Allergic airway disease, i.e. allergic rhinitis (AR) and asthma, is a common health problem. The prevalence is increasing in most countries of the world. Traffic-related air pollution has been found to induce and enhance allergic airway disease, but the underlying mechanisms are not known. Oxylipins are fatty acid metabolites, of which several have been linked to asthmatic airway inflammation. Oxylipin profiles have previously been investigated in bronchoalveolar lavage (BAL), mainly reflecting the peripheral lung, but not in bronchial wash (BW), which better reflect the proximal airways. The airway epithelium is covered by a respiratory tract lining fluid (RTLF) The RTLF contains antioxidants to protect from oxidative stress, which may be caused by exposure to air pollution. Previous studies have reported diminished levels of the antioxidant ascorbate (vitamin C) in the RTLF of patients with asthma. Little is known about the regulation of vitamin C in the lung. The aim of this thesis was to investigate airway inflammatory responses to diesel exhaust exposure in patients with AR and allergic asthma; to evaluate oxylipin profiles in different regions of the lung in patients with allergic asthma; and to study the distribution of vitamin C transporters in the airways of patients with allergic asthma. Diesel exhaust (PM10 100 μg/m3 for 2 h) induced a neutrophilic airway inflammation in healthy individuals evaluated 18 h after exposure. Patients with AR and asthma did not respond with an enhanced airway inflammation. However, a small increase in myeloperoxidase was found in BAL from patients with AR, as well as decreases in epithelial tryptase and BW stem cell factor. This indicates that other mechanisms than classical inflammation are responsible for the increased sensitivity to traffic-related air pollution in patients with allergic airway disease. Oxylipin baseline profiles differed between peripheral and proximal airways in both allergic asthmatics and healthy individuals. Total oxylipin concentrations, and five individual oxylipins, primarily from the lipoxygenase (LOX) pathway, were elevated in BW from asthmatics compared to healthy controls, supported by immunohistochemical staining of 15-LOX-1 in the bronchial epithelium. This suggests that lung compartment-specific sampling should be considered in future studies. Sodium dependent vitamin C transporter 2 (SVCT2) was, for the first time, found present in the human lung epithelium, localised mainly within goblet cells. A negative correlation between SVCT2+ goblet cells and vitamin C suggests that these cells may play a hitherto unknown function in ascorbate re-uptake and recycling at the air-lung interface.

p. 1-79 / Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-11T19:33:48Z No. of bitstreams: 1 Celina.pdf: 668831 bytes, checksum: 06a40d673b8f37dc78a3ea49d2d4cac0 (MD5) / Approved for entry into archive by Maria Creuza Silva(mariakreuza@yahoo.com.br) on 2013-05-04T17:20:37Z (GMT) No. of bitstreams: 1 Celina.pdf: 668831 bytes, checksum: 06a40d673b8f37dc78a3ea49d2d4cac0 (MD5) / Made available in DSpace on 2013-05-04T17:20:37Z (GMT). No. of bitstreams: 1 Celina.pdf: 668831 bytes, checksum: 06a40d673b8f37dc78a3ea49d2d4cac0 (MD5) Previous issue date: 2005 / A asma é um problema de saúde pública que afeta parcela significativa da população. A rinite alérgica freqüentemente coexiste com a asma. Reconhecendo a magnitude desses dois problemas e partindo do conhecimento científico de que são doenças passíveis de controle, o Ministério da Saúde elaborou um protocolo de atenção às pessoas com asma e rinite para a rede básica de saúde e se comprometeu em financiar os medicamentos necessários ao tratamento dessas duas doenças. Este estudo objetiva identificar limites e possibilidades do protocolo para asma e rinite na atenção básica elaborado pelo Ministério da Saúde em 2004. Trata-se de um estudo de natureza exploratória onde foram identificadas as percepções de diferentes atores sociais: profissionais de saúde e gestores - coordenadores municipais e estadual de programas de asma, sobre o referido protocolo. Utilizou-se o método de análise de conteúdo para a apreensão das percepções dos atores sociais relatadas nos questionários e entrevistas realizados no período de julho a outubro de 2005. De uma forma geral, as percepções dos atores sociais foram positivas do ponto de vista de necessidade, pertinência e atualização técnico-científica do protocolo. Há controvérsias quanto à contribuição do protocolo para a humanização das práticas e integralidade da atenção. Houve unanimidade em referir a capacitação continuada dos profissionais da atenção básica como principal desafio para implantação/implementação do protocolo. / Salvador