title: Acute Exacerbations of COPD Are Associated With Increased Expression of Heparan Sulfate and Chondroitin Sulfate in BAL.
abstract: BACKGROUND
  Acute exacerbations of COPD (AECOPDs) are associated with accelerated aggravation of clinical symptoms and deterioration of pulmonary function. The mechanisms by which exacerbations may contribute to airway remodeling and declined lung function are poorly understood. We investigated whether AECOPDs are associated with differential expression of glycosaminoglycans in BAL in a cohort of 97 patients with COPD.
  
  
  METHODS
  Patients with COPD with either stable disease (n = 53) or AECOPD (n = 44) and undergoing diagnostic bronchoscopy were matched for demographics and lung function parameters. Levels of heparan sulfate, chondroitin sulfate, dermatan sulfate, and matrix metalloproteinases (MMPs) in BAL were measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Heparan sulfate and chondroitin sulfate were significantly increased in BAL of patients during exacerbations. Levels of heparan sulfate were higher in the BAL of patients with microbial infections. Chondroitin sulfate was negatively correlated with FEV1 % predicted but not with diffusing capacity of lung for carbon monoxide % predicted, indicating that chondroitin sulfate is associated with airway remodeling, leading to obstruction rather than to emphysema. Furthermore, heparan sulfate and chondroitin sulfate were significantly correlated with MMP-9, MMP-2, and MMP-12 in BAL, indicating that they were cleaved from their respective proteoglycans by MMPs and subsequently washed out in BAL.
  
  
  CONCLUSIONS
  During AECOPD, there is increased expression of heparan sulfate and chondroitin sulfate in BAL. These molecules are significantly correlated with MMPs in BAL, indicating that they may be associated with airway remodeling and may lead to lung function decline during exacerbations of COPD.
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital of Basel, Basel, Switzerland; Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Eleni
authors.initials: E
authors.lastname: Papakonstantinou
authors.affiliation: Department of Pharmacology, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Klagas
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital of Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital of Basel, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital of Basel, Basel, Switzerland. Electronic address: daiana.stolz@usb.ch.
authors.forename: Daiana
authors.initials: D
authors.lastname: Stolz
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D056151:Airway Remodeling; D018893:Bronchoalveolar Lavage; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D001999:Bronchoscopy; D016022:Case-Control Studies; D002809:Chondroitin Sulfates / Q000378:metabolism*; D015331:Cohort Studies; D003871:Dermatan Sulfate / Q000378:metabolism*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D008297:Male; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*
chemical_list: D002809:Chondroitin Sulfates; D003871:Dermatan Sulfate; D006497:Heparan Sulfate; D053508:Matrix Metalloproteinase 12; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020782:Matrix Metalloproteinases; C522361:MMP2 protein, human; C579270:MMP9 protein, human; C507122:MMP12 protein, human
keywords: COPD; airway inflammation; airway obstruction; bronchoalveolar lavage