Evaluation of Ventilation Homogeneity as a Marker of Small Airway Disease in Active Smokers

Ventilation heterogeneity is a hallmark feature of most obstructive pulmonary diseases. In particular, chronic obstructive pulmonary disease (COPD) is pathologically and physiologically characterized by small airway destruction and marked airway cellular inflammation, which result in prominent expiratory airflow limitation, air trapping, hyperinflation and abnormal gas exchange. COPD is strongly linked with the exposition to inhaled irritants, most notably tobacco smoke, and is as such a potentially preventable disease. COPD-related morbidity, mortality and social costs are high: in Canada, COPD is the main cause of hospital admission among all chronic diseases and is the fourth leading cause of death. Diagnosis of COPD requires the objective demonstration of expiratory airflow limitation using spirometry. In the right clinical context, a post-bronchodilator forced vital capacity (FVC) / forced expiratory volume in 1 second (FEV1) ratio \<0.70 is considered indicative of the presence of COPD, and therefore pulmonary function testing is required to make the diagnosis. However, the natural history of COPD represents a slowly-progressive continuum: active smokers that do not meet the criteria for COPD are still at risk of developing the disease. In fact, when compared to healthy non-smokers, active smokers without overt COPD can already show some pathological and clinical features of the disease. Notably, they report increased levels of resting dyspnea, chronic cough, lower exercise capacity, exercise-induced dynamic hyperinflation and marked airway inflammatory cellular infiltration, while conserving normal pulmonary function test values. These findings highlight the negative, clinically-measurable effects of tobacco smoking on pulmonary function, but also the limitations of standard pulmonary function testing in identifying the presence of early, mild airway disease and quantifying physiological limitations in these subjects. As such, there is a need for a novel, s