PubMed · 2890999
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M E Noble. 1987-12-12. Ribavirin.. https://doi.org/10.1016/s0140-6736(87)91307-9
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Respiratory syncytial virus (RSV) respiratory infections are very common during infancy and account for the majority of hospitalizations during the fall and winter seasons. Patients vary in the severity of their illnesses, with most hospitalized patients needing oxygen and intravenous fluids. The objective of this study was to assess in hospitalized patients the severity of the disease in relation to age. We compared children who were <90 days old with children who were >90 days old for the duration of oxygen therapy, maximum oxygen concentration used, duration of stay and duration of intravenous fluids. We conducted a retrospective case review of national children <2 years admitted to the pediatric ward at Sheikh Khalifa Medical City with RSV proven bronchiolitis/pneumonia over a 3-month period from 1 September to 30 November 2001. Morbidity for group 1 (birth-90 days) and group 2 (91 days-2 years) was compared by the Mann-Whitney U-test using duration of oxygen therapy, maximum oxygen concentration used, duration of stay and duration of intravenous fluids. Multiple regression for duration of oxygen therapy was tested using the following risk factors as predictors: age group (1 or 2), previous ventilation, bronchopulmonary dysplasia (BPD) and prematurity. A total of 89 patients were admitted during this period. The mean age (SD) of group 1 (n = 28) and group 2 (n = 61) was 46.35 (25.57) days and 275.67 (156.79) days, respectively. The only statistically significant difference using the Mann-Whitney U-test was detected for duration of oxygen between the groups (p = 0.002). Using multiple regression, only age group acted as a predictor for duration of oxygen therapy (p < 0.001). This implies that the youngest children, group 1, are at a risk for prolonged oxygen therapy. Four patients from group 1 were admitted to the intensive care unit, of which two received ventilatory support. RSV respiratory infections affect infants <3 months old in a more severe form than older infants. Even though overall duration of stay was similar for both groups, young infants who in fact did require oxygen had a more protracted and severe illness compared with the older infants. This was evidenced by their longer duration of oxygen and more frequent need to be managed in the intensive care unit.
BACKGROUND: Viral bronchiolitis is a common cause of respiratory failure in infants and children, and accounts for a significant portion of intensive care unit (ICU) admissions during seasonal epidemics. Currently there is no evidence to support the use of anything but supportive care for this disease. Surfactant is a potentially promising therapy; alterations in its composition have been described in bronchiolitis, and it may play a role in the host immunity for this disease. OBJECTIVES: The objective of this review was to assess the efficacy of exogenous surfactant for the treatment of bronchiolitis in mechanically ventilated infants and children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006); MEDLINE (1966 to Week 1, February 2006); and EMBASE (1990 to September 2005). We reviewed reference lists of relevant articles and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing surfactant with placebo or surfactant with no surfactant in mechanically ventilated infants and children with viral bronchiolitis. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trial quality. Unpublished data were requested from trial authors when necessary. MAIN RESULTS: Three trials containing a total of 79 patients met the inclusion criteria. No mortality or adverse effects associated with surfactant administration were reported in any of these trials. In the three trials, use of surfactant was associated with a decrease in duration of mechanical ventilation by 2.6 days (95% confidence interval (CI) -5.34 to 0.18 days; P value 0.07) and a decrease in ICU length of stay by 3.3 days (95% CI -6.38 to -0.23 days; P value 0.04). In two studies with 59 patients, in which duration of mechanical ventilation in the control groups was more comparable, surfactant was associated with a decrease in ventilator days by 1.21 days (95% CI 0.75 to 1.67 days) and a decrease in ICU stay by 1.81 days (95% CI 1.19 days to 2.42 days). Individually the studies reported some short term benefit of surfactant on pulmonary mechanics and gas exchange. AUTHORS' CONCLUSIONS: Available data on surfactant were not sufficient to provide reliable estimates of its effects in mechanically ventilated infants and children with bronchiolitis. Future studies should be adequately powered and will need to address unresolved questions regarding which surfactant preparation may be best suited for the treatment of bronchiolitis, the appropriate dose and administration interval, and how the choice of ventilator strategy may modify its effects.
OBJECTIVE: Cellular immunity has classically been described as the defense mechanism for viral infections. The development of cellular or humoral immune responses will depend on a repertoire of cytokines produced by numerous cells, including CD4+ and CD8+ T cells. These lymphocytes can be subdivided into 2 subsets, T helper 1 (Th1) and Th2, on the basis of the cytokine profiles they synthesize. Type 1 T cells produce interferon gamma (IFN-gamma), an essential cytokine in the viral cell-mediated immune response. Th2 cells selectively produce interleukin 4 (IL-4) and IL-5 that participate in the development of humoral immunity and have a prominent role in immediate-type hypersensitivity. An imbalance in the Th1/Th2 cytokine immune response has been related to pathogenesis of the respiratory syncytial virus (RSV) bronchiolitis and to the severity of the infection. Glucocorticosteroids have a role in inhibiting the IFN-gamma response, acting directly on T cells or indirectly through IL-12. In this way, an increase in plasma cortisol would induce a decrease in the Th1 products with the imbalance between Th1/Th2 cytokines and a shift to Th2 response. We hypothesized that there is a relationship among endogenous cortisol response in acute RSV infection, severity of illness, and decreased Th1 cytokine response. METHODS: We studied 42 infants under 12 months of age during an acute RSV infection. Twenty-one infants with a median age of 6 months had a severe illness and required hospitalization, whereas 21 with mild diseases with a median age of 7 months were under ambulatory control. All of them had bronchial obstruction evidenced by wheezing and/or hyperinflation on chest radiograph and positive RSV antigen detected by indirect immunofluorescence in nasopharyngeal aspirates. The control group included 21 infants in good health matched by age and gender with median age of 6 months that required blood tests for minor surgery. They were evaluated during a non-RSV epidemic period. Heparinized blood was collected on enrollment from all participating children at 9 am for total leukocyte and differential cell count, determination of lymphocyte subsets, and for intracellular detection of cytokines in single cells; mononuclear cells were cultured to determine in the supernatant cytokine production. In addition, 1 mL of plasma was separated and kept frozen at -20 degrees C for cortisol assay. In the supernatant of the cultured peripheral blood mononuclear cells (PBMCs), we quantified IL-12, IFN-gamma, IL-4, IL-5, and IL-10. Lymphocyte phenotypes and CD4+ and CD8+ T cells with intracellular IL-4, IL-10, and IFN-gamma were analyzed by triple-color immunofluorescence of single cells on a FACScan flow cytometer. RESULTS: Infants with severe illness had significantly higher plasma cortisol levels than infants with mild disease, and in both groups of infected infants, those were higher than in the control group. A significantly decreased IL-12 and IFN-gamma production by PBMCs and a fall in the percentage of CD4+ T cells expressing IFN-gamma were observed only in the severely affected infants. IL-12 concentrations were 2 pg/mL in severe illness versus 13 pg/mL in mildly infected infants and 12 pg/mL in controls. PBMCs from infants with severe illness produced less IFN-gamma than mildly infected infants and than controls when compared with severe illness. No differences between the 3 groups of infants were observed during the acute phase of the disease for IL-4, IL-5, and IL-10. IL-12 and IFN-gamma production had an inverse correlation with plasma cortisol levels. During severe RSV bronchiolitis, infants developed lymphopenia, and significantly lower eosinophil counts and percentages and absolute counts of CD4+ and CD8+ T cells. Eighty days postinfection, all values had returned to normal levels. CONCLUSIONS: In this study, we demonstrate that during the acute phase of RSV infection, there is an increase in the level of plasma cortisol that is parallel to the decrease in IL-12 and IFN-gamma production. These findings suggest an association between increased plasma cortisol and a decreased Th1-type response. The increase in plasma cortisol was greater in infants with the more severe symptomatology in association with a lower level of IL-12 and IFN-gamma production. The potential causative role of endogenous cortisol in the imbalance of the Th1/Th2 response observed during severe RSV infection requires additional investigation. Our results suggest that the immunologic changes observed in the more severely ill patients may be partially explained by the increased levels of plasma cortisol. This finding should be taken into consideration when systemic steroids are prescribed to infants infected with the RSV because there is still controversy regarding the efficacy of systemic steroid use in severe bronchiolitis.