Airway Disease Section, Department of Otorhinolaryngology, Kansai Medical University, Osaka, Japan.
Allergy Center, Kansai Medical University Hospital, Osaka, Japan.
Front Immunol. 2018 Sep 25;9:2192. doi: 10.3389/fimmu.2018.02192. eCollection 2018.
Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis with nasal polyps in Japanese. ECRS highly associated with asthma is a refractory eosinophilic airway inflammation and requires comprehensive care as part of the united airway concept. We recently reported a series of ECRS patients with asthma treated with fine-particle inhaled corticosteroid (ICS) exhalation through the nose (ETN). To evaluate fine-particle ICS ETN treatment as a potential therapeutic option in ECRS with asthma. Twenty-three patients with severe ECRS under refractory to intranasal corticosteroid treatment were randomized in a double-blind fashion to receive either HFA-134a-beclomethasone dipropionate (HFA-BDP) metered-dose inhaler (MDI) ETN ( = 11) or placebo MDI ETN ( = 12) for 4 weeks. Changes in nasal polyp score, computed tomographic (CT) score, smell test, and quality of life (QOL) score from baseline were assessed. Fractionated exhaled nitric oxide (FENO) was measured as a marker of eosinophilic airway inflammation. Response to corticosteroids was evaluated before and after treatment. Additionally, deposition of fine-particles was visualized using a particle deposition model. To examine the role of eosinophils on airway inflammation, BEAS-2B human bronchial epithelial cells were co-incubated with purified eosinophils to determine corticosteroid sensitivity. HFA-BDP MDI ETN treatment improved all assessed clinical endpoints and corticosteroid sensitivity without any deterioration in pulmonary function. FENO and blood eosinophil number were reduced by HFA-BDP MDI ETN treatment. The visualization study suggested that ETN at expiratory flow rates of 10-30 L/min led to fine particle deposition in the middle meatus, including the sinus ostia. Co-incubation of eosinophils with BEAS-2B cells induced corticosteroid resistance. Additional HFA-BDP MDI ETN treatment was beneficial in patients with ECRS and should be considered as a potential therapeutic option for eosinophilic airway inflammation such as ECRS with asthma. (UMIN-CTR: R000019325) (http://www.umin.ac.jp/ctr/index.htm).
嗜酸粒细胞性慢性鼻-鼻窦炎(ECRS)是日本伴鼻息肉的慢性鼻-鼻窦炎的一个亚型。与哮喘密切相关的 ECRS 是一种难治性嗜酸性气道炎症,需要作为联合气道概念的一部分进行综合护理。我们最近报道了一系列伴哮喘的 ECRS 患者接受经鼻细颗粒吸入皮质类固醇(ICS)呼气治疗(ETN)。为了评估细颗粒 ICS ETN 治疗作为伴哮喘的 ECRS 的潜在治疗选择。23 例对鼻内皮质类固醇治疗难治的重度 ECRS 患者随机分为两组,接受 HFA-134a-丙酸倍氯米松(HFA-BDP)定量气雾剂(MDI)ETN(n = 11)或安慰剂 MDI ETN(n = 12)治疗 4 周。从基线评估鼻息肉评分、计算机断层扫描(CT)评分、嗅觉测试和生活质量(QOL)评分的变化。用分段呼出一氧化氮(FENO)作为嗜酸性气道炎症的标志物进行测量。在治疗前后评估对皮质类固醇的反应。此外,使用颗粒沉积模型观察细颗粒的沉积。为了研究嗜酸性粒细胞在气道炎症中的作用,将 BEAS-2B 人支气管上皮细胞与纯化的嗜酸性粒细胞共孵育,以确定皮质类固醇敏感性。HFA-BDP MDI ETN 治疗改善了所有评估的临床终点和皮质类固醇敏感性,而没有任何肺功能恶化。HFA-BDP MDI ETN 治疗降低了 FENO 和血嗜酸性粒细胞数。可视化研究表明,在 10-30 L/min 的呼气流量下,ETN 导致中鼻甲和窦口的细颗粒沉积。嗜酸性粒细胞与 BEAS-2B 细胞共孵育诱导了皮质类固醇耐药性。额外的 HFA-BDP MDI ETN 治疗对 ECRS 患者有益,应被视为伴哮喘的嗜酸粒细胞性气道炎症(如 ECRS)的潜在治疗选择。(UMIN-CTR:R000019325)(http://www.umin.ac.jp/ctr/index.htm)。