ArticlesSecondary prevention of asthma by the use of Inhaled Fluticasone propionate in Wheezy INfants (IFWIN): double-blind, randomised, controlled study
Introduction
Most cases of persistent wheezing and asthma begin in early childhood,1 and these can determine respiratory health throughout life.2, 3 Although wheeze is common in pre-school children, it can result from several different conditions,4 and it is difficult to predict whether or not a wheezy infant will develop asthma. Cohort studies suggest that around half of children who wheeze early in life become asymptomatic by school age.1 Lung function in these children tends to be diminished in infancy, and improved (but still lower than normal) by age 6 years.1 By contrast, lung function in children with persistent wheeze is normal in infancy, but reduced by age 6 years.1 Asthmatics with significant airway obstruction in mid-adult life (aged 30–40) already have reduced lung function by the age of 10 years.5 This evidence suggests that most asthmatic children have normal lung function at birth, but that an ongoing chronic inflammatory process could be associated with airway changes resulting in loss of lung function by early childhood, which then extends into adulthood.
Some researchers have suggested that treatment with inhaled corticosteroids (ICS) early in childhood asthma could improve long-term outcomes.6 However, others have reported that although such treatment of school-aged children with asthma improves symptom control, the benefits can disappear within months of stopping treatment.7 We postulated that to stop the progression of childhood wheezing and prevent loss of lung function, anti-inflammatory treatment needs to be started early in life. Thus, in the IFWIN study (Inhaled Fluticasone in Wheezy INnfants), we investigated whether the use of ICS early in the natural history of wheezing at the minimum dose required to control symptoms alters the progression of disease, prevents lung function decline, or reduces the incidence of asthma in later childhood.
Section snippets
Participants
Potential participants at risk of asthma (one parent atopic) were identified prenatally during recruitment for a birth cohort study in South Manchester, UK8 and followed prospectively from birth. A further group of young children with one atopic parent was referred by local doctors after the first confirmed episode of wheeze. All participants were followed-up through monthly telephone calls. In addition, parents were asked to contact the study team immediately if the child developed wheeze.
Results
The study profile is shown in figure 2. 1073 children were followed (820 from birth and 253 from their first wheezy episode). Of the 333 eligible for randomisation, 206 were randomised and 200 commenced treatment (median age 1·2 yrs, 130 male; 101 placebo, 99 study drug). By their fifth birthday, 13 children had been withdrawn, 55 moved into the observational group, and 43 children in the placebo group and 41 in the treatment group had received open-label fluticasone propionate. 173 (86·5%)
Discussion
Our results suggest that in very young children at risk of asthma, the use of ICS when they first start to wheeze has no significant effect on the natural history of wheezing, at least until age 5 years. In addition, there was no effect of this early intervention on lung function or airway reactivity by this age. We saw a small, but significant improvement in symptom scores and the number of unscheduled physician visits for wheeze in children in the treatment group, but only during the third
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