The connection between early life wheezing and subsequent asthma: The viral march
Several new lines of evidence suggest that alterations in immune responses which predispose to bronchial obstruction during acute respiratory infection, especially with rhinoviruses, may explain to a considerable extent the link between early life wheezing and subsequent asthma; above all among those schoolchildren who are prone to having recurrent asthma exacerbations. The nature of these alterations is currently the subject of considerable scrutiny, but cross-sectional studies suggest that deficits in innate immune responses mediated by interferon type I and III are present in lung macrophages and epithelial cells of adult asthmatics. Similarly, long-term follow-up studies suggest that deficits in interferon gamma responses in the first year of life predispose to recurrent episodes of wheezing from the preschool years and into early adolescence. A better understanding of the "viral march" could yield new therapeutic approaches for the prevention and treatment of acute severe airway obstruction during childhood. Several longitudinal studies have provided convincing evidence that, in most cases of asthma, the first symptoms of the disease occur during the preschool years.(1-3) Young children who will go on to develop asthma later in life usually have recurrent episodes of wheezing, cough, and difficulty to breathe ("persistent wheezers"),(4) and these episodes are associated with molecular evidence of viral respiratory infection in up to 90% of cases.(5) However, the majority of infants aged <1 year who wheeze remit by the age of 3 (the so-called transient wheezers(6)), and their episodes are also associated with viral infections. Until very recently, a predisposition to allergy was the main disease mechanisms believed to connect early life wheezing with subsequent asthma.(7) The purpose of this brief comment is to review the evidence which suggests that susceptibility to infection with rhinovirus may be a critical additional factor explaining this connection.
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