1. Respiratory Syncytial Virus Bronchiolitis in Infants Amanda Snodgrass Dr. Bill Grimes, Advisor Spring 2006

2. Objectives  Mechanisms involved in RSV infection and severity  Risk factors for severe RSV infection  Prophylaxis and treatment of RSV  Morbidity and Mortality

3. Case Study

5. RSV Facts  Most common cause of bronchiolitis & pneumonia in children under 1  25-40% of children develop bronchiolitis or pneumonia during first RSV infection  31/1,000 under 1 yr. are hospitalized with RSV  2% will die

6. Presentation  Cold-like sx  Audible wheezing  SOB  Anorexia  Poor sleeping  Irritability  Vomiting  Choking

7. Pathophysiology  Negative-strand RNA virus  Family Paramyxoviridae  RSV season late fall to early spring  Peak in January/February  Incubation 4-5 days, LRI between days 5-7

8. Severity of RSV Infection is Determined By:  Inhibition of certain interferons  Involvement of innate immune system  Interleukins and chemokines  Coinfection with other respiratory viruses

9. Inhibition of Interferons  Interferons believed to have antiviral properties  NS1 & NS2 inhibit IFN- alpha/beta  Inhibition of IFN-gamma causes enhanced IgE production

10. Innate Immune System  Activation contributes to inflammation & injury  RSV-F glycoprotein may inhibit T-cell activation  RSV-infected CD8+ cells unable to release IFN-gamma

11. Interleukins & Chemokines  Infection induces expression  Chemokines mimic RSV glycoproteins  Recruit monocytes, eosinophils, & neutrophils  IL-8 levels positively associated with severity

12. Coinfection  Rhinovirus contributes to increased severity in children with bronchiolitis  Metapneumovirus (hMPV) enhances or mimics symptoms of RSV bronchiolitis  70% were coinfected w/ hMPV & required amission to PICU

13. Risk Factors

14. Premature Birth  Likely to have chronic lung disease  Hypersensitive to stimuli  Underdeveloped airway & immunity  Lack adult maternal levels of IgG

15. CHD  Are more often hospitalized  Are more often admitted to PICU  Are more likely to die  Complications from pulmonary hypertension and increased hypoxia

16. Environmental & Demographics  Male infants  Age & birth month of infant  Crowding & day care attendance  Secondhand smoke

17. Factors NOT Positively Correlated  Socioeconomic status  Malnourishment  Breastfeeding

18. Prophylaxis  RSV-IGIV (RespiGam)  Children under 24 mo. w/ CHD or less than 35 wks. Gestation  Given IV monthly during RSV season  Volume overload possible  Not for infants w/ hemodynamically significant heart disease.

19. Prophylaxis  Palivizumab (Synagis)  Given IM monthly  Can reduce hospitalization of high risk infants by 45%  Expensive  Many providers reluctant to give  Many parents unaware

20. Treatment  Mostly symptomatic  Salbutamol MDI drug of choice  Also use epinephrine, ipratropium bromide, & oral steroids only if hospitalized

21. Morbidity & Mortality  More likely to visit a specialist  More likely to use respiratory therapy  More likely to receive diagnostic or therapeutic procedures  More likely to be hospitalized again  Subsequent hospitalization will be 3x as long

22. Morbidity & Mortality  More likely to suffer recurrent infections  Many have recurrent acute otitis media  Many likely to be hospitalized with another episode of acute respiratory distress

23. Morbidity & Mortality  Adolescents suffer from allergic asthma, allergic rhinoconjunctivitis, & more sensitive to inhaled allergens  More likely to have asthma, bronchial reactivity to methacholine, and reduced lung function  RSV ind. risk factor for reduced FEV% (FEV1/FVC)

24. Follow Up

25. References  ALA (2004) Respiratory Syncytial Virus referenced online October 15, 2005 http://www.ala.orghttp://www.ala.org  Braciale, Thomas J. (2005). Respiratory syncytial virus and T cells interplay between the virus and the host adaptive immune system. Proc Am Thorac Soc 2:141-146  Bradley, Joseph P., Bacharier, Leonard B., Bonfiglio, JoAnn, Schechtman, Kenneth B., Strunk, Robert, Storch, Gregory, Castro, Mario. (2005). Severity of respiratory syncytial virus bronchiolitis is affected by cigarette smoke exposure and atopy. Pediatrics 115;7-14  CDC. (2005). Respiratory Syncytial Virus referenced online October 15, 2005 http://www.cdc.govhttp://www.cdc.gov  Dakhama, Azzeddine, Park, Jung-Won, Taube, Christian, Chayama, Kosuke, Balhorn, Annette, Joetham, Anthony, Wei, Xu-Dong, et al. (2004). The role of virus-specific immunoglobulin E in airway hyperresponsiveness. Am J Respir Crit Care Med 170:952-959  Greensill, Julie, McNamara, Paul S., Dove, Winifred, Flanagan, Brian, Smyth, Rosalind L., Hart, Anthony. (2003). Human metapneumovirus in severe respiratory syncytial virus bronchiolitis. Emerging Infectious Diseases 9:3:372-375  Hoffman, Scott J., Laham, Federico R., Polack, Fernando P. (2004). Mechanisms of illness during respiratory syncytial virus infection: the lungs, the virus and the immune response. Microbes and Infection. 6:767-772  Kafetzis, D.A.; Astra, H.; Tsolia, M.; Liapi, G.; Mathioudakis, J.; Kallergi, K. (2003) Otitis and respiratory distress episodes following a respiratory syncytial virus infection. Clin Microbiol Infect 9:1006-1010  Korppi, Matti, Kotaniemi-Syrjanen, Anne, Waris, Matti, Vainionpaa, Raija, Reijonen, Tiina. (2004). Rhinovirus-associated wheezing in infancy comparison with respiratory syncytial virus bronchiolitis. The Pediatric Infectious Disease Journal 23:11;995-999  Korppi, M.; Piippo-Salvolainen, E.; Korhonen, K.; Remes, S. (2004) Respiratory morbidity 20 years after RSV infection in infancy. Pediatric Pulmonology 38:155-160  Meissner, H. Cody, Long, Sarah and the Committee on Infectious Diseases and Committee on Fetus and Newborn (2003). Revised indications for the use of palivizumab and respiratory syncytial virus immune globulin intravenous for the prevention of respiratory syncytial virus infections. Pediatrics 112:6;1447-1452  Moynihon, James; Kim, Tommy; Young, Tammy; Checchia, Paul (2004) Rate of palivizumab administration in accordance with current recommendations among hospitalized children. Journal of Pediatric Health Care 18:224-227  Plint, Amy; Johnson, David; Wiebe, Natasha; Bulloch, Blake; Pusic, Martin; Joubert, Gary; Pianosi, Paul; Turner, Troy; Thompson, Graham; Klassen, Terry. (2004) Practice variation among pediatric emergency departments in the treatment of bronchiolitis. Acad Emerg Med 11;4:353-360  Sampalis, John (2003) Morbidity and mortality after RSV-associated hospitalizations among premature Canadian infants. Journal of Pediatrics 143:S150-S156  Sigurs, Nele; Gustaffson, M.; Bjarnason, Ragnar; Lundberg, Fredrik; Schmidt, Susanne; Sigurbergsson, Fredrik; Kjellman, Bengt. (2005) Severe respiratory syncytial virus bronchiolitis in infancy and asthma and allergy at age 13. Am J Respir Crit Care Med 171:137-141  Smoes, Eric (2003) Environmental and demographic risk factors for respiratory syncytial virus lower respiratory tract disease. Journal of Pediatrics 143:S118-S126  Stevens, Timothy, Hall, Caroline. (2004). Controversies in palivizumab use. The Pediatric Infectious Disease Journal 23:11;1051- 1052  Welliver, Robert C. (2003). Review of epidemiology and clinical risk factors for severe respiratory syncytial virus (RSV) infection. J Pediatr 143:S112-S117