Gene complementation of airway epithelium in the cystic fibrosis mouse is necessary and sufficient to correct the pathogen clearance and inflammatory abnormalities

Increasingly, cystic fibrosis (CF) is regarded as an inflammatory disorder where the response of the lung to Pseudomonas aeruginosa is exaggerated as a consequence of processes mediated by the product of the CF gene, CFTR. Of importance to any gene-replacement strategy for treatment of CF is the identification of the cell type(s) within the lung milieu that need to be corrected and an indication whether this is sufficient to restore a normal inflammatory response and bacterial clearance. We generated G551D CF mice transgenically expressing the human CFTR gene in two tissue compartments previously demonstrated to mediate a CFTR-dependent inflammatory response: lung epithelium and alveolar macrophages. Following chronic pulmonary infection with P. aeruginosa, CF mice with epithelial-expressed but not macrophage-specific CFTR showed an improvement in pathogen clearance and inflammatory markers compared with control CF animals. Additionally, these data indicate the general role for epithelial cell-mediated events in the response of the lung to bacterial pathogens and the importance of CFTR in mediating these processes.

Cost comparison of hospital- and home-based treatment models for acute chronic obstructive pulmonary disease

This trial compared the cost of an integrated home-based care model with traditional inpatient care for acute chronic obstructive pulmonary disease (COPD). 25 patients with acute COPD were randomised to either home or hospital management following request for hospital admission. The acute care at home group costs per separation ($745, CI95% $595-$895, n = 13) were significantly lower (p < 0.01) than the hospital group ($2543, CI95% $1766-$3321, n = 12). There was an improvement in lung function in the hospital-managed group at the Outpatient Department review, decreased anxiety in the Emergency Department in the home-managed group and equal patient satisfaction with care delivery. Acute care at home schemes can substitute for usual hospital care for some patients without adverse effects, and potentially release resources. A funding model that allows adequate resource delivery to the community will be needed if there is a move to devolve acute care to community providers.

Mast cells and oral inflammation

Mast cells are mobile granule-containing secretory cells that are distributed preferentially about the microvascular endothelium in oral mucosa and dental pulp. The enzyme profile of mast cells in oral tissues resembles that of skin, with most mast cells expressing the serine proteases tryptase and chymase. Mast cells in oral tissues contain the pro-inflammatory cytokine tumour necrosis factor-alpha in their granules, and release of this promotes leukocyte infiltration during evolving inflammation in several conditions, including lichen planus, gingivitis, pulpitis, and periapical inflammation, through induction of endothelial-leukocyte adhesion molecules. Mast cell synthesis and release of other mediators exerts potent immunoregulatory effects on other cell types, while several T-lymphocyte-derived cytokines influence mast cell migration and mediator release. Mast cell proteases may contribute to alterations in basement membranes in inflammation in the oral cavity, such as the disruptions that allow cytotoxic lymphocytes to enter the epithelium in oral lichen planus. A close relationship exists among mast cells, neural elements, and laminin, and this explains the preferential distribution of mast cells in tissues. Mast cells are responsive to neuropeptides and, through their interaction with neural elements, form a neural immune network with Langerhans cells in mucosal tissues. This facilitates mast cell degranulation in response to a range of immunological and non-immunological stimuli. Because mast cells play a pivotal role in inflammation, therapies that target mast cell functions could have value in the treatment of chronic inflammatory disorders in the oral cavity.

The VCAM-1 gene that encodes the vascular cell adhesion molecule is a target of the Sry-related high mobility group box gene, Sox18

VCAM-1 (vascular cell adhesion molecule-1) and Sox18 are involved in vascular development. VCAM-1 is an important adhesion molecule that is expressed on endothelial cells and has a critical role in endothelial activation, inflammation, lymphatic pathophysiology, and atherogenesis. The Sry-related high mobility group box factor Sox18 has previously been implicated in endothelial pathologies. Mutations in human and mouse Sox18 leads to hypotrichosis and lymphedema. Furthermore, both Sox18 and VCAM-1 have very similar spatio-temporal patterns of expression, which is suggestive of crosstalk. We use biochemical techniques, cell culture systems, and the ragged opossum (RaOP) mouse model with a naturally occurring mutation in Sox18 to demonstrate that VCAM-1 is an important target of Sox18. Transfection, site-specific mutagenesis, and gel shift analyses demonstrated that Sox18 directly targeted and trans-activated VCAM-1 expression. Importantly, the naturally occurring Sox18 mutant attenuates the expression and activation of VCAM-1 in vitro. Furthermore, in vivo quantitation of VCAM-1 mRNA levels in wild type and RaOP mice demonstrates that RaOP animals show a dramatic and significant reduction in VCAM-1 mRNA expression in lung, skin, and skeletal muscle. Our observation that the VCAM-1 gene is an important target of SOX18 provides the first molecular insights into the vascular abnormalities in the mouse mutant ragged and the human hypotrichosis-lymphedematelangiectasia disorder.

In overweight patients with chronic hepatitis C, circulating insulin is associated with hepatic fibrosis: implications for therapy

Background/Aims: Host factors such as increased body mass index (BMI) and genotype-specific viral factors contribute to the development of steatosis in patients with chronic hepatitis C (HCV). We hypothesized that host metabolic factors associated with increased BMI may play a role in disease progression. Methods: Fasting serum was collected from 160 patients with chronic HCV at the time of liver biopsy and 45 age, gender and BMI matched controls, and assessed for levels of insulin, c-peptide and leptin. Results: Patients with viral genotype 3 had more severe steatosis (P = 0.0001) and developed stages 1 and 2 fibrosis at a younger age (P < 0.05) than patients with genotype 1. For both genotypes, overweight patients had significantly more steatosis and increased insulin and leptin levels. In contrast to lean patients, there was a statistically significant increase in circulating insulin levels with increasing fibrosis in overweight patients with chronic HCV (P = 0.03). Following multivariate analysis, insulin was independently associated with fibrosis (P = 0.046) but not inflammation (P = 0.83). There was no association between serum leptin levels and stage of fibrosis. Conclusions: Increasing circulating insulin levels may be a factor responsible for the association between BMI and fibrosis in patients with HCV, irrespective of viral genotype. (C) 2003 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Occupational exposure to environmental tobacco smoke in hospitality venues: are genetic- or proteomics-based biomarkers predictive of respiratory diseases?

Environmental tobacco smoke (ETS) is recognized as an occupational hazard in the hospitality industry. Although Portuguese legislation banned smoking in most indoor public spaces, it is still allowed in some restaurants/bars, representing a potential risk to the workers’ health, particularly for chronic respiratory diseases. The aims of this work were to characterize biomarkers of early genetic effects and to disclose proteomic signatures associated to occupational exposure to ETS and with potential to predict respiratory diseases development. A detailed lifestyle survey and clinical evaluation (including spirometry) were performed in 81 workers from Lisbon restaurants. ETS exposure was assessed through the level of PM 2.5 in indoor air and the urinary level of cotinine. The plasma samples were immunodepleted and analysed by 2D-SDSPAGE followed by in-gel digestion and LC-MS/MS. DNA lesions and chromosome damage were analysed innlymphocytes and in exfoliated buccal cells from 19 cigarette smokers, 29 involuntary smokers, and 33 non-smokers not exposed to tobacco smoke. Also, the DNA repair capacity was evaluated using an ex vivo challenge comet assay with an alkylating agent (EMS). All workers were considered healthy and recorded normal lung function. Interestingly, following 2D-DIGE-MS (MALDI-TOF/TOF), 61 plasma proteins were found differentially expressed in ETS-exposed subjects, including 38 involved in metabolism, acute-phase respiratory inflammation, and immune or vascular functions. On the other hand, the involuntary smokers showed neither an increased level of DNA/chromosome damage on lymphocytes nor an increased number of micronuclei in buccal cells, when compared to non-exposed non-smokers. Noteworthy, lymphocytes challenge with EMS resulted in a significantly lower level of DNA breaks in ETS-exposed as compared to non-exposed workers (P<0.0001) suggestive of an adaptive response elicited by the previous exposure to low levels of ETS. Overall, changes in proteome may be promising early biomarkers of exposure to ETS. Likewise, alterations of the DNA repair competence observed upon ETS exposure deserves to be further understood. Work supported by Fundação Calouste Gulbenkian, ACSS and FCT/Polyannual Funding Program.

Prevalência da doença pulmonar obstrutiva crónica em Lisboa, Portugal: estudo burden of obstructive lung disease

Introdução - A prevalência da doença pulmonar obstrutiva crónica (DPOC) apresenta valores muito heterogéneos em todo o mundo. A iniciativa Burden of Obstructive Lung Disease (BOLD) foi desenvolvida para que a prevalência da DPOC possa ser avaliada com metodologia uniformizada. O objetivo deste estudo foi estimar a prevalência da DPOC em adultos com 40 ou mais anos numa população alvo de 2 700 000 habitantes na região de Lisboa, de acordo com o protocolo BOLD. Métodos - A amostra foi estratificada de forma aleatória multifaseada selecionando-se 12 freguesias. O inquérito compreendia um questionário com informação sobre fatores de risco para a DPOC e doença respiratória autoreportada; adicionalmente, foi efetuada espirometria com prova de broncodilatação. Resultados - Foram incluídos 710 participantes com questionário e espirometria aceitáveis. A prevalência estimada da DPOC na população no estadio GOLD I+ foi de 14,2% (IC 95%: 11,1; 18,1) e de 7,3% no estadio ii+ (IC 95%: 4,7; 11,3). A prevalência não ajustada foi de 20,2% (IC 95%: 17,4; 23,3) no estadio i+ e de 9,5% (IC 95%: 7,6; 11,9) no estadio ii+. A prevalência da DPOC no estadio GOLD II+ aumentou com a idade, sendo mais elevada no sexo masculino. A prevalência estimada da DPOC no estadio GOLD I+ foi de 9,2% (IC 95%: 5,9; 14,0) nos não fumadores versus 27,4% (IC 95%: 18,5; 38,5) nos fumadores com carga tabágica de ≥ 20 Unidades Maço Ano. Detetou-se uma fraca concordância entre a referência a diagnóstico médico prévio e o diagnóstico espirométrico, com 86,8% de subdiagnósticos. Conclusões - O achado de uma prevalência estimada da DPOC de 14,2% sugere que esta é uma doença comum na região de Lisboa, contudo com uma elevada proporção de subdiagnósticos. Estes dados apontam para a necessidade de aumentar o grau de conhecimento dos profissionais de saúde sobre a DPOC, bem como a necessidade de maior utilização da espirometria nos cuidados de saúde primários.

Influence of environmental temperature and humidity on the acute ventilatory response to exercise in asthmatic adolescents

Asthma is a chronic inflammatory disorder of the respiratory airways affecting people of all ages, and constitutes a serious public health problem worldwide (6). Such a chronic inflammation is invariably associated with injury and repair of the bronchial epithelium known as remodelling (11). Inflammation, remodelling, and altered neural control of the airways are responsible for both recurrent exacerbations of asthma and increasingly permanent airflow obstruction (11, 29, 34). Excessive airway narrowing is caused by altered smooth muscle behaviour, in close interaction with swelling of the airway walls, parenchyma retractile forces, and enhanced intraluminal secretions (29, 38). All these functional and structural changes are associated with the characteristic symptoms of asthma – cough, chest tightness, and wheezing –and have a significant impact on patients’ daily lives, on their families and also on society (1, 24, 29). Recent epidemiological studies show an increase in the prevalence of asthma, mainly in industrial countries (12, 25, 37). The reasons for this increase may depend on host factors (e.g., genetic disposition) or on environmental factors like air pollution or contact with allergens (6, 22, 29). Physical exercise is probably the most common trigger for brief episodes of symptoms, and is assumed to induce airflow limitations in most asthmatic children and young adults (16, 24, 29, 33). Exercise-induced asthma (EIA) is defined as an intermittent narrowing of the airways, generally associated with respiratory symptoms (chest tightness, cough, wheezing and dyspnoea), occurring after 3 to 10 minutes of vigorous exercise with a maximal severity during 5 to 15 minutes after the end of the exercise (9, 14, 16, 24, 33). The definitive diagnosis of EIA is confirmed by the measurement of pre- and post-exercise expiratory flows documenting either a 15% fall in the forced expiratory volume in 1 second (FEV1), or a ≥15 to 20% fall in peak expiratory flow (PEF) (9, 24, 29). Some types of physical exercise have been associated with the occurrence of bronchial symptoms and asthma (5, 15, 17). For instance, demanding activities such as basketball or soccer could cause more severe attacks than less vigorous ones such as baseball or jogging (33). The mechanisms of exercise-induced airflow limitations seem to be related to changes in the respiratory mucosa induced by hyperventilation (9, 29). The heat loss from the airways during exercise, and possibly its post-exercise rewarming may contribute to the exercise-induced bronchoconstriction (EIB) (27). Additionally, the concomitant dehydration from the respiratory mucosa during exercise leads to an increased interstitial osmolarity, which may also contribute to bronchoconstriction (4, 36). So, the risk of EIB in asthmatically predisposed subjects seems to be higher with greater ventilation rates and the cooler and drier the inspired air is (23). The incidence of EIA in physically demanding coldweather sports like competitive figure skating and ice hockey has been found to occur in up to 30 to 35% of the participants (32). In contrast, swimming is often recommended to asthmatic individuals, because it improves the functionality of respiratory muscles and, moreover, it seems to have a concomitant beneficial effect on the prevalence of asthma exacerbations (14, 26), supporting the idea that the risk of EIB would be smaller in warm and humid environments. This topic, however, remains controversial since the chlorified water of swimming pools has been suspected as a potential trigger factor for some asthmatic patients (7, 8, 20, 21). In fact, the higher asthma incidence observed in industrialised countries has recently been linked to the exposition to chloride (7, 8, 30). Although clinical and epidemiological data suggest an influence of humidity and temperature of the inspired air on the bronchial response of asthmatic subjects during exercise, some of those studies did not accurately control the intensity of the exercise (2, 13), raising speculation of whether the experienced exercise overload was comparable for all subjects. Additionally, most of the studies did not include a control group (2, 10, 19, 39), which may lead to doubts about whether asthma per se has conditioned the observed results. Moreover, since the main targeted age group of these studies has been adults (10, 19, 39), any extrapolation to childhood/adolescence might be questionable regarding the different lung maturation. Considering the higher incidence of asthma in youngsters (30) and the fact that only the works of Amirav and coworkers (2, 3) have focused on this age group, a scarcity of scientific data can be identified. Additionally, since the main environmental trigger factors, i.e., temperature and humidity, were tested separately (10, 28, 39) it would be useful to analyse these two variables simultaneously because of their synergic effect on water and heat loss by the airways (31, 33). It also appears important to estimate the airway responsiveness to exercise within moderate environmental ranges of temperature and humidity, trying to avoid extreme temperatures and humidity conditions used by others (2, 3). So, the aim of this study was to analyse the influence of moderate changes in air temperature and humidity simultaneously on the acute ventilatory response to exercise in asthmatic children. To overcome the above referred to methodological limitations, we used a 15 minute progressive exercise trial on a cycle ergometer at 3 different workload intensities, and we collected data related to heart rate, respiratory quotient, minute ventilation and oxygen uptake in order to ensure that physiological exercise repercussions were the same in both environments. The tests were done in a “normal” climatic environment (in a gymnasium) and in a hot and humid environment (swimming pool); for the latter, direct chloride exposition was avoided.

Evaluation of lung function abnormalities prevalence in poultry workers

Introduction - Poultry workers can be at an increased risk of occupational respiratory diseases, like asthma, chronic obstructive pulmonary disease and extrinsic allergic alveolitis. Spirometry screening is fundamental to early diagnosis trough the identification of related ventilatory defects. Purpose - We aimed to assess the prevalence of lung function abnormalities in poultry workers.

Chronic pulmonary histoplasmosis in Brazil: report of two cases with cavitation diagnosed by transthoracic needle biopsy

Two cases of Chronic Pulmonary Histoplasmosis are reported and other eleven cases, collected from Brazilian literature, are commented. After being clinically cured, one of our patients presented an Aspergillus fungus ball inside a cavitation in the wall of which H. capsulatum was disclosed. Comments are also done on the diagnosis of the mycosis

Chronic interstitial pneumonitis in dogs naturally infected with Leishmania (Leishmania) chagasi: a histopathological and morphometric study

Eighteen mongrel dogs of unknown age and naturally infected with Leishmania (Leishmania) chagasi, were obtained from the City Hall of Belo Horizonte, Brazil. Four dogs were used as control. Lung samples were obtained and immediately fixed in formalin. The histopathological picture of all lung tissue sections was a chronic and diffuse interstitial pneumonitis. The thickened inter-alveolar septa were characterized by the cellular exudate (mostly macrophages, lymphocytes and plasmocytes) associated with collagen deposition. Morphometric analysis showed greater septal thickness in the infected animals than in controls. In fact, the morphometric study of collagen stained with ammoniac silver confirmed a larger deposition of collagen in the infected animals. The parasitologic method was carried out during the study of the lesions on the slides. However, we did not observe any correlation between the histopathologic and morphometric data and the clinical status of the animals. We conclude that the pulmonary lesions observed in all naturally infected dogs were correlated with the disease and that the morphometric method used was satisfactory for the analysis of septal thickness and of increased collagen deposition, confirming the presence of fibrosis.

Magnesium – association with inflammation and renal disease in systemic lupus erythematosus

Introduction: Recent studies suggest that magnesium deficiency may play a role in inflammation. In diabetes and cardio-vascular diseases, conditions with a component of chronic inflammation, C–reactive protein levels are higher and associated with low serum magnesium. The objective of this study is to evaluate serum magnesium levels in patients with systemic lupus erythematosus and its potential association with inflammation and renal manifestations. Methods: All patients with systemic lupus erythematosus followed in a Systemic Immune Diseases Unit, from January 2012 until January 2014, were included in this cross sectional analysis. Patients with infection, neoplasia, liver failure and chronic kidney disease (stage > 3) were excluded. Clinical information and laboratory results (serum magnesium, C-reactive protein, erythrocyte sedimentation rate, serum creatinine and spot urine test) were collected. A multivariate analysis was performed to explore possible predictive factors for hypomagnesaemia. Results: One hundred and two patients were included (94.1% female, 21-86 years). 33.4% had hypertension, 8.8% had diabetes and 20.6% had hypomagnesaemia (< 1.8mg/dL). There were no significant differences between the inflammatory parameters of patients with hypomagnesaemia or normomagnesaemia. Serum magnesium was significantly lower with increasing comorbidities (p = 0.01). Leukocyturia was significantly higher in the hypomagnesaemia group (p = 0.03) and haematuria had a negative correlation with serum magnesium (-0.23, p < 0.05). Multivariate analysis showed that patients with hypertension and diabetes had higher risk of hypomagnesaemia: OR 42.29 (95% CI, 1.43-1249.31). Leukocyturia was also individually and independently associated with hypomagnesaemia: OR 8.37 (95% CI, 1.40-49.97). Conclusion: The presence of hypomagnesaemia in our patients with systemic lupus erythematosus was high. There was no association between the levels of serum magnesium and the inflammatory parameters. Increasing comorbidities and leukocyturia were independent predictors of lower serum magnesium. Finally, the association of leukocyturia and haematuria with lower serum magnesium may suggest a relationship with a higher disease activity.

Mecanismos de inflamação brônquica resultantes da exposição a factores ambientais

RESUMO Tratando-se a asma de uma doença respiratória, desde há várias décadas que tem sido abordada a hipótese de que factores ambientais, nomeadamente os relacionados com a qualidade do ar inalado, possam contribuir para o seu agravamento. Para além dos aeroalergenos, outros factores ambientais como a poluição atmosférica estarão associados às doenças respiratórias. O ar respirado contém uma variedade de poluentes atmosféricos, provenientes quer de fontes naturais quer de origem antropogénica, nomeadamente de actividades industriais, domésticas ou das emissões de veículos. Estes poluentes, tradicionalmente considerados como um problema de foro ambiental, têm sido cada vez mais encarados como um problema de saúde pública. Também a qualidade do ar interior, tem sido associada a queixas respiratórias, não só em termos ocupacionais mas também em exposições domésticas. Dentro dos principais poluentes, encontramos a matéria particulada (como as PM10), o O3, NO2, e os compostos orgânicos voláteis (COVs). Se é verdade que os três primeiros têm como principais fontes de exposição a combustão fóssil associada aos veículos automóveis, já os COVs (como o benzeno, tolueno, xileno, etilbenzeno e formaldeído) são poluentes mais característicos do ar interior. Os mecanismos fisiopatológicos subjacentes à agressão dos poluentes do ar não se encontram convenientemente esclarecidos. Pensa-se que após a sua inalação, induzam um grau crescente de stress oxidativo que será responsável pelo desenvolvimento da inflamação das vias aéreas. A progressão do stress oxidativo e da inflamação, associarse- ão posteriormente a lesão local (pulmonar) e sistémica. Neste trabalho pretendeu-se avaliar os efeitos da exposição individual a diversos poluentes, do ar exterior e interior, sobre as vias aéreas, recorrendo a parâmetros funcionais, inflamatórios e do estudo do stress oxidativo. Neste sentido, desenvolveu-se um estudo de painel na cidade de Viseu, em que foram acompanhadas durante 18 meses, 51 crianças com história de sibilância, identificadas pelo questionário do estudo ISAAC. As crianças foram avaliadas em quatro Visitas (quatro medidas repetidas), através de diversos exames, que incluíram execução de espirometria com broncodilatação, medição ambulatória do PEF, medição de FENO e estudo do pH no condensado brônquico do ar exalado. O estudo dos 8-isoprostanos no condensado brônquico foi efectuado somente em duas Visitas, e o do doseamento de malonaldeído urinário somente na última Visita. Para além da avaliação do grau de infestação de ácaros do pó do colchão, para cada criança foi calculado o valor de exposição individual a PM10, O3, NO2, benzeno, tolueno, xileno, etilbenzeno e formaldeído, através de uma complexa metodologia que envolveu técnicas de modelação associadas a medições directas do ar interior (na casa e escola da criança) e do ar exterior. Para a análise de dados foram utilizadas equações de estimação generalizadas com uma matriz de correlação de trabalho uniforme, com excepção do estudo das associações entre poluentes, 8-isoprostanos e malonaldeído. Verificou-se na análise multivariável a existência de uma associação entre o agravamento dos parâmetros espirométricos e a exposição aumentada a PM10, NO2, benzeno, tolueno e etilbenzeno. Foram também encontradas associações entre diminuição do pH do EBC e exposição crescente a PM10, NO2, benzeno e etilbenzeno e associações entre valores aumentados de FENO e exposição a etilbenzeno e tolueno. O benzeno, o tolueno e o etilbenzeno foram associados com maior recurso a broncodilatador nos 6 meses anteriores à Visita e o tolueno com deslocações ao serviço de urgência. Os resultados dos modelos de regressão que incluíram o efeito do poluente ajustado para o grau de infestação de ácaros do pó foram, de uma forma geral, idênticos ao da análise multivariável anterior, com excepção das associações para com o FENO. Nos modelos de exposição com dois poluentes, com o FEV1 como variável resposta, somente o benzeno persistiu com significado estatístico. No modelo com dois poluentes tendo o pH do EBC como variável resposta, somente persistiram as PM10. Os 8-isoprostanos correlacionaram-se com alguns COVs, designadamente etilbenzeno, xileno, tolueno e benzeno. Os valores de malonaldeído urinário não se correlacionaram com os valores de poluentes. Verificou-se no entanto que de uma forma geral, e em particular mais uma vez para os COVs, as crianças mais expostas a poluentes, apresentaram valores superiores de malonaldeído na urina. Verificou-se que os poluentes do ar em geral, e os COVs em particular, se associaram com uma deterioração das vias aéreas. A exposição crescente a poluentes associou-se não só com obstrução brônquica, mas também com FENO aumentado e maior acidez das vias aéreas. A exposição crescente a COVs correlacionou-se com um maior stress oxidativo das vias aéreas (medido pelos 8-isoprostanos). As crianças com exposição superior a COVs apresentaram maiores valores de malonaldeído urinário. Este trabalho sugere uma associação entre exposição a poluentes, inflamação das vias aéreas e stress oxidativo. Vem reforçar o interesse dos poluentes do ar, nomeadamente os associados a ambientes interiores, frequentemente esquecidos e que poderão ser explicativos do agravamento duma criança com sibilância.-----------ABSTRACT: Asthma is a chronic respiratory disease that could be influenced by environmental factors, as allergens and air pollutants. The air breathed contains a diversity of air pollutants, both from natural or anthropogenic sources. Atmospheric pollution, traditionally considered an environmental problem, is nowadays looked as an important public health problem. Indoor air pollutants are also related with respiratory diseases, not only in terms of occupational exposures but also in domestic activities. Particulate matter (such as PM10), O3, NO2 and volatile organic compounds (VOCs) are the main air pollutants. The main source for PM10, O3, NO2 exposure is traffic exhaust while for VOCs (such as benzene, toluene, xylene, ethylbenzene and phormaldehyde) the main sources for exposure are located in indoor environments. The pathophysiologic mechanisms underlying the aggression of air pollutants are not properly understood. It is thought that after inhalation, air pollutants could induce oxidative stress, which would be responsible for airways inflammation. The progression of oxidative stress and airways inflammation, would contribute for the local and systemic effects of the air pollutants. The present study aimed to evaluate the effects of individual exposure to various pollutants over the airways, through lung function tests, inflammatory and oxidative stress biomarkers. In this sense, we developed a panel study in the city of Viseu, that included 51 children with a history of wheezing. Those children that were identified by the ISAAC questionnaire, were followed for 18 months. Children were assessed four times (four repeated measures) through the following tests: spirometry with bronchodilation test, PEF study, FENO evaluation and exhaled breath condensate pH measurement. 8-isoprostane in the exhaled breath condensate were also measured but only in two visits. Urinary malonaldehyde measurement was performed only in the last visit. Besides the assessment of the house dust mite infestation, we calculated for each child the value of individual exposure to a wide range of pollutants: PM10, O3, NO2, benzene, toluene, xylene, ethyl benzene and formaldehyde. This strategy used a complex methodology that included air pollution modelling techniques and direct measurements indoors (homes and schools) and outdoors. Generalized estimating equations with an exchangeable working correlation matrix were used for the analysis of the data. Exceptions were for the study of associations between air pollutants, malonaldehyde and 8-isoprostanes. In the multivariate analysis we found an association between worsening of spirometric outcomes and increased exposure to PM10, NO2, benzene, toluene and ethylbenzene. In the multivariate analysis we found also negative associations between EBC pH and exposure to PM10, NO2, benzene, ethylbenzene and positive associations between FENO and exposure to ethylbenzene and toluene. Benzene, toluene and ethylbenzene were associated with increased use of bronchodilator in the 6 months prior to the visit and toluene with emergency department visits. Results of the regression models that included also the effect of the pollutant adjusted for the degree of infestation to house dust mites, were identical to the previous models. Exceptions were for FENO associations. In the two-pollutant models, with the FEV1 as dependent variable, only benzene persisted with statistical significance. In the two pollutant model with pH of EBC as dependent variable, only PM10 persisted. 8-isoprostanes were well correlated with some VOCs, namely with ethylbenzene, xylene, toluene and benzene. Urinary malonaldehyde did not present any correlation with air pollutants exposure. However, those children more exposed to air pollutants (namely to VOCs), presented higher values of malonaldehyde. It was found that air pollutants in general, and namely VOCs, were associated with deterioration of the airways. The increased exposure to air pollutants was associated not only with airways obstruction, but also with increased FENO and higher acidity of the airways. The increased exposure to VOCs was correlated with increased airways oxidative stress (measured by 8-isoprostane). Children with higher levels of exposure to VOCs had higher values of urinary malonaldehyde. This study suggests a relation between air pollution, airways inflammation and oxidative stress. It suggests also that attention should be dedicated to air quality as air pollutants could cause airways deterioration.

EFFECTS OF VITAMIN C SUPPLEMENTATION ON THE CHRONIC PHASE OF CHAGAS DISEASE

Introduction:In order to examine the effectiveness of vitamin C (ascorbic acid) in combating the oxidative insult caused by Trypanosoma cruzi during the development of the chronic phase of Chagas disease, Swiss mice were infected intraperitoneally with 5.0 × 104 trypomastigotes of T. cruzi QM1strain.Methods:Mice were given supplements of two different doses of vitamin C for 180 days. Levels of lipid oxidation (as indicated by thiobarbituric acid reactive substances-TBARS), total peroxide, vitamin C, and reduced glutathione were measured in the plasma, TBARS, total peroxide and vitamin C were measured in the myocardium and histopathologic analysis was undertaken in heart, colon and skeletal muscle.Results:Animals that received a dose equivalent to 500 mg of vitamin C daily showed increased production of ROS in plasma and myocardium and a greater degree of inflammation and necrosis in skeletal muscles than those that received a lower dose or no vitamin C whatsoever.Conclusion:Although some research has shown the antioxidant effect of vitamin C, the results showed that animals subject to a 500 mg dose of vitamin C showed greater tissue damage in the chronic phase of Chagas disease, probably due to the paradoxical actions of the substance, which in this pathology, will have acted as a pro-oxidant or pro-inflammatory.

Budesonide Reverses Lung Hyperinflation in Childhood Asthma: a Controlled Study

Budesonide (800 mg bid, for 2 months) was administered to 12 asthmatic children (mean age, 11.293.3 years) with lung hyperinflation (TGV]130% predicted and:or RV]140% predicted) in a randomised, placebo controlled, double blind, crossover study. Body plethysmography (panting frequency controlled at 1·s 1) was performed at the beginning, 2 months afterwards (before crossover) and at the end of the study. Budesonide significantly reduced TGV (2.3590.90 l BTPS or 126924% predicted) compared with placebo (2.5491.08 l BTPS, P 0.014 or 140921% predicted, PB0.05). In addition, budesonide significantly increased mean specific conductance (0.0690.02 cm H2O 1 l s 1 to 0.0790.01 cm H2O 1 l s 1, PB0.05). It was concluded that budesonide reduced lung hyperinflation most likely by decreasing airway inflammation.