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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.JA

Abstract

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.

Authors+Show Affiliations

Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil. maridol@usp.brNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19361849

Citation

Dolhnikoff, Marisa, et al. "The Outer Wall of Small Airways Is a Major Site of Remodeling in Fatal Asthma." The Journal of Allergy and Clinical Immunology, vol. 123, no. 5, 2009, pp. 1090-7, 1097.e1.
Dolhnikoff M, da Silva LF, de Araujo BB, et al. The outer wall of small airways is a major site of remodeling in fatal asthma. J Allergy Clin Immunol. 2009;123(5):1090-7, 1097.e1.
Dolhnikoff, M., da Silva, L. F., de Araujo, B. B., Gomes, H. A., Fernezlian, S., Mulder, A., Lindeman, J. H., & Mauad, T. (2009). The outer wall of small airways is a major site of remodeling in fatal asthma. The Journal of Allergy and Clinical Immunology, 123(5), 1090-7, e1. https://doi.org/10.1016/j.jaci.2009.02.032
Dolhnikoff M, et al. The Outer Wall of Small Airways Is a Major Site of Remodeling in Fatal Asthma. J Allergy Clin Immunol. 2009;123(5):1090-7, 1097.e1. PubMed PMID: 19361849.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The outer wall of small airways is a major site of remodeling in fatal asthma. AU - Dolhnikoff,Marisa, AU - da Silva,Luiz F F, AU - de Araujo,Bianca B, AU - Gomes,Higor A P, AU - Fernezlian,Sandra, AU - Mulder,Adri, AU - Lindeman,Jan H, AU - Mauad,Thais, Y1 - 2009/04/10/ PY - 2008/08/18/received PY - 2009/02/25/revised PY - 2009/02/27/accepted PY - 2009/4/14/entrez PY - 2009/4/14/pubmed PY - 2009/5/27/medline SP - 1090-7, 1097.e1 JF - The Journal of allergy and clinical immunology JO - J Allergy Clin Immunol VL - 123 IS - 5 N2 - 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/19361849/The_outer_wall_of_small_airways_is_a_major_site_of_remodeling_in_fatal_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(09)00383-2 DB - PRIME DP - Unbound Medicine ER -