The outer wall of small airways is a major site of remodeling in fatal asthma

J Allergy Clin Immunol. 2009 May;123(5):1090-7, 1097.e1. doi: 10.1016/j.jaci.2009.02.032. Epub 2009 Apr 10.


Background: Structural and inflammatory changes in asthma involve both the large and small airways, with involvement of the distal lung being related to disease severity. We have previously shown that changes in the extracellular matrix (ECM) composition of the distal lung are associated with loss of alveolar attachments in patients with fatal asthma. However, major ECM elements, such as collagen I and fibronectin and their regulators, have not been addressed at the distal level.

Objective: We sought to evaluate ECM remodeling in the distal lungs of asthmatic patients.

Methods: Using immunohistochemistry and image analysis, we determined the content of collagen I and III, fibronectin, and matrix metalloproteinases (MMPs) 1, 2, and 9 and tissue inhibitors of metalloproteinase (TIMPs) 1 and 2 in the large and small airways and lung parenchyma of 24 patients with fatal asthma and compared the results with those of 11 nonasthmatic control subjects. Protein content was defined as the area of positive staining divided by basement membrane or septum length.

Results: We observed increased collagen I and decreased collagen III content in the small airways of asthmatic patients compared with that seen in control subjects. Greater fibronectin and MMP-1, MMP-2, and MMP-9 content was observed at the outer area of the small airways in asthmatic patients. MMP content was also increased in the peribronchiolar parenchyma in asthmatic patients. In contrast, TIMP expression was only increased in the large airways of asthmatic patients compared with that seen in control subjects.

Conclusions: The outer area of the small airways is a major site of ECM remodeling in fatal asthma, potentially contributing to functional changes and the loss of airway-parenchyma interdependence observed in patients with fatal asthma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Asthma / immunology
  • Asthma / metabolism
  • Asthma / pathology*
  • Collagen Type I / analysis
  • Collagen Type I / immunology
  • Collagen Type III / analysis
  • Collagen Type III / immunology
  • Extracellular Matrix / immunology
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology*
  • Female
  • Fibronectins / analysis
  • Fibronectins / immunology
  • Humans
  • Lung / immunology
  • Lung / metabolism
  • Lung / pathology*
  • Male
  • Matrix Metalloproteinases / analysis
  • Matrix Metalloproteinases / immunology
  • Middle Aged
  • Tissue Inhibitor of Metalloproteinases / analysis
  • Tissue Inhibitor of Metalloproteinases / immunology


  • Collagen Type I
  • Collagen Type III
  • Fibronectins
  • Tissue Inhibitor of Metalloproteinases
  • Matrix Metalloproteinases