T Betsuyaku, M Nishimura, A Yoshioka, K Takeyabu, K Miyamoto and Y Kawakami
First Department of Medicine, Hokkaido University School of Medicine, Sapporo, Japan.

To evaluate effects of current smoking on the breakdown of lung elastin, we measured levels of elastin-derived peptides (EDP) in unconcentrated bronchoalveolar lavage (BAL) fluid from 42 community- based older asymptomatic volunteers (60 +/- 11 yr [mean +/- SD]) and examined the relationships of the concentrations of EDP with immunologically detected neutrophil elastase (NE) bound with alpha(1)- proteinase inhibitor and with esterolytic activity against the NE- sensitive synthetic substrate, methoxysuccinyl-alanyl-alanyl-prolyl- valyl paranitroanilide (MEOSAAPVNA). The measurement of EDP levels was carried out by an indirect, competitive ELISA, using a sheep IgG fraction generated against insoluble human lung elastin as a primary antibody. EDP concentrations were significantly elevated in current smokers (n = 24) compared with age-matched noncurrent smokers (n = 18) (29.9 +/- 3.5 [mean +/- SE] versus 17.0 +/- 1.8 ng/mg BAL fluid albumin, p < 0.01). We found weak but significant correlations of EDP levels with NE-alpha(1)-proteinase inhibitor complex (r = 0.38, p < 0.05) and with the esterolytic activity against the NE-sensitive synthetic substrate in BAL fluid (r = 0.65, p < 0.001). In addition, EDP levels in BAL fluid had a significant positive relationship with plasma cotinine concentrations (r = 0.53, p < 0.001), though not with pack-years of smoking (r = 0.1, NS). These data provide further evidence that the concentrations of EDP increase in BAL fluid from current smokers compared with noncurrent smokers and that enhanced breakdown of the lung elastin is associated with the increased load of NE in the lung.

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