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UBC Theses and Dissertations

Effect of di-butyl phthalate exposure in the human airway and systemic immunology : a double-blind, crossover study Maestre-Batlle, Danay


Phthalates are used as softeners in commercial products. They leak into the environment and become wide-spread contaminants. Epidemiological studies suggest an association between phthalate inhalation and development/worsening of airway diseases, but a firm link has not been established. Asthma is a complex disorder associated with inflammation resulting in airway hyper-responsiveness (AHR). Increasing interest is focused on abnormal immune responses as an underlying mechanism contributing to increasing the risk of asthma. This study is the first to investigate airway and systemic effects in humans due to inhalation of a known concentration of a single phthalate. Di-butyl phthalate (DBP), exists in high concentrations in indoor air and has shown inflammatory potential. We hypothesize that DBP inhalation, prior to allergen inhalation will: a) enhance airway inflammation and responsiveness to allergen, and b) alter the activation state and functionality of immune cells in the airway and peripheral blood. In this novel double-blind, order-randomized, crossover study, 16 participants were exposed by inhalation to controlled levels of DBP or clean air (CA) for 3h, followed immediately by an allergen (dust-mite, grass or birch) inhalation. To assess lung function and airway inflammation, spirometry and exhaled nitric oxide was measured before, 3h and 20h post-DBP/CA exposure and allergen inhalation. Blood, bronchoalveolar wash and lavage (BAL) were collected for quantification and measurement of the activation pattern of immune cells and inflammatory mediator release. DBP inhalation followed by an allergen inhalation, significantly augmented the airflow decline (FEV1) in response to an inhaled allergen, compared to CA. Moreover, DBP enhanced the recruitment of BAL macrophages, specifically the M2 phenotype with increased expression of CD206 to the lungs. Meanwhile, the percent of T helper cells increased, while T regulatory and non-classical monocytes decreased, in peripheral blood. Only minor effects were observed for systemic inflammatory mediators. Moreover, significant effect modifications were observed for sex, AHR status and type of allergen inhaled. The results suggest significant effects of a common commercial chemical, DBP, on clinically relevant airway and systemic endpoints in the context of allergen exposure in sensitized individuals. Future research should aim to validate and connect these findings within relevant policy and public health contexts.

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