肺功能波动模式揭示与2型炎症无关的哮喘与COPD表型
2021/05/19
摘要
背景：在所有慢性气道疾病中，气道功能的动力学受到潜在的气道炎症和支气管高反应性的影响，同时由于气道和肺的重塑以及粘液堵塞导致其可逆性受限。每个组分的相对贡献转化为具体的临床症状模式、生活质量、急性发作风险和治疗。
目的：本研究旨在评估根据肺功能波动模式对阻塞性气道疾病患者进行分组能否鉴别出具有明显临床特征的特定表型。
方法：纳入134例来自欧洲BIOAIR队列的轻中度哮喘、重症哮喘或COPD患者，采用基于波动数据的聚类分析（Fluctuation-based clustering，FBC）的新方法，根据1年内记录的每天2次的FEV1值对患者进行聚类。
结果：FBC将患者分为与临床诊断无关的4个类簇，其肺功能的波动程度逐渐增加，与临床严重程度、急性发作风险增加以及生活质量降低相对应。鉴定出特定的气道疾病患者，这些患者的生物标志物与气道重塑（骨粘连蛋白）和细胞衰老（纤溶酶原激活物抑制剂-1）有关，并伴有气道可逆性下降、肺过度充气和弥散能力下降。此4个类簇在研究期间均保持稳定，且2型炎症标志物（血嗜酸粒细胞和骨膜蛋白）没有差异。
结论：基于FBC的表型分析提供了额外的信息，这种信息可补充临床诊断，且与嗜酸粒细胞炎症无关，从而识别出可能从特定的治疗策略或密切监测中受益的患者。
Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation
Delgado-Eckert E, James A, Meier-Girard D, Kupczyk M, Andersson LI, Bossios A, Mikus M, Ono J, Izuhara K, Middelveld R, Dahlén B, Gaga M, Siafakas NM, Papi A, Beghe B, Joos G, Rabe KF, Sterk PJ, Bel EH, Johnston SL, Chanez P, Gjomarkaj M, Howarth PH, Niżankowska-Mogilnicka E, Dahlén SE, Frey U
J Allergy Clin Immunol; 2021 Feb 3; S0091-6749(21)00162-7.
Abstract
Background: In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success.
Objective: We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics.
Methods: We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort.
Results: Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin).
Conclusions: FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.
背景：在所有慢性气道疾病中，气道功能的动力学受到潜在的气道炎症和支气管高反应性的影响，同时由于气道和肺的重塑以及粘液堵塞导致其可逆性受限。每个组分的相对贡献转化为具体的临床症状模式、生活质量、急性发作风险和治疗。
目的：本研究旨在评估根据肺功能波动模式对阻塞性气道疾病患者进行分组能否鉴别出具有明显临床特征的特定表型。
方法：纳入134例来自欧洲BIOAIR队列的轻中度哮喘、重症哮喘或COPD患者，采用基于波动数据的聚类分析（Fluctuation-based clustering，FBC）的新方法，根据1年内记录的每天2次的FEV1值对患者进行聚类。
结果：FBC将患者分为与临床诊断无关的4个类簇，其肺功能的波动程度逐渐增加，与临床严重程度、急性发作风险增加以及生活质量降低相对应。鉴定出特定的气道疾病患者，这些患者的生物标志物与气道重塑（骨粘连蛋白）和细胞衰老（纤溶酶原激活物抑制剂-1）有关，并伴有气道可逆性下降、肺过度充气和弥散能力下降。此4个类簇在研究期间均保持稳定，且2型炎症标志物（血嗜酸粒细胞和骨膜蛋白）没有差异。
结论：基于FBC的表型分析提供了额外的信息，这种信息可补充临床诊断，且与嗜酸粒细胞炎症无关，从而识别出可能从特定的治疗策略或密切监测中受益的患者。
(王霁1 张欣2 张红萍2 王刚1、3四川大学华西医院中西医结合科呼吸病组 610041 摘译)
（J Allergy Clin Immunol; 2021 Feb 3; S0091-6749(21)00162-7.）
（J Allergy Clin Immunol; 2021 Feb 3; S0091-6749(21)00162-7.）
Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation
Delgado-Eckert E, James A, Meier-Girard D, Kupczyk M, Andersson LI, Bossios A, Mikus M, Ono J, Izuhara K, Middelveld R, Dahlén B, Gaga M, Siafakas NM, Papi A, Beghe B, Joos G, Rabe KF, Sterk PJ, Bel EH, Johnston SL, Chanez P, Gjomarkaj M, Howarth PH, Niżankowska-Mogilnicka E, Dahlén SE, Frey U
J Allergy Clin Immunol; 2021 Feb 3; S0091-6749(21)00162-7.
Abstract
Background: In all chronic airway diseases, the dynamics of airway function are influenced by underlying airway inflammation and bronchial hyperresponsiveness along with limitations in reversibility owing to airway and lung remodeling as well as mucous plugging. The relative contribution of each component translates into specific clinical patterns of symptoms, quality of life, exacerbation risk, and treatment success.
Objective: We aimed to evaluate whether subgrouping of patients with obstructive airway diseases according to patterns of fluctuation in lung function allows identification of specific phenotypes with distinct clinical characteristics.
Methods: We applied the novel method of fluctuation-based clustering (FBC) to twice-daily FEV1 measurements recorded over a 1-year period in a mixed group of 134 adults with mild-to-moderate asthma, severe asthma, or chronic obstructive pulmonary disease from the European BIOAIR cohort.
Results: Independently of clinical diagnosis, FBC divided patients into 4 fluctuation-based clusters with progressively increasing alterations in lung function that corresponded to patterns of increasing clinical severity, risk of exacerbation, and lower quality of life. Clusters of patients with airway disease with significantly elevated levels of biomarkers relating to remodeling (osteonectin) and cellular senescence (plasminogen activator inhibitor-1), accompanied by a loss of airway reversibility, pulmonary hyperinflation, and loss of diffusion capacity, were identified. The 4 clusters generated were stable over time and revealed no differences in levels of markers of type 2 inflammation (blood eosinophils and periostin).
Conclusions: FBC-based phenotyping provides another level of information that is complementary to clinical diagnosis and unrelated to eosinophilic inflammation, which could identify patients who may benefit from specific treatment strategies or closer monitoring.
上一篇：
分泌的热激蛋白控制气道重塑：来自支气管热成形术的证据
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PI3Kδ的选择性抑制剂CPL302-253作为吸入治疗和预防哮喘的候选药物的临床前表征
