From the tracheobronchial tree structure models described by Weibel [1], Horsfield and Cumming [2], and others [3, 4], we know that in the normal lung, the airways follow a branching pattern from the trachea to the distal airways, which locks in a progressive increase in cumulative cross-sectional lumen area. In fact, in the healthy lung, this increase in cross-sectional lumen area is exponential! The small airways, <2 mm in diameter, which can appear as early as the fourth generation of airway branches [5], are believed to be the major site of airflow obstruction in patients with COPD [6]. This insight was based on small airway disease features, including airway narrowing and obliteration, as well as mucus plugging. Using micro-computed tomography (CT) imaging [7], the cross-sectional lumen area of the terminal bronchioles was also shown to be reduced by 99.7% in COPD patients relative to controls. Substantial decreases in the total cross-sectional lumen area in the small airways will necessarily result in deviations from the expected exponential relationship.