Secondary Prevention of Asthma by the Use of Inhaled Fluticasone Propionate in Wheezy Infants (IFWIN): Double-Blind, Randomised, Controlled Study

Abstract

Murray CS, Woodcock A, Langley SJ, Morris J, Custovic A; IFWIN Study Team. Lancet. 2006;368:754–762 PURPOSE OF THE STUDY. To determine if the early use of inhaled fluticasone propionate in wheezy infants helps to prevent loss of lung function and progression of asthma later in childhood. STUDY POPULATION. High-risk children (N = 1073) identified by having 1 atopic parent were followed prospectively until 2 wheezing episodes occurred or there was 1 wheezing episode longer than 1 month. Of these patients, 206 who met the inclusion criteria were randomly assigned: 104 to placebo and 102 to treatment. The median age was 1.2 years (range: 0.5–4.9 years). Eighty-six percent continued to be followed by their fifth birthday. METHODS. Children were excluded if they had wheeze caused by bronchiolitis, were preterm (<34 weeks’ gestation), had other chronic lung disease or chronic illness, had previous inhaled corticosteroid (ICS) use, or were unable to use the inhaler. The treatment group was started on fluticasone propionate 100 μg twice daily. Randomly assigned patients were followed by monthly telephone calls for the first 3 months, if controlled, and then every 3 months until their fifth birthday. If symptoms were not under control by 3 months, then open-label fluticasone propionate 100 μg was added. Treatment was adjusted to the minimum necessary to control symptoms. Participants were allowed to use β agonists as needed. Parents were asked to keep daily diaries of symptom scores, reliever use, and unscheduled visits. At the age of 5, specific airway resistance (sRAW), forced expiratory volume in 1 second (FEV1), airway reactivity, and postbronchodilator lung function were measured and compared. RESULTS. There was no significant difference between those in the treatment group versus placebo in the proportion of children with current wheeze, physician-diagnosed asthma, use of asthma medication, or current wheeze, even when factoring the addition of those participants who added open-label medication. There was also no significant difference in FEV1 (baseline or postbronchodilator), sRAW, or airway reactivity at 5 years of age in these groups. The 2 groups were similar in the number of children who required, and in the length of time to adding, open-label drug. Symptom scores, use of reliever medication, and unscheduled visits to the family doctor were similar until the third month, when children in the treatment group had lower median daily symptom scores, a trend toward less reliever medication, and significantly fewer visits than those in the placebo group. In the 2 open-label drug groups, there was a greater risk of current wheeze, current use of asthma medications, and current wheeze with asthma medications compared with those in the placebo group, although there was no difference in baseline or postbronchodilator FEV1. However, there was a significantly higher sRAW in the treated groups, which represented decreased lung function. CONCLUSIONS. The use of ICS in young children at risk for asthma with the earliest sign of recurrent wheezing had no significant effect on the natural history of wheezing, lung function, or airway reactivity by 5 years of age and only showed a small improvement on symptom scores and unscheduled physician visits after the third month of the study. Higher postbronchodilator sRAW showing reduced lung function was seen in children in the treated group compared with those in the placebo group. REVIEWER COMMENTS. Evidence for the efficacy of ICS in infants and very young children remains unclear. It has been suggested that early use of ICS could be detrimental to the lung development on the basis of the sRAW scores of ICS-treated patients. However, children in both the treatment and placebo groups required the addition of fluticasone equally, which suggests that perhaps those in the treatment group had worse disease. Prestudy lung function was not tested, and individual atopic status was not assessed to determine if these 2 groups were truly equivalent. Studies are needed to determine if atopy is a confounding factor and whether controlling for allergen exposure in addition to ICS has an effect on asthma outcomes. This study and other similar studies suggest that ICS can improve asthma symptoms, but early use does not modify the disease.