Abstract
Airway inflammation, airflow obstruction, and bronchial
hyperresponsiveness are characteristic phenotypic features of asthma.
Clinically, airflow obstruction in asthma often is not fully reversible,
and many asthmatic subjects experience an accelerated and progressive
loss of lung function over time. Histopathologic studies of the
asthmatic airway have demonstrated stereotypic changes that might
explain the loss of lung function that many patients with asthma
experience. The notion of airway remodeling in asthma postulates that
the alteration of the structure and function of key airway constituents,
including airway smooth muscle, epithelium, blood vessels, and mucus
glands, might explain, at least in part, the progressive loss of lung
function that is observed clinically. Inflammation driven by CD4(+)
lymphocytes and mediated by effector cells, particularly the eosinophil,
appears to modulate the function of mesenchymal cells, including
fibroblasts and myofibroblasts, changing the composition of the airway
wall matrix. Changes in the airway epithelium might alter the function
of the underlying smooth muscle and the composition of the matrix and
could drive inflammation. Alterations in the structure and function of
airway smooth muscle change the mechanical properties of the airway wall
and might also affect the function of other airway constituents. A
variety of experimental models have identified candidate mechanisms and
mediators for these observed changes, which are thus potential
therapeutic targets. However, clinical studies to date have been
disappointing, and it remains to be seen whether targeted therapies will
prevent the progressive loss of lung function seen in asthma.
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