Exercise has become a vital component of the therapy regimen prescribed to cystic fibrosis (CF) patients due to its systemic benefits, such as increased sputum expectoration, attenuation of the expected 2-3% annual decline in pulmonary function, and extended life expectancy. However, exercise still is not viewed as being as beneficial as pharmacological treatments by many CF patients and can be intimidating. My aims in this study were two-fold; first, to determine the ideal exercise intensity for individuals with CF; and second, to determine if exercise at this ideal intensity could provide improvements in ion regulation in the lungs, which was measured using exhaled breath condensate (EBC) collection and nasal potential difference (NPD), that were comparable to one of their standard pharmacological therapies, albuterol. I hypothesized that with moderate intensity exercise, Na⁺ absorption would decrease from baseline due to Na⁺ channel inhibition, rather than increase or remain unchanged, as was expected with albuterol, and cause an even greater increase Cl- secretion compared to albuterol due to activation of both CF-dependent and independent Cl- efflux with exercise. CF (n=14) and healthy (n=16) subjects completed three visits, a baseline screening and two treatment visits. I collected EBC at baseline, 30- and 60-minutes post-albuterol administration on one visit, and at baseline and during three separate 15 min exercise bouts at low, moderate and high intensity on the other visit. Following the EBC collection, NPD was performed at 30- and 80-minutes post albuterol or following moderate and high intensity exercise. We also measured spirometry and diffusing capacity of the lungs for nitric oxide (DLNO) during each visit at the various time points. In CF subjects, moderate intensity exercise resulted in greater improvements in DLNO (39 ± 29vs.15 ± 22% change from baseline, exercise vs. albuterol respectively), similar levels of bronchodilation compared to 60-minutes post-albuterol administration, no change in Na⁺ absorption, and a four-fold increase in Cl- secretion. Our results suggest that moderate intensity exercise is the best dose for CF patients, and can provide comparable changes as its pharmacological counterpart albuterol, when compared over a short term duration.

O objetivo do presente estudo foi avaliar o papel de um programa de condicionamento físico nos aspectos relacionados à qualidade de vida, níveis de ansiedade e depressão, sintomas e óxido nítrico exalado de pacientes com asma persistente moderada ou grave. Foram avaliados 39 pacientes divididos aleatoriamente em grupo controle (GC; N=20) e grupo treinado (GT; N=19). Foram avaliados a capacidade aeróbica máxima (VO2max), função pulmonar, qualidade de vida, sintomas, ansiedade, depressão e percepção subjetiva de esforço e óxido nítrico exalado com um intervalo de 3 meses. Não houve diferença entre os grupos antes do tratamento. O treinamento físico melhorou as capacidades máximas e submáximas ao esforço e os níveis de depressão (p < 0,05). O treinamento físico reduziu os níveis de ansiedade-traço (p < 0,05), mas não a ansiedade-estado. O treinamento físico também melhorou os domínios limitação física, freqüência de sintomas, psicossocial e escore total dos HRQL (p < 0,001). Houve aumento no número de dias livres de sintomas (p < 0,001) e nos valores de óxido nítrico exalado (p < 0,001) no grupo treinado. Nossos resultados sugerem que o condicionamento físico para pacientes asmáticos pode ser benéfico para reduzir sintomas e melhorar os escores de qualidade de vida e a co-morbidade psicossocial. Estes dados sugerem que o treinamento físico pode ter um papel adjuvante importante no controle clínico de pacientes com asma persistente moderada ou grave / The aim of the present study was to evaluate the effect of aerobic training on quality of life, functional capacity and exhaled nitric oxide (NOex) in patients with moderate and severe asthma. Twenty nine subjects were randomly divided in control group (n 20) (educational program + breathing exercises) and training group (n 19) (control + aerobic training, 70% maximal VO2peak) and followed during 3 months, twice a week. Aerobic capacity (VO2peak), quality of life, anxiety, depression, and pulmonary function were evaluated before and after treatment. FENO and symptoms were evaluated monthly. There was no change in inhaled glucocortiscosteroid during treatment. Our results show that patients submitted to an aerobic training presented a decrease on physical limitation (p < 0.05), frequency and gravity score, decrease in psychosocial limitation an increse in global score of quality of life (p < 0.05) as well as an improvement on VO2peak (p=0,001) when compared with control group. Compared with control group, training group also presented a increase in number of days without symptoms (p < 0,001). FENO it was also decreased (p < 0,001) after training in training group. No change was observed in lung function in both groups after treatment. Our results suggest that aerobic improves quality of life and decreases symptoms and exhaled nitric oxide on asthmatic patients reinforcing its importance on asthma treatment

No description available.

No description available.

Multiple biomarkers of oxidative stress have been measured and used in human medicine to diagnose and monitor airway disease. The purpose of the study was to determine if similar relationships existed between inflammatory and oxidative stress biomarkers in exhaled breath condensate (EBC), bronchoalveolar lavage fluid (BALF), red blood cells, white blood cells, and plasma; and cytokine expression in airway inflammatory cells and mucosal biopsies of RAO-affected horses and their controls. Sixteen horses in pairs were used: 8 non-RAO-affected (controls) and 8 RAO-affected horses. Samples from all horses were collected at remission (S1), during environmental challenge (S2) and at recovery (S3). RAO-affected horses had significant alterations in cellular glutathione peroxidase (cGPx) activity, ascorbic acid and pH in a number of biological samples. Concentrations of 8-isoprostanes, isofurans, amino acids and mRNA expression of interleukin 4 (IL4), gamma interferon (INFγ), inducible nitric oxide synthase (iNOS), extracellular glutathione peroxidase (GPx-3), and cytosolic superoxide dismutase (SOD-1) were not significantly different or were at the limits of detection. Conductivity was measured and assessed as a potential correctional factor for respiratory fluid dilution. The alterations in biomarker concentrations demonstrate that oxidative stress is an important component of airway inflammation in RAO-affected horses. Further research is warranted in the use of biomarkers and the effects of dietary interventions. / Master of Science

Background: Pulmonary Embolism (PE) is a potentially life-threatening condition that is characterized by one or several blood clots blocking the arteries in the lungs. The existing diagnostic tools for PE have their shortcomings, highlighting the importance of investigating new diagnostic methods. The development of non-invasive methods to collect microparticles from exhaled breath has opened possibilities to explore new potential biomarkers. SensAbues® is a sampling device that utilizes electrostatic filters to capture microparticles from the exhaled breath. The objective of this project was twofold: firstly, to assess the suitability of SensAbues® sampling device for a future proteomics study where the goal is to identify biomarkers for PE; and secondly, to evaluate the efficacy of various extraction solutions in retrieving proteins from the electrostatic filters. Materials and methods: Samples were collected from three healthy volunteers using the SensAbues® device. The electrostatic filters were then extracted using either PBS or 15% ethanol and the protein content was then estimated using a modified Bradford method. Additionally, two blank SensAbues® filter extracts, from PBS and 15% ethanol were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: The attempts to evaluate extraction solutions using the Bradford method were unsuccessful, as all the samples yielded negative values. The filter-blank extracts analyzed with LC-MS/MS contained a significant amount of polyethylene glycols of varying sizes. Conclusion: The polyethylene glycols from the SensAbues® filters may have interfered with the Bradford method. Polyethylene glycols can also interfere with proteins, making the SensAbues® sampling device unsuitable for the prospective proteomics study.

L’asthme se caractérise par une hyperréactivité, une inflammation et un remodelage bronchique. Les travaux exposés dans cette thèse ont permis, grâce à une approche transversale et multidisciplinaire basée sur l’étude physiopathologique de l’inflammation et du remodelage bronchique dans l’asthme, (i) de préciser l’intérêt de la mesure du NO exhalé chez l’asthmatique contrôlé, (ii) de déterminer la faisabilité du micro-scanner pour imager in vivo le remodelage bronchique grâce à la mesure non invasive de la densité péri-bronchique normalisée, et (iii) d’analyser le rôle de la chitinase YKL-40 dans la genèse du remodelage musculaire lisse. / Asthma is characterized by bronchial hyperresponsiveness, inflammation and remodelling. We used a translational and multidisciplinary approach to (i) clarify the interest of measuring exhaled NO in controlled asthmatics, (ii) determine the interest of micro-computed tomography for assessing bronchial remodelling in vivo by non-invasive measurement of the normalized peribronchial attenuation, and (iii) analyze the role of chitinase YKL-40 in smooth muscle remodelling.

Introdução: As doenças cardíacas ou do aparelho circulatório são as principais causas de morte na população brasileira, sendo responsável por um terço dos óbitos. Embora o tratamento conservador seja amplamente adotado, grande parte das doenças cardiovasculares necessita e tem como tratamento a cirurgia cardíaca, da qual as mais comuns são a cirurgia de revascularização do miocárdio (CRVM) e de troca valvar. Atualmente existem diversos estudos avaliando a função pulmonar ou a capacidade funcional para o acompanhamento do tratamento conservador ou em situação pré-operatória, porém estudos avaliando e correlacionando essas variáveis no pré-cirúrgico são escassos na literatura científica não sendo possível averiguar a existência da relação entre os níveis de nitrito e nitrato e o desempenho nos testes de capacidade funcional. Objetivo: Avaliar a correlação nitrito/nitrato (NOx) do condensado do exalado pulmonar (CEP) e a distância caminhada nos testes de caminhada de 6 minutos (TC6) e shuttle walk test (SWT), além de verificar se a utilização de medicações contendo betabloqueadores, nitrato ou enzima conversora de angiotensina (IECA) podem influenciar nas concentrações de nitrito/nitrato no CEP e nas distâncias caminhadas no TC6 e no SWT e comparar seu comportamento entre valvopatas e coronariopatas no pré operatório de cirurgia cardíaca. Metodologia: Foram selecionados 73 pacientes, dos quais 28 eram coronariopatas e 45 valvopatas, de ambos os sexos, com idade entre 20 e 80 anos, feita coleta do CEP para análise do NOx e submetidos ao TC6 e ao SWT para avaliação da distância caminhada. Resultados: Na análise das concentrações de NOx do CEP não foi encontrada diferença estatisticamente significativa entre as medicações utilizadas via oral contendo nitrato (dinitrato de isossorbida), IECA (captopril ou enalapril) e/ou betabloqueador ou entre os pacientes do grupo coronariopata e grupo valvopata (p>0,05). Houve diferença estatisticamente significativa no TC6 nos valores de frequência cardíaca (FC) inicial, final e repouso e no valor referente à dispnéia final, e no SWT nos valores de FC inicial, final e repouso, na pressão arterial sistólica (PAS) inicial e no valor referente à dispnéia final entre os grupos coronariopata e valvopata. No entanto, foram interrompidos 4 TC6 e 7 SWT do grupo coronariopata devido ao desencadeamento de dor precordial, fato não ocorrido no grupo valvopata, apresentando nível de significância. A FC inicial e de repouso no TC6 e a FC final no SWT dos pacientes que não ingeriram nenhum medicamento antes do teste é diferente em relação à dos pacientes que fizeram uso de quaisquer medicamentos descritos antes do teste sugerindo a ação de medicamentos que modulam a FC como os betabloqueadores. Foi constatado correlação positiva moderada entre o NOx do CEP e os valores de PAS inicial e final de coronariopatas e correlação negativa fraca a moderada entre o NOx do CEP e os valores de FC final e de dispnéia final nos valvopatas no TC6, além da correlação positiva moderada entre o NOx do CEP e os valores de PAS inicial de indivíduos coronariopatas e correlação negativa fraca a moderada entre o NOx do CEP e os valores de FC inicial nos valvopatas no SWT. Foi identificado correlação negativa moderada na distância caminhada no TC6 e no SWT apenas nos indivíduos coronariopatas. Conclusões: Não foram identificadas influências do uso de medicações betabloqueadoras, nitrato ou IECA sobre a dosagem de NOx ou a distância caminhada em nenhum dos testes e em nenhum dos grupos, no entanto coronariopatas com níveis mais elevados de NOx apresentaram uma distância deambulada menor. / Introduction: Heart disease or circulatory system diseases are the leading causes of death in our population, accounting for one third of deaths. Although conservative treatment is widely adopted, part of cardiovascular disease treatment demands heart surgery, of which the most common are coronary artery bypass grafting (CABG) and valve replacement. Currently there are many studies evaluating lung function or functional capacity for monitoring of conservative treatment or preoperative situation, but studies assessing and correlating these variables in pre surgical are rare in the literature is not possible to ascertain the existence of the relationship between levels of nitrite and nitrate (NOx) in exhaled breath condensate (EBC) and performance in functional ability tests. Methods: were selected 73 patients, 28 with coronary artery diseas and 45 with heart valve disease of both genders, aged 20 to 80 years old. The EBC was collected for analysis of NOx and performed the six minutes walking test (6MWT) and shuttle walk test (SWT) to evaluate the distance walked. Results: the analysis of the concentrations of NOx in EBC has no statistically significant difference found between the medications used, such as oral nitrate (isosorbide dinitrate), ace inhibitors (captopril or enalapril) and/or beta-blockers in both coronary artery disease and heart valve disease (p> 0.05). There was a statistically significant difference in 6MWT for HR initial, final and rest and final dyspnea, and in SWT for HR initial, final and rest, the initial SBP and the final dyspnea between the coronary artery disease e heart valve disease. However, were interrupted 4 6MWT and 7 SWT from coronary artery disease related to chest pain, this fact was not related in patients with valve disease, presenting a significance level. The initial and resting HR during the 6MWT and in SWT final HRr patients not ingesting any medication before the test is different from patients who used any medications before the test, suggesting the action of drugs that modulate the HR, such as beta blockers. Moderate positive correlation was found between the NOx in EBC and SBP initial and final in coronary disease and weak to moderate correlation between the NOx in EBC and final HR and final dyspnea in 6MWT from heart valve disease. Besides the positive moderate correlation between NOx in the EBC and the SBP initial in coronary disease during 6MWT and weak to moderate negative correlation between NOx in the EBC and the HR initial in valve disease during SWT. Moderate negative correlation was identified in the distance walked during the 6MWT and SWT only between individuals with coronary artery disease. Conclusions: the use of beta-blocker drugs, ace inhibitors or nitrate evidenciates no influence on the NOx or on the distance walked in any tests, and none of the groups, however, individuals with coronary artery disease showed higher NOx levels and performed lower distance walked.

<b>Background: </b>Exhaled nitric oxide (NO) is a marker of eosinophilic steroid-sensitive inflammation in the airways of patients with respiratory disease. Moreover, information about the localization of inflammation in the respiratory tree is obtained by estimates of bronchial and alveolar contributions to exhaled NO. <b>Aims: </b>The main aim of this thesis was to identify the determinants of exhaled NO, as well as determinants of bronchial and alveolar contributions to exhaled NO in health and disease. Smoking history, degree of IgE sensitization and effects of modulating the pharyngo-oral tract production of NO were specifically studied in this context. Other specific aims were to determine the association of exhaled NO with the presence of asthma and pulmonary hypertension (PH). <b>Methods: </b>Both population-based studies and experimental studies have been performed within the frame of the thesis. The population-based studies are based on data from the European Community Respiratory Health Survey II. NO measurements at several exhalation flow rates were performed in order to estimate alveolar and bronchial contributions to exhaled NO. <b>Results: </b>Both current and previous smoking were associated with decreased exhaled NO and bronchial NO flux levels. Alveolar NO concentrations were decreased in current smokers. The degree of IgE sensitization was positively related to the levels of exhaled NO and its bronchial contribution. Exhaled NO appeared to be a more specific marker of allergic inflammation than of rhinitis or asthma. Both allergic and non-allergic asthma were associated with increased exhaled NO levels, but only in never-smoking persons. The estimated alveolar NO increased after ingestion of nitrate in individuals with high nitrate turnover in the pharyngo-oral tract. Pulmonary arterial hypertension, but not other forms of PH, was associated with decreased bronchial NO flux, whereas PH of all etiologies was related to increased alveolar NO concentrations. <b>Conclusion: </b>Smoking history and IgE sensitization, that are known determinants of exhaled NO, affected the bronchial and alveolar contributions to exhaled NO differently. The limitations of the simple NO pulmonary exchange models were highlighted by the paradoxical effects on estimated alveolar NO when modulating the NO production proximally, in the pharyngo-oral tract. Predominance of non-eosinophilic inflammation in ever-smoking patients with asthma could explain the poor association between the presence of asthma and exhaled NO in these patients. Different pathophysiological changes in terms of bronchial NO production and exchange were related to the etiology of pulmonary hypertension.

Background: According to recent studies in children, IgE sensitization not only against perennial allergens, but also against food allergens, is related to asthma risk and increased airway inflammation. During the last decade, a new technique for IgE determination based on allergen components has become available, but its use in epidemiological studies has been limited. Aims: To investigate the relationship between the pattern of IgE sensitization to allergen components and the prevalence of asthma, airway inflammation and hyperresponsiveness in a population-based setting. To examine the relationship of IgE sensitization to allergen extract, and airway inflammation, airway hyperresponsiveness and blood eosinophilia in asthmatics. To examine the natural history of IgE sensitization to food allergens in adults. To compare extract-based and component-based IgE measurements in relation with new-onset respiratory disease and airway inflammation and hyperresponsiveness. Methods: The present thesis is based on cross-sectional and longitudinal analyses of the adult, the population-based study ECRHS (European Community Health Survey) and a cross-sectional, observational study of young subjects with asthma. IgE sensitization was examined by means of both extract-based and component-based tests. Airway inflammation was assessed by exhaled NO and airway hyperresponsiveness with methacholine test. Results: IgE sensitization to food allergens independently related to increased airway inflammation in both a population-based study and a study of asthmatics. Furthermore, a relation was found with increased blood eosinophils in asthmatics. The decrease in prevalence of IgE sensitization against food allergens during a 9-year follow-up was larger than the decrease of aeroallergens. Subjects with IgE sensitization to both cat extract and components showed more frequent airway inflammation, greater bronchial responsiveness and higher likelihood of developing asthma and rhinitis than subjects with IgE sensitization only to cat extract. Conclusions: The presence of IgE antibodies against food allergens was independently associated with airway and systemic inflammation. Both aeroallergens and food allergens should be examined in order to understand the signaling of local and systemic inflammation in asthma. Prevalence of IgE sensitization to food decreased in adults to a larger extent than IgE sensitization against aeroallergens. Measurement of IgE sensitization to cat allergen components appears to have a higher clinical value than extract-based measurement