Grant: Catalyst Grant: Sex as a Variable in Biomedical Research

Chronic obstructive lung disease (COPD) is a respiratory illness, mainly caused by smoking that affects 2.6 million Canadians over the age of 40. Patients with this devastating disease experience a variety of symptoms related to airway obstruction and reduced lung function, including breathlessness, cough, mucus production, and inflammation. There are roughly 85% more female COPD patients than male patients in Canada, who also experience worse symptoms than their male counterparts. Women have worse shortness of breath, poorer quality of life and health status and greater disability. Furthermore, these women are more likely to experience "lung attacks" (sudden and severe changes in symptoms leading to hospitalization). It is not clear, therefore, whether the differences in COPD health outcomes between men and women are due to different underlying biology between the sexes, or to factors such as differences in smoking habits. To answer this question, we will study gene changes across all known human genes in lung tissues and airway cells lining the airways (airway epithelium) from men and women. We will use samples from the world's largest and best-described patient cohorts for our study. We expect to discover genes that are more (or less) expressed in women vs. men. In particular we will study how genes change differently in men and women in response to smoking, and how these same genes may affect disease intensity and outcomes. This information will help us understand, at the gene level, sex differences in disease biology. For example, it will help us understand how genes that are targeted by inhaler drugs or genes that work as anti-oxidants seem to differ between the sexes. This will help guide inhaler treatments for both women and men suffering from COPD. The information will also help inform future clinical management guidelines and clinical studies to include more women and to actively compare the results of a given intervention between the two sexes.