A brief review of chronic obstructive pulmonary disease

Abstract

A recent study, based on a combination of multidetector computed tomography scanning of an intact specimen with microcomputed tomography and histological analysis of lung tissue samples, reported that the number of terminal bronchioles were reduced from approximately 44,500/lung pair in control (donor) lungs to approximately 4800/lung pair in lungs donated by individuals with very severe (Global initiative for chronic Obstructive Lung Disease stage 4) chronic obstructive pulmonary disease (COPD) treated by lung transplantation. The present short review discusses the hypothesis that a rapid rate of terminal bronchiolar destruction causes the rapid decline in lung function leading to advanced COPD. With respect to why the terminal bronchioles are targeted for destruction, the postulated mechanisms of this destruction and the possibility that new treatments are able to either prevent or reverse the underlying cause of airway obstruction in COPD are addressed.

Figure 1)

Data adapted from Fletcher and Peto (3) on the natural history of chronic obstructinve pulmonary disease (COPD) in relation to the four Global initiative for chronic Obstructive Lung Disease (GOLD) categories of COPD severity. It is postulated that the slow rates of decline in forced expiratory volume in 1 s (FEV₁) observed in nonsmokers and in the majority of those who either smoke or have stopped smoking is caused by a slow rate of loss of terminal bronchioles. It is further postulated that the rapid decline in FEV₁ observed in the susceptible minority and in those who fail to reach to reach the maximum expected FEV₁ at 25 years of age is caused by a significantly more rapid rate of terminal bronchiolar loss in this group of individuals

Figure 2)

The top row of images left to right show a microcomputed tomography (microCT) image of a normal terminal bronchiole dividing into two respiratory bronchioles where alveoli first appear. A normal bronchogram in which a bronchiole divides into a cluster preterminal and terminal bronchioles to form a normal lung lobule (middle); and a centrilobular emphysematous (CLE) space formed by the coalescence of destroyed respiratory bronchioles supplied by several different terminal bronchioles (right). The bottom row of images left to right show a diagram of Leopold and Gough’s (12) concept of a primary centrilobular lesion in which thick-walled narrowed terminal bronchioles (TB) supply destroyed respiratory bronchioles (RB). A circuit diagram (bottom center) of normal lung anatomy in which preterminal bronchioles (R3) supply terminal bronchioles R1 and R2 that supply alveoli labelled C1 and C2. As well as a second circuit diagram (bottom right) showing the abnormal situation in CLE in which destruction of a terminal bronchiole indicated by removal of R1 leave isolated normal alveoli C1 to be supplied by the enlarged low resistance collateral channels R4 opened by centrilobular emphysematous destruction that develops beyond thick-walled terminal bronchioles that survive the destructive process