Grant: Project Grant - PA: Epigenetics/epigenomics in human health or disease

Chronic obstructive pulmonary disease (COPD) is characterized by persistent shortness of breath, cough, and reduced exercise capacity. COPD affects 2.7 million Canadians and accounts for ~11,000 deaths/y in Canada. Increasing age is the leading risk factor for COPD. This has led some to speculate that COPD is a disease of accelerated ageing. Moreover, it is projected that over the next 15 years, the number of COPD patients will double in Canada, driven largely by the ageing population. Whether ageing-related factors can be developed for novel therapeutic and/or biomarker targets is not known. Here, we will test the hypothesis that age-related (blood) biological "clocks" are biomarkers to prognose and predict health outcomes in patients with COPD. In this project, we will take blood samples and estimate the "biological" age of individuals by evaluating their epigenetic changes that are related to ageing. We will then determine these biological clocks' ability to predict death, lung cancer, respiratory attacks, quality of life, and response to medications in patients with COPD. For this project we will use four cohorts: i) The CanCOLD study, which is a unique Canadian COPD cohort that includes 1,443 female and male participants; ii) PanCan Study, which is a Canadian lung cancer screening cohort; iii) Advair Biomarker in COPD Trial, which was a study comparing the effects of inhaled corticosteroids in COPD (n=224); and iv) the St. Paul's Hospital Bronchoscopy Cohort, which is an internal biobank of bronchoscopic and blood samples (n=100). Together, these experiments will show that epigenetic changes in blood of COPD can enable physicians to predict the prognosis and therapeutic responses in their patients with COPD. This will significantly improve the management of COPD patients and reduce unnecessary treatments, decreasing the cost of health care and risk of side effects in patients.