Azim Adnan, Newell Colin, Barber Clair, Harvey Matthew, Knight Deborah, Freeman Anna, Fong Wei Chern Gavin, Dennison Paddy, Haitchi Hans Michael, Djukanovic Ratko, Kurukulaaratchy Ramesh, Howarth Peter
Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
National Institute for Health Research (NIHR) Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Clin Exp Allergy. 2021 Jun;51(6):811-820. doi: 10.1111/cea.13841. Epub 2021 Feb 18.
Blood eosinophil measurement is essential for the phenotypic characterization of patients with difficult asthma and in determining eligibility for anti-IL-5/IL-5Rα biological therapies. However, assessing such measures over limited time spans may not reveal the true underlying eosinophilic phenotype, as treatment, including daily oral corticosteroid therapy, suppresses eosinophilic inflammation and asthma is intrinsically variable.
We interrogated the electronic healthcare records of patients in the Wessex AsThma CoHort of difficult asthma (WATCH) study (UK). In 501 patients being evaluated in this tertiary care centre for difficult to control asthma, all requested full blood count test results in a 10-year retrospective period from the index WATCH assessment were investigated (n = 11,176).
In 235 biological therapy-naïve participants who had 10 or more measures in this time period, 40.3% were eosinophilic (blood eosinophils ≥300 cells/µl) at WATCH enrolment whilst an additional 43.1%, though not eosinophilic at enrolment, demonstrated eosinophilia at least once in the preceding decade. Persistent eosinophilia was associated with worse post-bronchodilator airway obstruction and higher Fractional exhaled Nitric Oxide (FeNO). In contrast, the 16.6% of patients who never demonstrated eosinophilia at this blood eosinophil threshold showed preserved lung function and lower markers of Type 2 inflammation.
This highlights the central role that type 2 inflammation, as indicated by blood eosinophilia, has in difficult asthma and suggests that longitudinal electronic healthcare record analysis can be an important tool in clinical asthma phenotyping, providing insight that may help understand disease progression and better guide more specific treatment approaches.
血液嗜酸性粒细胞测量对于难治性哮喘患者的表型特征分析以及确定抗白细胞介素-5/白细胞介素-5受体α生物疗法的适用性至关重要。然而，在有限的时间跨度内评估此类指标可能无法揭示真正潜在的嗜酸性粒细胞表型，因为包括每日口服糖皮质激素治疗在内的治疗会抑制嗜酸性粒细胞炎症，且哮喘本身具有变异性。
我们查阅了英国韦塞克斯哮喘队列研究（WATCH）中难治性哮喘患者的电子医疗记录。在该三级医疗中心接受评估的501例难以控制哮喘的患者中，调查了自索引WATCH评估起10年回顾期内所有要求的全血细胞计数检测结果（n = 11176）。
在该时间段内有10次或更多测量值的235例未接受生物疗法的参与者中，40.3%在WATCH入组时为嗜酸性粒细胞增多（血液嗜酸性粒细胞≥300个细胞/微升），而另外43.1%尽管在入组时不是嗜酸性粒细胞增多，但在之前十年中至少有一次出现嗜酸性粒细胞增多。持续性嗜酸性粒细胞增多与支气管扩张剂后气道阻塞加重和呼出一氧化氮分数（FeNO）升高相关。相比之下，在该血液嗜酸性粒细胞阈值从未出现嗜酸性粒细胞增多的患者中，16.6%的患者肺功能保持良好，2型炎症标志物较低。
这突出了血液嗜酸性粒细胞增多所表明的2型炎症在难治性哮喘中的核心作用，并表明纵向电子医疗记录分析可成为临床哮喘表型分析的重要工具，提供有助于理解疾病进展并更好地指导更具体治疗方法的见解。
