Follow-up after hospital discharge consisted of scheduled visits to the pulmonary clinic, once in the fall and then again in the spring for the first 3 years after joining the study. Monthly telephone calls to assess health condition, including wheezing, were made to families throughout the study, and any significant information was recorded. During the first year of follow-up, children who developed wheezing and upper respiratory tract infection were instructed to come in for collection of respiratory tract secretions, which were tested for RSV by indirect immunofluorescent antibody techniques; viral cultures were also performed. Thereafter, indirect immunofluorescent antibody testing and viral cultures of a respiratory tract specimen were done only if the child developed wheezing during the time RSV was prevalent. During years 4 and 5, the visits were scheduled once a year. At each visit a pulse oximetry was done and a questionnaire was completed by the parent about the child's health. Any other physician contact was also documented if it dealt with respiratory tract symptoms (no attempts were made to review the actual private physician records). In the fifth year, at an age when the patients were expected to be cooperative, a PFT battery was performed, and the results were analyzed by a member of the Department of Pulmonary Medicine who was unaware of the patient's previous treatment status (the members of the Department of Pulmonary Medicine were unaware of the assignment status of the patients). Parents of the patients were also questioned about exposure of the child to smoking in the household. On the basis of the results from that PFT battery, patients were categorized into groups designated as normal, mild, moderate, or severe impairment. For evaluation of PFTs, the classification essentially was as follows: normal and mild, ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) greater than 80% and FVC greater than 80% predicted; moderate, FEV1/FVC less than 80% and FVC less than 80% predicted; and severe, FEV1/FVC less than 60%. Whereas patients 5 to 7 years old underwent PFTs, after 7 years of age a methacholine challenge was done by the procedure described by Chai et al.3 On the basis of their reactivity to methacholine administration, patients who underwent methacholine challenge testing were classified as follows: normal, nonreactive (ie, <20% decrease in FEV1) at all concentrations; mild, reactive (ie, 20% decrease in FEV1) at 25 mg/mL of inhaled methacholine; moderate, reactive (ie, 20% decrease in FEV1) at 1.25 to 10.00 mg/mL of inhaled methacholine (4 dose steps); and severe, reactive (ie, 20% decrease in FEV1) at less than 0.6 mg/mL of inhaled methacholine (4 dose steps). Patients with a baseline FEV1 less than 70% of predicted value were not tested. This aspect of the study also was approved independently by the Children's National Medical Center institutional review board, and the informed consent form for this challenge was obtained separately from parents. Precautions were taken addressing medications that could affect the test with omission or modification of the medication schedule. Baseline spirometry was recorded measuring FVC, FEV1, FEV1/FVC, and forced expiratory flow, midexpiratory phase (FEF25%-75%), and the best of the 3 methods was recorded. Patients inhaled 5 breaths of 1 mL buffered isotonic sodium chloride solution, followed by spirometry testing for 1.5 minutes, and FEV1 was obtained as a control. If FEV1 decreased less than 20%, the methacholine challenge proceeded. Patients with a 20% or greater decrease were not tested. Dilutions of methacholine and isotonic sodium chloride solution of 0.075, 0.15, 0.30, 0.60, 1.25, 2.5, 5.0, 10.0, and 25.0 mg/mL of concentration were used. The provocative dose (PD) causing a 20% fall in FEV1 was designated PD20 FEV1. The provocative tests were also scored by a pulmonologist (R.F., blinded) who was unaware of the treatment group assignment.