Role of Early-Life Environmental Influences in the Development of Asthma. How Painful Is It When You Catch a Bad Cold Too Early?

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Abstract
A number of studies have implicated lower respiratory tract viral infections early in life as a risk factor for the subsequent development of asthma. Despite extensive research, the precise molecular mechanisms and pathways by which virus infection causes airway inflammation and affects long-term control of airway function subsequent to the initial insult remain unclear. Compromised epithelial integrity, the elaboration of local pro-inflammatory mediators, and dysfunction of neural pathways may all influence airway responses to environmental stimuli. Our research has provided evidence that combined neuroimmune interactions primed by the virus can initiate and propagate a cascade of events leading to recurrent cycles of airway inflammation and obstruction. Nerve growth factor, or NGF, represents an ideal link between virus-infected respiratory epithelium and the dense subepithelial network of sensory fibers. Studies show that RSV infection promotes a large increase in the expression of NGF and its receptors in the respiratory tract of rodents and humans. Changes in neurotrophin expression in the respiratory tract may coordinate a variety of interactions between sensory afferent nerves and multiple components of the immune system and inflammatory pathways, thus generating a pathophysiological link between early-life viral infections and childhood asthma. Such pathways may provide new avenues for the prevention and treatment of asthma and allergy in the near future.