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UBC Theses and Dissertations

Blood-based biomarkers of asthma Yang, Chen Xi


Asthma is a chronic inflammatory airway disorder characterized by reversible airway obstruction and hyperresponsiveness. It affects more than 300 million people worldwide but remains poorly understood. Asthma can be induced by a variety triggers, including allergens, substances found in the workplace, cold air and exercises, and greatly diminishes the life quality of patients. In this thesis, I investigated two major categories of asthma: allergic asthma and occupational asthma. Two types of response are involved in allergic asthma. While 50% of the affected individuals only develop an acute early asthmatic response (EAR), the other individuals develop both the EAR and a chronic late asthmatic response (LAR). Those individuals who present an isolated EAR are classified as early responders (ERs) and individuals who present both the EAR and the LAR are classified as dual responders (DRs). In our study, patients with mild asthma were challenged with specific allergens and their blood was collected prior to the challenge. By measuring the gene expression and the protein levels of complement and coagulation molecules, I demonstrated that the complement and coagulation system may play a role in the LAR of allergic asthma. Occupational asthma is caused by sensitivity to specific molecules found in the working environment. Western red cedar asthma (WRCA) is the most common form of occupational asthma in the Pacific Northwest region of North America, including British Columbia. It is due to sensitivity to a low molecular weight molecule, plicatic acid (PA), found in the dust of western red cedar wood. The current diagnosis of WRCA is through multiple bronchial challenges, which are time-consuming, complicated and expensive. Blood samples were collected from individuals who were suspected to have WRCA prior to the bronchial challenges. Gene expression was measured using the NanoString platform. Using a pathway-directed approach of random forest and leave-one-out cross-validation, I identified and validated a blood-based two-gene biomarker panel which may help distinguish patients with WRCA from those with asthma due to non-western red cedar causes at baseline. Having such a biomarker panel may greatly simplify the current diagnosis of WRCA by way of a simple blood test.

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