Although asthma is often seen as an eosinophilic disease associated with atopy, patients with noneosinophilic asthma represent a substantial part of the population with asthma. To apply an unsupervised clustering method in a cohort of 588 patients with noneosinophilic asthma (sputum eosinophils < 3%) recruited from an asthma clinic of a secondary care center. Our cluster analysis of the whole cohort identified 2 subgroups as cluster 1 (n = 417) and cluster 2 (n = 171). Cluster 1 comprised a predominantly female group with late disease onset, a low proportion of atopy (24%), and a substantial smoking history (53%). In this cluster, treatment burden was low (<50% of inhaled corticosteroid users); asthma control and quality of life were poor, with median Asthma Control Test, Asthma Control Questionnaire, and Asthma Quality of Life scores of 16, 1.7, and 4.5, respectively, whereas lung function was preserved with a median postbronchodilation forced expiratory volume in 1 second of 93% predicted. Cluster 2 was a predominantly male group, almost exclusively comprising patients with atopy (99%) with early disease onset and a moderate treatment burden (median inhaled corticosteroids dose 800 µg/d equivalent beclomethasone). In cluster 2, asthma was partially controlled, with median Asthma Control Test and Asthma Control Questionnaire scores reaching 18 and 1.3, respectively, and lung function well preserved with a median postbronchodilation of 95% predicted. Although systemic and airway neutrophilic inflammation was the dominant pattern in cluster 1, cluster 2 essentially comprised paucigranulocytic asthma with moderately elevated fraction exhaled nitric oxide. Noneosinophilic asthma splits into 2 clusters distinguishing by disease onset, atopic status, smoking history, systemic and airway inflammation, and disease control and quality of life.

中文翻译：

---

非嗜酸性粒细胞性哮喘患者中 2 个集群的证据

尽管哮喘通常被视为与特应性相关的嗜酸性粒细胞疾病，但非嗜酸性粒细胞性哮喘患者占哮喘人群的很大一部分。对从二级护理中心的哮喘诊所招募的 588 名非嗜酸性粒细胞性哮喘（痰嗜酸性粒细胞 < 3%）患者进行队列应用无监督聚类方法。我们对整个队列进行聚类分析，确定了 2 个亚组：聚类 1 (n = 417) 和聚类 2 (n = 171)。第 1 组主要由女性群体组成，她们发病较晚，特应性比例较低（24%），并且有大量吸烟史（53%）。在该组中，治疗负担较低（吸入皮质类固醇使用者的比例<50%）；哮喘控制和生活质量较差，哮喘控制测试、哮喘控制问卷和哮喘生活质量评分中位数分别为 16、1.7 和 4.5，而肺功能保留，支气管扩张后 1 秒用力呼气量中位数93% 的人预测。第 2 组主要是男性群体，几乎全部由特应性患者 (99%) 组成，这些患者具有早期疾病发作和中等治疗负担（中位吸入皮质类固醇剂量为 800 µg/d 相当于倍氯米松）。在第二组中，哮喘得到部分控制，哮喘控制测试和哮喘控制问卷评分中位数分别达到 18 和 1.3，肺功能保存良好，预计支气管扩张后中位数为 95%。虽然全身性和气道中性粒细胞炎症是第 1 组的主要模式，但第 2 组主要包括少粒细胞性哮喘，呼出一氧化氮分数中度升高。非嗜酸性粒细胞性哮喘根据发病情况、特应性状态、吸烟史、全身和气道炎症、疾病控制和生活质量分为两类。