Department of Clinical Sciences, Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, Quebec, Canada.
Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, Milano, Italy.
PLoS One. 2020 Oct 22;15(10):e0239561. doi: 10.1371/journal.pone.0239561. eCollection 2020.
Pulmonary hypertension and cor pulmonale are complications of severe equine asthma, as a consequence of pulmonary hypoxic vasoconstriction. However, as pulmonary hypertension is only partially reversible by oxygen administration, other etiological factors are likely involved. In human chronic obstructive pulmonary disease, pulmonary artery remodeling contributes to the development of pulmonary hypertension. In rodent models, pulmonary vascular remodeling is present as a consequence of allergic airway inflammation. The present study investigated the presence of remodeling of the pulmonary arteries in severe equine asthma, its distribution throughout the lungs, and its reversibility following long-term antigen avoidance strategies and inhaled corticosteroid administration. Using histomorphometry, the total wall area of pulmonary arteries from different regions of the lungs of asthmatic horses and controls was measured. The smooth muscle mass of pulmonary arteries was also estimated on lung sections stained for α-smooth muscle actin. Reversibility of vascular changes in asthmatic horses was assessed after 1 year of antigen avoidance alone or treatment with inhaled fluticasone. Pulmonary arteries showed increased wall area in apical and caudodorsal lung regions of asthmatic horses in both exacerbation and remission. The pulmonary arteries smooth muscle mass was similarly increased. Both treatments reversed the increase in wall area. However, a trend for normalization of the vascular smooth muscle mass was observed only after treatment with antigen avoidance, but not with fluticasone. In conclusion, severe equine asthma is associated with remodeling of the pulmonary arteries consisting in an increased smooth muscle mass. The resulting narrowing of the artery lumen could enhance hypoxic vasoconstriction, contributing to pulmonary hypertension. In our study population, the antigen avoidance strategy appeared more promising than inhaled corticosteroids in controlling vascular remodeling. However, further studies are needed to support the reversibility of vascular smooth muscle mass remodeling after asthma treatment.
肺动脉高压和肺心病是严重马气喘的并发症,是由于肺缺氧性血管收缩引起的。然而,由于氧气治疗仅能部分逆转肺动脉高压,因此可能涉及其他病因。在人类慢性阻塞性肺疾病中,肺动脉重塑导致肺动脉高压的发展。在啮齿动物模型中,由于过敏性气道炎症,存在肺血管重塑。本研究调查了严重马气喘中肺动脉重塑的存在、其在肺部的分布以及长期抗原回避策略和吸入皮质类固醇治疗后的可逆转性。使用组织形态计量学,测量了来自气喘马和对照组肺部不同区域的肺动脉总壁面积。还通过对α-平滑肌肌动蛋白染色的肺切片估计了肺动脉平滑肌的质量。在单独进行抗原回避或用吸入氟替卡松治疗 1 年后,评估气喘马血管变化的可逆性。气喘马在急性发作和缓解期的肺尖和背侧肺区域的肺动脉均显示出壁面积增加。肺动脉平滑肌质量也相应增加。两种治疗均逆转了壁面积的增加。然而,仅在进行抗原回避治疗后,而不是在使用氟替卡松治疗后,才观察到血管平滑肌质量正常化的趋势。总之,严重马气喘与肺动脉重塑有关,表现为平滑肌质量增加。由此导致的动脉管腔变窄可能会增强缺氧性血管收缩,导致肺动脉高压。在我们的研究人群中,与吸入皮质类固醇相比,抗原回避策略在控制血管重塑方面似乎更有前景。然而,需要进一步的研究来支持气喘治疗后血管平滑肌质量重塑的可逆性。