Treatment and prevention of respiratory syncytial virus lower respiratory tract infection. Long-term effects on respiratory outcomes.

Abstract

The association between respiratory syncytial virus (RSV) bronchiolitis and asthma has been established for more than 30 yr. However, the question of causality remains unanswered: Does severe RSV lower respiratory tract infection (LRTI) cause long-term pulmonary morbidity or do factors that predispose a child to wheeze later in life also predispose the child to severe RSV LRTI? In several human studies (1–4), obstructive airway disease appears to occur up to 10 yr after an initial RSV infection. The Tucson Children’s Respiratory Study showed an effect at 10 yr (5) but not by 13 yr (6). Hall and coworkers prospectively monitored 29 children who were hospitalized during infancy for RSV LRTI for 8 yr (7). Six children continued to have lower respiratory tract disease and six (21%) had persistently low oxyhemoglobin levels (Sa O2 ) at follow-up. Sigurs and colleagues found that children who had experienced RSV LRTI were more likely to have asthma and recurrent wheeze for 7 yr (4). Weber and colleagues (8) determined in Gambia that RSV LRTI predisposed children to recurrent wheeze, but only for 2 yr; after 3 yr, there was no significant difference between RSV-infected children and control children with respect to wheezing episodes. Many of the patients in the Tucson study had only RSV upper respiratory tract infections and none were hospitalized (5, 6). Patients in the study by Sigurs and coworkers (4), Hall and colleagues (7), and those in the Gambia study (8) had severe RSV disease. The reason for the observed varying degree and length of long-term sequelae may lie in the differing degrees of severity of illness studied (mild versus severe), or differences in location (developed versus developing countries), or ecological differences in sensitizing allergens (desert versus temperate versus tropical), or other undetermined factors. It remains to be determined whether severe RSV LRTI causes the pulmonary sequelae observed in longitudinal studies (i.e., a causeand-effect relationship) or whether inherent genetic or structural abnormalities that predispose a child to wheeze later in life also predispose the child to severe RSV LRTI. If causality exists, reducing severe RSV LRTI would reduce subsequent wheezing; if causality does not exist, reducing severe RSV LRTI would have no effect on subsequent wheezing. This is, therefore, a key clinical issue, which has been addressed in three sets of studies: antiviral therapy for RSV LRTI, antiinflammatory therapy for RSV LRTI, and prevention of RSV LRTI.