RSV, Ribaviran, and Subsequent Asthma

ABSTRACT & COMMENTARY

Synopsis: A five-year follow-up of children post RSV bronchiolitis showed a good prognosis. Infants treated with ribaviran had less "bronchitis," but similar rates of asthma were present and similar PFTs were found in treated and untreated groups.

Source: Krilov LR, et al. Follow-up of children with respiratory syncytial virus bronchiolitis in 1986 and 1987: Potential effect of ribavirin on long-term pulmonary function. Pediatr Inf Dis J 1997;16:273-276.

One hundred patients who were treated for RSV bronchiolitis in 1986 and 1987 at seven teaching hospitals were followed up 6-7 years later. History of subsequent respiratory symptoms were obtained from the families. Pulmonary function tests including forced vital capacity, forced expiratory volume, and maximal midexpiratory flow rate were performed. In the follow-up exam, the PFTs of the entire group were within the normal range. When the 33 children who received ribavirin therapy were compared to 67 untreated children, there were no differences in PFTs or reactive airway disease.

COMMENT BY THOMAS DOLAN, MD, FAAP

When ribavarin was first approved by the FDA, it was believed that this drug reduced mortality in respiratory syncytial virus (RSV) bronchiolitis, particularly in infants with congenital heart disease and bronchopulmonary dysplasia. More recently, the mortality rate of bronchiolitis in high-risk infants has been markedly reduced without the use of ribavarin. Analyses of a number of studies comparing ribavarin with placebo or control have failed to show significantly better outcome (i.e., mortality, days hospitalized, or length of stay on respirators).1,2 The expense, practical problems in delivering the drug by aerosol, possible teratogenic effects, and anecdotal tales of sudden increased bronchospasm after inhalation have made use of this therapy obsolescent in most institutions.

Krilov and colleagues show that although ribavarin was not particularly beneficial during an acute episode of RSV bronchiolitis, there were no long-term deleterious effects. The incidence of recurrent wheezing in later life (referred to by the authors as reactive airway disease) was identical in both groups (50%).

The long-term prognosis for the wheezing in these infants was good. This is not surprising because a prospective study of a large cohort of newborns has shown that 60% have ceased wheezing by their sixth birthday.3

It is obvious that RSV infections cause great morbidity in infants and toddlers, and, annually, they are the most common cause of admission to an infant ward from November to March. Hyper-immune globulin prophylaxis has shown to be helpful to certain high-risk infants, but treatment is only partially successful, expensive, and labor intensive.4 We still must await a successful RSV candidate vaccine.

Finally, I would like to take exception to the phrase "reactive airway disease (RAD)." All airways are reactive, but in diseases such as asthma or recurrent wheezing, airways are hyper-responsive to a variety of stimuli. This airway narrowing is usually reversible. Too many physicians use the term RAD as a diagnosis rather than an inappropriately labeled symptom. I would prefer using the term recurrent wheezing of infancy for a few attacks in the first two to three years of life and asthma for any more frequent attacks. I think this will allow more patients to receive indicated long-term asthma therapy. (Dr. Dolan is Professor of Pediatrics at Yale University School of Medicine.)

References

1. Randalph AG, Wang FFL. Ribavarin in respiratory syncytial virus. Lower respiratory tract infection: A systemic overview. Arch Pediatr Adolesc Med 1996;150:942-947.

2. Wang FFL, et al. Pediatric investigators collaborative network in infections in Canada (PICNJC) study of admission and management variation in patients hospitalized with respiratory syncytial lower respiratory tract infections. J Pediatr 1996;129:390-395.

3. Martinez FD, et al. Asthma and wheezing in the first six years of life. N Engl J Med 1995;332:133-138.

4. Prevent Study Group. Reduction of RSV hospitalizations among premature infants and infants with bronchopulmonary dyspl asia using RSV immunoglobulin prophylaxis. Pediatrics 1997;99:93-99.