Abstract
Asthmatic airways are inflamed and undergo remodelling. Inhaled corticosteroids and long-acting β2-agonist combinations are more effective than inhaled corticosteroid monotherapy in controlling disease exacerbations, but their effect on airway remodelling and inflammation remains ill-defined. This study evaluates the contribution of inhaled fluticasone and salmeterol, alone or combined, to the reversal of bronchial remodelling and inflammation. Severely asthmatic horses (6 horses/group) were treated with fluticasone, salmeterol, fluticasone/salmeterol, or with antigen avoidance for 12 weeks. Lung function, central and peripheral airway remodelling, and bronchoalveolar inflammation were assessed. Fluticasone/salmeterol and fluticasone monotherapy decreased peripheral airway smooth muscle remodelling after 12 weeks (p = 0.007 and p = 0.02, respectively). On average, a 30% decrease was observed with both treatments. In central airways, fluticasone/salmeterol reversed extracellular matrix remodelling after 12 weeks, both within the lamina propria (decreased thickness, p = 0.005) and within the smooth muscle layer (p = 0.004). Only fluticasone/salmeterol decreased bronchoalveolar neutrophilia (p = 0.03) to the same extent as antigen avoidance already after 8 weeks. In conclusion, this study shows that fluticasone/salmeterol combination decreases extracellular matrix remodelling in central airways and intraluminal neutrophilia. Fluticasone/salmeterol and fluticasone monotherapy equally reverse peripheral airway smooth muscle remodelling.
Highlights
Bronchial wall remodelling is a hallmark of asthma resulting from chronic inflammation and bronchospasm-induced mechanical stress[1, 2]
Airway remodelling is a hallmark of asthma affecting both the Airway smooth muscle (ASM) and the extracellular matrix (ECM) of peripheral and central bronchi, and its reversibility following treatment is a matter of debate[1]
Our study examined reversibility of peripheral ASM and ECM airway remodelling following administration of fluticasone, salmeterol, or their combination in an equine model of neutrophilic asthma
Summary
Bronchial wall remodelling is a hallmark of asthma resulting from chronic inflammation and bronchospasm-induced mechanical stress[1, 2]. Fluticasone/salmeterol reduced submucosal remodelling as indicated by EBUS at 12 weeks (Fig. 5b), concomitantly with a reduction of the ECM fraction of central ASM (Fig. 6c) and of the lamina propria thickness, which reacquired values similar to those reported in healthy horses[19] (Fig. 6d).
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call