BackgroundAcute viral bronchiolitis is one of the most common causes of hospitalisation during infancy in our region with respiratory syncytial virus (RSV) historically being the major causative agent. Many infants with early-life RSV bronchiolitis have sustained bronchial hyperreactivity for many years after hospitalisation and the reasons for this are probably multifactorial. The principal aim of the present study was to investigate if children hospitalised for any acute viral bronchiolitis during infancy in our region, and not only those due to RSV, had more episodes of subsequent wheezing up to age seven years and reduced lung function at that age compared to children not hospitalised for acute bronchiolitis during infancy. A secondary aim was to compare the hospitalised infants with proven RSV bronchiolitis (RS+) to the hospitalised infants with non-RSV bronchiolitis (RS-) according to the same endpoints.Methods57 infants hospitalised at least once with acute viral bronchiolitis during two consecutive winter seasons in 1993–1994 were examined at age seven years. An age-matched control group of 64 children, who had not been hospitalised for acute viral bronchiolitis during infancy, were recruited from a local primary school. Epidemiological and clinical data were collected retrospectively from hospital discharge records and through structured clinical interviews and physical examinations at the follow-up visit.ResultsThe children hospitalised for bronchiolitis during infancy had decreased lung function, more often wheezing episodes, current medication and follow-up for asthma at age seven years than did the age matched controls. They also had lower average birth weight and more often first order family members with asthma. We did not find significant differences between the RSV+ and RSV- groups.ConclusionChildren hospitalised for early-life bronchiolitis are susceptible to recurrent wheezing and reduced pulmonary function by seven years compared to age-matched children not hospitalised for early-life bronchiolitis. We propose that prolonged bronchial hyperreactivity could follow early-life RSV negative as well as RSV positive bronchiolitis.

BackgroundRespiratory syncytial virus (RSV) infection is a common cause of pediatric hospitalization. microRNA, key regulators of the immune system, have not previously been investigated in respiratory specimens during viral infection. We investigated microRNA expression in the nasal mucosa of 42 RSV-positive infants, also comparing microRNA expression between disease severity subgroups.MethodsNasal mucosa cytology specimens were collected from RSV-positive infants and healthy controls. 32 microRNA were selected by microarray for qPCR verification in 19 control, 16 mild, 7 moderate and 19 severe disease samples.ResultsCompared to healthy controls, RSV-positive infants downregulated miR-34b, miR-34c, miR-125b, miR-29c, mir125a, miR-429 and miR-27b and upregulated miR-155, miR-31, miR-203a, miR-16 and let-7d. On disease subgroups analysis, miR-125a and miR-429 were downregulated in mild disease (p = 0.03 and 0.02, respectively), but not in severe disease (p = 0.3 and 0.3).ConclusionmicroRNA expression in nasal epithelium cytology brushings of RSV-positive infants shows a distinct profile of immune-associated miRNA. miR-125a has important functions within NF-κB signaling and macrophage function. The lack of downregulation of miR-125a and miR-429 in severe disease may help explain differences in disease manifestations on infection with RSV.

With relatively high specificity and likelihood ratio CRP, WBC count and hypoxemia may be beneficial in ruling in a positive chest radiograph in suspected pneumonia and bacterial etiology in proven pneumonia, but with low sensitivity, the clinical utility is limited. What is Known: • Pneumonia is recommended to be a clinical diagnosis, and neither clinical features nor inflammatory markers can reliably distinguish etiology. • The etiology of pneumonia has changed after routine pneumococcal conjugate vaccine. What is New: • High CRP and WBC counts were associated with infiltrates in children with suspected pneumonia and with bacterial infection in proven pneumonia. • In the post-pneumococcal vaccination era, viral etiology is expected, and in cases of pneumonia with low CRP and WBC counts, a watch-and-wait strategy for antibiotic treatment may be applied.

We identified the majority of 265 cases with radiology proven pneumonia as single viral infections, predominantly respiratory syncytial virus and a much lower proportion of bacterial causes. These findings may impact pneumonia management guidelines in areas where widespread pneumococcal vaccination is provided and contribute to reduced antibiotic overuse in pediatric pneumonia.

The association between gene expression at birth of 11 candidate genes with important innate and adaptive immune functions and later respiratory syncytial virus (RSV) disease was investigated. Cord blood was collected from 2108 newborns. Forty-seven were subsequently RSV positive. Gene expression analysis by quantitative reverse transcription-polymerase chain reaction was compared to 17 controls. There was downregulation of interleukin 7 receptor (IL7R) (P = .0001) and chemokine receptor 7 (CCR7) (P = .002), and in the severe disease subcategory, downregulation of Toll-like receptor 4 (TLR4) (P = .003). IL7R and CCR7 facilitate communication between adaptive and innate immune systems. TLR4 activates the innate immune system on RSV exposure. Delayed innate and adaptive immune activation may predispose children to more severe RSV disease.

Viral lower respiratory tract infection (VLRTI) is the most common cause of hospital admission among small children in high-income countries. Guidelines to identify children in need of admission are lacking in the literature. In December 2012, our hospital introduced strict guidelines for admission. This study aims to retrospectively evaluate the safety and efficacy of the guidelines. We performed a single-center retrospective administrative database search and medical record review. ICD-10 codes identified children < 24 months assessed at the emergency department for VLRTI for a 10-year period. To identify adverse events related to admission guidelines implementation, we reviewed patient records for all those discharged on primary contact followed by readmission within 14 days. During the study period, 3227 children younger than 24 months old were assessed in the ED for VLRTI. The proportion of severe adverse events among children who were discharged on their initial emergency department contact was low both before (0.3%) and after the intervention (0.5%) (p=1.0). Admission rates before vs. after the intervention were for previously healthy children > 90 days 65.3% vs. 53.3% (p<0.001); for healthy children ≤ 90 days 85% vs. 68% (p<0.001); and for high-risk comorbidities 74% vs. 71% (p=0.5).Conclusion: After implementation of admission guidelines for VLRTI, there were few adverse events and a significant reduction in admissions to the hospital from the emergency department. Our admission guidelines may be a safe and helpful tool in the assessment of children with VLRTI. What is Known:• Viral lower respiratory tract infection, including bronchiolitis, is the most common cause of hospitalization for young children in the developed world. Treatment is mainly supportive, and hospitalization should be limited to the cases in need of therapeutic intervention.• Many countries have guidelines for the management of the disease, but the decision on whom to admit for inpatient treatment is often subjective and may vary even between physicians in the same hospital. What is New:• Implementation of admission criteria for viral lower respiratory tract infection may reduce the rate of hospital admissions without increasing adverse events.

BackgroundRespiratory syncytial virus (RSV) is one of the most important causes of pediatric hospital admissions in the developed world. The ribonuclease Dicer is an important regulator of gene expression and cellular function via RNA interference, and may also have anti-viral functions. A previous microarray analysis of the cord blood of 5 patients with RSV disease suggested downregulation of Dicer. In order to further investigate whether reduced Dicer expression can predispose newborns to RSV disease, we have analyzed the gene expression of Dicer in the cord blood of 37 infants with confirmed RSV disease.MethodsThe cord blood of 2108 newborns was collected. 51 had a positive nasopharyngeal aspirate for RSV <1 year, and were grouped according to disease severity. 37 had sufficient cord blood RNA of good quality. Dicer gene expression was assessed by qPCR analysis of cord blood using a TaqMan low-density array and compared to control infants who did not present with RSV disease using the Mann-Whitney test.ResultsThere was significant downregulation of Dicer in the severe disease group: relative quantity 0.69 (95% CI: 0.56 - 0.87), p = 0.002. There was no significant downregulation in the mild disease group.ConclusionsWe demonstrate reduced Dicer expression in the cord blood of infants with severe RSV disease, prior to RSV exposure. We theorize that this may predispose to RSV disease by disruption of leukocyte gene regulation or direct anti-viral RNA interference mechanisms.

Background Respiratory syncytial virus (RSV) infection is an important cause of hospitalization in previously healthy infants. Immunological mechanisms predisposing infants to severe disease are poorly understood. Early biomarkers for disease severity may assist clinical decisions. We investigated T-cell receptor excision circles (TREC), episomal DNA made during thymic T-cell receptor rearrangement, and a marker for thymus activity, both during disease and in neonatal screening cards as a risk factor for RSV disease severity.MethodsOne hundred thirteen patients hospitalized with RSV infection <12 months of age, grouped by disease severity, were available for this investigation, in which we conducted both a prospective and a case-control study. The prospective study included 47 RSV positive infants (mild n = 13, moderate n = 10, severe n = 24). TREC counts were determined by PCR of DNA extracted from EDTA-blood collected on hospitalization, and corrected for lymphocytes using ANCOVA. The case-control study included 85 newborns who later in infancy became RSV positive (mild n = 32, moderate n = 24, severe n = 29) and 47 newborns who never developed RSV disease as healthy controls included from health centres in the same catchment area. TRECs were measured using DNA extracted from dry blood spots from stored neonatal screening cards, followed by PCR. Student’s T-test compared patients with controls, ANOVA compared disease severity groups.ResultsDuring RSV infection patients in the severe disease group had significantly lower (p = 0.017) TREC/200 μL blood compared to the other two disease groups, after correction for lymphocyte count. Newborn TREC levels, were significantly higher in RSV patients compared to controls (p < 0.0001). No significant differences in TREC copies at birth were found between disease severities.ConclusionDuring acute RSV infection a lower number of TREC is found in the severe disease group. TREC has potential as an immunological marker for severe RSV infection. Higher neonatal TREC counts indicate that infants later presenting with severe RSV do not have reduced thymic activity at birth and probably no congenital T-cell defect.