Managed Care - November 2008 - (Page RSV5)

ies? Do inherent abnormalities that predispose a child to wheeze later in life also predispose the child to develop a severe RSV LRTI? The causal relationship of early RSV infection to later wheezing seemed to be supported by a study conducted by Stein (1999) in which a cohort of 207 children who had an RSV-associated lower respiratory tract illness during the first 3 years of life were prospectively followed for up to 13 years. Their risk for frequent or infrequent wheeze was increased up to the age of 11 years compared with children who had no lower respiratory tract illness during their first 3 years. For infrequent wheeze, the adjusted odds ratios were 3.2, 2.5, and 1.7 at age 3, 6, and 11 years, respectively, and for frequent wheeze, 4.3, 1.9, and 2.4 at the same time points. All these odds ratios were statistically significant (P<.05), except for frequent wheeze at 6 years. Conflicting results emerged from a study conducted by Lemanske (2005) in which a cohort of newborns were followed for up to 3 years. To be enrolled in this study, an infant needed to have at least one parent with respiratory allergies, or a history of physician-diagnosed asthma, or both. After stratifying by the severity of RSV illness, the percentage of children wheezing in their third year of life was most strongly associated with the severity of rhinovirus wheezing illnesses during infancy rather than the severity of RSV illnesses. More recently, this association was found to exist up until the age of 6 years (Jackson 2008). My colleagues and I conducted a nested (1:5) casecontrol study (Stensballe 2006) in Denmark of 2,564 children under 18 months of age with RSV hospitalization compared with 12,816 control children who had been prospectively followed from birth to 18 months of age without RSV hospitalization as participants in the Danish national birth cohort. The point estimates of the adjusted relative risk (RR) of RSV hospitalization were 1.11 for maternal atopic dermatitis, 1.72 for maternal asthma, and 1.23 for paternal asthma. Infrequent wheezing in the child was associated with an RR of subsequent hospitalization of 2.98 and recurrent wheezing with an RR of 5.90. We concluded that asthmatic disposition and wheezing were strong determents of subsequent RSV hospitalization in Danish children less than 18 months of age. In this study, up to a third of children had experienced wheezing prior to RSV hospitalization. Our subsequent studies of RSV immunoprophylaxis have addressed the role of RSV in the causation of subsequent recurrent wheezing. These studies also provide insight into resolving this apparent conundrum. In one such study (Wenzel 2002), we evaluated pulmonary function and atopy in 13 children at high risk for respiratory disease 7 to 10 years after they had received immunoprophylaxis with RSV immunoglobulin. We compared them with 26 high-risk controls matched for age and GA. The children who had received RSV immunoprophylaxis had better lung function and less atopy than the control group. This small study suggests that preventing or blunting RSV infections might decrease the risk for asthma later in life, but larger prospective studies of children at high risk for asthma are warranted to confirm this association. Following that study, we conducted a multicentered study (Simões 2007b) in Europe and Canada using palivizumab. Beginning at a mean age of 19 months, we prospectively followed for 24 months a cohort of preterm infants who had received RSV immunoprophylaxis with 3 or more doses of palivizumab in infancy and who never had been hospitalized for RSV (n=191) and a cohort who never received palivizumab (n=230), including 76 who were hospitalized for RSV and 154 who were not. The mean GA in the palivizumabtreated and the untreated groups was 29.9 and 31.4 weeks, respectively. At follow up at 4 to 5 years of age, the proportion of children with recurrent wheezing was reduced by 49 percent in the palivizumab-treated group relative to the proportion in the untreated group (13 percent [25/191] versus 26 percent [59/230]; P=.001). Likewise, there was a relative reduction of 51 percent in the palivizumab-treated group in the proportion of children with physician-diagnosed recurrent wheezing (8 percent [15/191] versus 16 percent [37/230]; P=.011). Taken together, our studies in Europe and in the United States have shown that in up to a third of children with RSV hospitalization, an atopic disposition may be responsible for the hospitalization. In preterm infants, we have shown that RSV infection may cause up to 50 percent of the recurrent wheezing seen at the age of 3 to 4 years. How long this wheezing continues is unknown; however, a study in Tucson, Ariz., (Stein 1999) suggests that in normal infants, RSV infection in the first 3 years of life predisposes them to recurrent wheezing up to 11 years of age but disappears by age 13. In children with a strong atopic background, rhinovirus rather than RSV may be a more important inciting factor for the development of asthma seen at 6 years of age (Jackson 2008). Summary Infants younger than 1 year, and especially premature infants, are susceptible to severe RSV disease, which accounts for up to 126,000 hospitalizations each year. In the United States, the RSV season generally extends from November though March, but varies considerably both temporally and geographically. Studies, such as the one we have conducted in Colorado, indicate that the RSV season can even vary among local communities. In addition to seasonal variability, other independent risk factors also have to be taken into consideration when considering RSV immunoprophylaxis. Among these are a GA of less than 33 weeks, infants with CLD or CHD or who are immunosuppressed, male sex, household crowding, and SUPPLEMENT / RSV 5

Table of Contents Feed for the Digital Edition of Managed Care - November 2008

Managed Care - November 2008 Editor’s Memo Contents News and Commentary Legislation & Regulation Letters Medication Management Compensation Monitor Do It Yourself for Less Biomarkers Promise, but Do They Deliver? Oncologists Complain About Drug Payment Consider Blood Pressure Self-Monitoring Q&A: Keep Industry in the Game Formulary Files Plan Watch Tomorrow’s Medicine Outlook Respiratory Syncytial Virus Managed Care Considerations Contents Continuing Education Objectives RSV Disease in the Pediatric Population In the Trenches RSV Infection in the Adult Population Health Plan Medical Director Health Plan Pharmacy Director RSV Issues and Solutions Assessment/Evaluation/Certificate Request Post-Test

Managed Care - November 2008

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