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The Influence Of Estrogen And Glucocorticoid On Th2 Cell Survival And Transcriptional Activation Of Crth2, Jenna H. Fortunato

Electronic Thesis and Dissertation Repository

Women are more likely to have severe asthma than men. Recent data suggest this could be due to women having more circulating CD4⁺CRTh2⁺ T cells (Th2 cells). Glucocorticosteroids (GC)s are the main therapy for asthma as they inhibit cytokine production and eliminate inflammatory cells by apoptosis. The current study examined whether the female sex hormone estrogen influences the anti-inflammatory action of GC. Experiments show that ER⍺ agonist reduced GC-induced apoptosis of primary Th2 cells and enhanced GC-mediated transcriptional activation of the proximal CRTh2 promoter. Genetic variation within CRTh2 is associated with asthma and allergic phenotypes. Using constructs …

Prematurity, Socioeconomic Status, And Childhood Asthma: A Canadian Cohort Study, Crystal P. Mcleod

Electronic Thesis and Dissertation Repository

Introduction: Preterm birth (PTB) and socioeconomic status (SES) have both been associated previously with the onset of childhood asthma in high income countries. Yet, these factors have been studied minimally outside of an exposure or confounded relationship, and amongst the Canadian population.

Materials and Methods: Merging household interview data from Cycles 2 to 5 of the Canadian Health Measures Survey, this study analyzed data from weighted respondents in early (3-5 years, n = 1,096,609) and middle (6-11 years, n = 2,112,059) childhood. Bivariate, stepwise logistic regression, and logit decomposition were performed using STATA software. Intersectionality guided the study’s methodology.

Results: …

Structure And Function Of Asthma Evaluated Using Pulmonary Imaging, Rachel L. Eddy

Electronic Thesis and Dissertation Repository

Asthma has been understood to affect the airways in a spatially heterogeneous manner for over six decades. Computational models of the asthmatic lung have suggested that airway abnormalities are diffusely and randomly distributed throughout the lung, however these mechanisms have been challenging to measure in vivo using current clinical tools. Pulmonary structure and function are still clinically characterized by the forced expiratory volume in one-second (FEV₁) – a global measurement of airflow obstruction that is unable to capture the underlying regional heterogeneity that may be responsible for symptoms and disease worsening. In contrast, pulmonary magnetic resonance imaging (MRI) …

Effect Of Estrogen And Glucocorticoid Signaling On Th2 Cells – Implications For Severe Asthma, Meerah Vijeyakumaran

Electronic Thesis and Dissertation Repository

T helper (Th2) cells are increased in asthma and mediate allergic inflammation through production of type 2 cytokines (interleukin-4, -5 and -13). One pathway to activate Th2 cells is through chemoattractant-homologous receptor expressed on Th2 cells (CRTh2), a receptor for prostaglandin D₂ (PGD₂). Glucocorticoids (GCs) are the main treatment for allergic disease, due to their ability to suppress type 2 cytokine production and induce apoptosis. Incidence and severity of asthma is greater in women than men, which may be related to sex-specific efficacy of GCs. Recently, our laboratory found that severe asthmatic women had more circulating Th2 …

Imaging Biomarkers Of Pulmonary Structure And Function, Dante Capaldi

Electronic Thesis and Dissertation Repository

Asthma and chronic obstructive pulmonary disease (COPD) are characterized by airflow limitations resulting from airway obstruction and/or tissue destruction. The diagnosis and monitoring of these pulmonary diseases is primarily performed using spirometry, specifically the forced expiratory volume in one second (FEV₁), which measures global airflow obstruction and provides no regional information of the different underlying disease pathologies. The limitations of spirometry and current therapies for lung disease patients have motivated the development of pulmonary imaging approaches, such as computed tomography (CT) and magnetic resonance imaging (MRI). Inhaled hyperpolarized noble gas MRI, specifically using helium-3 (³He) and …

Evaluating Small Airways Disease In Asthma And Copd Using The Forced Oscillation Technique And Magnetic Resonance Imaging, Heather M. Young

Electronic Thesis and Dissertation Repository

Obstructive lung disease, including asthma and chronic obstructive pulmonary disease (COPD), is characterized by heterogeneous ventilation. Unfortunately, the underlying structure-function relationships and the relationships between measurements of heterogeneity and patient quality-of-life in obstructive lung disease are not well understood. Hyperpolarized noble gas MRI is used to visualize and quantify ventilation distribution and the forced oscillation technique (FOT) applies a multi-frequency pressure oscillation at the mouth to measure respiratory impedance to airflow (including resistance and reactance). My objective was to use FOT, ventilation MRI and computational airway tree modeling to better understand ventilation heterogeneity in asthma and COPD. FOT-measured respiratory system …

The Effect Of Glucocorticosteroids On Th2 Cells, Tharsan Kanagalingam

Electronic Thesis and Dissertation Repository

The abundance of Th2 cells in both the airways and circulation associates with asthma severity. Activation of CRTh2 expressed by Th2 cells mediates production of Th2 cytokines and inhibits apoptosis. Glucocorticosteroid effects occur through suppression of Th2 cytokines and induction of apoptosis. However, recent evidence shows that the total daily dose of inhaled glucocorticosteroids was positively correlated with the percentage of circulating Th2 cells. As such, we chose to examine regulation of Th2 cells by glucocorticosteroids. We used CCRF-CEM cells as a Th2 cell model and in vitro differentiated primary Th2 cells to study the effect of dexamethasone. Low dose …

Pulmonary Image Segmentation And Registration Algorithms: Towards Regional Evaluation Of Obstructive Lung Disease, Fumin Guo

Electronic Thesis and Dissertation Repository

Pulmonary imaging, including pulmonary magnetic resonance imaging (MRI) and computed tomography (CT), provides a way to sensitively and regionally measure spatially heterogeneous lung structural-functional abnormalities. These unique imaging biomarkers offer the potential for better understanding pulmonary disease mechanisms, monitoring disease progression and response to therapy, and developing novel treatments for improved patient care. To generate these regional lung structure-function measurements and enable broad clinical applications of quantitative pulmonary MRI and CT biomarkers, as a first step, accurate, reproducible and rapid lung segmentation and registration methods are required. In this regard, we first developed a 1H MRI lung segmentation algorithm that …

Multi-Nuclear Magnetic Resonance Imaging Of Obstructive Lung Disease, Khadija Sheikh

Electronic Thesis and Dissertation Repository

Obstructive lung diseases such as chronic-obstructive-lung-disease (COPD), bronchiectasis, and asthma are characterized by airflow obstruction. They affect over six million Canadians costing the economy $12 billion/year. Despite decades of research, therapies that modify obstructive-lung-disease progression and control are lacking because patient diagnosis, monitoring, and response to therapy are currently made using airflow measurements that may conceal the independent contributions of underlying pathologies. One goal of obstructive-lung-disease research is to develop ways to identify patients with specific underlying pathological phenotypes to improve patient care and outcomes. Thoracic computed-tomography (CT) and magnetic-resonance-imaging (MRI) provide ways to regionally identify the underlying pathologies associated …

A Link Between Paediatric Asthma And Obesity: Are They Caused By The Same Environmental Conditions?, Phylicia Gonsalves

Electronic Thesis and Dissertation Repository

The highly associated paediatric conditions of asthma and overweight have seen dramatic increases over the past few decades. This thesis explored air pollution exposure as a potential underlying mechanism of co-morbid asthma and overweight among adolescents aged 12 to 18 years. Data from the Canadian Community Health Survey were merged with a database containing estimates of air pollution as assessed by particulate matter ≤ 2.5 microns (PM_2.5) concentrations at the postal code centroid in southwestern Ontario. Logistic regression was used to conduct the analysis. Adolescents were more likely to be overweight as PM_2.5 concentrations increased. There was …

Pulmonary Imaging To Better Understand Asthma, Sarah Svenningsen

Electronic Thesis and Dissertation Repository

Asthma is characterized using the spirometry measurement of the forced expiratory volume in one second (FEV₁). Simple and inexpensive, FEV₁ provides a global estimate of lung function but this metric cannot regionally identify airways responsible for airflow limitation, asthma symptoms or control. Work that brought about an understanding that airway abnormalities are heterogeneously distributed within the lung in asthma patients has motivated the development of pulmonary imaging approaches, such as hyperpolarized helium-3 (³He) and xenon-129 (¹²⁹Xe) magnetic resonance imaging (MRI). These methods provide a way to visualize and quantify lung regions accessed by …

The Relative Influences Of Knowledge, Beliefs And Preferences On Adherence To Asthma Medication, Naomi J. Gryfe Saperia

Electronic Thesis and Dissertation Repository

Purpose: Patients’ decisions about whether or not to adhere to their prescribed regimens are shaped not only by their knowledge and beliefs about their condition and its treatment options, but also by what they value in these domains. This study represents an integration of theory and methods from nursing/public health, psychology and economics to explore the additive effects of knowledge, beliefs and preferences on adherence to preventer medication in a sample of patients with asthma. It was hypothesized that knowledge, beliefs and preferences pertaining to long term outcomes would independently predict improved adherence. Method: 140 patients with asthma were asked …