Allergic diseases and the effect of inhaled epinephrine in children with acute bronchiolitis: follow-up from the randomised, controlled, double-blind, Bronchiolitis ALL trial.

BACKGROUND: Although use of inhaled bronchodilators in infants with acute bronchiolitis is not supported by evidence-based guidelines, it is often justified by the belief in a subgroup effect in individuals developing atopic disease. We aimed to assess if inhaled epinephrine during acute bronchiolitis in infancy would benefit patients with later recurrent bronchial obstruction, atopic eczema, or allergic sensitisation. METHODS: In the randomised, double-blind, multicentre Bronchiolitis ALL trial, 404 infants with moderate-to-severe acute bronchiolitis were recruited from eight hospitals in Norway to receive either inhaled epinephrine or saline up to every second hour throughout the hospital stay. Randomisation was done centrally, and the two study medications (20 mg/mL racemic epinephrine or 0.9% saline) were prepared in identical bottles. The dose given depended on the infant's weight: 0.10 mL, less than 5 kg; 0.15 mL, 5-6.9 kg; 0.2 mL, 7-9.9 kg; and 0.25 mL, 10 kg or more; all dissolved in 2 mL of 0.9% saline before nebulisation. The primary outcome was the length of hospital stay. In this follow-up study, 294 children were reinvestigated at 2 years of age with an interview, a clinical examination, and a skin prick test for 17 allergens, determining bronchial obstruction, atopic eczema, and allergic sensitisation, on which subgroup analyses were done. Analyses were done by intention to treat. The trial has been completed and is registered at ClinicalTrials.gov (number NCT00817466) and EUDRACT (number 2009-012667-34). FINDINGS: Length of stay did not differ between patients who received inhaled epinephrine versus saline in the subgroup of infants who developed recurrent bronchial obstruction by age 2 years (143 [48.6%] of 294 patients; p(interaction)=0.40). However, the presence of atopic eczema or allergic sensitisation by the age of 2 years (n=77) significantly interacted with the treatment effect of inhaled epinephrine (p(interaction)=0.02); the length of stay (mean 80.3 h, 95% CI 72.8-87.9) was significantly shorter in patients receiving inhaled epinephrine versus saline in patients without allergic sensitisation or atopic eczema by 2 years (-19.9 h, -33.1 to -6.3; p=0.003). No significant differences were found in length of hospital stay in response to epinephrine or saline in children with atopic eczema or allergic sensitisation by 2 years (+16.2 h, -11.0 to 43.3; p=0.24). INTERPRETATION: Contrary to our hypothesis, hospital length of stay for bronchiolitis was not reduced by administration of inhaled epinephrine in infants who subsequently developed atopic eczema, allergic sensitisation, or recurrent bronchial obstruction. The present study does not support an individual trial of inhaled epinephrine in acute bronchiolitis in children with increased risk of allergic diseases. FUNDING: Medicines for Children Network, Norway.

Rotavirus gastroenteritis in Norway: analysis of prospective surveillance and hospital registry data.

We aimed to evaluate rotavirus morbidity and describe rotavirus epidemiology in hospitalized children in Norway to provide information before the introduction of new rotavirus vaccines. We retrospectively reviewed 14,973 gastroenteritis hospitalizations in children aged <5 y for the period 1995 to 2004, and prospectively surveyed for rotavirus in 311 children aged <5 y admitted with diarrhoea to 3 hospitals in 2006-2008. The proportion of rotavirus among all gastroenteritis hospitalizations was estimated at 14.5% from the retrospective data and at 62.9% in the prospective data. The annual incidence of rotavirus hospitalizations is estimated to be 3 per 1000 children <5 y of age, corresponding to approximately 900 (range 735-1092) hospitalizations each year. Children aged 6-23 months accounted for 61% of all confirmed rotavirus cases, and average duration of hospital stay for rotavirus cases was 1.3 days. We observed a predominance of rotavirus infections from March through May, similar to the seasonality of diarrhoea-associated hospitalizations with viral and unspecified aetiology. No rotavirus-associated deaths were reported. It is estimated that two thirds of all gastroenteritis hospitalizations in children <5 y of age may be attributable to rotavirus in Norway. Continued surveillance and further studies are needed to assess the full burden of rotavirus disease and its economic impact in Norway.

Detection and characterization of group A rotaviruses in children hospitalized with acute gastroenteritis in Norway, 2006-2008.

To assess the genetic diversity of rotavirus strains in Norway, the distribution of rotavirus genotypes was studied in children admitted to hospital with acute gastroenteritis. The detection of rotavirus in stool samples was compared using an enzyme-linked immunosorbent assay (ELISA), an immunochromatographic test and RT-PCR. Children <5 years of age admitted to hospital with diarrhea in three large hospitals were enrolled prospectively from March 2006 to February 2008. Rotavirus was detected in 58% of the children by the immunochromatographic test, in 63% by ELISA and 72% by RT-PCR. A total of 219 (70%) rotavirus isolates were characterized in order to determine the genotype. The predominant G types included G1 (53%), G9 (16%), and G3 (13%), and the frequency of G3 varied more than G9 between seasons (8-20%). The P[8] genotype was identified in 188 (86%) of samples, and the globally common genotype combinations G1P[8], G2P[4], G3P[8], G4P[8], and G9P[8] accounted together for >80% of infection. No unusual rotavirus strains were detected, and only four samples contained mixed infections. This study demonstrates that ELISA has similar specificity but lower sensitivity compared to RT-PCR. The immunochromatographic test had the lowest sensitivity and specificity compared to the other assays. Rotaviruses causing severe gastroenteritis leading to hospitalization of children <5 years of age in Norway include the common genotypes, however, a considerable geographical and seasonal variation was observed in the distribution of these genotypes. These data may be important for assessing the need for introducing rotavirus vaccines into immunization programs in Norway.