Department of Respiratory Medicine, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Frederiksberg, Denmark.
J Allergy Clin Immunol Pract. 2021 Nov;9(11):4029-4036.e2. doi: 10.1016/j.jaip.2021.07.021. Epub 2021 Jul 28.
Patients with asthma are heterogeneous in clinical presentation and in response to treatment. Despite this, tools to guide treatment are limited and include mainly measures of eosinophilic inflammation and symptoms. Airway hyperresponsiveness (AHR) to mannitol is present in patients across inflammatory phenotypes and improve with inhaled corticosteroids.
To investigate whether measuring AHR to mannitol in addition to eosinophilic inflammation and symptoms adds information to the phenotypic characterization of patients with asthma.
A total of 317 patients with asthma from 6 different cohorts were included in the analysis. All patients had measures of AHR to mannitol, blood eosinophils, and Asthma Control Questionnaire 5 available. A cluster analysis using Ward minimum variance method was performed. The distribution of fraction of exhaled nitric oxide, immunoglobulin E, lung function, induced sputum inflammatory cell count, age of onset, and severity of disease was compared between clusters.
Four clusters were identified. Three of the clusters had proportionate levels of AHR, eosinophilic inflammation, and symptoms, but 1 cluster presented with low levels of eosinophilic inflammation and a significant symptom burden. Half of the subjects in this cluster presented with AHR to inhaled mannitol. Lung function, fraction of exhaled nitric oxide, body mass index, and immunoglobulin E were normal.
Information on AHR to mannitol in addition to blood eosinophils and symptoms identifies a subgroup of asthma patients with symptomatic, noneosinophilic disease. Airway hyperresponsiveness to mannitol may provide a treatable trait in a subgroup of patients with noneosinophilic asthma.
哮喘患者在临床表现和治疗反应方面存在异质性。尽管如此，指导治疗的工具仍然有限，主要包括嗜酸性粒细胞炎症和症状的测量。甘露醇诱导的气道高反应性（AHR）存在于各种炎症表型的患者中，并可通过吸入皮质类固醇改善。
研究在评估嗜酸性粒细胞炎症和症状的基础上，测量甘露醇诱导的 AHR 是否能为哮喘患者的表型特征提供更多信息。
共纳入来自 6 个不同队列的 317 例哮喘患者进行分析。所有患者均有甘露醇诱导的 AHR、血嗜酸性粒细胞计数和哮喘控制问卷 5 项（ACQ-5）的测量结果。采用 Ward 最小方差法进行聚类分析。比较不同聚类组间呼出气一氧化氮分数、免疫球蛋白 E、肺功能、诱导痰炎症细胞计数、发病年龄和疾病严重程度的分布。
共识别出 4 个聚类。其中 3 个聚类的 AHR、嗜酸性粒细胞炎症和症状水平相当，但 1 个聚类表现为低水平的嗜酸性粒细胞炎症和显著的症状负担。该聚类组中约一半的患者对吸入性甘露醇有 AHR。肺功能、呼出气一氧化氮分数、体重指数和免疫球蛋白 E 均正常。
除血液嗜酸性粒细胞和症状外，甘露醇诱导的 AHR 信息可识别出具有症状性非嗜酸性粒细胞疾病的哮喘患者亚组。甘露醇诱导的气道高反应性可能为非嗜酸性粒细胞哮喘患者的亚组提供一种可治疗的特征。
