Isolated airways in equine respiratory pharmacology: They never lie

Abstract

Pre-clinical studies on human isolated bronchi have relevant translational value in human in vivo, conversely no investigation has been performed to assess whether data resulting from equine isolated airways can have any translational application in asthmatic horses. Thus, a meta-regression analysis via random-effect method was carried out to correlate the pharmacological characteristics of bronchodilators resulting from experiments performed in equine isolated bronchi with their impact on the lung function outcomes in asthmatic horses. Data on the potency of different bronchodilators were extracted from four ex vivo studies involving 68 horses, and related with the maximum change in transpulmonary pressure (ΔPplmax), pulmonary resistance (RL), and dynamic lung compliance (Cdyn) resulting from the meta-analysis of clinical trials aimed to assess the effect of different bronchodilator classes, namely antimuscarinic agents and β2-adrenoreceptor (β2-AR) agonists, on lung function of asthmatic horses. The potency (pEC50) detected in equine isolated bronchi for each specific bronchodilator did not significantly (P > 0.05) influence the bronchorelaxant effect resulting from clinical trials. RL was characterized by a flatter meta-regression line (slope 0.01, 95%CI -0.25 – 0.28) with respect to ΔPplmax (slope 0.90, 95%CI -4.06 – 2.26) and Cdyn (slope 0.09, 95%CI -0.21 – 0.04). The quality of evidence was moderate for RL and ΔPplmax and low for Cdyn. This quantitative synthesis provides the indirect evidence that pre-clinical investigations performed by using equine isolated airways may produce useful data to predict the impact of bronchodilators on the RL of asthmatic horses. Further translational studies are needed to directly confirm the results of this research.