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AbstractBackground:In spite of the known role of cigarette smoking in the development of airflow limitation (AL), fewer than 20% of smokers actually develop chronic obstructive pulmonary disease (COPD). Objectives:We examined how smoking histories and indices in blood are related to the degree of AL in asymptomatic smokers in order to determine whether they can predict the development of AL. Methods:Spirometry and peripheral blood tests were examined in 433 Japanese asymptomatic current smokers at the initial examination. Forced expiratory volume in 1 s (FEV1) was measured periodically for 2 or more years (2–13 years) in 66 of the subjects. Results:AL defined as an FEV1/vital capacity of less than 0.7, was found in 11.3% (49 of 433) of the smokers. Pack-years of smoking, serum amounts of α1-proteinase inhibitor, and serum procollagen III peptide activities were correlated with the degree of AL. Fifteen percent (10 of 66) of subjects underwent rapid declines in FEV1that were found to be related not with smoking amounts or initial FEV1, but with low FEV1(%pred) adjusted by pack-years and an elevated serum neutrophil elastase/α1-proteinase inhibitor ratio. These results suggest that smokers with a low FEV1out of proportion to pack-years are susceptible smokers at a high risk of developing COPD, and further, that increased proteinase burden relative to antiproteinase activity may contribute to the development of COPD. Conclusions:We conclude that the serum neutrophil elastase/α1-proteinase inhibitor ratio and FEV1(%pred) adjusted by pack-years can be reliable predictors of the development of COPD.Copyright © 2000 S. Karger AG, Basel