Longitudinal study of lung structure and airflow limitation in smokers using computed tomography and spirometry

Early detection of chronic obstructive pulmonary disease (COPD) is crucial since the protective effect from smoking cessation diminishes when the disease becomes severe. Little is known about early changes before the onset of airflow limitation. In addition, the natural history of COPD has not been extensively investigated in longitudinal studies. In this work, I firstly compared quantitative CT densitometry between low- and regular-dose CT images, and between different CT scanners. I found a significant overestimation of “emphysema” using densitometry measurements from low-dose CT images, while measurements were comparable between the two scanners. Secondly, I validated a CT measurement of %overinflation using both a dynamic cutoff (maximal lung inflation) and CT cluster analysis, by comparing them to the histological gold standard for emphysema, the lung surface area to volume ratio. In addition, CT cluster analysis supplemented CT lung density in quantifying pulmonary emphysema. Thirdly, I tested the contributions of parenchymal overinflation and airways’ remodeling to airflow limitation in a cross-sectional study design. In COPD subjects, the “airway-dominant” phenotype had less severe airflow limitation but smaller airway lumen area compared to the “emphysema-dominant” phenotype. Smokers who had normal spirometry showed less parenchymal overinflation but there was considerable overlap with those who had established COPD. The fourth original investigation is a longitudinal study of spirometry and CT analyses in heavy smokers without COPD. I found that baseline parenchymal overinflation was significantly associated with the subsequent rate of decline in lung function. This novel finding suggests that CT analysis could serve as a useful biomarker to identify those “susceptible” smokers who will develop COPD. Lastly, I showed that progressive airflow limitation was associated with worsening airway abnormalities only in smokers without COPD at baseline, whereas it was only associated with progression in parenchymal destruction in smokers with pre-existing COPD. In addition, smokers who had, or did not have, established COPD at baseline showed a comparable rate of progression of airflow limitation and parenchymal overinflation. In summary, these cross sectional and longitudinal studies of a unique cohort of smokers, using validated CT measurement tools, provide important insights regarding the onset and natural history of COPD.Medicine, Faculty ofMedicine, Department ofExperimental Medicine, Division ofGraduat