Sasaki Hisashi, Miyata Jun, Irie Akiko, Kuwata Ayako, Kouzaki Yuji, Ueki Shigeharu, Kawana Akihiko
Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan.
Department of Internal Medicine, Japan Self-Defense Forces Central Hospital, Tokyo, Japan.
Front Pharmacol. 2022 Jan 13;12:826790. doi: 10.3389/fphar.2021.826790. eCollection 2021.
Eosinophilic bronchiolitis is a rare allergic disorder caused by eosinophilic inflammation in the bronchioles of the lungs. An effective treatment strategy is needed in cases resistant to steroids. However, its pathophysiology remains unclear owing to the limited number of cases. We herein present the case of a 31-year-old man who experienced eosinophilic bronchiolitis with eosinophil ETosis (EETosis) in the mucus plugs. The patient was diagnosed with asthma. His respiratory symptoms worsened with eosinophilia when treated with the standard asthma regimen, including inhaled corticosteroids, long-acting β2-agonist, long-acting muscarinic antagonist, and leukotriene receptor antagonist. Chest computed tomography revealed bronchial wall thickening and centrilobular nodules in the lower lobes of both lungs. Bronchoscopy showed obstruction of the subsegmental bronchus with mucus plugs. Histological analysis demonstrated abundant eosinophils in the mucus plugs. Cytolytic eosinophils together with Charcot-Leyden crystal formations and deposition of major basic proteins were also observed, indicating the occurrence of EETosis. Introduction of benralizumab, an anti-interleukin-5 receptor α antibody, successfully controlled the patient's condition and reduced the amount of systemic corticosteroids administered. Our findings confirm that this antibody strongly decreases airway eosinophils in patients with severe asthma. Thus, benralizumab might be an optimal therapeutic agent for the treatment of mucus plug-forming and/or EETosis-occurring eosinophilic lung diseases, including eosinophilic bronchiolitis.
嗜酸性粒细胞性细支气管炎是一种罕见的过敏性疾病,由肺部细支气管的嗜酸性粒细胞炎症引起。对于对类固醇耐药的病例,需要一种有效的治疗策略。然而,由于病例数量有限,其病理生理学仍不清楚。我们在此报告一例31岁男性,其患有嗜酸性粒细胞性细支气管炎,在黏液栓中出现了嗜酸性粒细胞脱颗粒(EETosis)。该患者被诊断为哮喘。当采用包括吸入性糖皮质激素、长效β2受体激动剂、长效毒蕈碱拮抗剂和白三烯受体拮抗剂在内的标准哮喘治疗方案时,他的呼吸道症状随着嗜酸性粒细胞增多而恶化。胸部计算机断层扫描显示两肺下叶支气管壁增厚和小叶中心结节。支气管镜检查显示亚段支气管被黏液栓阻塞。组织学分析表明黏液栓中有大量嗜酸性粒细胞。还观察到细胞溶解性嗜酸性粒细胞以及夏科-莱登结晶形成和主要碱性蛋白沉积,表明发生了EETosis。引入抗白细胞介素-5受体α抗体贝那利珠单抗成功控制了患者的病情,并减少了全身糖皮质激素的给药量。我们的研究结果证实,这种抗体能显著减少重度哮喘患者气道中的嗜酸性粒细胞。因此,贝那利珠单抗可能是治疗包括嗜酸性粒细胞性细支气管炎在内的黏液栓形成和/或发生EETosis的嗜酸性粒细胞性肺部疾病的最佳治疗药物。