Grant: Project Grant

Chronic obstructive pulmonary disease (COPD) - commonly referred to as chronic bronchitis or emphysema - is a progressive and debilitating disorder of the lungs. In most cases, it is caused by long-term exposure of susceptible individuals to tobacco smoke. Typically, COPD is characterised by persistent inflammation of the lungs leading to difficulty in breathing and, ultimately, premature death. An acute attack of COPD, known as an exacerbation, describes a rapid worsening of a patient's disease above normal day-to-day variability. Such attacks can be life threatening, are one of the leading cause of hospitalizations in North America and have a detrimental impact on ease of breathing and quality of life. Treatment of COPD is limited and mortality remains high. However, it is known that patients with COPD who experience exacerbations derive benefit from a class of drugs collectively known as LABAs. It is believed by many investigators that LABAs protect against exacerbations by opening the airway passages. However, recent research from our laboratory suggests that the beneficial effects of LABAs may also be due to their ability to switch-on a variety of genes in the lungs that, together, suppress inflammation, improve breathing and reduce the severity of attacks. To test this idea, we will explore the biology of candidate genes switched-on by LABAs using lung cells from normal healthy subjects and smoking individuals with COPD. We will also conduct a clinical study to measure the effect of a LABA on gene expression changes in the lungs of patients with COPD to confirm results obtained with isolated cells. We believe this research is important because acute attacks of COPD are associated with a considerable risk of death. The work proposed here should improve our understanding of how LABAs benefit patients with COPD and identify novel genes that could be exploited therapeutically.