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Airway remodeling in asthma: New insights
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 111 (2): 215-225 (февраля 2003)
DOI: {10.1067/mai.2003.128}
Аннотация
Asthma is increasing in prevalence worldwide as a result of factors
associated with a Western lifestyle. The prevalence and chronic nature
of the disease represent significant economic burdens. Despite advances
in understanding the inflammatory and immunologic components of asthma,
there is relatively little understanding of the cellular and molecular
mechanisms underlying the structural changes seen in the asthmatic lung
(airway remodeling). These changes include hypertrophy of bronchial
smooth muscle, transformation of fibroblasts to myofibroblasts, and
deposition of subepithelial collagen. Airway remodeling is linked to
bronchial hyperresponsiveness to diverse triggers and a steeper
trajectory of long-term decrease in lung function in asthmatic patients.
Until recently, these remodeling changes have been considered to be
secondary phenomena, developing late in the disease process as a
consequence of persistent inflammation. We discuss an alternative view
of asthma pathogenesis by emphasizing the importance of the airway
microenvironment (the epithelial mesenchymal trophic unit) in the
origins of the disease. Our proposals are supported by the recent
identification of ADAM33 as an asthma susceptibility gene, the
expression of which is abundant in airway fibroblasts and smooth muscle
but absent from T lymphocytes or inflammatory cells that infiltrate the
airway wall in patients with asthma. (J Allergy Clin Immunol
2003;111:215-25.).
