Respirology Research

The University of Toronto’s Division of Respirology is world renowned for its clinical and research programs in lung transplantation, sleep-related breathing disorders/control of breathing, and cystic fibrosis (CF). Divisional research is conducted at the University of Toronto campus as well as at all 5 University of Toronto affiliated hospitals: University Health Network, Mount Sinai Hospital, St. Michael’s Hospital, Sunnybrook Health Sciences Centre and West Park Health Care Centre. The research is broad in scope and spans a wide variety of methodologies from basic molecular biology, genetics and immunology, to integrative physiology, epidemiology, randomized clinical trials, knowledge translation and qualitative research. Respirology is heavily invested in its faculty and their research efforts with a view to improving quality of care and patient outcomes locally, nationally and internationally.

Toronto houses the largest and most successful lung transplant program in the world. However, life expectancy following transplant is often limited by acute and chronic rejection and chronic lung allograft dysfunction (CLAD). Accordingly, a major research focus in lung transplantation is to improve graft survival. Investigators are examining factors that might contribute to better donor – host matching to improve graft retention as well determining basic molecular and immunological factors leading to CLAD and potential therapeutic approaches to it. Another approach being pursued is the potential contribution of air pollution to chronic graft rejection. The roles of frailty and sarcopenia in determining quality of life and outcomes from advanced lung disease pre- and post-lung transplantation are also being investigated.

Similarly, research in sleep-related breathing disorders and control of breathing runs the gamut from studies of basic mechanism to assessing patient centred outcomes of quality of care. Investigators are engaged in basic molecular and pharmacologic research on factors affecting upper airway patency during sleep. Mechanisms by which opiates suppress breathing and factors that could counteract this to prevent deaths from opiate overdoses are being pursued. Other investigators are examining the effects of opiates and other sedatives on outcomes in sleep apnea and COPD. The role of fluid retention and overnight rostral fluid shift in the pathogenesis and treatment of sleep apnea in patients with various fluid overload states are being actively pursued. In addition, a multinational randomized trial, ADVENT-HF, is being conducted to determine if treating sleep apnea in patients with heart failure using adaptive servo-ventilation will reduce morbidity and mortality.

Toronto houses the largest adult CF clinic in Canada. Investigators are interested in determining why CF patients in Canada live 10 years longer than their counterparts in the US. The influence of genotype-phenotype relationships on CF outcomes is another research focus.

Productive research is also being carried out in several other areas. A major initiative, the RECOVER program, is investigating long-term medical and psychosocial outcomes of patients and their caregivers following discharge from an intensive care unit. The mechanisms driving sustained ICU acquired weakness in critical illness survivors, and the influence of delirium and its management by sedatives on intensive care outcomes is also being pursued. In airways diseases, investigators are examining ways to better define COPD and determine factors that affect COPD outcomes using large data bases and knowledge translation techniques. Molecular mechanisms of skeletal muscle atrophy and frailty in end-stage COPD are being explored while ways to improve outcomes of respiratory rehabilitation for COPD are being tested. Cell phone apps are being developed to improve delivery of guideline-based asthma therapy at point-of-care. Some investigators are pursuing factors involved in development of occupational asthma, while others conduct randomized trials of asthma therapy.

In mycobacterial disease, research is being carried out on the influence of immunosuppression on development of, and outcomes from both TB and non-tuberculous mycobacterium. The Division is also involved in educational research to examine the influence of professionalism on medical education. Research in quality improvement and patient safety has focused on use of D-dimer testing to reduce costly and unnecessary CT and ventilation/ perfusion scans to diagnose venous thrombosis and pulmonary embolism. In relation to this, research is also being carried out on prophylaxis for and treatment of venous thrombosis and pulmonary embolism in hospitalized patients following trauma and surgery. Other investigators are looking to improve and reduce the cost of lung cancer staging via endobronchial ultrasound (EBUS).

There are several programs involving rare lung diseases. In hereditary hemorrhagic telangiectasia (HHT), researchers are examining mechanisms of pulmonary arteriovenous malformation development. With respect to interstitial lung disease (ILD), a focus is on investigating the efficacy, safety and complications of open lung biopsy for diagnosing various forms of ILD. The pulmonary hypertension program is engaged in research into the pathophysiology and various causes of pulmonary hypertension and right heart failure. Researchers are also investigating new therapeutic approaches to hepato-pulmonary syndrome.

The Division of Respirology is committed to ensuring that its legacy of research excellence carries through to the next generation. To this end, under the leadership of current director, Dr. Doug Bradley, the division has instituted a research rotation for all Respirology trainees to encourage them to get involved in research, and pave the road to an academic career with a research component. In addition, recognizing the difficulty for early-career faculty to obtain external grant funding, the Division has established a competitive intramural grant program. This program, funded by the Godfrey S. Pettit Chair in Respiratory Medicine, is administered by the Research Advisory Committee and is designed principally to support research projects of early-career faculty. This has proven to be an effective springboard to subsequent success in obtaining external peer-reviewed grants.