在ATLANTIS队列中通过聚类分析识别不同的哮喘表型
2026/02/02
摘要
背景：既往的聚类分析已识别出哮喘的不同亚组。然而，仅有少数研究纳入了小气道功能障碍（SAD）的参数，或反映潜在疾病机制的基因表达谱。我们旨在利用ATLANTIS研究（该研究主要关注识别哮喘中SAD的患病率及其在哮喘控制、急性加重和生活质量中的作用）的现有数据，识别临床上不同的哮喘表型，超越GINA哮喘严重程度分级。
方法：ATLANTIS研究纳入了773名哮喘患者（平均年龄44岁，58%为女性，76%从不吸烟，GINA分级1-5级）。对受试者进行了全面评估，包括症状、大小气道功能障碍参数、血液和痰液细胞分类计数，以及鼻拭子全基因组基因表达谱分析。使用自组织映射-Ward方法生成聚类。
结果：识别出四个不同的聚类：A类（N = 62；8%）：特征为最频繁的急性加重、较低的支气管扩张剂后FEV1占预计值百分比、较多的小气道功能障碍、较高的痰液和血液嗜酸性粒细胞计数，以及高表达的哮喘相关基因。B类（N = 206；27%）：由具有早发性哮喘、症状未控制、肺功能和支气管高反应性正常，同时鼻上皮中哮喘相关基因高表达的特应性患者组成。C类（N = 277；36%）：主要为男性既往吸烟者，哮喘控制良好，有轻度阻塞性肺疾病，中性粒细胞水平相对较高。D类（N = 228；29%）：肺功能正常，血液和痰液嗜酸性粒细胞计数低。
结论：识别出四个不同的聚类，其中SAD的存在与高水平的2型炎症、较低的肺功能和频繁的急性加重相关。SAD可能是哮喘控制不佳的一个标志，应被视为一项重要的临床特征。
Cluster Analysis to Identify Distinct Asthma Phenotypes in the ATLANTIS Cohort
P. J. M. Kuks, T. Karp, J. E. Hartman, M. Kraft, S. Siddiqui, L. M. Fabbri, et al.
Abstract
BACKGROUND:Previous cluster analyses have identified subgroups of asthma. However, only a few studies included parameters of small airways dysfunction (SAD), or gene expression profiles reflecting underlying disease mechanisms. We aimed to identify clinically distinct asthma phenotypes, beyond GINA asthma severity, using available data from the ATLANTIS study which focused on identifying the prevalence of SAD in asthma and its role in asthma control, exacerbations and quality of life.
METHODS:The ATLANTIS study included 773 asthma patients (mean age 44 years, 58% female, 76% never-smoker, GINA 1-5). Subjects were extensively characterized, including symptoms, parameters of large and small airways dysfunction, blood and sputum differential cell counts, and genome-wide gene expression profiling from nasal brushes. Clusters were generated using the Self-Organizing Map-Ward's method.
RESULTS: Four distinct clusters were identified: A (N = 62; 8%) characterized by the most frequent exacerbations, lower post-bronchodilator FEV1 % predicted, more small airways dysfunction, higher sputum and blood eosinophils, and high expression of asthma-related genes. B (N = 206; 27%) consisting of atopic patients with early-onset asthma, uncontrolled symptoms, and normal lung function and bronchial hyperresponsiveness, along with a high expression of asthma-related genes in the nasal epithelium. C (N = 277; 36%), predominantly male former smokers, with well-controlled asthma, mild obstructive lung disease, and relatively high neutrophil levels. D (N = 228; 29%), with normal lung function and low blood and sputum eosinophils.
CONCLUSION:Four distinct clusters were identified, where the presence of SAD was associated with high type-2 inflammation, lower lung function, and frequent exacerbations. SAD may be a marker of poorly controlled asthma and should be considered as an important clinical trait.
背景：既往的聚类分析已识别出哮喘的不同亚组。然而，仅有少数研究纳入了小气道功能障碍（SAD）的参数，或反映潜在疾病机制的基因表达谱。我们旨在利用ATLANTIS研究（该研究主要关注识别哮喘中SAD的患病率及其在哮喘控制、急性加重和生活质量中的作用）的现有数据，识别临床上不同的哮喘表型，超越GINA哮喘严重程度分级。
方法：ATLANTIS研究纳入了773名哮喘患者（平均年龄44岁，58%为女性，76%从不吸烟，GINA分级1-5级）。对受试者进行了全面评估，包括症状、大小气道功能障碍参数、血液和痰液细胞分类计数，以及鼻拭子全基因组基因表达谱分析。使用自组织映射-Ward方法生成聚类。
结果：识别出四个不同的聚类：A类（N = 62；8%）：特征为最频繁的急性加重、较低的支气管扩张剂后FEV1占预计值百分比、较多的小气道功能障碍、较高的痰液和血液嗜酸性粒细胞计数，以及高表达的哮喘相关基因。B类（N = 206；27%）：由具有早发性哮喘、症状未控制、肺功能和支气管高反应性正常，同时鼻上皮中哮喘相关基因高表达的特应性患者组成。C类（N = 277；36%）：主要为男性既往吸烟者，哮喘控制良好，有轻度阻塞性肺疾病，中性粒细胞水平相对较高。D类（N = 228；29%）：肺功能正常，血液和痰液嗜酸性粒细胞计数低。
结论：识别出四个不同的聚类，其中SAD的存在与高水平的2型炎症、较低的肺功能和频繁的急性加重相关。SAD可能是哮喘控制不佳的一个标志，应被视为一项重要的临床特征。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Allergy. 2026 Jan;81(1):185-196.DOI: 10.1111/all.70127.）
（Allergy. 2026 Jan;81(1):185-196.DOI: 10.1111/all.70127.）
Cluster Analysis to Identify Distinct Asthma Phenotypes in the ATLANTIS Cohort
P. J. M. Kuks, T. Karp, J. E. Hartman, M. Kraft, S. Siddiqui, L. M. Fabbri, et al.
Abstract
BACKGROUND:Previous cluster analyses have identified subgroups of asthma. However, only a few studies included parameters of small airways dysfunction (SAD), or gene expression profiles reflecting underlying disease mechanisms. We aimed to identify clinically distinct asthma phenotypes, beyond GINA asthma severity, using available data from the ATLANTIS study which focused on identifying the prevalence of SAD in asthma and its role in asthma control, exacerbations and quality of life.
METHODS:The ATLANTIS study included 773 asthma patients (mean age 44 years, 58% female, 76% never-smoker, GINA 1-5). Subjects were extensively characterized, including symptoms, parameters of large and small airways dysfunction, blood and sputum differential cell counts, and genome-wide gene expression profiling from nasal brushes. Clusters were generated using the Self-Organizing Map-Ward's method.
RESULTS: Four distinct clusters were identified: A (N = 62; 8%) characterized by the most frequent exacerbations, lower post-bronchodilator FEV1 % predicted, more small airways dysfunction, higher sputum and blood eosinophils, and high expression of asthma-related genes. B (N = 206; 27%) consisting of atopic patients with early-onset asthma, uncontrolled symptoms, and normal lung function and bronchial hyperresponsiveness, along with a high expression of asthma-related genes in the nasal epithelium. C (N = 277; 36%), predominantly male former smokers, with well-controlled asthma, mild obstructive lung disease, and relatively high neutrophil levels. D (N = 228; 29%), with normal lung function and low blood and sputum eosinophils.
CONCLUSION:Four distinct clusters were identified, where the presence of SAD was associated with high type-2 inflammation, lower lung function, and frequent exacerbations. SAD may be a marker of poorly controlled asthma and should be considered as an important clinical trait.
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