Purpose of the Study
Influenza virus infection is a cause of major morbidity each year, especially in patients with chronic disease such as asthma. Although current recommendations are to administer influenza vaccine to children and adults with asthma, compliance is suboptimal because of various reasons including fear that the vaccine itself may trigger an asthma exacerbation. The purpose of this study was to assess the safety of influenza vaccine in patients with asthma.
Two hundred sixty-two patients (114 males and 148 females) ages 18 to 75 years with a history of asthma, defined as recurrent episodes of airway obstruction that resolved on treatment, and whose diagnosis had been made by a clinical specialist.
Participants were randomly assigned to receive in a double-blind, crossover design, either the vaccine or placebo separated by 2 weeks. The primary clinical outcome measure was an asthma exacerbation within 72 hours of injection, defined by a decline in early-ampeak expiratory flow (PEF) of more than 20% compared with the lowest of the best three early morning PEF values during the 3 days before the injection. Secondary outcome measures were: changes in upper/lower respiratory symptoms, systemic symptoms, and inhaled β2-agonist use 72 hours before and after injection; antibiotic and oral steroid therapy use 7 days after injection; and unscheduled medical consultations and hospital admissions for an exacerbation within 7 days of each injection.
Among the 255 participants with complete paired data, a total of 11 (4.3%) participants had an asthma exacerbation (with a decrease in PEF of at least 20%) after vaccine compared with 3 (1.2%) after placebo (P = .06). Five of these 11 participants were determined to have a cold by the nature of their upper respiratory symptoms. When the data from these 5 participants was excluded, 6 (2.4%) had a decrease in PEF of at least 20% after vaccine compared with 3 (1.2%) after placebo (P = .51). However, 5 (2.0% overall) of these 6 patients had a drop in PEF of >30% after vaccine compared with none (0%) after placebo (P = .06). This approached statistical significance. The mean decrease in PEF for the 6 subjects was 17.6%. There was no significant difference in all the secondary parameters except in systemic symptoms after the vaccine compared with placebo. Lastly, 5 out of 6 reactions with the vaccine, compared with 1 out of 3 with placebo, were among the 97 first-time vaccine recipients.
Although pulmonary function changes can certainly occur as a complication of the influenza vaccine in patients with asthma, the risk is very small and outweighed by the benefits of vaccination.
Approximately 15% of patients with asthma are infected with influenza virus each year. From previous studies it is estimated that 75% of asthmatic children with serologically proven influenza infection had a decrease in forced expiratory volume in 1 second (FEV1) of 20% or more. Influenza vaccine prevents about 75% of influenza infections. Therefore, given this data, and the complication rates with vaccine from this study, it is clear that the vaccine prevents far more exacerbations of asthma than it causes.