MORPHOLOGICAL AND CELLULAR BASIS FOR AIR-FLOW LIMITATION IN SMOKERS

Airflow limitation has two well-defined components, increased resistan ce, which is found predominantly in the small airways, and loss of ela stic recoil. Small airways contribute to the increased resistance to f low by the narrowing of the airway lumen. Morphometric studies have sh own that smokers have increased epithelial abnormalities, cellular inf lammatory infiltrates in the airway wall, increased muscle and fibrosi s, when compared with nonsmokers. Along with these anatomical changes, an increased percentage of airways <400 mu m in diameter is found. In addition to the measured changes, other nommeasurable, dynamic events occur in the airways of smokers, which further decrease lumen diamete r. There is ample evidence to show that the airways of smokers react t o nonspecific stimuli by constricting, which results in increased resi stance and decreased forced expiratory volume in one second (FEV(1)). The pathological changes found in smokers, that could be responsible f or active muscle constriction and airway narrowing include: 1) airway epithelial damage, resulting in increased permeability and impairment of other epithelial function; 2) chronic airway inflammation; 3) struc tural changes in the airway wall; and 4) loss of alveolar attachments. However, not all smokers develop the abovementioned airway abnormalit ies. We describe how smokers could develop either centrilobular emphys ema (CLE), or panlobular emphysema (PLE). We have found that smokers w ith CLE have more abnormal and narrower small airways, and flow limita tion is correlated with the small airway abnormalities and not with lo ss of recoil. In contrast, smokers with PLE have much less severe airw ay abnormalities, diffuse emphysema that can be detected microscopical ly at a stage when FEV(1) might be only mildly abnormal, and early cha nges in elastic recoil as evidenced by the changes in the pressure-vol ume curve of the lung. Furthermore, in PLE, airflow limitation is corr elated with loss of recoil but not with abnormalities in the small air ways. We believe that the mechanisms involved in the pathogenesis of t he two types of emphysema in smokers are different; an airborne mechan ism for CLE, possibly related to airway hyperresponsiveness, and a blo odborne mechanism for PLE, which may be related to dysfunction of alph a(1)-antiproteases. We conclude that the separation of smokers based o n their emphysema type is essential if we are to understand the pathog enesis of chronic obstructive pulmonary disease (COPD) in these subjec ts.