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Respiratory syncytial virus (RSV) lower respiratory tract infection (LRTI) is often followed by recurrent wheezing episodes during childhood. The effect of postbronchiolitis wheezing on the well-being of the child is not known. This study aimed to determine the impact of RSV LRTI hospitalization before age 13 months on health-related quality of life (HRQoL) at age 3 years.HRQoL was measured in a previously described cohort of children with a history of RSV infection and compared with control term children from the open population. HRQoL was determined during the winter season in index and control children. We used a validated questionnaire, which measures the health status of children in 13 domains weighted by the impact of the health status problems on well-being. The lung domain was the focus of this study. In addition daily respiratory symptoms of the index children were recorded prospectively up to age 3 years and correlated with HRQoL scores.HRQoL was lower in index children (n = 128) than in control children (n = 340) for the lung, gastrointestinal tract and sleeping domains. HRQoL scores for social and developmental domains were similar for index and control children. As anticipated the largest difference between index and control children was found in the lung domain (77.6 ± 2.2 vs. 93.9 ± 0.8, P < 0.01). HRQoL in the lung domain was lower during the winter than during the summer season (77.6 ± 2.2 vs. 85.6 ± 1.9, P < 0.01), which was explained by increased airway morbidity during the winter season. We found a high correlation between lung HRQoL scores and total number of wheezing days during follow-up.Postbronchiolitis wheezing has broad implications for long-term well-being of children. Decreased HRQoL was attributed to postbronchiolitis wheezing, but not to preexistent risk factors, such as premature birth. This study underscores the importance of developing new strategies to prevent and treat long term airway morbidity after RSV LRTI.