The specific treatment of emphysema.
Cigarette smoking is the major risk factor for development of emphysema. Many people are unable to stop smoking despite skilled support. The elastase-antielastase imbalance hypothesis for the pathogenesis of emphysema suggests that treatment with a supplemental elastase inhibitor might prevent development of emphysema in susceptible people. Many elastase inhibitors have been developed. Poorly soluble inhibitors do not prevent emphysema when tested in an animal model of elastase-induced emphysema. Irreversible inhibitors are effective in a dose-response manner. Reversible but tight-binding large molecular weight inhibitors, which clear slowly from the lungs, are effective in vivo. Small molecular weight, reversible inhibitors prevent haemorrhage after human neutrophil elastase instillation into the lungs but may potentiate emphysema. Only 15% of long-term smokers are susceptible to the development of emphysema. Susceptible smokers can be identified by the development of airflow obstruction. An outcome study of efficacy of elastase inhibitor therapy would be prohibitively expensive. However, a study of the process of development of elastase-induced emphysema is feasible. Measurement of alterations in elastase load of the lungs, elastase derived fibrinopeptides, circulating elastin peptides and urinary desmosines could be used for this purpose.
Boston Veterans Administration Medical Center, MA 02130.
G L
GL
Snider
P J
PJ
Stone
E C
EC
Lucey
D000818:Animals; D001897:Boronic Acids / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006224:Cricetinae; D005541:Forced Expiratory Volume; D006801:Humans; D009842:Oligopeptides / Q000627:therapeutic use; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors*; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011656:Pulmonary Emphysema / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D015842:Serine Proteinase Inhibitors / Q000627:therapeutic use; D012907:Smoking / Q000009:adverse effects
D001897:Boronic Acids; D009842:Oligopeptides; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D015842:Serine Proteinase Inhibitors; C048437:methyl-O-succinyl-alanyl-alanyl-prolyl-borovaline-pinacol; D010196:Pancreatic Elastase