EFFECT OF HIGH-DOSE IBUPROFEN IN PATIENTS WITH CYSTIC-FIBROSIS

Background. Since the inflammatory response to chronic infection contr ibutes to lung destruction in patients with cystic fibrosis, we hypoth esized that antiinflammatory therapy might slow the progression of lun g disease. Methods. In a double-blind trial, 85 patients, 5 to 39 year s of age, with mild lung disease (forced expiratory volume in one seco nd [FEV(1)], greater than or equal to 60 percent of the predicted valu e) were randomly assigned to receive ibuprofen or placebo orally twice daily for four years. Doses were adjusted individually to achieve pea k plasma concentrations of 50 to 100 mu g per milliliter. Changes in p ulmonary function, the percentage of ideal body weight, the chest-radi ograph score, and the frequency of hospitalization were assessed. Resu lts. Patients randomly assigned to ibuprofen had a slower annual rate of change in FEV(1) than the patients assigned to placebo (mean [+/-SE ] slope, -2.17+/-0.57 percent vs. -3.60+/-0.55 percent in the placebo group; weight) was better maintained in the former group (P = 0.02), A mong the patients who took ibuprofen for four years and had at least a 70 percent rate of compliance, the annual rate of change in FEV(1) wa s even slower (-1.48+-0.69 percent vs. -3.57+/-0.65 percent in the pla cebo group, P=0.03), and this group of patients also had a significant ly slower rate of decline in forced vital capacity, the percentage of ideal body weight, and the chest-radiograph score. There was no signif icant difference between the ibuprofen and placebo groups in the frequ ency of hospitalization. One patient was withdrawn from the study beca use of conjunctivitis, and one because of epistaxis related to ibuprof en. Conclusions. In patients with cystic fibrosis and mild lung diseas e, high-dose ibuprofen, taken consistently for four years, significant ly slows the progression of the lung disease without serious adverse e ffects.