Influenza Vaccination in Children With Asthma: Randomized Double-Blind Placebo-Controlled Trial

Abstract

Bueving HJ, Bernsen RM, de Jongste JC, et al. Am J Respir Crit Care Med. 2004;169:488–493To investigate if influenza vaccination in children with asthma prevents asthma exacerbations provoked by influenza infectionSubjects were asthmatic children aged 6 to 18 years who had no other chronic illness. There were 347 children assigned to the vaccine group and 349 assigned to the placebo group.The primary outcome was the number of asthma exacerbations associated with virologically proven influenza infection. Study subjects and their families scored daily symptoms in a diary, and when symptoms reached a predefined level, a pharyngeal swab for influenza was taken. The symptom diary was maintained from the day after administration of inactivated influenza vaccine or placebo on approximately November 1 until April 1 of the following year. Secondary outcomes included the duration and severity of the asthma exacerbations, adverse effects of vaccination, and the number, duration, and severity of all asthma exacerbations. Influenza virus–specific antibody titers were measured before vaccination, 14 to 21 days afterward, and at the end of the influenza season.In each group, 344 participants provided diary data for the primary outcome. The groups were generally similar in baseline characteristics, with almost 90% of children having used maintenance medication for asthma in the previous 12 months. There were 486 reports of symptom scores that met the predefined criteria for an asthma exacerbation (vaccine group: 251; placebo group: 235), with 42 of the resultant throat swabs testing positive for influenza (vaccine group: 24; placebo group: 18). The difference in the number of asthma exacerbations was not significant (95% confidence interval: 34% reduction to 161% increase). There were no significant differences found between the 2 groups for any of the secondary outcomes measured. Antibody levels 14 to 21 days after vaccination were increased only in the vaccine group. However, when comparing the 14- to 21-day titers to those at the end of the season, ∼23% of subjects in the placebo group and 10% in the vaccine group had a fourfold increase in influenza-specific titers.The authors concluded that influenza vaccination was not more effective than placebo in reducing the number of asthma exacerbations caused by influenza infections in children.Current guidelines that recommend the use of influenza vaccination in asthmatics are based on epidemiologic evidence. A recent Cochrane review on influenza vaccination in asthmatics found insufficient evidence to make conclusions about the risks or benefits of influenza vaccination, primarily because of a lack of randomized trials. Although this study was a randomized trial, the low attack rate of influenza (∼6% of subjects tested positive by pharyngeal swab) makes it difficult to draw conclusions from the results. The study’s sample size was calculated based on the assumption of a 30% influenza attack rate, leaving it significantly underpowered to detect an effect at such a low attack rate. If the question of efficacy of influenza vaccine in reducing asthma morbidity is ever to be answered convincingly, a large randomized trial, probably over several influenza seasons, will be needed.