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Respiratory syncytial virus (RSV) infection is the most frequent reason for hospitalization of infants in developed countries. Premature birth without or, especially, with chronic lung disease of prematurity, congenital heart disease, and T-cell immunodeficiency are conditions that predispose to more severe forms of RSV infection. Incomplete development of the airway, damage to the airway, and airway hyperreactivity underlie the increased morbidity of RSV infection in prematurely born infants. Pulmonary hypertension and cyanosis are associated with worse outcomes in infants with congenital heart disease, and prolonged viral replication accounts for more severe illness in immunocompromised individuals.

Viral infections are a common cause of wheezing at all ages. In addition, it has been suggested that viral infections can induce a long-term asthma diathesis. Because asthma is increasingly understood to be an inflammatory disease, there is great interest in the immunologic mechanisms that may underlie virus-induced wheezing. Viral infections may induce inflammatory responses that closely resemble those characteristic of asthma, including airway infiltration with lymphocytes and eosinophils and release of mediators of airway obstruction. Certain viruses preferentially enhance pre-existing inflammatory responses in atopic individuals. Alternatively, viral infections may induce an altered reactivity favoring the expression of atopy. Finally, immunologic responses to viral infections may serve only as markers of the subsequent development of atopy.

Objective: To examine the effectiveness of respiratory syncytial virus immune globulin administered intravenously (RSV-IGIV) in reducing hospitalization for treatment of RSV in children with congenital heart disease (CHD)., Methods: Children younger than 4 years of age were randomly assigned to a treatment group receiving RSV-IGIV, 750 mg/kg, monthly or to a control group not receiving infusions. Surveillance for respiratory tract infections was carried out and management decisions were made by physicians blinded to treatment group., Results: Hospitalization for treatment of an RSV infection occurred in 32 of 214 (15%) of control children and 21 of 202 (10%) of the children receiving RSV-IGIV, a 31% reduction (P = .16). However, in infants younger than 6 months of age at study entry, 20 of 82 (24%) in the control group and 10 of 96 (10%) in the RSV-IGIV group had RSV hospitalizations (58% reduction, P = .01). The incidence of hospitalization for any respiratory tract symptomatology was lower in the RSV-IGIV group (34 of 202, 17%) than in the control group (57 of 214, 27%; P = .02). There was a significantly higher frequency of unanticipated cyanotic episodes and of poor outcomes after surgery among children with cyanotic CHD in the RSV-IGIV group (22 of 78, 28%) than in the control group (4 of 47, 8.5%; P = .009)., Conclusion: RSV-IGIV should not be used for prophylaxis of RSV disease in children with cyanotic CHD. RSV-IGIV did not reduce RSV hospitalization in all children with CHD, but it was effective in preventing RSV hospitalization in infants younger than 6 months of age. Further studies in these children are indicated.

Acute otitis media (AOM) has been associated with respiratory syncytial virus (RSV) infection; AOM develops in up to one third of children with RSV illness. A masked multicenter trial used an immune globulin enriched with RSV-neutralizing antibodies (RSVIG) to prevent RSV infection of the lower respiratory tract in 249 children with either bronchopulmonary dysplasia, congenital heart disease, or prematurity. To determine whether monthly RSVIG therapy might decrease the incidence of AOM, we retrospectively analyzed the records of 109 children in two of the centers. RSVIG was administered during RSV season of a high dose of 750 mg/kg monthly or a low dose of 150 mg/kg monthly; control children received no RSVIG. Children were examined for AOM by masked observers using pneumatic otoscopy. No difference in sex, race, underlying diagnosis, number of persons in the home, exposure to smoking, or atopy was found between groups studied. In recipients of high doses of RSVIG, significantly less AOM developed per season than in control children (mean episodes, 0.15 vs 0.78; p = 0.003), and fewer episodes of RSV-related AOM occurred (0 vs 5; p = 0.047). Low doses of RSVIG did not have a clinically significant impact. High doses of RSVIG appeared to have a significant impact on preventing AOM (both RSV- and non-RSV-related AOM) in these-high risk populations. This finding may have important implications in the development of improved preventive modalities for AOM.

Eosinophil cationic protein (ECP), a cytotoxic protein contained in the granules of eosinophils, has been suggested as having an important role in the pathogenesis of asthma. To determine whether ECP plays a similar role in bronchiolitis, we tested samples of nasopharyngeal secretions, obtained from a group of 47 children with various forms of illness related to respiratory syncytial virus (RSV) and from 26 children with non-RSV upper respiratory tract illness or bacterial pneumonia, for the presence of ECP by means of a double-antibody radioimmunoassay. Concentrations of ECP in children with RSV bronchiolitis were significantly higher (166.8 ng/ml) than the mean concentration of ECP in both groups of children with RSV upper respiratory tract illness (43.5 ng/ml, p less than 0.002) and RSV lower respiratory tract disease without wheezing (29.1 ng/ml; p less than 0.0002). Children with non-RSV upper respiratory tract illness or bacterial pneumonia had levels of ECP in nasopharyngeal secretions similar to those of children with RSV upper respiratory tract illness or RSV pneumonia. High ECP levels in nasopharyngeal secretions (greater than 50 ng/ml) were predictive of the development of bronchiolitis at the time of RSV infection (p less than 0.001), and the individual ECP levels correlated with severity of the disease as determined by the initial PaO2 concentrations (p less than 0.05). These data suggest that eosinophil degranulation in the respiratory tract occurs during RSV bronchiolitis and may play a significant role in the development of virus-induced airway obstruction.

In order to determine the role of parainfluenza virus-specific IgE antibody production and release of histamine in the pathogenesis of lower respiratory disease caused by parainfluenza virus infection, we studied 84 infants and children at the time of parainfluenza virus infection. Parainfluenza virus-IgE antibody was detected in samples of nasopharyngeal secretions by means of an enzyme-linked immunosorbent assay, and histamine content of nasopharyngeal secretions was determined by a fluorometric technique. Virus-specific IgE responses appeared earlier and were of greater magnitude in patients with croup, wheezing, and croup with wheezing caused by parainfluenza virus infection than in patients with parainfluenza virus-induced upper respiratory illness. Histamine was detectable in nasopharyngeal secretions of patients with parainfluenza virus-related croup significantly more often than in patients with upper respiratory illness caused by parainfluenza virus. These observations suggest a role for immunologic mechanisms in the pathogenesis of severe forms of respiratory illness caused by parainfluenza virus infection.

Serum antibody responses to primary and secondary infections with respiratory syncytial virus were determined in 67 hospitalized infants. Responses in IgG, IgM, and IgA immunoglobulin fractions were assayed using an indirect immunofluorescent technique. Infection was confirmed by identification of RSV antigen in nasopharyngeal secretions using indirect immunofluorescence, and by recovery of the virus in tissue culture. IgM specific antibody response was commonly observed within a few days of onset of primary infection and persisted from two to ten weeks. Increases in titer of virus-specific IgG and IgA were observed in infants aged 6 months or more at the time of infection than in younger infants. At one year after primary infection, IgA and IgM specific antibody was undetectable, and IgG antibody was absent or present in low titer. Subsequent reinfection result ed in accelerated antibody response in all three classes of serum immunoglobulin. High titers of RSV-specific IgG, IgM, and IgA antibody were detectable at five and seven days after reinfection. These observations may explain the relatively mild nature of clinical illness associated with RSV reinfections in childhood.

To determine whether the magnitude of the respiratory syncytial virus (RSV)-specific IgE response at the time of an episode of RSV bronchiolitis in infancy accurately predicts the development of subsequent wheezing episodes, we observed 38 infants prospectively from the time of an episode of infantile bronchiolitis through 48 months of age. Peak RSV-IgE titers were measured at the time of the bronchiolitis episode using an ELISA procedure. Notation was made of both the number of subsequent wheezing episodes reported by parents and the number documented by a physician. Subsequent wheezing was documented by a physician in 20% of infants who did not develop an RSV-IgE response at the time of the bronchiolitis episode and in 70% of those with the highest responses (P less than 0.025). These results suggest that the magnitude of the RSV-IgE response at the time of RSV bronchiolitis is a useful prognostic indicator for recurrent wheezing.

The possibility that cell-mediated immunity might play a role in the pathogenesis of infection with respiratory syncytial virus was evaluated in a study of 39 infants. Infection with RSV was confirmed by identification of virus in nasopharyngeal secretions using immunofluorescence, and by tissue culture infectivity. CMI, as determined by a whole blood lymphocyte transformation technique, was evaluated in samples taken 0 to 10 and 20 to 60 days after the onset of illness. Patients diagnosed as having RSV-induced bronchiolitis or recurrence of asthma had evidence of significantly (P less than 0.01) higher degree of CMI in the 0 to 10-day period than patients with RSV pneumonia or upper respiratory illness. Higher CMI activity in the 20 to 60-day period was also seen in patients with more severe illness, with moderate-to-severe degree of hypoxia. A positive correlation was observed between the degree of LTF activity in samples taken 20 to 60 days after the onset of illness ard subsequent episodes of wheezing. Eleven patients had one or more episodes of wheezing in the first six months after RSV infection. LTF activity in samples taken during the 20 to 60-day period from these patients was significantly higher (P less than 0.02) than LTF activity in corresponding samples from six patients who were free of wheezing in the six months after RSV infection. The results suggest that alterations of RSV-specific cell-mediated immune mechanisms may result in an increased tendency toward airway reactivity on primary and subsequent exposure to RSV and possibly to other agents.

A review of the medical literature and two case reports of M. pneumoniae infections with exanthems are presented. Erythematous maculopapular and vesicular exanthems were most common. The duration of rash was more than seven days in the majority of instances, and most patients had associated pneumonia. A striking difference in prevalence and clinical symptomatology by sex was noted; 16 of 20 patients analyzed were males, and they frequently dad severe mucocutaneous syndromes. In contrast, severe conjunctivitis, generalized ulcerative stomatitis, and vesicular or bullous exanthems were not seen in females. Clinicians should suspect infection with M. pneumoniae in patients with exanthem and pneumonia, although other etiologic possibilities should also be considered.