Fachbereich Veterinärmedizin



    Charakterisierung der fibrinolytischen Aktivität in der bronchoalveolären Lavageflüssigkeit beim chronisch lungenkranken Pferd und der Einfluss einer inhalativen Glukokortikoidtherapie (2016)

    Wirth, Caroline Michaela Johanna (WE 17)
    Berlin: Mensch und Buch Verlag, 2016 — XVI, 235 Seiten
    ISBN: 978-3-86387-717-0
    URL (Volltext): http://www.diss.fu-berlin.de/diss/receive/FUDISS_thesis_000000102234
    Klinik für Pferde, allgemeine Chirurgie und Radiologie

    Oertzenweg 19 b
    14163 Berlin
    +49 30 838 62299

    Abstract / Zusammenfassung

    A main characteristic of chronic respiratory disease is the long-lasting and recurring inflammatory process in the small airways – resulting in fibrosis of the alveolar tissue and thus an irreversible loss of respiratory capacity. In various human respiratory diseases like bronchial asthma a pro-coagulatory and antifibrinolytic environment has been shown to cause progressive fibrosis.
    Observations from veterinary medicine hint at a comparable misbalance of the hemostasis in chronic airway diseases of the horse.

    The goal of this prospective clinical study including a healthy control group was to measure the fibrinolytic activity in the bronchoalveolar lavage fluid (BALF) of horses with chronic pulmonary disease and evaluate a possible pathogenetic association.
    Fibrinogen, D-dimers, plasminogen-activator-inhibitor-1 (PAI-1) and urokinase (u-PA) were to be examined in this study. Unfortunately, all tested assays for PAI-1 and u-PA showed unreliable and inconsistent results. In addition to the hemostatic parameters, serum-amyloid-A in the BALF was determined as an acute-phase protein. Furthermore, all parameters were examined regarding changes to an inhalative therapy with glucocorticoids and low-dust environment.
    In this clinical trial 61 horses were presented to the Equine clinic for surgery and radiology of the Freie Universität Berlin under stationary conditions and underwent a three day preparticipation examination including general and specific clinical examinations, venous and arterial blood gas analyses, exercise tests, interpleural pressure measurements, radiography of the thorax, endoscopic and cytologic examinations of BALF. The subjects were classified as “healthy controls“ (group 1, n=15), “COB in exacerbation“ (group 2, n=18), “IAD/COB in remission“ (group 3, n=14), “interstitial pneumopathy“ (group 4, n=11) and “acute/subacute pneumonia“ (group 5, n=3). Eight patients from group 2 and four patients from group 3 received a ten day inhalation therapy with the glucocorticoid budesonide (3 μg/kg BDW, bid) and were housed in a lowdust environment. A control examination largely identical to the preparticipation examination followed. Further laboratory analyses were conducted with the supernatant of the centrifuged BALF. Fibrinogen and D-dimers were determined on a fully-automatic analyzer using the immunoturbidimetric method. SAA was measured by the ELISA method. This quantitative analysis procedure was also intended to be applied for the examination of PAI-1 and u-PA, however, this turned out to not be technically feasible. The median of fibrinogen in patients with lung diseases was considerably higher than the one in healthy horses. Moreover, the healthy control group showed a significantly (p=.03) lower detectability of about 60%, compared to group 2 (“COB in exacerbation”), where fibrinogen concentrations could be measured in 94% of the cases. Thus, cases with a fibrinogen level above the determination limit of 0.001 g/l were eleven times more likely of being diagnosed “COB in exacerbation” than being classified as “healthy” (Exp(B)=11.33). Furthermore, there was a weak positive correlation (rs=.377; p=.004) between the fibrinogen content and the percentage of neutrophils in the BALF. D-dimers could be detected exclusively in patients with the diagnosis “COB in exacerbation”
    and “acute/subacute pneumonia”. The majority of these results could be obtained only subsequent to a protein enrichment procedure. There was a positive correlation (rs=.511; p=.03) between the amount of D-dimers and the average respiratory rate. SAA could not be detected in more than two thirds of the samples (67.2%), while the median was 0.05 μg/ml for both controls and affected horses. The therapeutic intervention resulted in a partial decrease of specifically the fibrinogen levels, but also the D-Dimer levels in the BALF. However, these differences could not be classified as significant.
    Due to a lack of appropriate testing methods to determine specific parameters of fibrinolysis, the aims of the presented study could only be reached in part. However, the observations reveal new insights for basic research in chronic respiratory diseases of the horse. The results allow the assumption that a misbalance in hemostasis accompanied by increased fibrin turnover plays a key role in the pathomechanism of equine pulmonary disease. Particularly with regard to irreversible alterations of lung tissue and persistent pulmonary function impairment, this research approach should be further pursued to reveal possible changes in fibrinolytic activity.