico Pediatric Quality of Life (PedsQL) 4.0. Aplicou-se o questionário em duas ocasiões, em 31 crianças com BOPI e em 80 crianças hígidas, de 8-17 anos, de ambos os sexos. Os dados foram submetidos ao teste t de Student e correlação linear de Pearson. As propriedades psicométricas do questionário foram avaliadas pela diferença mínima importante, pelo α de Cronbach e Correlação Intraclasse. Resultados: A idade média das crianças com BOPI foi de 11,2 ± 2,6 anos, 67,7% meninos, a média de anos de estudos foi 4,3 ± 2,2, apresentavam-se eutróficas 77,4% e a média do VEF1 na espirometria foi de 45%. Com relação a qualidade de vida houve diferença na média total dos escores e nos respectivos domínios entre os grupos, mas não foram diferenças estatisticamente significativas. Quanto as propriedades psicométricas do questionário, o α de Cronbach foi ≥ 0,7 no escore total e nos domínios físico, psicossocial e social nas crianças com BOPI e apenas no psicossocial nas crianças hígidas. A reprodutibilidade do questionário foi ≥ 0,7 no global e em todos os domínios, para ambos os grupos. Conclusões: Não houve diferenças na QV das crianças com BOPI em relação às hígidas. Na sua condição de questionário genérico, o PedsQL4.0 demonstrou-se confiável e, portanto, utilizável como elemento complementar no acompanhamento da saúde dessas crianças. / Objective: It aims at evaluating the quality of life in patients with postinfectious bronchiolitis obliterans (PBO) comparing their quality of life scores to the ones of healthy children. Also, at verifying the associations between the quality of life scores and the lung functioning data of PBO children. It also has the objective of describing the socio-demographic and clinical characteristics of children who were involved in the study. It aims at evaluating the psychometrical properties of the questionnaire by its reliability and validity. Methodology: After the accomplishment of ethical demands, the data about quality of life were obtained by means of the Pediatric Quality of Life (PedsQL) 4.0 generic questionnaire. It was applied in two occasions, to 31 PBO children and 80 healthy ones, between 8 and 17 years of age, of both genders. The data were submitted to the Student’s t-test and Pearson’s linear correlation. The psychometric properties of the questionnaire were assessed by the minimum important difference, by Cronbach’s α and the intraclass correlation. Results: The average age of PBO children was 11.2 ± 2.2, 67.7% were boys, with an average of 4.3 ± 2.2 years of studies, 77.4% were eutrophic and with an average of 45% of FEV1 in spirometry. In relation to the quality of life, there was a difference in the total average of scores and in the respective domains between the groups, but they were not statistically meaningful differences. Concerning the psychometric properties of the questionnaire, Cronbach’s α was ≥ 0.7 in the total score and in the physical, psychosocial and social domains of children with PBO and only in the psychosocial one in the healthy children. The reproductibility of the questionnaire was globally ≥ 0.7 and in all domains for both groups. Conclusions: There were no differences in quality of life of PBO children in relation to the healthy ones. In its condition of generic questionnaire, PedsQL 4.0 showed to be reliable and therefore applicable as a complementary element in the follow-up of these children’s health.

A bronquiolite obliterante pós-infecciosa é considerada uma complicação rara da bronquiolite viral aguda, ocorrendo em aproximadamente 1% dos casos. No entanto, observa-se que em países situados no hemisfério sul essa doença vem ocorrendo com maior freqüência. É uma doença que se caracteriza por obstrução fixa e irreversível do fluxo aéreo, como conseqüência de lesão irreversível dos bronquíolos, com formação de áreas de fibrose e preenchimento da luz bronquiolar por tecido fibroso e ocorre com maior freqüência no sexo masculino. Este estudo compreendeu um grupo de 25 pacientes já estudados por Zhang et al. com diagnóstico de bronquiolite obliterante pós-infecciosa, com o objetivo de realizar exames de imagem e compará-los com aqueles obtidos na época do primeiro estudo, a fim de identificar a evolução da doença, em termos de imagem, no período de tempo entre os dois estudos. Também foram realizados testes de função pulmonar. O estudo compreendeu um total de 21 pacientes do sexo masculino e 4 do sexo feminino. Para a comparação, foi criado um escore, o qual foi utilizado nos exames de imagem do estudo contemporâneo e também nos exames de imagem do primeiro estudo, onde maiores pontuações identificariam maior grau de lesão pulmonar. Foram obtidos exames de Tomografia Computadorizada de Alta Resolução (TCAR), cintilografia pulmonar perfusional e radiografias de tórax de todos os pacientes do estudo. As variáveis estudadas na TCAR foram espessamento de paredes brônquicas, bronquiectasias, atelectasias, áreas de hipo e hiperatenuação de parênquima pulmonar, padrão de granularidade, espessamento de septos conjuntivos e consolidação As variáveis estudadas ao radiograma convencional de tórax foram espessamento de paredes brônquicas, bronquiectasis, atelectasias, consolidação, rarefação de vasculatura pulmonar, retificação de cúpulas diafragmáticas, deformidade de caixa torácica e aumento de espaço retroesternal. Na cintilografia pulmonar perfusional foram avaliados o grau de déficit pulmonar perfusional nesse grupo de pacientes. Ao compararmos 22 exames de TCAR dos dois períodos de tempo, observamos que através da aplicação do escore, 17 (77,2%) pacientes reduziram seus valores no escore do estudo contemporâneo quando comparado ao escore do estudo anterior, 2 (9%) permaneceram com os mesmos valores e 3 (13,6%) apresentaram piora no valor dos escores. Ao compararmos exames de radiogramas de tórax de 25 pacientes, nos dois períodos de tempo, observamos que 14 (56%) apresentaram no estudo contemporâneo um aumento nos valores do escore, 8 (32%) reduziram o valor do escore e 3 (12%) permaneceram com os mesmos valores nos dois períodos de tempo. Ao compararmos os exames de cintilografia perfusional dos 25 pacientes, observamos que houve grande variabilidade nas lesões, tendo estas desaparecido em 5 (20%) pacientes, permanecido em 19 (76%) e com ausência em ambos os estudos em apenas 1 (4%) paciente. Nas provas de função pulmonar a alteração mais freqüentemente observada foi o distúrbio ventilatório obstrutivo, com variáveis graus de aprisionamento aéreo na pletismografia. Observamos então neste estudo que houve um diferente grau de evolução das lesões com o passar do tempo nesse grupo de pacientes, sendo que alguns apresentaram melhora em determinadas variáveis aos estudos de imagem, outros tiveram uma estabilização das lesões e outros apresentaram piora das lesões no decorrer de tempo entre os dois estudos. No entanto, observamos também que a bronquiolite obliterante pós-infecciosa não apresenta uma evolução fatal de curso rápido como se acreditava anteriormente, variando sua evolução de forma não uniforme entre os pacientes. / Postinfectious bronchiolitis obliterans is described as a rare complication of acute viral bronchiolitis, occurring in approximately 1% of patients. However, it has been shown that in some countries in the South Hemisphere this illness occurs more frequently. It is characterized by fixed and irreversible obstruction of airflow, as a consequence of irreversible damage to the bronchioles, causing areas of fibrosis and scarring in the bronchiolar lumen. Postinfectious bronchiolitis obliterans has been shown to occur more frequently in males. The present study included 25 patients, who had already been diagnosed as having postinfectious bronchiolitis obliterans and who were previously studied by Zhang and cols. The objectives of the present study were to perform image studies in the same patients, in order to investigate the evolution of this illness by comparing the results obtained from both studies. Tests of pulmonary function were also considered in the present study. For comparison, a score was created to study radiological images more carefully and it was applied to both studies. Bigger scores meant a greater degree of pulmonary lesions. High resolution computed tomography, pulmonary perfusion scans and chest radiographs were performed in all patients of this study. We concluded that the evolution of this illness developed distinctly in this group of patients; some presented improvement in some variables, others had a stabilization of pulmonary lesions and others presented worsening of lesions. However, we also observed that postinfectious bronchiolitis obliterans does not present with a uniform evolution, being apparently more benign than previously thought. The majority of patients presented stabilization of the illness with permanence of the lesions in the TCAR, which is the best exam to be performed together with radiological studies within this group of patients. The pulmonary function tests showed an obstructive pattern which was the most commonly observed alteration, and showed variable degrees of air trapping in body plethismography.

Bronchiolitis obliterans syndrome (BOS), a form of chronic lung allograft dysfunction, represents a major cause of mortality after lung transplantation. This disease is associated with a progressive fibro-obliteration of small airways (known as obliterative bronchiolitis) which leads to respiratory impairment and graft failure. The mechanisms behind airway occlusion remain unclear, and no curative treatment is available at the moment. Myofibroblasts are considered central effectors in this fibrotic process, but their origin is controversial. They can arise either from donor cells (resident fibroblasts and epithelial cells) or recipient cells (bone marrow-derived cells).The purpose of this project was to identify the precursors of mesenchymal cells responsible for post-transplant airway fibro-obliteration. Lineage-tracing tools were used to track or deplete potential sources of myofibroblasts in the heterotopic tracheal transplantation model, which produces a surrogate of obliterans bronchiolitis. Confocal analysis showed that myofibroblasts in the allografts were mostly recipient-derived, even though immunosuppression with tacrolimus induced a mild increase of donor-derived myofibroblasts. Occasional epithelial-to-mesenchymal transition was detected, but only in tacrolimus-treated recipients. On the other hand, fate-mapping techniques demonstrated that myeloid cells gave rise to the majority of mesenchymal cells in occluded airways. Accordingly, specific ablation of Cx3cR1+ mononuclear phagocytes significantly decreased allografts fibrosis. In parallel, single-cell RNA-sequencing unveiled surprising similarities between myeloid-derived cells (i.e. fibrocytes and macrophages) from the allografts and both murine and human samples of pulmonary fibrosis. Finally, analysis of BOS lesions from transplanted patients allowed us to translate our results to a clinical level. Indeed, confocal microscopy revealed that myofibroblasts expressing the macrophage marker CD68 were increased in BOS explants when compared to controls, and their numbers seemed correlated with the intensity of fibrosis.Collectively, these findings indicate that recipient mononuclear phagocyte system constitutes a clinically relevant source of mesenchymal cells infiltrating the airways after allogeneic transplantation. Therefore, therapies targeting migration and differentiation of mononuclear phagocytes and fibrocytes could prevent fibrotic remodelling of small airways and improve long-term outcomes after lung transplantation. / La bronchiolite oblitérante (bronchiolitis obliterans syndrome, BOS), une forme de dysfonction chronique du greffon, représente une des majeures causes de mortalité après transplantation pulmonaire. Cette pathologie est associée à une oblitération progressive et irréversible des petites voies aériennes par de la fibrose, qui mène à une perte de fonction respiratoire jusqu’à la défaillance du greffon. Les mécanismes impliqués dans la fibroproliferation ne sont pas encore bien compris, et il n’existe pas de traitement efficace de la BOS à l’heure actuelle. Les myofibroblastes joueraient un rôle majeur dans le développement de la fibrose, mais leur origine reste controversée. Ils pourraient dériver des cellules du donneur (fibroblastes in situ ou cellules épithéliales) ou bien du receveur (à partir de la moelle osseuse). L’objectif de cette étude était d’identifier les précurseurs des cellules mésenchymateuses responsables de l’obstruction des voies aériennes après transplantation allogénique. Nous avons utilisé des techniques de lineage tracing pour identifier les sources potentielles de myofibroblastes dans un modèle de transplantation hétérotopique de trachée, lequel permet d’obtenir une maladie fibro-oblitérante du greffon qui simule histologiquement la bronchiolite oblitérante. Les analyses par microscopie confocale ont montré que les cellules du receveur constituent la source principale de myofibroblastes dans les allogreffons, malgré une faible augmentation de la proportion de cellules mésenchymateuses dérivées du donneur lors du traitement immunosuppresseur. En plus, une minime fraction de myofibroblastes d’origine épithéliales a également été détectée, mais seulement dans les greffons traités par tacrolimus. D’autre part, nous avons établi que la lignée myéloïde produit la plupart des cellules mésenchymateuses détectés dans les voies aériennes oblitérées. Par ailleurs, la délétion spécifique de phagocytes mononucléaires Cx3cR1+ était associée avec une diminution significative du nombre de myofibroblastes et de la fibrose endoluminale dans les allogreffons. En parallèle, l’utilisation des techniques de séquençage en single cell a permis de révéler des ressemblances inattendues entre des populations de cellules d’origine myéloïdes (macrophages et fibrocytes) retrouvés dans les greffons et celles impliqués dans le développement de la fibrose pulmonaire chez l’homme et la souris. In fine, l’analyse par microscopie confocale des lésions pulmonaires de patients atteints de BOS nous a permis de transposer en clinique nos résultats expérimentaux. En effet, nous avons observé que la fraction de myofibroblastes positifs pour le CD68, un marqueur typiquement exprimé par les macrophages, était significativement augmentée dans les greffons avec bronchiolite oblitérante par rapport aux contrôles. De plus, leur nombre était corrélé avec la sévérité de la fibrose. L’ensemble de ces résultats indique que le système phagocytaire mononuclée constitue une source significative de cellules mésenchymateuses et contribue à la fibro-oblitération des voies aériennes après transplantation. L’utilisation de thérapies ciblant la migration et la différenciation des phagocytes mononuclées et des fibrocytes pourrait bloquer la destruction du greffon pulmonaire et améliorer la survie à long terme des patients transplantés. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Background: Patients with steroid-refractory intestinal acute graft-versus-host disease (aGvHD) and bronchiolitis obliterans syndrome (BOS) represent a population with a high need for alternative and effective treatment options. Methods: We report real-life data from 18 patients treated with extracorporeal photopheresis (ECP). This cohort consisted of nine patients with steroid-refractory intestinal aGvHD and nine patients with BOS. Results: We document partial or complete clinical response and reduction of symptoms in half of the patients with intestinal acute GvHD and patients with BOS treated ECP. Responding patients tended to stay on treatment longer. In patients with BOS, stabilization of lung function and forced expiratory volume was observed, whereas, less abdominal pain, less diarrhea, and a reduction of systemic corticosteroids were seen in patients with intestinal acute GvHD. Conclusions: ECP might not only abrogate symptoms but also reduce mortality caused by complications from high-dose steroid treatment. Taken together, ECP offers a serious treatment avenue for patients with steroid-refractory intestinal acute GvHD and BOS.

La bronchiolite oblitérante (BO) est la principale cause de décès à long terme après transplantation pulmonaire. La BO se manifeste par une diminution des capacités respiratoires liée à l’obstruction des petites voies aériennes par un tissu inflammatoire et fibroprolifératif. Dans cette thèse nous avons étudié l’hypothèse de l’implication de la kinase nucléaire MSK1 dans la BO. Nous avons utilisé la transplantation hétérotopique de trachée comme modèle murin de BO. La pertinence du choix de ce modèle a été confirmée par l’étude de la re-vascularisation fonctionnelle de la greffe après transplantation. Dans ce modèle nous avons montré une augmentation de l’expression et de l’activité de MSK1 pendant le développement de la BO. Le traitement des souris transplantées avec des inhibiteurs pharmacologiques de MSK1 a permis d’inhiber l’inflammation et la fibroprolifération, montrant le rôle de MSK1 dans la BO. Nous avons également mis en place un essai de criblage utilisant la technologie HTRF pour rechercher de nouveaux inhibiteurs de MSK1. Les résultats décrits dans cette thèse, montrent que la kinase MSK1 est une potentielle cible thérapeutique pour combattre la BO. / Obliterative bronchiolitis (OB) is the chronic rejection after lung transplantation and is the main cause for late death post-transplantation. OB is characterized by decrease of the pulmonary function caused by obstruction of the small airways by inflammatory and fibroproliferative tissue. We studied the hypothesis of the implication of the nuclear kinase MSK1 in the OB. The relevance of the model was demonstrated by showing the rapid functional re-vascularization of the graft. In this model the allograft, shows an increased MSK1 expression and activity. We therefore treated mice with pharmacological inhibitors of the MSK1 activity and we demonstrated an inhibition of the inflammation and the fibroproliferation during OB. We next set up an enzymatic assay using the heterogeneous time-resolved fluorescence, to proceed for a screening for new MSK1 inhibitors. In summary, this study proposed MSK1 as potential therapeutic target to combat OB.

A Bronquiolite Obliterante pós-infecciosa (BO) é conseqüência de agressão ao epitélio do trato respiratório inferior que se caracteriza por obstrução da via aérea distal. Autores ressaltam que além do diagnóstico oportuno da BO, do tratamento agressivo das infecções e da oxigenoterapia, é importante um plano nutricional adequado para evolução clínica favorável desta enfermidade. O objetivo do presente estudo é avaliar o estado nutricional de crianças e adolescentes portadores de BO, e, analisar a associação com aspectos clínicos e nutricionais. Para tanto, foi realizado estudo transversal em crianças (<10 anos) e adolescentes (10-18 anos), com diagnóstico clínico/tomográfico de BO, em acompanhamento ambulatorial. Para a determinação do estado nutricional nas crianças foram analisados os escores-Z de peso por idade (ZPI), estatura por idade (ZEI) e peso por estatura (ZPE), e nos adolescentes analisou-se o ZEI e a distribuição dos percentis do Índice de Massa Corporal (IMC). Entre os ≤ 5 anos, os índices foram avaliados com base no padrão da Organização Mundial da Saúde (WHO, 2006), e, a partir dos cinco anos adotou-se a referência do Centers for Disease Control (CDC, 2000). Na avaliação da composição corporal, adotou-se a referência de Frisancho, 1990, foram analisadas as dobras cutâneas tricipital (DCT) e subescapular (DCS) e a soma das duas (SDCTS) para reserva de gordura e a circunferência muscular do braço (CMB) para determinar reserva muscular. O consumo alimentar foi identificado pelo recordatório alimentar de 24 horas (RA24H). A função pulmonar foi avaliada, em pacientes maiores de oito anos, onde se realizou a espirometria e o teste de caminhada de 6 minutos (TC6). Na avaliação do estado nutricional, destaca-se o alto percentual de indivíduos com desnutrição e/ou risco para desnutrição 21,7% e 17,5% respectivamente. Encontrou-se um percentual de pacientes com 8,8% de sobrepeso e 10,5% de obesidade. Quando estratificados por faixa etária, observou-se nas crianças, que o PI e o EI apresentaram maior percentual de desnutrição 21,6% e 16,2%, respectivamente, enquanto que o PE subestimou o diagnóstico de desnutrição. Entre os adolescentes, a aplicação do IMC demonstrou um alto percentual de pacientes com desnutrição (25%) e risco para desnutrição (20%). Quanto a composição corporal, 51% dos indivíduos apresentaram desnutrição por baixa reserva muscular estimada pela CMB, e a maioria dos pacientes apresentou reserva de gordura dentro dos valores de normalidade, quando avaliada por DCT, DCS e SDCTS (68,4%, 64,9% e 63,2%, respectivamente). No que se refere ao consumo alimentar, a metade dos pacientes relataram apresentar ingestão energética abaixo do recomendado. Na avaliação da função pulmonar, observou-se alto percentual de distúrbio obstrutivo moderado (53,5%) e grave (28,5%) (Espirometria VEF1%), e, no desempenho ao exercício (TC6) a maioria dos pacientes (59,2%) apresentou resultados inferiores aos valores de referência. O prejuízo da função pulmonar indicado pelo VEF1% se associou com menor desempenho ao exercício indicado pelo TC6 (r=0,434; p=0,024). O diagnóstico de desnutrição e/ou risco nutricional, e também a baixa reserva muscular apresentaram associação significativa com o TC6 (p=0,032; p=0,030). Não se observou associação entre a função pulmonar, avaliada pelo VEF1%, com as variáveis nutricionais (estado nutricional, composição corporal, ingestão alimentar). Estes resultados sugerem a necessidade de intervenção nutricional, e também, observou-se que, além da utilização dos indicadores de peso e estatura faz-se necessária à associação da análise da composição corporal, com isso, um número maior de pacientes com desnutrição e/ou com risco aumentado de desenvolvê-la seriam identificados e adequadamente manejados. / Post-infectious bronchiolitis obliterans (BO) is the result of aggression suffered by the epithelium of the lower respiratory tract and which obstructs the distal airways. Authors state that, in addition to early diagnosis of BO, aggressive treatment of infections and oxygen therapy, an appropriate nutritional plan is also important to favorable clinical evolution in this disease. The objective of the present study was to assess the nutritional status of children and adolescents with BO and to analyze associations with clinical and nutritional factors. A cross-sectional study was carried out of children (<10 years) and adolescents (10-18 years) in outpatients follow-up with a clinical/tomographic diagnosis of BO. The nutritional status of the children was determined using z scores for weight for age (ZWA), height for age (ZHA) and weight for height (ZWH), and for the adolescents, ZHA was analyzed together with the distribution of Body Mass Index (BMI) percentiles. For those aged ≤ 5 years, indices were assessed on the basis of the World Health Organization reference standards (WHO, 2006), and, from 5 years onwards, the Centers for Disease Control references were adopted (CDC, 2000). Body composition was evaluated according to the references published in Frisancho, 1990, where tricipital skinfolds (TSF), subscapular skinfolds (SSF) and the sum of the two (STSSF) were used to gauge body fat reserves and the muscular circumference of the arm (MCA) was used to gauge muscle reserves. Dietary intake was identified using a 24-hour dietary recall (24HDR). Pulmonary function was evaluated in patients over 8 years old, using spirometry and a 6-minute walking test (6WT). Of note in the nutritional status assessment was the high percentage of individuals with malnutrition and/or at risk of malnutrition, 21.7% and 17.5% respectively. The percentage of overweight patients was 8.8% and the percentage of obesity was 10.5%. When broken down by age group, it was observed that among the children WA and HA detected higher percentages of malnutrition, 21.6% and 16.2% respectively, while WH underestimated malnutrition diagnoses. Among the adolescents, application of the BMI demonstrated a high percentage of patients with malnutrition (25%) and at risk from malnutrition (20%). With relation to body composition, 51% of the individuals exhibited malnutrition in terms of low muscle reserves, estimated using the MCA, and the majority of patients exhibited fat reserves within the limits of normality, when assessed according to TSF, SSF and STSSF (68.4%, 64.9% and 63.2%, respectively). With relation to nutritional intake, half of the patients reported an energy intake below the recommended level. The pulmonary function assessment revealed a high percentage of moderate (53.5%) and severe (28.5%) obstructive disorders (Spirometry VEF1%), and, the majority of patients (59.2%) had worse performance at the exercise test (6WT) than the reference figures. The compromised pulmonary function indicated by the VEF1% was associated with weaker performance at exercise, as indicated by the 6WT (r=0.434; p=0.024). Diagnoses of malnutrition and/or nutritional risk, and also low muscle reserves, exhibited significant associations with the 6WT results (p=0.032; p=0.030). No association was observed between pulmonary function, assessed by VEF1%, and nutritional variables (nutritional status, body composition, nutritional intake). These results suggest the need for nutritional intervention, and it can also be observed that, in addition to using weight and height indices, it is necessary to combine these with an analysis of body composition, so that a larger number of patients with malnutrition and/or at an increased risk of developing malnutrition may be identified and correctly managed.

A Bronquiolite Obliterante pós-infecciosa (BO) é conseqüência de agressão ao epitélio do trato respiratório inferior que se caracteriza por obstrução da via aérea distal. Autores ressaltam que além do diagnóstico oportuno da BO, do tratamento agressivo das infecções e da oxigenoterapia, é importante um plano nutricional adequado para evolução clínica favorável desta enfermidade. O objetivo do presente estudo é avaliar o estado nutricional de crianças e adolescentes portadores de BO, e, analisar a associação com aspectos clínicos e nutricionais. Para tanto, foi realizado estudo transversal em crianças (<10 anos) e adolescentes (10-18 anos), com diagnóstico clínico/tomográfico de BO, em acompanhamento ambulatorial. Para a determinação do estado nutricional nas crianças foram analisados os escores-Z de peso por idade (ZPI), estatura por idade (ZEI) e peso por estatura (ZPE), e nos adolescentes analisou-se o ZEI e a distribuição dos percentis do Índice de Massa Corporal (IMC). Entre os ≤ 5 anos, os índices foram avaliados com base no padrão da Organização Mundial da Saúde (WHO, 2006), e, a partir dos cinco anos adotou-se a referência do Centers for Disease Control (CDC, 2000). Na avaliação da composição corporal, adotou-se a referência de Frisancho, 1990, foram analisadas as dobras cutâneas tricipital (DCT) e subescapular (DCS) e a soma das duas (SDCTS) para reserva de gordura e a circunferência muscular do braço (CMB) para determinar reserva muscular. O consumo alimentar foi identificado pelo recordatório alimentar de 24 horas (RA24H). A função pulmonar foi avaliada, em pacientes maiores de oito anos, onde se realizou a espirometria e o teste de caminhada de 6 minutos (TC6). Na avaliação do estado nutricional, destaca-se o alto percentual de indivíduos com desnutrição e/ou risco para desnutrição 21,7% e 17,5% respectivamente. Encontrou-se um percentual de pacientes com 8,8% de sobrepeso e 10,5% de obesidade. Quando estratificados por faixa etária, observou-se nas crianças, que o PI e o EI apresentaram maior percentual de desnutrição 21,6% e 16,2%, respectivamente, enquanto que o PE subestimou o diagnóstico de desnutrição. Entre os adolescentes, a aplicação do IMC demonstrou um alto percentual de pacientes com desnutrição (25%) e risco para desnutrição (20%). Quanto a composição corporal, 51% dos indivíduos apresentaram desnutrição por baixa reserva muscular estimada pela CMB, e a maioria dos pacientes apresentou reserva de gordura dentro dos valores de normalidade, quando avaliada por DCT, DCS e SDCTS (68,4%, 64,9% e 63,2%, respectivamente). No que se refere ao consumo alimentar, a metade dos pacientes relataram apresentar ingestão energética abaixo do recomendado. Na avaliação da função pulmonar, observou-se alto percentual de distúrbio obstrutivo moderado (53,5%) e grave (28,5%) (Espirometria VEF1%), e, no desempenho ao exercício (TC6) a maioria dos pacientes (59,2%) apresentou resultados inferiores aos valores de referência. O prejuízo da função pulmonar indicado pelo VEF1% se associou com menor desempenho ao exercício indicado pelo TC6 (r=0,434; p=0,024). O diagnóstico de desnutrição e/ou risco nutricional, e também a baixa reserva muscular apresentaram associação significativa com o TC6 (p=0,032; p=0,030). Não se observou associação entre a função pulmonar, avaliada pelo VEF1%, com as variáveis nutricionais (estado nutricional, composição corporal, ingestão alimentar). Estes resultados sugerem a necessidade de intervenção nutricional, e também, observou-se que, além da utilização dos indicadores de peso e estatura faz-se necessária à associação da análise da composição corporal, com isso, um número maior de pacientes com desnutrição e/ou com risco aumentado de desenvolvê-la seriam identificados e adequadamente manejados. / Post-infectious bronchiolitis obliterans (BO) is the result of aggression suffered by the epithelium of the lower respiratory tract and which obstructs the distal airways. Authors state that, in addition to early diagnosis of BO, aggressive treatment of infections and oxygen therapy, an appropriate nutritional plan is also important to favorable clinical evolution in this disease. The objective of the present study was to assess the nutritional status of children and adolescents with BO and to analyze associations with clinical and nutritional factors. A cross-sectional study was carried out of children (<10 years) and adolescents (10-18 years) in outpatients follow-up with a clinical/tomographic diagnosis of BO. The nutritional status of the children was determined using z scores for weight for age (ZWA), height for age (ZHA) and weight for height (ZWH), and for the adolescents, ZHA was analyzed together with the distribution of Body Mass Index (BMI) percentiles. For those aged ≤ 5 years, indices were assessed on the basis of the World Health Organization reference standards (WHO, 2006), and, from 5 years onwards, the Centers for Disease Control references were adopted (CDC, 2000). Body composition was evaluated according to the references published in Frisancho, 1990, where tricipital skinfolds (TSF), subscapular skinfolds (SSF) and the sum of the two (STSSF) were used to gauge body fat reserves and the muscular circumference of the arm (MCA) was used to gauge muscle reserves. Dietary intake was identified using a 24-hour dietary recall (24HDR). Pulmonary function was evaluated in patients over 8 years old, using spirometry and a 6-minute walking test (6WT). Of note in the nutritional status assessment was the high percentage of individuals with malnutrition and/or at risk of malnutrition, 21.7% and 17.5% respectively. The percentage of overweight patients was 8.8% and the percentage of obesity was 10.5%. When broken down by age group, it was observed that among the children WA and HA detected higher percentages of malnutrition, 21.6% and 16.2% respectively, while WH underestimated malnutrition diagnoses. Among the adolescents, application of the BMI demonstrated a high percentage of patients with malnutrition (25%) and at risk from malnutrition (20%). With relation to body composition, 51% of the individuals exhibited malnutrition in terms of low muscle reserves, estimated using the MCA, and the majority of patients exhibited fat reserves within the limits of normality, when assessed according to TSF, SSF and STSSF (68.4%, 64.9% and 63.2%, respectively). With relation to nutritional intake, half of the patients reported an energy intake below the recommended level. The pulmonary function assessment revealed a high percentage of moderate (53.5%) and severe (28.5%) obstructive disorders (Spirometry VEF1%), and, the majority of patients (59.2%) had worse performance at the exercise test (6WT) than the reference figures. The compromised pulmonary function indicated by the VEF1% was associated with weaker performance at exercise, as indicated by the 6WT (r=0.434; p=0.024). Diagnoses of malnutrition and/or nutritional risk, and also low muscle reserves, exhibited significant associations with the 6WT results (p=0.032; p=0.030). No association was observed between pulmonary function, assessed by VEF1%, and nutritional variables (nutritional status, body composition, nutritional intake). These results suggest the need for nutritional intervention, and it can also be observed that, in addition to using weight and height indices, it is necessary to combine these with an analysis of body composition, so that a larger number of patients with malnutrition and/or at an increased risk of developing malnutrition may be identified and correctly managed.

A Bronquiolite Obliterante pós-infecciosa (BO) é conseqüência de agressão ao epitélio do trato respiratório inferior que se caracteriza por obstrução da via aérea distal. Autores ressaltam que além do diagnóstico oportuno da BO, do tratamento agressivo das infecções e da oxigenoterapia, é importante um plano nutricional adequado para evolução clínica favorável desta enfermidade. O objetivo do presente estudo é avaliar o estado nutricional de crianças e adolescentes portadores de BO, e, analisar a associação com aspectos clínicos e nutricionais. Para tanto, foi realizado estudo transversal em crianças (<10 anos) e adolescentes (10-18 anos), com diagnóstico clínico/tomográfico de BO, em acompanhamento ambulatorial. Para a determinação do estado nutricional nas crianças foram analisados os escores-Z de peso por idade (ZPI), estatura por idade (ZEI) e peso por estatura (ZPE), e nos adolescentes analisou-se o ZEI e a distribuição dos percentis do Índice de Massa Corporal (IMC). Entre os ≤ 5 anos, os índices foram avaliados com base no padrão da Organização Mundial da Saúde (WHO, 2006), e, a partir dos cinco anos adotou-se a referência do Centers for Disease Control (CDC, 2000). Na avaliação da composição corporal, adotou-se a referência de Frisancho, 1990, foram analisadas as dobras cutâneas tricipital (DCT) e subescapular (DCS) e a soma das duas (SDCTS) para reserva de gordura e a circunferência muscular do braço (CMB) para determinar reserva muscular. O consumo alimentar foi identificado pelo recordatório alimentar de 24 horas (RA24H). A função pulmonar foi avaliada, em pacientes maiores de oito anos, onde se realizou a espirometria e o teste de caminhada de 6 minutos (TC6). Na avaliação do estado nutricional, destaca-se o alto percentual de indivíduos com desnutrição e/ou risco para desnutrição 21,7% e 17,5% respectivamente. Encontrou-se um percentual de pacientes com 8,8% de sobrepeso e 10,5% de obesidade. Quando estratificados por faixa etária, observou-se nas crianças, que o PI e o EI apresentaram maior percentual de desnutrição 21,6% e 16,2%, respectivamente, enquanto que o PE subestimou o diagnóstico de desnutrição. Entre os adolescentes, a aplicação do IMC demonstrou um alto percentual de pacientes com desnutrição (25%) e risco para desnutrição (20%). Quanto a composição corporal, 51% dos indivíduos apresentaram desnutrição por baixa reserva muscular estimada pela CMB, e a maioria dos pacientes apresentou reserva de gordura dentro dos valores de normalidade, quando avaliada por DCT, DCS e SDCTS (68,4%, 64,9% e 63,2%, respectivamente). No que se refere ao consumo alimentar, a metade dos pacientes relataram apresentar ingestão energética abaixo do recomendado. Na avaliação da função pulmonar, observou-se alto percentual de distúrbio obstrutivo moderado (53,5%) e grave (28,5%) (Espirometria VEF1%), e, no desempenho ao exercício (TC6) a maioria dos pacientes (59,2%) apresentou resultados inferiores aos valores de referência. O prejuízo da função pulmonar indicado pelo VEF1% se associou com menor desempenho ao exercício indicado pelo TC6 (r=0,434; p=0,024). O diagnóstico de desnutrição e/ou risco nutricional, e também a baixa reserva muscular apresentaram associação significativa com o TC6 (p=0,032; p=0,030). Não se observou associação entre a função pulmonar, avaliada pelo VEF1%, com as variáveis nutricionais (estado nutricional, composição corporal, ingestão alimentar). Estes resultados sugerem a necessidade de intervenção nutricional, e também, observou-se que, além da utilização dos indicadores de peso e estatura faz-se necessária à associação da análise da composição corporal, com isso, um número maior de pacientes com desnutrição e/ou com risco aumentado de desenvolvê-la seriam identificados e adequadamente manejados. / Post-infectious bronchiolitis obliterans (BO) is the result of aggression suffered by the epithelium of the lower respiratory tract and which obstructs the distal airways. Authors state that, in addition to early diagnosis of BO, aggressive treatment of infections and oxygen therapy, an appropriate nutritional plan is also important to favorable clinical evolution in this disease. The objective of the present study was to assess the nutritional status of children and adolescents with BO and to analyze associations with clinical and nutritional factors. A cross-sectional study was carried out of children (<10 years) and adolescents (10-18 years) in outpatients follow-up with a clinical/tomographic diagnosis of BO. The nutritional status of the children was determined using z scores for weight for age (ZWA), height for age (ZHA) and weight for height (ZWH), and for the adolescents, ZHA was analyzed together with the distribution of Body Mass Index (BMI) percentiles. For those aged ≤ 5 years, indices were assessed on the basis of the World Health Organization reference standards (WHO, 2006), and, from 5 years onwards, the Centers for Disease Control references were adopted (CDC, 2000). Body composition was evaluated according to the references published in Frisancho, 1990, where tricipital skinfolds (TSF), subscapular skinfolds (SSF) and the sum of the two (STSSF) were used to gauge body fat reserves and the muscular circumference of the arm (MCA) was used to gauge muscle reserves. Dietary intake was identified using a 24-hour dietary recall (24HDR). Pulmonary function was evaluated in patients over 8 years old, using spirometry and a 6-minute walking test (6WT). Of note in the nutritional status assessment was the high percentage of individuals with malnutrition and/or at risk of malnutrition, 21.7% and 17.5% respectively. The percentage of overweight patients was 8.8% and the percentage of obesity was 10.5%. When broken down by age group, it was observed that among the children WA and HA detected higher percentages of malnutrition, 21.6% and 16.2% respectively, while WH underestimated malnutrition diagnoses. Among the adolescents, application of the BMI demonstrated a high percentage of patients with malnutrition (25%) and at risk from malnutrition (20%). With relation to body composition, 51% of the individuals exhibited malnutrition in terms of low muscle reserves, estimated using the MCA, and the majority of patients exhibited fat reserves within the limits of normality, when assessed according to TSF, SSF and STSSF (68.4%, 64.9% and 63.2%, respectively). With relation to nutritional intake, half of the patients reported an energy intake below the recommended level. The pulmonary function assessment revealed a high percentage of moderate (53.5%) and severe (28.5%) obstructive disorders (Spirometry VEF1%), and, the majority of patients (59.2%) had worse performance at the exercise test (6WT) than the reference figures. The compromised pulmonary function indicated by the VEF1% was associated with weaker performance at exercise, as indicated by the 6WT (r=0.434; p=0.024). Diagnoses of malnutrition and/or nutritional risk, and also low muscle reserves, exhibited significant associations with the 6WT results (p=0.032; p=0.030). No association was observed between pulmonary function, assessed by VEF1%, and nutritional variables (nutritional status, body composition, nutritional intake). These results suggest the need for nutritional intervention, and it can also be observed that, in addition to using weight and height indices, it is necessary to combine these with an analysis of body composition, so that a larger number of patients with malnutrition and/or at an increased risk of developing malnutrition may be identified and correctly managed.

The inhalation lesion is one of the biggest mortality causes in fire exposed patients at closed places. Medium and long follow-up respiratory consequences are still rarely reported at world literature. Alveolar-capillary membrane commitment caused by inhaled particles can persist during several years and progress to bronchiolitis obliterans. Thereby, the objective of this work was to evaluate the Diffusing Capacity for Carbon Monoxide (DLCO) lung test, at patients that inhaled toxic smoke at a fire in the nightclub Kiss at January 2013, in Santa Maria, parallel 29°, south Brazil, after first year follow-up. Were included 64 patients that were submited to DLCO and 6-minutes Walk Test (WT6) measurements. Dates were obtained by standard formularies including demographic characteristics, respiratory symptoms and inhalatory medication use. DLCO average was 63% (20,95 mL/mmHg/min) from predict and WT6 distance was 505,55 meters. At studied sample, 21,8% were asthmatics and when compared to no-asthmatics, they had better DLCO (p = 0,017). There was no statistical significance when compared other variables how: tracheal intubation, dyspnea, tabagism, dessaturation at WT6, smoke exposure time and intubation duration to DLCO results. Studied patients had a DLCO reduction greater than current literature. Development of chronic pulmonary complications, especially bronchiolitis obliterans, is a concrete possibility and must be better clarified and adequate screened. Late development of this kind of complication makes a prolonged ambulatorial follow-up indispensable. / A lesão inalatória é uma das grandes causas de mortalidade em pacientes expostos a incêndios fechados. As consequências respiratórias a médio e longo prazo nos sobreviventes ainda é pouco relatada na literatura mundial. O comprometimento da membrana alvéolo capilar pelas partículas inaladas pode persistir ao longo dos anos e progredir para bronquiolite obliterante. Desta forma, o objetivo deste trabalho foi avaliar o teste de difusão do monóxido de carbono (DLCO), nos pacientes que inalaram fumaça tóxica no incêndio ocorrido na Boate Kiss em Janeiro de 2013, em Santa Maria, paralelo 29°, no Sul do Brasil, após o primeiro ano do incêndio. Ao todo foram incluídos 64 pacientes, os quais foram submetidos à medida da DLCO e ao teste de caminhada de seis minutos (TC6). Os dados foram obtidos através de questionário contendo informações que incluíam características dos pacientes, sintomas respiratórios e uso de medicação inalatória. A DLCO média foi 63% do previsto (20,95 mL/mmHg/min) e a média da distancia no TC6 foi 505,5 metros. Na amostra estudada, 21,8% eram asmáticos e quando comparados a não asmáticos, possuíam melhor DLCO com p 0,017. Não houve significância estatística quando comparados outras variáveis como: intubação orotraqueal, dispneia, tabagismo, dessaturação no TC6, tempo de exposição, dias de intubação ao resultado da DLCO. Os pacientes estudados apresentaram redução na DLCO maior que a encontrada na literatura. O desenvolvimento de complicações pulmonares crônicas, em especial, bronquiolite obliterante, é uma possibilidade concreta e deve ser esclarecida e adequadamente rastreada. A característica tardia dessas complicações torna o seguimento ambulatorial prolongado imprescindível.

Abstract Dyspnoea associated with respiratory infection is a common symptom in infancy and early childhood. Inspiratory stridor is the main symptom in cases of croup and expiratory wheezing in cases of bronchiolitis, obstructive bronchitis and acute asthma exacerbations. Dyspnoea associated with respiratory infection is a common cause of emergency department visits and unplanned hospital admissions among infants and preschool children. The assessment of dyspnea associated with acute childhood respiratory infection is largely subjective, and evidence regarding the severity of acute dyspnoea is needed in order to target hospital admissions more accurately. Wheezing associated with respiratory infection in infancy has been recognized as an important predictor of recurrent wheezing and asthma at school age. The aims of this study were to determine the risk factors for croup, to evaluate factors that reliably predict the need for hospitalizing children with acute wheezing and to find out whether respiratory infection with wheezing during infancy has a positive association with the development of asthma during childhood. The work included two register-based surveys and one prospective cohort study. It is concluded that a family history of croup is an exceptionally strong risk factor for croup and its recurrence in childhood. The early phase of bronchiolitis is unstable in infants below 6 months of age. These infants are most likely to need medical interventions in the first 5 days after onset of the disease. A positive respiratory syncytial -virus test result, a fever of more than 38°C and low initial oxygen saturation are predictors of the need for hospitalization and medical interventions. An initial oxygen saturation &gt;93% effectively identifies children aged more than 6 months with mild wheezing, and this limit can be used to avoid unplanned hospital admissions. There is an association between early respiratory syncytial -virus infections and subsequent wheezing and asthma, in that such infections select children who are prone to wheezing and asthma before school age, but the symptoms tend to decrease with time and an early respiratory syncytial -virus infection will not permanently alter bronchial reactivity. / Tiivistelmä Hengitysvaikeus on yleinen oire lapsilla virusten aiheuttamien hengitystieinfektioiden yhteydessä. Kurkunpäätulehdukseen liittyy sisäänhengitysvaikeus. Ilmatiehyttulehdukseen, ahtauttavaan keuhkoputkentulehdukseen ja akuuttiin astmakohtaukseen liittyy uloshengitysvaikeus. Hengitystieinfektioihin liittyvä hengitysvaikeus on yksi yleisimmistä syistä päivystyspoliklinikkakäynteihin ja äkillisiin sairaalahoitojaksoihin lapsipotilailla. Hengitystieinfektioiden taudinkulun tuntemisella ja hengitysvaikeuden vaikeusasteen arvioinnilla on tärkeä merkitys näiden potilaiden hoidon toteuttamisessa. Hengitystieinfektioon liittyvää hengitysvaikeutta on pidetty riskitekijänä astman kehittymiselle. Tämän tutkimuksen tarkoituksena oli selvittää kurkunpäätulehduksen riskitekijöitä ja sairaalahoitoon vaikuttavia tekijöitä hengitystieinfektioon liittyvän uloshengitysvaikeuden hoidossa sekä varhaislapsuudessa sairastetun hengitystieinfektion yhteyttä myöhempään astma- ja allergiasairastavuuteen. Tutkimukseen sisältyi kaksi rekisteriaineistoa ja yksi seurantatutkimusaineisto. Tutkimuksessa todettiin, että kurkunpäätulehduksen uusiutuminen on erittäin tavallista ja sisarusten ja vanhempien sairastama kurkunpäätulehdus on merkittävin riskitekijä kurkunpäätulehdukselle ja sen uusiutumiselle. Alle 6 kuukauden ikäisillä lapsilla ilmatiehyttulehduksen taudinkuva on epävakaa ensimmäisen 5 oirepäivän aikana. Kuume, matala happisaturaatioarvo ja respiratory syncytial -virusinfektio ennustavat osastohoidon ja invasiivisten toimenpiteiden tarvetta ilmatiehyttulehduksen yhteydessä. Yli 6 kuukauden ikäisillä lapsilla happisaturaatioarvo &gt; 93 % ennustaa lievää taudinkuvaa hengitystieinfektioon liittyvän uloshengitysvaikeuden hoidossa. Käyttämällä tätä happisaturaatioarvoa raja-arvona, kun arvioidaan sairaalahoidon tarvetta, voidaan merkittävästi ja turvallisesti vähentää sairaalahoidon tarvetta lasten hengitystieinfektioon liittyvän uloshengitysvaikeuden hoidossa. Alle 6 kuukauden iässä sairastettu respiratory syncytial -virusinfektio on riskitekijä varhaislapsuudessa ilmeneville astmaoireille, mutta tämä riski vähenee iän myötä ja 8 vuoden iässä ei ole havaittavissa eroja astma- ja allergiasairastavuudessa, kun verrataan näitä potilaita muun hengitystieinfektion sairastaneisiin potilaisiin ja terveisiin kontrollipotilaisiin.