The role of airway smooth muscle in the pathogenesis of airway wall remodeling in chronic obstructive pulmonary disease

Proc Am Thorac Soc. 2005;2(4):347-54; discussion 371-2. doi: 10.1513/pats.200504-028SR.


Airway wall remodeling processes are present in the small airways of patients with chronic obstructive pulmonary disease, consisting of tissue repair and epithelial metaplasia that contribute to airway wall thickening and airflow obstruction. With increasing disease severity, there is also increased mucous metaplasia and submucosal gland hypertrophy, peribronchial fibrosis, and an increase in airway smooth muscle mass. Apart from its contractile properties, airway smooth muscle produces inflammatory cytokines, proteases, and growth factors, which may contribute to the remodeling process and induce phenotypic changes of the muscle. Airflow limitation responds minimally to beta-agonists and corticosteroid therapy, unlike asthma, perhaps because of alterations in beta-receptor or glucocorticoid receptor numbers, alterations in receptor signaling, or the constrictive limitation imposed by peribronchial fibrosis. Better response is observed with the combination of inhaled long-acting beta-agonists and corticosteroids. This could result from effects at the level of airway smooth muscle. Airway wall remodeling may involve the release of growth factors from inflammatory or resident cells. The influence of smoking cessation or of current therapies on airway wall remodeling is unknown. Specific therapies for airway wall remodeling may be necessary, together with noninvasive methods of imaging small airway wall remodeling to assess responses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Bronchi / pathology*
  • Bronchi / physiopathology
  • Humans
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / pathology*
  • Muscle, Smooth / physiopathology
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Respiratory Mucosa / pathology
  • Respiratory Mucosa / physiopathology