|Institution:||The University of British Columbia|
|Keywords:||Asthma, Allergic Asthma, bronchial allergen-induced inflammation, Airway Inflammation, Asthma Exacerbation, Pulmonary Immunology, Lung Tissue Immunohistochemistry, Ambient Air Pollution|
|Full text PDF:||https://open.library.ubc.ca/cIRcle/collections/ubctheses/24/items/1.0300223|
Asthma is a chronic condition described by inflammation of the airways. There are no specific treatments for asthma yet but understanding the potential triggers of an asthma attack can effectively control this disease and make it more manageable for many sufferers. Therefore, there is intense interest in studying the negative impacts of air pollutants on respiratory diseases. Diesel exhaust (DE) is a primary source of emissions from motor vehicles and is also a significant cause of increased airway responsiveness in asthma. The main particulate fraction of diesel exhaust consists of fine particles (PM₂․₅), which are inhaled efficiently into the lung. Inhalation of these particles can exacerbate asthma and trigger other harmful processes in the lung. The effect of traffic-related air pollution, such as DE on asthma exacerbations is well-established but the biological mechanism underlying this association is still not well understood. DE is thought to interact with allergen exposures to mediate adverse effects, but most of the studies done in this area are based on animal models and there remains poor appreciation of the mechanisms of allergen-DE synergy in human models. In this research project, we aim to elucidate if DE increases bronchial allergen-induced inflammation and cellular immune response in mild atopic asthmatic human subjects. Volunteer participants were exposed to DE (300 μg.m-³ of PM₂․₅) or filtered air for two hours in a blinded crossover study design with a four-week washout period. One hour following either filtered air or DE exposure, subjects were exposed to allergen or saline via bronchoscopic segmental challenge. Forty-eight hours post-exposure, endobronchial biopsies were collected. Tissue sections were immunostained for tryptase, eosinophil cationic protein (ECP), neutrophil elastase (NE), CD138, CD4 and interleukin (IL)-4. The percent positivity of positive cells were quantified in the bronchial submucosa by Aperio ImageScope Software. We have shown that in vivo allergen and DE co-exposure results in elevated CD4, IL-4, CD138 and NE in the respiratory submucosa of atopic subjects, while eosinophils and mast cells are not changed. Here we demonstrated, for the first time, the effect of DE exposure in promoting allergen-induced inflammatory responses directly within the lungs of atopic human.