Deprivation, ethnicity and prematurity in infant respiratory failure in PICU in the UK.

AIM: To describe the epidemiology of infants admitted to Paediatric Intensive Care (PIC) with acute respiratory failure including bronchiolitis. METHODS: Data from all consecutive admissions from 2004 to 2007 in all 29 designated Paediatric Intensive Care Units (PICUs) in England and Wales were collected. Admission rates, risk-adjusted mortality, length of stay, ventilation status, preterm birth, deprivation and ethnicity were studied. RESULTS: A total of 4641 infants under 1 year of age had an unplanned admission to PIC with acute respiratory failure (ARF), an admission rate of 1.80 per 1000 infants per year. There was a reduced rate of admission with bronchiolitis in South Asian children admitted to PICU, which is not explained by case-mix. Children born preterm had a higher rate of admission and longer stay, but a similar low mortality. Risk-adjusted mortality was higher in South Asian infants and the highest in those with ARF (OR 1.76, 95% CI 1.20-2.57) compared with the rest of the PICU population. CONCLUSION: Acute respiratory failure in infants causes most of the seasonal variation in unplanned admission to intensive care. Socioeconomic deprivation and prematurity are additional risk factors for admission. Fewer South Asian infants are admitted to PICU with a diagnosis of bronchiolitis, but risk-adjusted mortality is higher in South Asian infants overall.

Modelling the impact of pandemic influenza A(H1N1) on UK paediatric intensive care demand.

BACKGROUND: Each winter seasonal respiratory virus infections account for large variations in unplanned admission to UK paediatric intensive care units (PICU). The emergence of pandemic influenza A(H1N1) has been associated with a notable predominance in children and may be expected to have a significant impact on PICU provision. AIMS: To derive conservative projections for PICU demand from current data and examine the effect of regional variations in bed provision. METHODS AND RESULTS: PICU demand was estimated with the FluSurge 2.0 model using age-stratified data for the UK population and recently published conservative estimates for epidemiological parameters. The data suggest that a significant proportion of current total capacity may be required at the peak of the pandemic. Variation in per capita critical care provision across the UK leads to a wide range in potential impact at a regional level. CONCLUSIONS: Contingency measures for children needing paediatric intensive care are needed to absorb the likely increase in activity expected due to pandemic influenza this winter. Because of variations in provision by region, the role of paediatric retrieval services will be especially important.

Lymphocyte apoptosis in acute respiratory syncytial virus bronchiolitis.

Respiratory syncytial virus (RSV) infection may have an effect on the development of T cell memory responses. RSV bronchiolitis in infants is associated with a transient decline in circulating lymphocytes. We hypothesized that the mechanism underlying this lymphopenia is apoptosis. Blood was taken from 32 infants during primary RSV bronchiolitis and three months later. Using flow cytometry, we found that absolute numbers of both CD3+/CD4+ T-helper lymphocytes (P = 0.029) and CD3+/CD8+ cytotoxic lymphocytes (CTL) (P = 0.043) were significantly reduced during acute infection. Up-regulated expression both of Fas (P < 0.001) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor (P < 0.001) was found during acute illness on both CD3+/CD4+ and CD3+/CD8+ lymphocytes, when compared with convalescent samples. Expression of Fas on CD4+ lymphocytes was inversely related to CD4+ number (P = 0.03). Plasma levels of soluble Fas ligand (P = 0.028) and caspase-1 (P = 0.037), determined by enzyme-linked immunosorbent assay, were increased during bronchiolitis. Plasma interleukin-18, a product of caspase-1 activity, was not raised. Taken together, these data suggest that in acute RSV infection, CD4+ helper lymphocytes and CD8+ cytotoxic lymphocytes are primed to undergo apoptosis. This is a mechanism through which lymphopenia may occur and T cell memory may be altered.

Induction of CD95 (Fas) and apoptosis in respiratory epithelial cell cultures following respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) infection is associated with epithelial cell death and vigorous inflammation. In mouse models, and in immunosuppressed patients, CD8(+) T cells are necessary for RSV clearance. In vitro, RSV has been shown to induce expression of several proteins on the respiratory epithelial cell, including RSV proteins, ICAM-1, and MHC class I, that can potentially interact with CD8(+) T cells in initiating apoptosis of the target cell. One mechanism of T-cell-directed cell death is the interaction of FasL on the CD8(+) T lymphocytes and Fas expressed on the target cell. In order to determine the ability of RSV to induce Fas on the respiratory epithelium, we studied the RSV infection of a human respiratory epithelial cell line (A549) in vitro. Fas mRNA and protein levels are increased two-to-fourfold following RSV infection, and transcriptional upregulation of Fas was demonstrated using promoter/reporter gene constructs. RSV infection directly resulted in cellular apoptosis, and the frequency of apoptotic cells was further increased by cross-linking with antibodies to Fas. These data demonstrate that RSV infection induces cellular apoptosis and suggest that interactions of surface Fas with T cells may further augment this process in vivo.

Respiratory syncytial virus RNA in cells from the peripheral blood during acute infection.

It is not known whether respiratory syncytial virus spreads beyond the respiratory tract. With the use of reverse transcriptase polymerase chain reaction, we found viral and transcribed RNA in cells from the arterial blood of four children with bronchiolitis but none in serum or cerebrospinal fluid. Respiratory syncytial virus might therefore spread outside the respiratory tract.

Anaphylactic sensitization to aeroantigen during respiratory virus infection.

BACKGROUND: Virus infections frequently exacerbate asthma, and in some cases may even precipitate its onset. Although this association is well known, experimental investigation has been hampered by the lack of adequate models. OBJECTIVE: The effects of acute respiratory virus infection on sensitization to aereoallergen were investigated in this study. METHODS: Nebulized ovalbumin was used as an aeroantigen in normal mice, and in those infected with respiratory syncytial virus or influenza A. RESULTS: Both viruses caused transient illness. Ovalbumin inhalation did not induce specific serum antibodies unless the mice were infected at the time of nebulization. In exposed uninfected mice cutaneous challenge with ovalbumin caused no response, but caused acute systemic illness and collapse if previous pulmonary exposure had occurred during respiratory infection. Mice that collapsed in response to cutaneous ovalbumin were found to have IgG1 specific to ovalbumin that was not found in the other mice. Intracellular cytokine staining of splenocyte cultures showed ovalbumin-specific production of IL-4 was enhanced by virus infection during exposure. In CD8+ T cells, ovalbumin-specific interferon-gamma production was also enhanced by co-infection with influenza. Both viruses were equally associated with the induction of anaphylaxis. CONCLUSION: These results show that infection with respiratory viruses powerfully augments cellular and humoral immune responses to aeroantigen and provide an experimental model that allows such effects to be investigated.