title: Microfibrillar-associated protein 4: a potential biomarker of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Microfibrillar-associated protein 4 (MFAP4) is a matricellular glycoprotein that co-localises with elastic fibres and is highly expressed in the lungs. The aim of this study was to test the hypothesis that plasma MFAP4 (pMFAP4) reflects clinical outcomes in chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  pMFAP4 was measured by an AlphaLISA immunoassay in stable COPD (n = 69) at baseline and at follow-up until 24 months after inclusion and in acute exacerbations of COPD (AECOPD) (n = 14) at baseline and until 6 months after inclusion.
  
  
  RESULTS
  The majority of patients (89%) were in GOLD II and III. Multiple linear regressions showed positive associations between pMFAP4 and the Global initiative for Obstructive Lung Disease (GOLD) grade (p = 0.01), modified Medical Research Council score (p < 0.0001) and BODE index (p = 0.04). Negative associations were found with 6-min walking distance (p = 0.04) and bronchodilator-induced reversibility (p = 0.02). The pMFAP4 levels varied less than 25% between the baseline and a 3 month follow-up in 83% of the patients. The pMFAP4 levels appeared unaffected in the acute phase of severe AECOPD but rose to an increased stable level within one month after hospitalization.
  
  
  CONCLUSIONS
  Increased pMFAP4 was associated to the severity in COPD and has the potential to serve as a stable disease biomarker. This observation warrants confirmation in a larger longitudinal COPD population.
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark.
authors.forename: Sofie Lock
authors.initials: SL
authors.lastname: Johansson
authors.affiliation: Respiratory Section, Hvidovre Hospital, Kettegård Allé 30, 2650 Hvidovre, Denmark.
authors.forename: Nassim Bazeghi
authors.initials: NB
authors.lastname: Roberts
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark.
authors.forename: Anders
authors.initials: A
authors.lastname: Schlosser
authors.affiliation: Department of Pathology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Claus B
authors.initials: CB
authors.lastname: Andersen
authors.affiliation: Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Carlsen
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark.
authors.forename: Helle
authors.initials: H
authors.lastname: Wulf-Johansson
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark; Department of Clinical Immunology, Næstved Hospital, Ringstedgade 61, 4700 Næstved, Denmark.
authors.forename: Susanne Gjørup
authors.initials: SG
authors.lastname: Sækmose
authors.affiliation: Department of Respiratory Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark.
authors.forename: Ingrid L
authors.initials: IL
authors.lastname: Titlestad
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Tornoe
authors.affiliation: GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Miller
authors.affiliation: GlaxoSmithKline, 709 Swedeland Road, King of Prussia, PA 19406, USA.
authors.forename: Ruth
authors.initials: R
authors.lastname: Tal-Singer
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark.
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.affiliation: Department of Respiratory Medicine, Odense University Hospital, Sdr. Boulevard 29, 5000 Odense C, Denmark; The University of Manchester, Manchester Academic Health Science Centre, 46 Grafton Street, M13 9NT Manchester, UK; University Hospital South Manchester NHS Foundation Trust, NIHR South Manchester Respiratory and Allergy Clinical Research Facility, Wythenshawe Hospital, Southmoor Road, Wythenshawe, Manchester, Greater Manchester M23 9LT, UK.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Vestbo
authors.affiliation: Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, JB Winsløws Vej 25.3, 5000 Odense C, Denmark. Electronic address: glsorensen@health.sdu.dk.
authors.forename: Grith Lykke
authors.initials: GL
authors.lastname: Sorensen
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000097:blood* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000502:physiology; D006023:Glycoproteins / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis* / Q000503:physiopathology; D012720:Severity of Illness Index; D014797:Vital Capacity / Q000502:physiology
chemical_list: D015415:Biomarkers; D002352:Carrier Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; C400752:MFAP4 protein, human
keywords: Acute exacerbation of COPD; BODE index; Biomarkers; Chronic obstructive pulmonary disease; Microfibrillar-associated protein 4; Modified Medical Research Council score