title: Similar matrix alterations in alveolar and small airway walls of COPD patients.
abstract: BACKGROUND
  Remodelling in COPD has at least two dimensions: small airway wall thickening and destruction of alveolar walls. Recent studies indicate that there is some similarity between alveolar and small airway wall matrix remodelling. The aim of this study was to characterise and assess similarities in alveolar and small airway wall matrix remodelling, and TGF-β signalling in COPD patients of different GOLD stages.
  
  
  METHODS
  Lung tissue sections of 14 smoking controls, 16 GOLD II and 19 GOLD IV patients were included and stained for elastin and collagens as well as hyaluronan, a glycosaminoglycan matrix component and pSMAD2.
  
  
  RESULTS
  Elastin was significantly decreased in COPD patients not only in alveolar, but also in small airway walls. Interestingly, both collagen and hyaluronan were increased in alveolar as well as small airway walls. The matrix changes were highly comparable between GOLD stages, with collagen content in the alveolar wall increasing further in GOLD IV. A calculated remodelling index, defined as elastin divided over collagen and hyaluronan, was decreased significantly in GOLD II and further lowered in GOLD IV patients, suggesting that matrix component alterations are involved in progressive airflow limitation. Interestingly, there was a positive correlation present between the alveolar and small airway wall stainings of the matrix components, as well as for pSMAD2. No differences in pSMAD2 staining between controls and COPD patients were found.
  
  
  CONCLUSIONS
  In conclusion, remodelling in the alveolar and small airway wall in COPD is markedly similar and already present in moderate COPD. Notably, alveolar collagen and a remodelling index relate to lung function.
authors.forename: Irene M J
authors.initials: IM
authors.lastname: Eurlings
authors.forename: Mieke A
authors.initials: MA
authors.lastname: Dentener
authors.forename: Jack P M
authors.initials: JP
authors.lastname: Cleutjens
authors.forename: Carine J
authors.initials: CJ
authors.lastname: Peutz
authors.forename: Gernot G U
authors.initials: GG
authors.lastname: Rohde
authors.forename: Emiel F M
authors.initials: EF
authors.lastname: Wouters
authors.affiliation: Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Department of Respiratory Medicine, University Hospital Maastricht, P,O, Box 5800, 6202 AZ Maastricht, The Netherlands. n.reynaert@maastrichtuniversity.nl.
authors.forename: Niki L
authors.initials: NL
authors.lastname: Reynaert
mesh_terms: D056151:Airway Remodeling; D001707:Biopsy, Needle; D001980:Bronchi / Q000473:pathology*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D024022:Fibrillar Collagens / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000473:pathology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology* / Q000503:physiopathology; D012016:Reference Values; D012720:Severity of Illness Index; D051899:Smad2 Protein / Q000378:metabolism
chemical_list: D024022:Fibrillar Collagens; D051899:Smad2 Protein; D004549:Elastin