title: Evaluation of coagulation activation after rhinovirus infection in patients with asthma and healthy control subjects: an observational study.
abstract: BACKGROUND
  Asthma exacerbations are frequently triggered by rhinovirus infections. Both asthma and respiratory tract infection can activate haemostasis. Therefore we hypothesized that experimental rhinovirus-16 infection and asthmatic airway inflammation act in synergy on the haemostatic balance.
  
  
  METHODS
  28 patients (14 patients with mild allergic asthma and 14 healthy non-allergic controls) were infected with low-dose rhinovirus type 16. Venous plasma and bronchoalveolar lavage fluid (BAL fluid) were obtained before and 6 days after infection to evaluate markers of coagulation activation, thrombin-antithrombin complexes, von Willebrand factor, plasmin-antiplasmin complexes, plasminogen activator inhibitor type-1, endogenous thrombin potential and tissue factor-exposing microparticles by fibrin generation test, in plasma and/or BAL fluid. Data were analysed by nonparametric tests (Wilcoxon, Mann Whitney and Spearman correlation).
  
  
  RESULTS
  13 patients with mild asthma (6 females, 19-29 y) and 11 healthy controls (10 females, 19-31 y) had a documented Rhinovirus-16 infection. Rhinovirus-16 challenge resulted in a shortening of the fibrin generation test in BAL fluid of asthma patients (t = -1: 706 s vs. t = 6: 498 s; p = 0.02), but not of controls (t = -1: 693 s vs. t = 6: 636 s; p = 0.65). The fold change in tissue factor-exposing microparticles in BAL fluid inversely correlated with the fold changes in eosinophil cationic protein and myeloperoxidase in BAL fluid after virus infection (r = -0.517 and -0.528 resp., both p = 0.01).Rhinovirus-16 challenge led to increased plasminogen activator inhibitor type-1 levels in plasma in patients with asthma (26.0 ng/mL vs. 11.5 ng/mL in healthy controls, p = 0.04). Rhinovirus-16 load in BAL showed a linear correlation with the fold change in endogenous thrombin potential, plasmin-antiplasmin complexes and plasminogen activator inhibitor type-1.
  
  
  CONCLUSIONS
  Experimental rhinovirus infection induces procoagulant changes in the airways of patients with asthma through increased activity of tissue factor-exposing microparticles. These microparticle-associated procoagulant changes are associated with both neutrophilic and eosinophilic inflammation. Systemic activation of haemostasis increases with Rhinoviral load.
  
  
  BACKGROUND
  This trial was registered at the Dutch trial registry (http://www.trialregister.nl): NTR1677.
authors: Department of Respiratory Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. c.j.majoor@amc.uva.nl.
authors: Christof J
authors: CJ
authors: Majoor
authors: Marianne A
authors: MA
authors: van de Pol
authors: Pieter Willem
authors: PW
authors: Kamphuisen
authors: Joost C M
authors: JC
authors: Meijers
authors: Richard
authors: R
authors: Molenkamp
authors: Katja C
authors: KC
authors: Wolthers
authors: Tom
authors: T
authors: van der Poll
authors: Rienk
authors: R
authors: Nieuwland
authors: Sebastian L
authors: SL
authors: Johnston
authors: Peter J
authors: PJ
authors: Sterk
authors: Elisabeth H D
authors: EH
authors: Bel
authors: Rene
authors: R
authors: Lutter
authors: Koenraad F
authors: KF
authors: van der Sluijs
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D055815:Young Adult; D001249:Asthma / Q000175:diagnosis / Q000378:metabolism / Q000821:virology; D001777:Blood Coagulation / Q000502:physiology; D006487:Hemostasis / Q000502:physiology; D010850:Picornaviridae Infections / Q000175:diagnosis / Q000378:metabolism / Q000821:virology; D012229:Rhinovirus