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.

TRIAL REGISTRATION:

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

• Authors: Christof J Majoor, Marianne A van de Pol, Pieter Willem Kamphuisen, Joost C M Meijers, Richard Molenkamp, Katja C Wolthers, Tom van der Poll, Rienk Nieuwland, Sebastian L Johnston, Peter J Sterk, Elisabeth H D Bel, Rene Lutter, Koenraad F van der Sluijs
• Journal: Respiratory research (Respir Res) Vol. 15 Pg. 14 (Feb 07 2014) ISSN: 1465-993X [Electronic] England
• PMID: 24502801 (Publication Type: Clinical Trial, Journal Article, Observational Study, Research Support, Non-U.S. Gov't)

Topics

• Adult
• Asthma (diagnosis, metabolism, virology)
• Blood Coagulation (physiology)
• Female
• Hemostasis (physiology)
• Humans
• Male
• Picornaviridae Infections (diagnosis, metabolism, virology)
• Rhinovirus
• Young Adult