Study Findings
Every category of outcome favored the palivizumab group over the placebo group:
• Less RSV-related hospitalization (0.9% vs 5.1%, respectively) and less likelihood of any visit for RSV not resulting in hospitalization;
• Fewer total days of parent-reported wheezing (1.8% vs 4.5%);
• Fewer children diagnosed with recurrent wheeze (11.2% vs 20.9%);
• Less all-cause hospitalization (12.6% vs. 21.9%); and
• Less bronchodilator use (13% vs 23%).
Blanken and colleagues concluded that treatment of healthy preterm infants with palivizumab resulted in a significant reduction in total wheezing days during the first year of life, and they suggest that these findings strongly implicate RSV infection in infancy in the later development of recurrent wheezing and possibly asthma.
Viewpoint
This study raises some important questions. First, because it is impossible to do a study in which children are randomly assigned to RSV infection or not, this may be the closest proxy approach we will ever be able to use to evaluate the role of RSV infection in causing or potentiating asthma. In this study, not only were the reductions in the primary and secondary outcomes statistically significant, but very large clinical effects were also found: a 61% reduction in total wheezing days, a 50% reduction in total wheezing episodes, and a 57% reduction in hospitalization.
The findings pose a dilemma, given that insurance reimbursement is not generally available for palivizumab in this age group. It seems that it might be fairly easy to do a cost-effectiveness evaluation to find out whether the reduced morbidity experienced by the infants, including the lower hospitalization rate, offsets the cost of universal application of palivizumab to this group of preterm infants. Even more intriguing is the possibility that prophylactic treatment to prevent RSV infection in the first place provides even longer-term protection against development of asthma, an outcome that would certainly shift the cost curve in favor of prevention of RSV infection.
The relatively short follow-up in this study is perhaps one of its most significant limitations, so I am hopeful that this cohort will be followed for longer-term outcomes. Of note, parents obtained respiratory swabs during only about one third of the respiratory illnesses. Although this probably biased the results toward underdetection of RSV, it is equally probable that the inconsistently obtained respiratory samples were random and did not represent a systematic difference between the 2 groups.
Abstract