Effects of cigarette smoking and drugs on respiratory tract proteases and antiproteases.

Increased pulmonary proteolytic (elastolytic) activity is thought to be the primary cause of emphysema and may also play a rôle in the pathology of bronchitis. These diseases are common amongst tobacco smokers. Serum-derived alpha 1-proteinase inhibitor (alpha 1PI) and locally produced protease inhibitors normally protect the pulmonary epithelium from proteolytic attack, but tobacco smoke can inactivate these antiproteases by oxidative and non-oxidative mechanisms. Bronchoalveolar lavage fluid (BALF) samples lung surface components and most studies show that there is elevated elastolytic activity in smokers' BALF. Whether antiproteolytic capacity is reduced in these samples remains debatable. A selective lavage technique is described which independently samples central and peripheral epithelium from the same subject. Analysis demonstrates a protease-antiprotease imbalance which can differ in central and peripheral lavage and which could be significant in the development of obstructive airways disease. Therapeutic approaches include augmenting antiprotease potential using genetically engineered, oxidant-resistant alpha 1PI or synthetic peptide inhibitors.