Pediatr Allergy Immunol 2002;13(s15):38-43
University of Wisconsin-Madison Medical School, Madison, WI, USA.
Although asthma is probably a heterogeneous disease or syndrome, three factors and/or events consistently emerge for their ability to significantly influence asthma inception in the first decade of life: immune response aberrations, which appear to be defined best by the concept of cytokine dysregulation; lower respiratory tract infections, in particular respiratory syncytial virus (RSV); and some form of gene-environment interaction that needs to occur at a critical time-period in the development of the immune system or the lung. It remains to be firmly established, however, how any one or all of these factors, either independently or interactively, influence the development of childhood asthma. For example, cytokine dysregulation (T helper 1/T helper 2 imbalance) appears to track best epidemiologically with allergic diseases. As not everyone who undergoes allergic sensitization develops asthma, some other host-environment interaction must need to occur to target this chronic allergic inflammatory response to the lower airway. Some evidence suggests that this event might be an environmental insult in the form of a virus infection, particularly with RSV, which has a predilection for infecting, destroying, and/or in some way biologically altering lower airway epithelium. However, only a fraction of children develop recurrent wheezing following RSV infections, despite the fact that nearly all children have been infected at least once by 2 years of age. Thus, although RSV infections may have the potential of targeting the inflammatory response to the lower airway, they may only be able to do so during a vulnerable time-period during development of the immune system or lung. This developmental component may further reflect important gene-environment interactions that regulate both short- and long-term airway physiological alterations that manifest themselves clinically as childhood asthma. Efforts to determine and define the importance of these three factors to asthma pathogenesis are the focus and goal of the COAST (Childhood Origins of Asthma) project.