title: Controlled and uncontrolled asthma display distinct alveolar tissue matrix compositions.
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.
authors.affiliation: Lung Biology Unit, Department of Experimental Medical Science, BMC, D12, Lund University, Lund, SE-221 84, Sweden. maria.weitoft@med.lu.se.
authors.forename: Maria
authors.initials: M
authors.lastname: Weitoft
authors.forename: Cecilia
authors.initials: C
authors.lastname: Andersson
authors.forename: Annika
authors.initials: A
authors.lastname: Andersson-Sjöland
authors.forename: Ellen
authors.initials: E
authors.lastname: Tufvesson
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
authors.forename: Jonas
authors.initials: J
authors.lastname: Erjefält
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000378:metabolism; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9