Abstract
Airflow limitation has two well-defined components, increased resistance, which is found predominantly in the small airways, and loss of elastic recoil. Small airways contribute to the increased resistance to flow by the narrowing of the airway lumen. Morphometric studies have shown that smokers have increased epithelial abnormalities, cellular inflammatory infiltrates in the airway wall, increased muscle and fibrosis, when compared with nonsmokers. Along with these anatomical changes, an increased percentage of airways < 400 microns in diameter is found. In addition to the measured changes, other nonmeasurable, dynamic events occur in the airways of smokers, which further decrease lumen diameter. There is ample evidence to show that the airways of smokers react to nonspecific stimuli by constricting, which results in increased resistance and decreased forced expiratory volume in one second (FEV1). The pathological changes found in smokers, that could be responsible for 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) structural changes in the airway wall; and 4) loss of alveolar attachments. However, not all smokers develop the abovementioned airway abnormalities. We describe how smokers could develop either centrilobular emphysema (CLE), or panlobular emphysema (PLE). We have found that smokers with CLE have more abnormal and narrower small airways, and flow limitation is correlated with the small airway abnormalities and not with loss of recoil. In contrast, smokers with PLE have much less severe airway abnormalities, diffuse emphysema that can be detected microscopically at a stage when FEV1 might be only mildly abnormal, and early changes in elastic recoil as evidenced by the changes in the pressure-volume curve of the lung. Furthermore, in PLE, airflow limitation is correlated with loss of recoil but not with abnormalities in the small airways. We believe that the mechanisms involved in the pathogenesis of the two types of emphysema in smokers are different; an airborne mechanism for CLE, possibly related to airway hyperresponsiveness, and a bloodborne mechanism for PLE, which may be related to dysfunction of alpha 1-antiproteases. We conclude that the separation of smokers based on their emphysema type is essential if we are to understand the pathogenesis of chronic obstructive pulmonary disease (COPD) in these subjects.
Highlights
Small airways contribute to the increased resistance to flow by the narrowing of the airway lumen
We conclude that the separation of smokers based on their emphysema type is essential if we are to understand the pathogenesis of chronic obstructive pulmonary disease (COPD) in these subjects
This study showed that these patients had similar but much more extensive abnormalities in the small airways than those described by NIEWOEHNER et al [3], probably due to the fact that the patients studied at McGill University were older, had smoked more, and had some degree of COPD
Summary
Morphological and cellular basis for airflow limitation in smokers. M. When the FEV1 was normal, an increasing number of abnormal tests of small airway function, such as volume of isoflow, closing volume as a percentage of vital capacity, and slope of phase III of the single-breath nitrogen wash-out were associated with increasingly severe fibrosis scores in membranous bronchioles and with worsening intraluminal and mural inflammatory scores of respiratory bronchioles (respiratory bronchiolitis). These studies demonstrate that cigarette smoke can elicit an inflammatory reaction in the membranous and respiratory bronchioles early in life, and this abnormality can be detected by tests of small airway function, such as slope of phase III of the nitrogen wash-out These early pathological and physiological abnormalities do not progress in all smokers, and the tests designed to detect the early physiological abnormalities in the small airways do not predict the 15–20% of smokers who progress to chronic airflow limitation [10]. Once the pathological changes in the airways are established, the striking correlation between the progression of physiological impairment and the degree of small airway disease suggests that inflammation of the small airways makes an important contribution to the functional deterioration seen in COPD, even in the presence of emphysema
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