A controlled trial of colchicine to reduce the elastase load in the lungs of ex-cigarette smokers with chronic obstructive pulmonary disease.
A great deal of experimental evidence suggests that emphysema in smokers is caused by the action of neutrophil elastase on lung elastin. In order to test this hypothesis, it is necessary to find a drug that reduces the load of neutrophil elastase in the lungs of patients with emphysema. In a previous study we treated smokers with emphysema with colchicine, a drug that prevents neutrophil elastase secretion, to determine if it would reduce the elastase burden in the lungs. Colchicine was unable to reduce the elastase load while the stimulus of smoking continued. In this study we treated ex-smokers with emphysema to determine if colchicine could reduce the elastase burden in the lungs. The objective of the study was to determine if colchicine can reduce the elastase load and putative indicators of elastase load in the lungs of patients with chronic obstructive pulmonary disease. The study was a prospective, double-blind, randomized, and placebo-controlled clinical trial. The subjects were outpatients seeking treatment at the University of Texas Health Center at Tyler. We studied 16 ex-cigarette smokers between 45 and 75 yr of age with lung disease defined by FEV1 less than 70% of predicted but greater than 1.2 L whose airflow obstruction was less than 20% reversible with bronchodilators. Colchicine or placebo was taken by mouth in disguised capsules, 0.6 mg three times per day. Volunteers were placed on a baseline bronchodilator regimen of theodur by mouth and albuterol by inhalation. Blood, urine, and bronchoalveolar lavage fluids were obtained after 1 wk of stabilization.(ABSTRACT TRUNCATED AT 250 WORDS)
Cohen
A B
AB
Department of Medicine, University of Texas Health Science Center, Tyler 75710.
Girard
W
W
Mclarty
J
J
Starcher
B
B
Davis
D
D
Stevens
M
M
Rosenbloom
J
J
Kucich
U
U
D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000201:enzymology; D003078:Colchicine / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D019272:Leukocyte Elastase; D008168:Lung / Q000378:metabolism*; D008173:Lung Diseases, Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D008875:Middle Aged; D010196:Pancreatic Elastase / Q000187:drug effects*; D012907:Smoking / Q000503:physiopathology*
D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D003078:Colchicine