title: Faecal Lactoferrin, Calprotectin, PMN-elastase, CRP, and White Blood Cell Count as Indicators for Mucosal Healing and Clinical Course of Disease in Patients with Mild to Moderate Ulcerative Colitis: Post Hoc Analysis of a Prospective Clinical Trial.
abstract: OBJECTIVE
  We evaluated the performance of blood and faecal biomarkers for differentiating between endoscopic inflammation and mucosal healing, and clinically active disease and sustained clinical remission, and determined the predictive value for a flare in patients with ulcerative colitis [UC].
  
  
  METHODS
  Clinical Activity Index [CAI], faecal lactoferrin [FLA], calprotectin [CAL], PMN-elastase [PMN-e], C-reactive protein [CRP], white blood cells [WBC], Endoscopic Index [EI], and UC-Disease Activity Index [DAI] were determined repeatedly during 12 months and at acute flares.
  
  
  RESULTS
  Of 91 patients [45 female; mean age 48.1±13.4 years] entering in remission, 42 [46%] patients developed a clinical flare. A total of 529 CAI and 179 EI assessments were performed. Median levels for active disease confirmed by EI [n = 35] vs clinical remission with endoscopic inflammation [n = 37] vs mucosal healing [n = 107] for FLA were 44/37/4 µg/g, CAL 25/20/10 µg/g [both p < 0.0001], PMN-e 0.06/0.03/0.02 µg/g, CRP 0.7/0.2/0.2mg/dl [both p < 0.001], and WBC 7.0/6.5/6.4/nl [p = 0.1]. There was no difference for any of the markers for defining mucosal healing by EI = 0 vs EI = 1 with the exception of PMN-e [p = 0.03], where the difference was very small and with questionable clinical relevance. Using manufacturers' cut-offs, only FLA at baseline was associated with a significant higher relative risk [RR] of flaring [RR 1.69; p = 0.018]. Using optimised cut-offs, CAL, PMN-e, and CRP were also predictive of a flare.
  
  
  CONCLUSIONS
  Faecal biomarkers FLA, CAL, and PMN-e were able to distinguish between UC patients with mucosal healing from clinical remission and mild disease, showed significant correlations with endoscopy, and were predictive of a flare.
authors.affiliation: Department of Integrative Gastroenterology, Kliniken Essen-Mitte, Essen, Germany Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany jost.langhorst@gmx.de.
authors.forename: Jost
authors.initials: J
authors.lastname: Langhorst
authors.affiliation: TechLab®, Blacksburg, VA, USA.
authors.forename: James
authors.initials: J
authors.lastname: Boone
authors.affiliation: Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
authors.forename: Romy
authors.initials: R
authors.lastname: Lauche
authors.affiliation: Enterosan, Labor L+S, Bad Bocklet-Großenbrach, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rueffer
authors.affiliation: Department of Internal and Integrative Medicine, Kliniken Essen-Mitte, Faculty of Medicine, University of Duisburg-Essen, Essen, Germany.
authors.forename: Gustav
authors.initials: G
authors.lastname: Dobos
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005243:Feces / Q000737:chemistry; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007413:Intestinal Mucosa / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D007781:Lactoferrin / Q000378:metabolism*; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000378:metabolism*; D039841:Leukocyte L1 Antigen Complex / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012074:Remission Induction; D012720:Severity of Illness Index; D012812:Sigmoidoscopy; D014945:Wound Healing
chemical_list: D015415:Biomarkers; C490098:LTF protein, human; D039841:Leukocyte L1 Antigen Complex; D002097:C-Reactive Protein; D007781:Lactoferrin; D019272:Leukocyte Elastase
keywords: CRP; PMN-elastase; Ulcerative colitis; calprotectin; faecal lactoferrin; monitoring; mucosal healing; relapse; white blood cell count