ACUTE CHEST SYNDROME with RESPIRATORY Syncytial VIRUS and SEASONAL INFLUENZA In CHILDREN with SICKLE CELL DISEASE

Respiratory syncytial virus (RSV) has been recognized as a cause of acute chest syndrome (ACS) in children with sickle cell disease (SCD). However, the proportion of children with RSV and SCD that are admitted to hospital or develop ACS is unknown. In studies of young children without SCD, RSV has traditionally been associated with more hospitalizations in the first three years of life then influenza has. To compare the relative severity of RSV vs. seasonal influenza in children with SCD, we compared the clinical characteristics and complications associated with these infections at a single tertiary care hospital.

We defined a case as laboratory-confirmed RSV infection in a patient <18 years with SCD who was evaluated at Johns Hopkins Hospital from 1 September 1993 to June 30 2008. Through July 2006, we searched the discharge and billing databases for Johns Hopkins Hospital to identify those with SCD and laboratory testing for respiratory infections. Thereafter, we prospectively identified cases through divisional records. We confirmed the diagnosis of RSV by review of microbiology results in each patient's paper and/or electronic medical record. We used Fisher's exact test to compare proportions, Student's t-test or Wilcoxon rank-sum test to compare continuous variables, and logistic regression to evaluate associations.

We identified 47 patients with SCD and RSV and 76 with influenza during the study period. Clinical symptoms, such as reported fever (83% vs. 89%), cough (98% vs. 93%), and rhinorrhea (90% vs. 80%), were similar for RSV and influenza as were complications, including acute chest syndrome (Table). Treatments given for RSV and influenza including antibacterials (100% vs. 97%), transfusions (7% vs. 11%), and invasive ventilation (4% vs. 0%, p=0.15),with possibly more bronchodilator use for RSV (50% vs. 33%, p=0.055). In a multivariable logistic regression model, older age (OR 1.3 per year, 95% CI 1.04 –1.5, P=.02) and increased white blood cell count (WBC) at presentation (OR 1.2 per 1000/ul increase, 95% CI 1.03 – 1.4, P=0.02) were independently associated with increased risk of ACS in children with RSV.

Laboratory confirmed RSV infection was predominantly identified in infants and toddlers, while influenza infection was identified in children of all ages. This parallels RSV hospitalizations in the general population, where children are most likely to be hospitalized in the first few years of life. Both older age and high WBC at presentation may be a risk factor for more severe disease. This is unlikely to reflect referral bias (with only the sickest older children being referred for tertiary pediatric care) as a similar pattern was not seen for influenza infection. We conclude that RSV infection is often associated with ACS and similar in severity to influenza infection in children with SCD. An episode of ACS in the first three years of life was associated with more frequent ACS episodes later in childhood in the Dallas Newborn cohort. Since a significant proportion of patients with RSV develop ACS at a young age, RSV infection may represent a modifiable risk factor for recurrent ACS. An area for further study would be the efficacy or cost effectiveness of prevention of RSV-related hospitalizations. Palivizumab, a monoclonal antibody to RSV, has been shown to prevent complications related to RSV in other high risk groups and could be considered as an intervention in SCD that may decrease morbidity.

No relevant conflicts of interest to declare.