title: Mannose-binding lectin protein and its association to clinical outcomes in COPD: a longitudinal study.
abstract: BACKGROUND
  Functional deficiency of mannose-binding lectin (MBL) may contribute to the pathogenesis of chronic obstructive pulmonary disease. We hypothesized that specific MBL2 gene polymorphisms and circulating MBL protein levels are associated with clinically relevant outcomes in the Predicting Outcome using systemic Markers In Severe Exacerbations of COPD PROMISE-COPD cohort.
  
  
  METHODS
  We followed 277 patients with stable COPD GOLD stage II-IV COPD over a median period of 733 days (IQR 641-767) taking survival as the primary outcome parameter. Patients were dichotomized as frequent (≥ 2 AECOPD/year) or infrequent exacerbators. Serum MBL levels and single nucleotide polymorphisms of the MBL2 gene were assessed at baseline.
  
  
  RESULTS
  The MBL2-HYPD haplotype was significantly more prevalent in frequent exacerbators (OR: 3.33; 95% CI, 1.24-7.14, p = 0.01). The median serum MBL concentration was similar in frequent (607 ng/ml, [IQR; 363.0-896.0 ng/ml]) and infrequent exacerbators (615 ng/ml, [IQR; 371.0-942.0 ng/ml]). Serum MBL was not associated with lung function characteristics or bacterial colonization in sputum. However, high serum MBL at stable state was associated with better survival compared to low MBL (p = 0.046, log rank test).
  
  
  CONCLUSIONS
  In COPD, the HYPD haplotype of MBL2 gene is associated with frequent exacerbations and high serum MBL is linked to increased survival. The PROMISE-COPD study was registered at www.controlled-trials.com under the identifier ISRCTN99586989.
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Petersgraben, 44031, Basel, Switzerland.
authors.forename: Jyotshna
authors.initials: J
authors.lastname: Mandal
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Petersgraben, 44031, Basel, Switzerland.
authors.forename: Bijaya
authors.initials: B
authors.lastname: Malla
authors.affiliation: Department of Clinical Immunology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Rudi
authors.initials: R
authors.lastname: Steffensen
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Petersgraben, 44031, Basel, Switzerland.
authors.forename: Luigi
authors.initials: L
authors.lastname: Costa
authors.affiliation: Infection Disease Department, University Hospital Basel, Basel, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Egli
authors.affiliation: Department of Biomedicine and Division of Internal Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Marten
authors.initials: M
authors.lastname: Trendelenburg
authors.affiliation: Department of Pathophysiology and Transplantation, Università degli Studi di Milano, IRCCS Fondazione Cà Granda Policlinico, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Blasi
authors.affiliation: Thessaly Medical School, Thessaloniki, Greece.
authors.forename: Kostantinos
authors.initials: K
authors.lastname: Kostikas
authors.affiliation: Medical School Hannover, Hannover, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Welte
authors.affiliation: Hospital Clinic, Barcelona, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Torres
authors.affiliation: University of Liege, Liege, Belgium.
authors.forename: Renaud
authors.initials: R
authors.lastname: Louis
authors.affiliation: Medisch Centrum Alkmaar, Alkmaar, Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Boersma
authors.affiliation: Faculty of Medicine, University of Belgrade; Clinic for Pulmonary Diseases, Belgrade, Serbia.
authors.forename: Branislava
authors.initials: B
authors.lastname: Milenkovic
authors.affiliation: Amphia Hospital, Breda, Netherlands.
authors.forename: Joachim
authors.initials: J
authors.lastname: Aerts
authors.affiliation: Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Gernot G U
authors.initials: GG
authors.lastname: Rohde
authors.affiliation: Department of Microbiology, Hospital Universitari Germans Trias i Pujol, CIBER Enfermedades Respiratorias, Badalona, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Lacoma
authors.affiliation: Department of Laboratorial Medicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Rentsch
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Petersgraben, 44031, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Roth
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Petersgraben, 44031, Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Tamm
authors.affiliation: Clinic of Pulmonary Medicine and Respiratory Cell Research, University Hospital Basel, Petersgraben, 44031, Basel, Switzerland. daiana.stolz@usb.ch.
authors.forename: Daiana
authors.initials: D
authors.lastname: Stolz
mesh_terms: D000368:Aged; D018450:Disease Progression; D005060:Europe; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008168:Lung / Q000503:physiopathology; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood* / Q000235:genetics*; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology / Q000628:therapy; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin