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Abnormal apoptotic mechanisms are associated with disease pathogenesis. Because the asthmatic bronchial epithelium is characteristically damaged with loss of columnar epithelial cells, we postulated that this is due to unscheduled apoptosis. Using an antibody directed toward the caspase cleavage product of poly(ADP-ribose) polymerase, immunohistochemistry applied to endobronchial biopsies showed higher levels of staining in the bronchial epithelium of subjects with asthma as compared with normal control subjects (% epithelial staining [median (range) ‫؍‬ 10.5 (1.4-24.5) versus 0.4 (0.0-9.7)]; P Ͻ 0.001). Because we were unable to determine whether this difference was due to ongoing inflammation in vivo , cultures of normal and asthmatic bronchial epithelial cells were used to study apoptosis in vitro . In complete growth medium, these cells showed no difference in their rate of proliferation or viability. However, cells from subjects with asthma were more susceptible to the apoptotic effects of H 2 O 2 than cells from normal control subjects (% apoptotic cells ‫؍‬ 32.2 [8.8-54.9] versus 14.3 [6.4-24.7]; P Ͻ 0.05), even though both were similarly affected by treatment with actinomycin D. These data indicate that the susceptibility of asthmatic bronchial epithelium to oxidants is greater than normal. This susceptibility may contribute to the rising trends in asthma associated with air pollution and diets low in antioxidants.

Background: Considerable research has been conducted into the nature of airway inflammation in chronic obstructive pulmonary disease (COPD) but the relationship between proximal airways inflammation and both dynamic collapse of the peripheral airways and HRCT determined emphysema severity remains unknown. A number of research tools have been combined to study smokers with a range of COPD severities classified according to the GOLD criteria. Methods: Sixty five subjects (11 healthy smokers, 44 smokers with stage 0-IV COPD, and 10 healthy nonsmokers) were assessed using lung function testing and HRCT scanning to quantify emphysema and peripheral airway dysfunction and sputum induction to measure airway inflammation. Results: Expiratory HRCT measurements and the expiratory/inspiratory mean lung density ratio (both indicators of peripheral airway dysfunction) correlated more closely in smokers with the severity of airflow obstruction (r = 20.64, p,0.001) than did inspiratory HRCT measurements (which reflect emphysema severity; r = 20.45, p,0.01). Raised sputum neutrophil counts also correlated strongly in smokers with HRCT indicators of peripheral airway dysfunction (r = 0.55, p,0.001) but did not correlate with HRCT indicators of the severity of emphysema. Conclusions: This study suggests that peripheral airway dysfunction, assessed by expiratory HRCT measurements, is a determinant of COPD severity. Airway neutrophilia, a central feature of COPD, is closely associated with the severity of peripheral airway dysfunction in COPD but is not related to the overall severity of emphysema as measured by HRCT.