Effects of pentoxifylline on sputum neutrophil elastase and pulmonary function in patients with cystic fibrosis: preliminary observations.
High concentrations of free human neutrophil elastase in bronchial epithelial fluid are believed to be a major factor in the evolution of pulmonary injury in cystic fibrosis (CF). To test this hypothesis, we studied pentoxifylline, a compound that inhibits tumor necrosis factor alpha transcription and its stimulatory effect on polymorphonuclear neutrophils, in patients with CF who had chronic Pseudomonas bronchitis. Subjects older than 11 years of age randomly received placebo or pentoxifylline (1600 mg/day) orally, in a double-blind fashion, for 6 months. Pulmonary function and sputum elastase concentrations were determined before therapy and bimonthly during therapy; compliance was determined by measuring serum drug concentrations. Of the 16 patients who completed the study, 9 received pentoxifylline. The sputum elastase concentrations among placebo recipients were significantly increased from baseline at 4 and 6 months (F = 3.44; p < 0.05); the values remained unchanged in the treatment group. The mean forced vital capacity for the placebo group decreased from 59.2% +/- 15.4% predicted at baseline to 52.0% +/- 12.9% predicted at 6 months; the values in the treatment group remained largely unchanged. The forced vital capacity improved between baseline and 6 months for four of nine pentoxifylline recipients and none of the seven control patients (p = 0.09). During the study, four of seven placebo recipients experienced a significant pulmonary exacerbation compared with one of nine treated patients (p = 0.077). These findings support the hypothesis that polymorphonuclear neutrophil elastase is a factor in the evolution of CF lung disease; further studies are needed to define the role of pentoxifylline in the treatment of CF.
Aronoff
S C
SC
Department of Pediatrics, West Virginia University School of Medicine, Morgantown 25506.
Quinn
F J
FJ
Carpenter
L S
LS
Novick
W J
WJ
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001991:Bronchitis / Q000188:drug therapy* / Q000201:enzymology / Q000382:microbiology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid; D002648:Child; D002908:Chronic Disease; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D019272:Leukocyte Elastase; D008297:Male; D010196:Pancreatic Elastase / Q000032:analysis; D010431:Pentoxifylline / Q000494:pharmacology / Q000627:therapeutic use*; D011552:Pseudomonas Infections; D012129:Respiratory Function Tests; D013183:Sputum / Q000737:chemistry; D013997:Time Factors; D014797:Vital Capacity / Q000187:drug effects
D010196:Pancreatic Elastase; D019272:Leukocyte Elastase; D010431:Pentoxifylline