Evaluation of Ventilation Homogeneity as a Marker of Small Airway Disease in Active Smokers
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, simple and reliable
 method of quantifying airway disease in this population.

 Quantitative lung ventilation single-photon emission computed tomography (SPECT) allows an
 objective quantification of the regional heterogeneity of ventilation in humans. The
 coefficient of variation (CV) of the distribution of a radioactive tracer, inhaled during the
 test, allows the generation of heterogeneity maps and density curves of small elements of the
 lung. These variables are sensitive to the presence of COPD, asthma, air trapping and are
 correlated to even slight anomalies in pulmonary function testing in otherwise healthy
 subjects. As such, SPECT could prove useful as an early marker of airway disease in active
 smokers at risk of developing COPD, but its use in this context has never been formally
 tested.

 This pilot study addresses the question of whether lung SPECT could provide clinically
 relevant information on airway disease in active smokers without overt lung disease on
 pulmonary lung function testing.
For Smokers group:

 Inclusion Criteria:

 -  Active tobacco smoking of at least 10 cigarettes/day AND total smoking history of at
 least 15 pack-years.

 -  Normal lung function testing, defined as: FVC/FEV1 ratio, FEV1 and FVC all greater
 than the lower limit of normal; mean forced expiratory flow at 25 to 75% of CVF
 (FEF25-75%) >80% of predicted value and absence of concavity on the forced expiratory
 flow curve, as evaluated by a trained respirologist; total lung capacity (TLC) greater
 than the lower limit of normal; residual volume (RV), functional residual capacity
 (FRC), expiratory reserve volume (ERV), inspiratory capacity (IC) and VR/TLC ratio all
 >80% predicted value and diffusion capacity of the lung for carbon monoxide (DLCO)
 >80% predicted value when corrected for hemoglobin level.

 -  Body mass index (BMI) <30 kg/m2

 Exclusion criteria:

 • Post-bronchodilator change in FEV1 and FVC of more than 6% and/or 100 ml.

 For Non-smokers group:

 Inclusion Criteria:

 -  No history of tobacco-smoking.

 -  Normal lung function testing, defined as: FVC/FEV1 ratio, FEV1 and FVC all greater
 than the lower limit of normal; mean forced expiratory flow at 25 to 75% of CVF
 (FEF25-75%) >80% of predicted value and absence of concavity on the forced expiratory
 flow curve, as evaluated by a trained respirologist; total lung capacity (TLC) greater
 than the lower limit of normal; residual volume (RV), functional residual capacity
 (FRC), expiratory reserve volume (ERV), inspiratory capacity (IC) and VR/TLC ratio all
 >80% predicted value and diffusion capacity of the lung for carbon monoxide (DLCO)
 >80% predicted value when corrected for hemoglobin level.

 -  Body mass index (BMI) <30 kg/m2

 Exclusion criteria:

 • Post-bronchodilator change in FEV1 and FVC of more than 6% and/or 100 ml.