Evaluation of coagulation activation after Rhinovirus infection in patients with asthma and healthy control subjects: an observational study

Respiratory Research

Koenraad F van der Sluijs²  Rene Lutter⁸  Elisabeth HD Bel⁴  Peter J Sterk⁴  Sebastian L Johnston⁹  Rienk Nieuwland⁶  Tom van der Poll⁵  Katja C Wolthers³  Richard Molenkamp³  Joost CM Meijers⁷  Pieter Willem Kamphuisen¹  Marianne A van de Pol⁸  Christof J Majoor⁴ 

[1] Department of Vascular Medicine, University Medical Centre Groningen, Hanzeplein 1, 9700 HB Groningen, The Netherlands;Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Department of Medical Microbiology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Department of Respiratory Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Center of Experimental and Molecular Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Experimental Clinical Chemistry, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Experimental Vascular Medicine, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Experimental Immunology, Academic Medical Centre, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Airway Disease Infection Section, National Heart and Lung Institute, Imperial College London, Norfolk Place, London W2 1PG, UK

关键词: Inflammation;    Microparticles;    Asthma;    Fibrinolysis;    Coagulation;    Rhinovirus;   

Others  :  790625
DOI  :  10.1186/1465-9921-15-14

 received in 2013-10-08, accepted in 2014-01-31,  发布年份 2014

【 摘 要 】

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.

Trial registration

This trial was registered at the Dutch trial registry (http://www.trialregister.nl webcite): NTR1677.

【 授权许可】

   
2014 Majoor et al.; licensee BioMed Central Ltd.

【 图 表 】

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