Treatments vary for bronchiolitis related to RSV, new treatment in trials

IDC NY 2011

NEW YORK — There are several current and emerging treatments for respiratory syncytial virus in pediatric patients, but oxygen and fluids remain effective therapy, according to a presentation here by Robert C. Welliver Sr., MD, during the 24th Annual Infectious Diseases in Children Symposium.

Welliver, CMRI Hobbs-Recknagel Chair in Pediatrics, and chief of the section of infectious diseases at University of Oklahoma Health Sciences Center, discussed the management of bronchiolitis during a continuing medical education symposium sponsored by MedImmune.

The pathogenesis of bronchiolitis is partially unrestricted viral replication, and the routine management of bronchiolitis includes administering humidified oxygen and nasal suctioning to clear upper airway, according to Welliver. It is important to monitor for apnea, hypoxemia and impending respiratory failure. The best predictors of respiratory failure are an initial oxygen saturation of less than 90% and aged younger than 2 months. Patients should be rehydrated with oral or IV fluids, and hydration status should be monitored.

In a 1998 study by Dobson and colleagues published in Pediatrics, there was no difference in mean oxygen saturation between patients who received nebulized albuterol therapy and those who received placebo. There was also no difference in length of hospital stay between the two groups.

“Bronchodilators don’t help, but many of us struggle when we see a gasping infant and reach for the bronchodilators. But many studies have shown that they do not help,” Welliver said.

Corticosteroids also had no benefit in 598 patients who presented to the ED. These patients were given dexamethasone 1 mg or placebo. There was no difference in respiratory rate, oxygen saturation and respiratory assessment change score between the groups after 4 hours, and no difference in the percentage of infants eventually hospitalized.

“Corticosteroids work in asthma, but they do not work in bronchiolitis. It seems like a logical jump that drugs that work in asthma would work, but they don’t,” Welliver said.

Use of hypertonic saline appeared to show a benefit in bronchiolitis in a study of 96 infants aged 3 weeks to 18 months who were randomly assigned to 3% hypertonic saline or 0.9% normal saline. The length of stay in the pediatric ICU was 2.6 days for patients who received hypertonic saline vs. 3.5 days for patients who received normal saline, for a reduction of 26%.

“Saline may soften the secretions if you can get it down far enough into the lung, or it may simply induce coughing, but its true beneficial effects are not really known. Further study is needed before this can be accepted as standard therapy," he said.

In a study of montelukast (Singulair, Merck) for bronchiolitis, 979 patients were randomly assigned to montelukast 4 mg, montelukast 8 mg or placebo. There was no difference in symptom-free days, cough-free days, exacerbations or steroid usage between the three groups.

“A trial by Bisgaard in 2008 of montelukast for bronchiolitis had negative results. About one-third of days that were symptom-free, but two-thirds of patients continued to have symptoms,” Welliver said. “This was as negative of a study as you could find, unfortunately.”

Newer treatment

Studies of motavizumab have shown that this therapy also did not shorten the number of days in the hospital for patients with bronchiolitis, and that oxygen had as good of a result as motavizumab.

A 2010 study by DeVincenzo and colleagues indicated that short interfering RNS (siRNA) in respiratory syncytial virus (RSV) infection had no change in peak viral load, symptoms, physical exam and mucus weight. Although this was not a positive result, a current study in transplant patients with RSV is under way, according to Welliver.

Those who received the ALN-RSV01 had a 44.2% positive culture compared with 71.4% in those who received saline. There was no difference in peak viral load, symptoms, physical exam or mucus weight. Fusion inhibitors, replication inhibitors and other RNA interference treatments are currently in development.

Disclosure: Dr. Welliver receives consulting fees from Akebia and MedImmune.

H. Cody Meissner

Bronchiolitis is a leading cause of hospitalization among children in the first year of life. The number of viruses recognized to cause bronchiolitis has expanded in recent years, but RSV continues to account for more than 50% of cases. Morbidity due to RSV respiratory infection is high, resulting in hospitalization of approximately 2% to 3% of all infants in the first year of life. Mortality rates due to RSV infection have fallen in recent years to fewer than 400 deaths annually. Therapy for hospitalized, RSV-infected infants remains limited. The promise of a safe and effective vaccine or anti-viral agent remains distant goals.

H. Cody Meissner, MD
Infectious Diseases in Children Editorial Board

Disclosure: Dr. Meissner reports no relevant financial disclosures.

For more information:

• Bisgaard H. Am J Respir Crit Care Med. 2008;178:854-860.
• DeVencenzo J. Proc Natl Acad Sci U S A. 2010;107:8800-8805.
• Dobson JV. Pediatrics. 1998;101:361-368.
• Welliver RC. RSV management: current and emerging treatments. Presented at: the 24th Annual Infectious Diseases in Children Symposium; Nov. 19-20, 2011; New York.

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