The association of variants of genes encoding interleukin (IL)-4 and the IL-4 receptor alpha chain (IL-4Ralpha) with respiratory syncytial virus (RSV) bronchiolitis was examined in hospitalized infants. Polymorphisms in IL-4 (C-590T) and IL-4Ralpha (I50V and Q551R) were genotyped by restriction fragment-length polymorphism analysis. Control subjects included parents of the hospitalized children (for the transmission/disequilibrium test), and a random population sample (for the case-control study). Results were also analyzed in a combination of these 2 tests, using Fisher's method. The IL-4 590T allele was found more frequently among children hospitalized with RSV than expected in the case-control (odds ratio [OR], 1.43; P=.04) and combination (OR, 1.41; P=.02) tests. Among children who were >6 months old when they were hospitalized, compared with the control group or with the <6 months old who were hospitalized for RSV infection, higher frequencies of both the IL-4 590T allele and the IL-4Ralpha R551 allele were found. These results indicate that gain-of-function variants of T helper type 2 cytokine genes may play a role in increasing the severity of RSV disease, which appears more pronounced after the first half-year of life.

Previously, we reported genetic associations between severe respiratory syncytial virus (RSV) bronchiolitis in infants and polymorphisms in the interleukin (IL)-4 and IL-4 receptor alpha (IL-4Ralpha) genes, providing evidence for involvement of T helper type 2 cytokines in the pathogenesis of RSV bronchiolitis. We expanded our studies to polymorphisms in genes encoding IL-9, IL-10, and tumor necrosis factor (TNF)-alpha, using both a transmission/disequilibrium test and a case-control approach. Children homozygous for the IL-10 -592C or -592A allele had a higher risk of hospitalization for RSV bronchiolitis than did heterozygous carriers (odds ratio [OR], 1.73 vs. 2.55; 95% confidence interval [CI], 1.13-2.66 vs. 1.21-5.39). In children hospitalized at < or =6 months of age, a significant association between RSV bronchiolitis and the IL-10 -592C allele was found (OR, 1.61; 95% CI, 1.10-2.35). No significant associations of TNF-alpha and IL-9 polymorphisms with RSV bronchiolitis were observed. We also explored the interactions between different polymorphisms and found an interaction between the IL-4Ralpha Q551R and IL-10 C-592A polymorphisms.

A novel recombinant respiratory syncytial virus (RSV) subunit vaccine, designated BBG2Na, was administered to 108 healthy adults randomly assigned to receive 10, 100, or 300 microg of BBG2Na in aluminum phosphate or saline placebo. Each subject received 1, 2, or 3 intramuscular injections of the assigned dose at monthly intervals. Local and systemic reactions were mild, and no evidence of harmful properties of BBG2Na was reported. The highest ELISA and virus-neutralizing (VN) antibody responses were evident in the 100- and 300-microg groups; second or third injections provided no significant boosts against RSV-derived antigens. BBG2Na induced > or 2-fold and > or =4-fold increases in G2Na-specific ELISA units in up to 100% and 57% of subjects, respectively; corresponding RSV-A-specific responses were 89% and 67%. Furthermore, up to 71% of subjects had > or =2-fold VN titer increases. Antibody responses to 2 murine lung protective epitopes were also highly boosted after vaccination. Therefore, BBG2Na is safe, well tolerated, and highly immunogenic in RSV-seropositive adults.

The prediction rule reliably estimates individual monthly risks of hospitalization for RSV infection in the population studied. It provides an improved index for passive immunization but further validation in other populations is required.

ObjectiveTo test the responsiveness of the Infant/Toddler Quality of Life Questionnaire (ITQOL) to five health conditions. In addition, to evaluate the impact of the child’s age and gender on the ITQOL domain scores.MethodsObservational study of 494 Dutch preschool-aged children with five clinical conditions and 410 healthy preschool children randomly sampled from the general population. The clinical conditions included neurofibromatosis type 1, wheezing illness, bronchiolitis, functional abdominal complaints, and burns. Health-related quality of life (HRQoL) was assessed by a mailed parent-completed ITQOL. Mean ITQOL scale scores for all conditions were compared with scores obtained from the reference sample. The effect of patient’s age and gender on ITQOL scores was assessed using multi-variable regression analysis.ResultsIn all health conditions, substantially lower scores were found for several ITQOL scales. The conditions had a variable effect on the type of ITQOL domains and a different magnitude of effect. Scores for ‘physical functioning’, ‘bodily pain’, and ‘general health perceptions’ showed the greatest range. Parental impact scales were equally affected by all conditions. In addition to disease type, the child’s age and gender had an impact on HRQoL.ConclusionsThe five health conditions (each with a distinct clinical profile) affected the ITQOL scales differently. These results indicate that the ITQOL is sensitive to specific characteristics and symptom expression of the childhood health conditions investigated. This insight into the sensitivity of the ITQOL to health conditions with different symptom expression may help in the interpretation of HRQoL results in future applications.