Site and nature of airway obstruction in chronic obstructive lung disease: 50 years on

It has been 50 years since Hogg, Macklem and Thurlbeck published the highly influential paper, The Site and Nature of Airway Obstruction in Chronic Obstructive Lung Disease in the New England Journal of Medicine (NEJM). Their study demonstrated, for the first time, that the major site of increased airway resistance in obstructive lung disease was the small airways of the lung. This landmark paper changed our understanding of the pathophysiology of obstructive lung disease and ushered in intense study of small airway anatomy, physiology and pathology that continues to this day. To commemorate this important publication I have reviewed the events that led up to its publication and the subsequent investigations which have firmly established the small airways as the critical site of pathology in a variety of lung diseases. The work described in the NEJM paper was part of James (Jim) Cameron Hogg’s PhD thesis project, Flow and Ventilation Distribution (McGill University 1969). Additional papers from that thesis included one more in the NEJM, two in the Journal of Clinical Investigation and one in the Journal of Applied Physiology. Jim was doing his PhD at McGill University jointly supervised by two giants in the field of lung physiology and pathology Peter T. Macklem and William (Whitey) Thurlbeck. He came under the mentorship of these individuals by a circuitous route. Jim spent his teenage years in Sioux Lookout Ontario, an isolated small community in North Western Ontario, which was a wonderful place for a boy to grow up. In the winter months and most of the rest of the year, he was preoccupied by hockey. He played left wing, could skate fast, shoot accurately and hold his own body checking. But he did not impress a former NHL player who was also the playing coach of the local senior men’s team who had invited him to play in a few games when they were shorthanded. When he asked the coach for a recommendation to try out with the Flin Flon Bombers, a high quality junior hockey team located on the Manitoba-Saskatchewan border, where many NHL players started their hockey career, the coach said no! His recovery from that disappointment led him, on a convoluted trajectory, to respiratory medicine and research and ultimately to a lifelong fascination with small airways’ disease. It also armed him for the many rejections faced by innovative researchers! Persistence became his most important trait. Since a hockey career was not an option he chose to study medicine and this led him to the University of Manitoba in Winnipeg. During his physiology course, Jim was influenced by the legendary Joe Doupe (http:// news.umanitoba.ca/lecture-honours-joe-doupe-the-man-whorevived-u-of-ms-medical-school/. Dr. Doupe stimulated students to think critically and his influence on Investigative Medicine in Canada has been profound. As for many before and after him, Doupe sparked in Jim an interest in research. Jim was also influenced by another giant in the Canadian Respiratory field Dr. Rueben Cherniack. Dr. Cherniack taught the Respiratory portion of the first year physiology course and gave lectures on clinical respiratory physiology in the second year. In addition, Jim did a clinical clerkship and a 2-month rotation during his internship on Chernicack’s service and Dr. Cherniack continued to serve as a mentor throughout his career. Jim’s family was not wealthy and his mother, a nurse, was raising 4 children as a single mother because of the premature death of Jim’s father. To get through medical school, Jim enlisted with the Royal Canadian Airforce. The Air Force supported him for years 2–4 in medical school and during his rotating internship and committed him to serve 3 years with the RCAF. The first two of these he spent as a general medical Officer in Greenwood Nova Scotia, and the final year was spent at the Institute of Aviation Medicine in Toronto where he met the charismatic physician and physiologist Dr. Charlie Bryan who had completed his PhD at McGill studying the distribution of ventilation using trace amounts of radioactive Xenon gas. When Jim expressed an interest in further research study, Charlie arranged an interview with Dr. David Bates who was head of the combined Cardio-Pulmonary Division at the Royal Victoria Hospital at McGill University in Montreal. Initially, Jim was told there were no positions available, but when Jim mentioned that he also planned to get some training in Pathology, Bates called William (Whitey) Thurlbeck who immediately offered him a position to do a new project jointly supervised by himself and Peter Macklem. When Jim told Charlie about the offer, he strongly suggested that Jim go to Montreal and be under