Prospective follow-up and pulmonary functions from a placebo-controlled randomized trial of ribavirin therapy in respiratory syncytial virus bronchiolitis

Objective: To determine any long-term differences in adverse effects and pu lmonary function between infants with respiratory syncytial virus and lower respiratory tract infection who were treated with ribavirin and a control group. Study Design; Long-term follow-up included enumeration of episodes of respi ratory illness, wheezing, and pneumonia and, ultimately, administration of pulmonary function rests (PFTs). Pulse oximetry was done at each visit. Dur ing the first 3 years we conducted follow-up in the fall and spring. In yea rs 4 and 5 we conducted 1 visit per year. During years 5 through 7 we condu cted PFTs, and starting with year 7 a methacholine chloride challenge was d one if forced expiratory volume in 1 second (FEV1) was greater than 70% Of predicted value. Results: We prospectively enrolled (December 1983 to February 1985) in a ra ndomized trial of ribavirin vs placebo children who were previously healthy , were premature, or had chronic pulmonary disease. One pulmonologist (R.F. ; blinded) scored and interpreted the results of the PFTs. We studied 42 pa tients aged 1 to 33 months; 2 patients died (1 receiving ribavirin and 1 re ceiving placebo) and 5 patients receiving placebo were lost to follow-up; 3 5 patients (24 taking ribavirin and 11 taking placebo) attended 212 visits. Four patients were premature (3 in the ribavirin and 1 in the placebo grou p), and 3 of these had bronchopulmonary dysplasia (2 in the ribavirin and 1 in the placebo group). From years 1 to 3, there was more reactive airway d isease, wheezing, and pneumonia in the placebo than in the ribavirin group (mean score, 22.3 for 12 placebo-treated patients vs 15.8 for 23 ribavirin- treated patients; P=.07 by Kruskal-Wallis rest); for all years, it was 22.0 for 11 placebo-treated patients vs 16.0 for 22 ribavirin-treated patients (P =.10). After informed consent was given, 19 patients completed PFTs (13 receiving ribavirin and 6 receiving placebo); 7 of 13 ribavirin-treated pat ients (53%) had normal or mild PFT results vs 0 of 6 placebo-treated patien ts (P =.04 by Fisher exact test). On methacholine challenge (7 ribavirin-tr eated patients and 5 placebo-treated patients), there was more reactivity i n the placebo vs the ribavirin group (exact P =.07). Scoring done by weight ing for severity for 19 patients (13 ribavirin-treated patients and 6 place bo-treated patients) (even after correcting for asthma) showed a significan t difference in favor of previously ribavirin-treated patients (exact P =.0 2). Conclusions: No outward effects were identified from ribavirin exposure. We observed no increase in reactive airway disease, wheezing, and pneumonia i n the ribavirin compared with the placebo group. Weighted severity scores s uggest long-term beneficial effect of ribavirin therapy, however, larger nu mbers should be evaluated.