Ferrari Claudenir R, Cooley Jim, Mujahid Nisma, Costa Lais R, Wills Robert W, Johnson Melanie E, Swiderski Cyprianna E
1 Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, MS, USA.
2 Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA.
Vet Pathol. 2018 Jan;55(1):144-158. doi: 10.1177/0300985817741729.
Severe equine asthma, formerly recurrent airway obstruction (RAO), is the horse counterpart of human asthma, affecting horses maintained indoors in continental climates. Equine pasture asthma, formerly summer pasture RAO, is clinically similar but affects grazing horses during hot, humid conditions in the southeastern United States and United Kingdom. To advance translational relevance of equine pasture asthma to human asthma, histologic features of airway remodeling in human asthma were scored in lung lobes from 15 pasture asthma-affected and 9 control horses of mixed breeds. All noncartilaginous airways were scored using a standardized grading rubric (0-3) in hematoxylin and eosin (HE) and Movat's pentachrome-stained sections; 15 airways were chosen randomly from each lobe for analysis. Logistic regression identified disease, age, and lobe effects on probability of histologic outcomes. Airway smooth muscle (odds ratio [OR] = 2.5, P < .001), goblet cell hyperplasia/metaplasia (OR = 37.6, P < .0001), peribronchiolar elastic system fibers (OR = 4.2, P < .001), peribronchiolar fibrosis (OR = 3.8, P = .01), airway occlusion by mucus/inflammation (OR = 4.2, P = .04), and airway adventitial inflammation (OR = 3.0, P = .01) were significantly greater in diseased airways. A novel complex tissue disorganization, designated terminal bronchiolar remodeling, was overrepresented in diseased airways (OR = 3.7, P < .0001). Distribution of terminal bronchiolar remodeling corresponded to putative sites of air trapping in human asthma, at secondary pulmonary lobules. Age (>15 years) was an independent risk factor for increased peribronchiolar fibrosis, elastic system fibers, and terminal bronchiolar remodeling. Remodeling differed significantly between lung lobes, congruent with nonhomogeneous remodeling in human asthma. Equine pasture asthma recapitulates airway remodeling in human asthma in a manner not achieved in induced animal asthma models, endorsing its translational relevance for human asthma investigation.
严重马哮喘，以前称为复发性气道阻塞（RAO），是人类哮喘在马身上的对应病症，影响生活在大陆性气候室内环境中的马匹。马牧场哮喘，以前称为夏季牧场RAO，在临床上与之相似，但在美国东南部和英国炎热潮湿的条件下影响放牧的马匹。为了提高马牧场哮喘与人类哮喘的转化相关性，对15匹受牧场哮喘影响的混种马和9匹对照马的肺叶进行了人类哮喘气道重塑的组织学特征评分。在苏木精和伊红（HE）染色及莫瓦特五色染色切片中，使用标准化分级标准（0 - 3）对所有非软骨气道进行评分；从每个肺叶中随机选择15个气道进行分析。逻辑回归确定了疾病、年龄和肺叶对组织学结果概率的影响。患病气道中的气道平滑肌（优势比[OR]=2.5，P <.001）、杯状细胞增生/化生（OR = 37.6，P <.0001）、细支气管周围弹性系统纤维（OR = 4.2，P <.001）、细支气管周围纤维化（OR = 3.8，P =.01）、黏液/炎症导致的气道阻塞（OR = 4.2，P =.04）和气道外膜炎症（OR = 3.0，P =.01）明显更严重。一种新的复杂组织紊乱，称为终末细支气管重塑，在患病气道中过度存在（OR = 3.7，P <.0001）。终末细支气管重塑的分布与人类哮喘中推测的气体陷闭部位相对应，位于次级肺小叶。年龄（>15岁）是细支气管周围纤维化、弹性系统纤维和终末细支气管重塑增加的独立危险因素。肺叶之间的重塑差异显著，这与人类哮喘中不均匀的重塑一致。马牧场哮喘以诱导动物哮喘模型未达到的方式重现了人类哮喘中的气道重塑，支持了其在人类哮喘研究中的转化相关性。
