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 branchial epi thelial fluid are believed to be a major factor in the evolution of pu lmonary injury in cystic fibrosis (CF). To test this hypothesis,we stu died pentoxifylline, a compound that inhibits tumor necrosis factor al pha transcription and its stimulatory effect on polymorphonuclear neut rophils, in patients with Or who had chronic Pseudomonas bronchitis. S ubjects older than 11 years of age randomly received placebo or pentox ifylline (1600 mg/day) orally, in a double-blind fashion, for 6 months . Pulmonary function and sputum elastase concentrations were determine d before therapy and bimonthly during therapy; compliance was determin ed by measuring serum drug concentrations. Of the 16 patients who comp leted the study, 9 received pentoxifylline. The sputum elastase concen trations among placebo recipients were significantly increased from ba seline at 4 and 6 months (F = 3.44; p < 0.05); the values remained unc hanged 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 gro up remained largely unchanged. The forced vital capacity improved betw een baseline and 6 months for four of nine pentoxifylline recipients a nd none of the seven control patients (p = 0.09). During the study, fo ur of seven placebo recipients experienced a significant pulmonary exa cerbation compared with one of nine treated patients (p = 0.077). Thes e findings support the hypothesis that polymorphonuclear neutrophil el astase is a factor in the evolution of OF lung disease; further studie s are needed to define the role of pentoxifylline in the treatment of CF.