Airflow limitation during respiratory syncytial virus lower respiratory tract infection predicts recurrent wheezing.

BACKGROUND: Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is frequently followed by recurrent wheezing. Thus far no clinical risk factors have been identified to predict which infants will have wheezing episodes subsequent to RSV LRTI. OBJECTIVE: To determine clinical predictors for airway morbidity after RSV LRTI. METHODS: In a 1-year follow-up study we investigated the predictive value of auscultatory findings characteristic of airflow limitation (wheezing) during RSV LRTI for subsequent airway morbidity. Clinical characteristics, including the presence or absence of signs of airflow limitation, of hospitalized infants with RSV LRTI were prospectively recorded during 2 winter epidemics. During a 1-year follow-up period parents of 130 infants recorded daily airway symptoms. OUTCOME MEASURE: Recurrent wheezing defined as > or = 2 episodes of wheezing. RESULTS: Signs of airflow limitation during RSV LRTI were absent in 47 (36%) infants and present in 83 (64%) infants. Recurrent wheezing was recorded in 10 (21%) infants without signs of airflow limitation and in 51 (61%) with signs of airflow limitation during initial RSV LRTI (relative risk, 0.29, P < 0.001). In a multiple logistic regression model, airflow limitation during initial RSV LRTI proved independent from other clinical parameters, including age, parental history of asthma and smoke exposure. CONCLUSIONS: A sign of airflow limitation during RSV LRTI is the first useful clinical predictor for subsequent recurrent wheezing.

Monocyte IL-10 production during respiratory syncytial virus bronchiolitis is associated with recurrent wheezing in a one-year follow-up study.

Respiratory syncytial virus (RSV) bronchiolitis is associated with subsequent recurrent wheezing episodes. To determine whether cytokine responses during infection can be of predictive value for the development of recurrent wheezing, we performed a follow-up study in 50 hospitalized children with RSV bronchiolitis. Monocyte and lymphocyte cytokine responses in vitro were studied during the acute phase of disease, and again during the convalescent phase, 3 to 4 wk later. Monocyte cytokine responses, including interleukin-10 (IL-10), were measured in whole blood cultures, stimulated with lipopolysaccharide and interferon-gamma (LPS + IFN-gamma). In addition, T-cell cytokine responses, including IFN-gamma and IL-4 production, were measured in whole-blood cultures stimulated with phytohemagglutinin (PHA) or alphaCD2 + alphaCD28. Cytokine responses were analyzed in relation to the development of recurrent episodes of wheezing, documented by parents in a diary during a 1-yr follow-up period. IL-10 responses during the acute phase of RSV bronchiolitis were comparable to those in healthy control subjects. During the convalescent phase, IL-10 responses were significantly increased in patients as compared with those in healthy control subjects (p < 0.001). At follow-up, 27 children (58%) had recurrent episodes of wheezing. IL-10 levels, measured during the convalescent phase, were significantly higher in patients who developed recurrent wheezing during the year after RSV bronchiolitis than in patients without recurrent episodes of wheezing (p = 0.006). Moreover, IL-10 responses during the convalescent phase correlated significantly with the number of wheezing episodes (r = 0.42, n = 46, p = 0.004). Interestingly, no association was found between IFN-gamma responses, IL-4 responses, or IFNgamma/IL-4 ratios and recurrent wheezing. We conclude that monocyte IL-10 responses in vitro upon stimulation with nonspecific stimuli may have predictive value for the development of recurrent wheezing after RSV bronchiolitis. Moreover, our results indicate that not only allergen-driven Th2 cytokine responses can lead to asthmatic symptoms but also virus-induced changes in cytokine responses may result in asthmatic symptoms.

Peripheral blood cytokine responses and disease severity in respiratory syncytial virus bronchiolitis.

The role of cellular immunity in disease severity in respiratory syncytial virus (RSV) bronchiolitis is largely unknown. This study investigated the association between disease severity and systemic cytokine responses in hospitalized ventilated and nonventilated RSV bronchiolitis patients. In whole blood cultures stimulated with phytohaemagglutinin (PHA), lymphoproliferative responses and interferon (IFN)-gamma and interleukin (IL)-4 production during acute illness were measured. In addition, plasma cytokines were measured. Measurements were repeated in the convalescent phase, 3-4 weeks after admission. Fifty patients were included. The median age in ventilaled patients was significantly lower than in nonventilated patients (1 versus 4 months, p<0.05). In comparison with nonventilated patients, the ventilated patients had significantly lower lymphoproliferative responses and a lower production of IFN-gamma and IL-4. In fact, IFN-gamma and IL-4 production in ventilated patients was almost completely undetectable. Plasma IL-8 levels in ventilated patients were significantly higher than in nonventilated patients. In the convalescent phase, lymphoproliferative and cytokine responses as well as plasma IL-8 levels were normal in both patient groups. Since RSV bronchiolitis is associated with the subsequent development of asthma, the possible skewing of the T-helper (Th1/Th2) cytokine balance was investigated. This was found neither in the acute nor in the convalescent phase. In conclusion, the data indicate that depressed lymphocyte function and elevated plasma interleukin-8 levels are markers of severe disease. It is suggested that age and maturation related immune mechanisms could explain the occurrence of severe respiratory syncytial virus bronchiolitis requiring mechanical ventilation in young infants.