PDF(Pubmed)
Abstract：
Background: Severe asthma often remains uncontrolled despite optimized inhaled treatment. The rise of biologic therapy in severe asthma represented a major advance for the disease management. However, correct phenotyping and monitoring of severe asthma patients is key to the success of targeted biologic therapy. Materials and Methods: We present the case of a 63-year-old female, never a smoker, diagnosed with asthma at the age of 45 and associated persistent mild rhinitis, without other notable comorbidities. She was prescribed medium-dose ICS/LABA, administered inconstantly in the first years after the diagnosis, with poor overall control of the disease. After several exacerbation episodes, treatment compliance improved, but the control of the disease remained poor despite adding an antileukotriene. In January 2019, she presented an exacerbation episode requiring treatment with oral corticosteroids (OCS) and she was afterwards put on high-dose ICS/LABA and continued the antileukotriene. She was referred for a skin allergy test, which revealed mild sensitization to Dermatophagoides pteronyssinus and farinae, with a total IgE level of 48.3 IU/mL. The blood eosinophil level was 270 cells/mm3. The lung function was variable, going from mild impairment to severe fixed obstruction during exacerbations. Despite optimized inhaled treatment, good adherence and inhaler technique, and allergen avoidance strategies, asthma control was not achieved, and she continued to experience severe episodes of exacerbation requiring OCS. Results: In October 2019, she was initiated on biologic therapy with omalizumab, which allowed asthma control to be achieved and maintained for 18 months, with preserved lung function, good symptom control, no exacerbations and slightly elevated blood eosinophil level (340-360 cells/mm3). In April 2021, she started experiencing exacerbation episodes requiring OCS (three episodes within 6 months), with a progressive increase in blood eosinophil level (up to 710 cells/mm3), and progressive deterioration of asthma control and lung function, despite continuation of previous therapy. A specific IgE test against Aspergillus was negative, and total IgE level was 122.4 IU/mL. In December 2021, the patient was switched from omalizumab to benralizumab. Asthma control was again achieved, lung function improved significantly and the patient did not experience any other exacerbation episodes up until today, which allowed for a reduction in ICS dose. Intriguingly, a relapsing eosinophilia was also noted under anti-IL5-R treatment prior to the dose administration, but with preserved asthma control. Conclusions: This case underscores the pivotal role of meticulous phenotyping in severe asthma management on one side, and careful monitoring of patient evolution and possible side effects of treatment on the other side. By showcasing how diverse inflammatory pathways can coexist within a single patient and impact treatment outcomes, it highlights the necessity of tailored biologic therapy for sustained control.
摘要：
背景：尽管优化了吸入治疗，但重度哮喘通常仍未得到控制。严重哮喘中生物治疗的兴起代表了疾病管理的重大进展。然而,对重症哮喘患者进行正确的表型鉴定和监测是靶向生物治疗成功的关键.材料和方法：我们介绍了一名63岁的女性，从不吸烟，在45岁时被诊断出患有哮喘和相关的持续性轻度鼻炎，没有其他明显的合并症。给她开了中等剂量的ICS/LABA,在诊断后的头几年不连续给药，对疾病的总体控制不佳。在经历了几次恶化之后,治疗依从性提高，但是，尽管添加了抗白三烯，这种疾病的控制仍然很差。2019年1月，她出现了恶化发作，需要口服皮质类固醇（OCS）治疗，随后接受了大剂量ICS/LABA治疗，并继续使用抗白三烯。她被推荐做皮肤过敏测试，显示对翼状细胞和粉刺的轻度敏感，总IgE水平为48.3IU/mL。血液嗜酸性粒细胞水平为270细胞/mm3。肺功能是可变的，恶化期间从轻度损伤到严重的固定梗阻。尽管优化了吸入治疗，良好的依从性和吸入器技术，和避免过敏原的策略，哮喘没有得到控制，并且她继续经历需要OCS的严重加重发作。结果：2019年10月，她开始接受奥马珠单抗的生物治疗，这使得哮喘控制得以实现并维持18个月，具有保留的肺功能，良好的症状控制，没有恶化和血液嗜酸性粒细胞水平略有升高（340-360细胞/mm3）。2021年4月，她开始经历需要OCS的恶化发作（6个月内发作3次），随着血液嗜酸性粒细胞水平的逐渐增加（高达710个细胞/mm3），哮喘控制和肺功能的进行性恶化，尽管继续以前的治疗。针对曲霉的特异性IgE测试为阴性，总IgE水平为122.4IU/mL。2021年12月，患者从奥马珠单抗转为贝那利珠单抗。哮喘再次得到控制，肺功能明显改善，直到今天，患者没有经历任何其他加重发作，这允许减少ICS剂量。有趣的是，在给药前，在抗IL5-R治疗下也注意到复发性嗜酸性粒细胞增多，但保持哮喘控制。结论：本病例一方面强调了细致的表型在重症哮喘管理中的关键作用，并仔细监测患者的进展和治疗的可能副作用。通过展示不同的炎症途径如何在单个患者中共存并影响治疗结果，它强调了为持续控制量身定制的生物治疗的必要性。
