| 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. |