In infants with respiratory syncytial virus (RSV) bronchiolitis, we investigated whether disease severity is associated with the genotype of the infecting virus, or with the infant's immunological response to the infection, as determined by measurement of interleukin-8 mRNA in the nasopharyngeal aspirate. This was a cross-sectional observational study, performed in the Accident and Emergency Department, wards, and Intensive Care Unit of a large pediatric hospital. Participants included 276 infants with respiratory syncytial virus infection. Outcome variables included: disease severity (infants requiring oxygen or ventilation were classified as having severe disease); RSV virus genotype (determined according to typing scheme based on the nucleoprotein and G glycoprotein genes); and amount of interleukin-8 mRNA in the nasopharyngeal aspirate, as measured by a semiquantitative polymerase chain reaction assay. This was corrected for the amount of cellular material in the sample by expressing it relative to mRNA for a constitutively expressed gene, HGPRT. We found a highly significant association between the ratio of interleukin-8 mRNA/HGPRT mRNA in the nasopharyngeal aspirate and the occurrence of severe disease. Odds ratio per unit increase of interleukin-8 mRNA/HGPRT mRNA was 1.15 (95% CI, 1.06, 1.24), P = 0.0004. There was no association between virus genotype and either disease severity or amount of interleukin-8 mRNA/HGPRT mRNA. In conclusion, there is a strong, dose-related association between interleukin-8 mRNA produced locally in the airways and disease severity, and a lack of association with virus genotype. This suggests that clinical manifestations of respiratory syncytial virus bronchiolitis are determined by local immunological responses to infection, rather than by characteristics of the infecting virus.

The prolonged presence of aerobic Gram-negative bacilli (AGNB) in the oropharynx is termed 'carriage'. AGNB carriage rates are low in populations of healthy individuals. Previously, severity of underlying disease has been positively correlated with oropharyngeal AGNB carriage rate. Overgrowth of AGNB at the oropharynx poses a significant risk of endogenous infection in end-stage chronic obstructive pulmonary disease (COPD) patients. The aims of this study were to undertake an epidemiological survey of the oropharyngeal flora of COPD patients and to correlate oropharyngeal carriage of AGNB with severity of disease. Two oral rinses were obtained, within a 2-day interval, from 40 COPD patients comprising three disease severity groups: 1. mild, 2. moderate and 3. severe. Eighty oral rinses were quantitatively (1:10 dilution series) cultured for AGNB and yeasts using broth enrichment. The mean AGNB carriage rate was 15%. AGNB carriage rates of 0, 7.7 and 29.4% were observed within the mild, moderate and severe disease groups, respectively. The mean yeast carriage rate was 33.3%. Yeast carriage rates of 33.3, 15.4 and 64.7% were observed within the mild, moderate and severe disease groups, respectively. Carriage of Staphylococcus aureus was 5%. Rates of oropharyngeal carriage of AGNB (1/23 vs. 5/17) and yeasts (5/23 vs. 11/17) were significantly higher within the severe disease group than in non-severe disease groups. Oropharyngeal carriage of AGNB in end-stage COPD patients (forced expiratory volume in 1 sec, FEV1 < 50% predicted) presents a potential source of Gram-negative endogenous pneumonia. This outcome may be promoted by intubation and some flora-suppressing antibiotic therapies.

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Bronchiolitis caused by respiratory syncytial virus (RSV) infection is an important cause of severe lung disease in infants, and increasing evidence suggests that it is immunologically mediated. Experiments in mice suggest that this may be due to differential T-cell activation producing either type 1 or type 2 cytokines. We investigated this hypothesis in man by studying 24 infants ventilated with severe RSV bronchiolitis and by measuring messenger RNA (mRNA) for interleukin-4 (IL-4) and interferon-gamma (IFN-gamma), by polymerase chain reaction, in nasopharyngeal aspirates (NPAs) and bronchoalveolar lavage (BAL) fluids. A semiquantitative assay was used to estimate concentrations of mRNA for these cytokines in comparison to mRNA of the constitutively expressed hypoxanthine guanine phosphoribosyl transferase gene. BAL from 18/24 infants showed polarization of cytokine production: 6 with only IFN-gamma mRNA, and 12 with only IL-4 mRNA. For the 6/24 infants in whom both IL-4 mRNA and IFN-gamma mRNA were detected in BAL fluid, each was present in low amounts, compared with those with mRNA for IL-4 or IFN-gamma alone. IL-4 and IFN-gamma mRNA were not detected in any of the NPAs.These findings provide the first direct evidence in infants that in RSV bronchiolitis there are divergent T-cell responses and suggest that more than one mechanism may be responsible for immune-mediated disease enhancement.