Effect of di-butyl phthalate exposure in the human airway and systemic immunology : a double-blind, crossover study
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Maestre-Batlle, Danay
issued: 2019-10-18T15:14:43Z
issued: 2019
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: 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 periph…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/71941
note: EFFECT OF DI-BUTYL PHTHALATE EXPOSURE IN THE HUMAN AIRWAY AND SYSTEMIC IMMUNOLOGY: A DOUBLE-BLIND, CROSSOVER STUDY by Danay Maestre-Batlle HBSc, The University of Havana, 2009 A DISSERTATION SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) October 2019 © Danay Maestre-Batlle, 2019 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Effect of di-butyl phthalate exposure in the human airway and systemic immunology: a double-blind, crossover study submitted by Danay Maestre-Batlle in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Experimental Medicine Examining Committee: Dr. Christopher Carlsten Supervisor Dr. Scott Tebbutt Supervisory Committee Member Dr. Stuart Turvey Supervisory Committee Member Dr. Karen Bartlett University Examiner Dr. Vincent Duronio University Examiner Additional Supervisory Committee Members: Dr. Neil Alexis Supervisory Committee Member iii Abstract 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 …
has type: Thesis/Dissertation
date issued: 2019-11
is shown at: 10.14288/1.0384593
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/71941