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Controlled and uncontrolled asthma display distinct alveolar tissue matrix compositions

Weitoft, Maria LU ; Andersson, Cecilia LU ; Andersson Sjöland, Annika LU ; Tufvesson, Ellen LU ; Bjermer, Leif LU ; Erjefält, Jonas LU and Westergren-Thorsson, Gunilla LU (2014) In Respiratory Research 15.
Abstract
Objective: Whether distal inflammation in asthmatics also leads to structural changes in the alveolar parenchyma remains poorly examined, especially in patients with uncontrolled asthma. We hypothesized that patients who do not respond to conventional inhaled corticosteroid therapy have a distinct tissue composition, not only in central, but also in distal lung. Methods: Bronchial and transbronchial biopsies from healthy controls, patients with controlled atopic and patients with uncontrolled atopic asthma were processed for immunohistochemical analysis of fibroblasts and extracellular matrix molecules: collagen, versican, biglycan, decorin, fibronectin, EDA-fibronectin, matrix metalloproteinase (MMP)-9 and tissue-inhibitor of matrix... (More)
Objective: Whether distal inflammation in asthmatics also leads to structural changes in the alveolar parenchyma remains poorly examined, especially in patients with uncontrolled asthma. We hypothesized that patients who do not respond to conventional inhaled corticosteroid therapy have a distinct tissue composition, not only in central, but also in distal lung. Methods: Bronchial and transbronchial biopsies from healthy controls, patients with controlled atopic and patients with uncontrolled atopic asthma were processed for immunohistochemical analysis of fibroblasts and extracellular matrix molecules: collagen, versican, biglycan, decorin, fibronectin, EDA-fibronectin, matrix metalloproteinase (MMP)-9 and tissue-inhibitor of matrix metalloproteinase (TIMP)-3. Results: In central airways we found increased percentage areas of versican and decorin in patients with uncontrolled asthma compared to both healthy controls and patients with controlled asthma. Percentage area of biglycan was significantly higher in both central airways and alveolar parenchyma of patients with uncontrolled compared to controlled asthma. Ratios of MMP-9/TIMP-3 were decreased in both uncontrolled and controlled asthma compared to healthy controls. In the alveolar parenchyma, patients with uncontrolled asthma had increased percentage areas of collagen, versican and decorin compared to patients with controlled asthma. Patients with uncontrolled asthma had significantly higher numbers of myofibroblasts in both central airways and alveolar parenchyma compared to patients with controlled asthma. Conclusions: Tissue composition differs, in both central and distal airways, between patients with uncontrolled and controlled asthma on equivalent doses of ICS. This altered structure and possible change in tissue elasticity may lead to abnormal mechanical properties, which could be a factor in the persistent symptoms for patients with uncontrolled asthma. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Asthma, Controlled, Uncontrolled, ICS, Remodeling, Alveolar parenchyma, Extracellular matrix, Myofibroblasts
in
Respiratory Research
volume
15
publisher
BioMed Central
external identifiers
  • wos:000338670600001
  • scopus:84902707564
ISSN
1465-9921
DOI
10.1186/1465-9921-15-67
language
English
LU publication?
yes
id
8e8f3276-39e5-4376-9dda-af96300811af (old id 4602375)
date added to LUP
2014-09-05 08:49:38
date last changed
2017-08-20 03:17:02
@article{8e8f3276-39e5-4376-9dda-af96300811af,
  abstract     = {Objective: Whether distal inflammation in asthmatics also leads to structural changes in the alveolar parenchyma remains poorly examined, especially in patients with uncontrolled asthma. We hypothesized that patients who do not respond to conventional inhaled corticosteroid therapy have a distinct tissue composition, not only in central, but also in distal lung. Methods: Bronchial and transbronchial biopsies from healthy controls, patients with controlled atopic and patients with uncontrolled atopic asthma were processed for immunohistochemical analysis of fibroblasts and extracellular matrix molecules: collagen, versican, biglycan, decorin, fibronectin, EDA-fibronectin, matrix metalloproteinase (MMP)-9 and tissue-inhibitor of matrix metalloproteinase (TIMP)-3. Results: In central airways we found increased percentage areas of versican and decorin in patients with uncontrolled asthma compared to both healthy controls and patients with controlled asthma. Percentage area of biglycan was significantly higher in both central airways and alveolar parenchyma of patients with uncontrolled compared to controlled asthma. Ratios of MMP-9/TIMP-3 were decreased in both uncontrolled and controlled asthma compared to healthy controls. In the alveolar parenchyma, patients with uncontrolled asthma had increased percentage areas of collagen, versican and decorin compared to patients with controlled asthma. Patients with uncontrolled asthma had significantly higher numbers of myofibroblasts in both central airways and alveolar parenchyma compared to patients with controlled asthma. Conclusions: Tissue composition differs, in both central and distal airways, between patients with uncontrolled and controlled asthma on equivalent doses of ICS. This altered structure and possible change in tissue elasticity may lead to abnormal mechanical properties, which could be a factor in the persistent symptoms for patients with uncontrolled asthma.},
  articleno    = {67},
  author       = {Weitoft, Maria and Andersson, Cecilia and Andersson Sjöland, Annika and Tufvesson, Ellen and Bjermer, Leif and Erjefält, Jonas and Westergren-Thorsson, Gunilla},
  issn         = {1465-9921},
  keyword      = {Asthma,Controlled,Uncontrolled,ICS,Remodeling,Alveolar parenchyma,Extracellular matrix,Myofibroblasts},
  language     = {eng},
  publisher    = {BioMed Central},
  series       = {Respiratory Research},
  title        = {Controlled and uncontrolled asthma display distinct alveolar tissue matrix compositions},
  url          = {http://dx.doi.org/10.1186/1465-9921-15-67},
  volume       = {15},
  year         = {2014},
}