Background Cystic fibrosis (CF) is characterized by inflammation, progressive lung disease, and respiratory failure. Although the relationship is not well understood, patients with CF are thought to have a higher prevalence of asthma than the general population. CF Foundation (CFF) annual registry data in 2017 reported a prevalence of asthma in CF of 32%. It is difficult to differentiate asthma from CF given similarities in symptoms and reversible obstructive lung function in both diseases. However, a specific asthma phenotype (type 2 inflammatory signature), is often identified in CF patients and this would suggest potential responsiveness to biologics targeting this asthma phenotype. A type 2 inflammatory condition is defined by the presence of an interleukin (IL)-4high, IL-5high, IL-13high state and is suggested by the presence of an elevated total IgE, specific IgE sensitization, or an elevated absolute eosinophil count (AEC). In this manuscript we report the effects of using mepolizumab in patients with CF and type 2 inflammation. Results We present three patients with CF (63, 34 and 24 year of age) and personal history of asthma, who displayed significant eosinophilic inflammation and high total serum IgE concentrations (type 2 inflammation) who were treated with mepolizumab. All three patients were colonized with multiple organisms including Pseudomonas aeruginosa and Aspergillus fumigatus and tested positive for specific IgE to multiple allergens. We examined the effect of mepolizumab on patients' lung function (FEV1), blood markers of type 2 inflammation, systemic corticosteroid use and frequency of CF exacerbations. One patient had a substantial increase in lung function after starting mepolizumab and all three patients had a substantial benefit in regards to reduced oral CCS use. While none of the patients showed significant changes in the exacerbation rates there was markedly reduced requirements for oral CCS with exacerbations. In addition, mepolizumab had a positive effect on type 2 inflammatory markers, reducing markers of allergic inflammation in all 3 patients. Conclusions Mepolizumab appears to have a positive effect on clinical course in patients with CF presenting with a type 2 phenotype characterized by allergic sensitization and hyper-eosinophilia.

中文翻译：

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在患有囊性纤维化和嗜酸性粒细胞表型的成年患者中使用美泊利单抗：病例系列。

背景 囊性纤维化 (CF) 以炎症、进行性肺病和呼吸衰竭为特征。虽然这种关系尚不清楚，但人们认为 CF 患者的哮喘患病率高于普通人群。CF 基金会 (CFF) 2017 年的年度登记数据显示，CF 中哮喘的患病率为 32%。鉴于两种疾病的症状和可逆的阻塞性肺功能相似，很难区分哮喘和 CF。然而，特定的哮喘表型（2 型炎症特征）通常在 CF 患者中发现，这表明对针对这种哮喘表型的生物制剂的潜在反应。2 型炎症状态定义为存在白细胞介素 (IL)-4high、IL-5high、IL-13 处于高状态，并由总 IgE 升高、特异性 IgE 致敏或嗜酸性粒细胞绝对计数 (AEC) 升高提示。在这份手稿中，我们报告了使用美泊利单抗对 CF 和 2 型炎症患者的影响。结果 我们介绍了三名患有 CF（63、34 和 24 岁）和个人哮喘病史的患者，他们表现出显着的嗜酸性粒细胞炎症和高总血清 IgE 浓度（2 型炎症），他们接受了美泊利单抗治疗。所有三名患者都被多种生物定植，包括铜绿假单胞菌和烟曲霉，并且对多种过敏原的特异性 IgE 检测呈阳性。我们检查了美泊利单抗对患者肺功能 (FEV1)、2 型炎症的血液标志物、全身性皮质类固醇的使用和 CF 恶化的频率。一名患者在开始使用美泊利单抗后肺功能显着增加，所有三名患者在减少口服 CCS 使用方面都获得了显着益处。虽然没有患者表现出急性加重率的显着变化，但急性加重时对口服 CCS 的需求显着降低。此外，美泊利单抗对 2 型炎症标志物有积极作用，降低了所有 3 名患者的过敏性炎症标志物。结论美泊利单抗似乎对表现为过敏性致敏和嗜酸性粒细胞增多症的 2 型表型的 CF 患者的临床病程产生积极影响。一名患者在开始使用美泊利单抗后肺功能显着增加，所有三名患者在减少口服 CCS 使用方面都获得了显着益处。虽然没有患者表现出急性加重率的显着变化，但急性加重时对口服 CCS 的需求显着降低。此外，美泊利单抗对 2 型炎症标志物有积极作用，降低了所有 3 名患者的过敏性炎症标志物。结论美泊利单抗似乎对表现为过敏性致敏和嗜酸性粒细胞增多症的 2 型表型的 CF 患者的临床病程产生积极影响。一名患者在开始使用美泊利单抗后肺功能显着增加，所有三名患者在减少口服 CCS 使用方面都获得了显着益处。虽然没有患者表现出急性加重率的显着变化，但急性加重时对口服 CCS 的需求显着降低。此外，美泊利单抗对 2 型炎症标志物有积极作用，降低了所有 3 名患者的过敏性炎症标志物。结论美泊利单抗似乎对表现为过敏性致敏和嗜酸性粒细胞增多症的 2 型表型的 CF 患者的临床病程产生积极影响。mepolizumab 对 2 型炎症标志物具有积极作用，降低了所有 3 名患者的过敏性炎症标志物。结论美泊利单抗似乎对表现为过敏性致敏和嗜酸性粒细胞增多症的 2 型表型的 CF 患者的临床病程产生积极影响。mepolizumab 对 2 型炎症标志物具有积极作用，降低了所有 3 名患者的过敏性炎症标志物。结论美泊利单抗似乎对表现为过敏性致敏和嗜酸性粒细胞增多症的 2 型表型的 CF 患者的临床病程产生积极影响。