Comparision of serum interleukin-4, interleukin-13, interferon-gamma levels and risk of recurrent wheezing, atopy between Respiratory syncytial virus and nonrespiratory syncytial virus bronchiolitis

AIM: Acute bronchiolitis (AB) is the most frequent disorder of lower respiratory tract, particularly in children below 2 years of age. The disease is one of the most common causes of hospitalization in children below 1 year of age. Respiratory syncytial virus (RSV) is responsible from 50-90% of the cases. It has been demonstrated in a number of studies that recurrent wheezing episodes might be encountered and the risk for asthma is increased in infants suffered from RSV infection during their early lives. The aims of this study are (i) to detect the relationship between the recurrent wheezing episodes in children suffered from RSV infection and atopy and serum cytokine [interleukin-4 (IL-4), IL-13, and interferon-gamma (IFN-gamma)] levels, (ii) to compare these children with those suffered from non-RSV viral bronchiolitis, and (iii) to discuss the role of cytokines in the etiopathogenesis of recurrent wheezing.SUBJECTS AND METHOD: The study was conducted between January 2006 and November 2008 in Department of Pediatrics, Medical Faculty, Dokuz Eylul University. Children aged between 0-36 months who were diagnosed to have AB for the first time following evaluation in Division of Pediatric Pulmonology and Allergy, Division of Pediatric Emergency Medicine or pediatric inpatient unit and nasopharyngeal lavage fluid of whom were analyzed with PCR for RSV antigen were recruited for the study. The patients were evaluated biannually by the same physician. During the follow-up, data regarding gender, gestational age, birth weight, exposure to cigarette smoke, duration of breastfeeding, maternal educational level, family income, the number of siblings, the properties of the house being lived, presence of feathery pet at the home, family history for asthma, allergic rhinitis and atopy, the age at the time of first bronchiolitis, allergic rhinitis, atopy, and recurrent wheezing episodes in the study patient were recorded. A blood sample, only for once, was obtained once the patients were followed for at least one year. Total eosinophil count, serum immunoglobulin E (IgE), IL-4, IL-13, and IFN-gamma levels were measured. Skin prick test was performed in each patient in order to evaluate atopy.FINDINGS: A total of 70 patients were included in the study. Among them, 40 (57.1%) were in RSV positive group and 30 (42.9%) in RSV negative group. Twenty-nine of the patients (41.4%) were females and 41 (58.6%) males. Premature born children were excluded from the study. There were no differences between the two groups regarding the type of birth, prenatal and postnatal exposure to cigarette smoke, maternal education level, mean monthly family income, the properties of the house being lived, day care center attendance, and family history for allergic disease. Birth weight was found to be lower in RSV negative group (p=0.015). Mean age at admission to hospital was 6.4 months (1-33) in RSV positive group and 9.5 months (1-30) in RSV negative group; the age at admission was found to be lower in RSV negative group (p=0.031). Recurrent wheezing episode was observed in 35% of the patients in RSV positive group and in 53.3% of RSV negative group. No significant difference was detected between the two groups regarding recurrent wheezing (p=0.064). Total eosinophil count and serum IgE levels were similar in the two groups. Mean serum IL-4 level was detected to be 20.43 pg/mL in RSV positive group and 40.77 pg/mL in RSV negative group, significantly higher in RSV negative group (p=0.002). Mean serum IL-13 level was 22.61 pg/mL in RSV positive group and 63.68 pg/mL in RSV negative group. Serum IL-13 levels were comparable between the two groups (p=0.565). Mean serum IFN-gamma levels were detected to be 90.12 pg/mL in RSV positive and 162.57 pg/mL in RSV negative group, significantly higher in RSV negative group (p=0.003). No significant relation was detected between recurrent wheezing episodes and total eosinophil count, serum IgE, IL-4, IL-13, and IFN-gamma levels. Skin prick test positivity was found in only one patient in each group and evaluation regarding atopy could not be made. No correlation was observed between recurrent wheezing and birth weight, type of birth, prenatal and postnatal exposure to cigarette smoke, maternal education level, mean monthly family income, family history for allergy, properties of the house being lived, and day care center attendance.CONCLUSION: No difference could be detected between Respiratory syncytial virus and non-RSV bronchiolitis regarding subsequent recurrent wheezing episodes. Total eosinophil count, IL-13, and IgE levels were similar in the two groups and no significant relation of solely these parameters could be detected with recurrent wheezing episodes. Serum IL-4 and IFN-gamma levels were detected higher in RSV negative group, however, significant correlation of these findings was not detected with recurrent wheezing episodes. The pathogenesis of wheezing and asthma is multifactorial. Viruses other than Respiratory syncytial virus might lead to recurrent wheezing. More studies are needed to understand the pathogenesis better and to detect the most responsible viral agent in pathogenesis of wheezing.