欧洲重症哮喘及其缓解前景研究（SHARP）：基于欧洲重症哮喘登记处的多中心观察性研究见解
2026/06/30
摘要
背景：重度哮喘影响少数哮喘患者；然而，它对发病率、医疗服务使用以及全身皮质类固醇相关损害产生重大影响。尽管生物治疗的应用日益增多，但重度哮喘缓解的实现仍然遥不可及。值得注意的是，欧洲关于重度哮喘疾病负担和缓解潜力的真实世界数据仍然有限。我们旨在填补这一知识空白，提供具有全球相关性的见解。
方法：本横断面观察性研究利用欧洲重度异质性哮喘注册研究、以患者为中心的临床研究协作组（SHARP CRC）中登记的13455名成年重度哮喘患者的数据，评估了欧洲范围内重度哮喘的负担以及与缓解相关的临床领域（急性发作、哮喘控制、气流受限和维持性口服皮质类固醇的使用），并考察了它们与疾病持续时间、生物治疗和2型生物标志物（血嗜酸性粒细胞、呼出气一氧化氮分数[FeNO]和总IgE）的关系。重度哮喘患者根据当地原则和指南，并按照欧洲呼吸学会/美国胸科学会指南登记入国家注册研究；3%（13885名患者中的430名）患者因未同意参加国际研究和/或缺少用药数据而被排除。
结果：患者以女性为主（59%；13453名患者中的7999名），成年起病哮喘患者占比82%（10711名患者中的8751名），疾病持续时间中位数为23年（95%置信区间20 - 26年）。59%（7006名患者中的4148名）患者的FEV1/FVC为0.7或更低，62%（7568名患者中的4680名）患者的FEV1低于预测值的80%，89%（3968名患者中的3519名）患者至少有一个活跃的疾病领域。尽管79%（13453名患者中的10632名）患者接受了生物治疗，但超过66%（3968名患者中的2621名）患者仍至少有两个活跃的疾病领域。尽管广泛使用生物治疗和维持性口服皮质类固醇治疗，2型生物标志物升高的情况仍然存在（89%[3153名患者中的2806名]至少有一种生物标志物升高）。一部分未接受过生物治疗的患者（35%；3018名患者中的1069名）在不到10年的时间内疾病负担迅速累积，提示可能存在加速进展轨迹。
解读：这项泛欧洲重度哮喘分析显示，尽管采用了先进的治疗方法，但仍存在显著的临床异质性和巨大的疾病负担，凸显了2型炎症的持续性、现有治疗方法下当前缓解策略可能的不足，以及早期识别高危患者的必要性。
Severe asthma and remission prospects in Europe (SHARP): insights from a multicentre observational study based on the European Severe Asthma Registry
Evangelia Fouka, Aruna T Bansal, Kjell Erik Julius Håkansson, Fabienne Jaun, Renaud Louis, Shane Hanon, Guy Brusselle, Stéphanie Ziant, Virginie Paulus, Sanja Popović-Grle, Gordana Pavlisa, Marina Lampalo, Mirna Vergles, Eugenija Basioli Kasap, Vratislav Sedlak, Marianne Søndergaard, Susanne Hansen, Svetlana Sergejeva, Jeanne-Marie Perotin, Camille Taillé, Gilles Devouassoux, Caroline Giboin, Eve Klising, Candice Estellat, Dounya Metdaoui, Eckard Hamelmann, Konstantinos Samitas, Konstantinos Porpodis, Eleftherios Zervas, Mina Gaga, Zsuzsanna Csoma, Ildiko Horvath, Dóra Lúdvíksdóttir, Kristín Dóra Sigurdardóttir, Giorgio Walter Canonica, Enrico Heffler, Cristina Cardini, Anna Alloni, Iveta Kroiča, Dace Matisa, Kristina Bieksiene, Jolita Palacionyte, Nils Christian, Romain Tching, Ilse Boudewijn, Jacob K Sont, Simone Hashimoto, Piotr Kuna, Maria Morawska, Claudia Chaves Loureiro, João A Fonseca, Diogo Canhoto, Hadassa Santos, Ana Mendes, Inês Belchior, Carlos Lopes, Florin Mihaltan, Sanja Hromis, Mihailo Stjepanovic, Vojislav Cupurdija, Vesna Tomic-Spiric, Sabina Skrgat, Peter Kopac, David Ramos-Barbon, Luis Pérez de Llano, Victor Lozoya Garcia, David Morenos Martos, Barbro Dahlén, Valentyna Yasinska, Oksana Tenselius, Christer Janson, Arne Egesten, Jens Richter, Össur Ingi Emilsson, Joerg Leuppi, Bilun Gemicioglu, Gulfem Celik, Ebru Damadoglu, Ozlem Goksel, Liam Heaney, John Busby, Charlene Redmond, Matthew Masoli, Rekha Chaudhuri, Patrick Dennison, Simon Doe, Ramesh Kurukulaaratchy, Elisabeth Bel, Ratko Djukanovic, Arnaud Bourdin, Anneke Ten Brinke, Florence Schleich, Celeste Porsbjerg, Apostolos Bossios
Abstract
Background: Severe asthma affects a minority of patients with asthma; however, it substantially impacts morbidity, health-care use, and systemic corticosteroid-related harm. Despite the increasing use of biological treatments, achievement of severe asthma remission remains elusive. Notably, real-world data on the disease burden and remission potential of severe asthma in Europe remain limited. We aimed to close this knowledge gap, offering insights with global relevance.
Methods: Using data from 13 455 adults with severe asthma enrolled in the European Severe Heterogeneous Asthma Registry, Patient-centred Clinical Research Collaboration (SHARP CRC), this cross-sectional observational study evaluated the burden of severe asthma and remission-related clinical domains (exacerbations, asthma control, airflow limitation, and maintenance oral corticosteroid use) across Europe and examined their relationship with disease duration, biological therapy, and type 2 biomarkers (blood eosinophils, fractional exhaled nitric oxide [FeNO], and total IgE). Patients with severe asthma had been enrolled in national registries according to local principles and guidelines and in accordance with the European Respiratory Society/American Thoracic Society guidelines; 3% (430 of 13 885) of patients were excluded due to no consent for the international study and/or missing medication data.
Findings: Patients were predominantly female (59%; 7999 of 13 453), with adult-onset asthma (82%; 8751 of 10 711), and a median disease duration of 23 years (95% CI 20-26 years). 59% (4148 of 7006) of patients had FEV1/FVC of 0·7 or less, 62% (4680 of 7568) had FEV1 lower than 80% predicted, and 89% (3519 of 3968) had at least one active disease domain. Despite 79% (10 632 of 13 453) receiving biological therapy, more than 66% (2621 of 3968) still had at least two active domains. Elevation of type 2 biomarkers persisted (89% [2806 of 3153] with at least one elevated biomarker) despite widespread biological and maintenance oral corticosteroid treatment. A subset of biologic-naive patients (35%; 1069 of 3018) exhibited a rapid accumulation of disease burden within less than 10 years, suggesting a potentially accelerated progression trajectory.
Interpretation: This pan-European analysis of severe asthma revealed significant clinical heterogeneity and a substantial disease burden despite advanced therapies, highlighting the enduring nature of type 2 inflammation, the potential inadequacy of current remission strategies with available therapeutic approaches, and the necessity for early identification of high-risk patients.
背景：重度哮喘影响少数哮喘患者；然而，它对发病率、医疗服务使用以及全身皮质类固醇相关损害产生重大影响。尽管生物治疗的应用日益增多，但重度哮喘缓解的实现仍然遥不可及。值得注意的是，欧洲关于重度哮喘疾病负担和缓解潜力的真实世界数据仍然有限。我们旨在填补这一知识空白，提供具有全球相关性的见解。
方法：本横断面观察性研究利用欧洲重度异质性哮喘注册研究、以患者为中心的临床研究协作组（SHARP CRC）中登记的13455名成年重度哮喘患者的数据，评估了欧洲范围内重度哮喘的负担以及与缓解相关的临床领域（急性发作、哮喘控制、气流受限和维持性口服皮质类固醇的使用），并考察了它们与疾病持续时间、生物治疗和2型生物标志物（血嗜酸性粒细胞、呼出气一氧化氮分数[FeNO]和总IgE）的关系。重度哮喘患者根据当地原则和指南，并按照欧洲呼吸学会/美国胸科学会指南登记入国家注册研究；3%（13885名患者中的430名）患者因未同意参加国际研究和/或缺少用药数据而被排除。
结果：患者以女性为主（59%；13453名患者中的7999名），成年起病哮喘患者占比82%（10711名患者中的8751名），疾病持续时间中位数为23年（95%置信区间20 - 26年）。59%（7006名患者中的4148名）患者的FEV1/FVC为0.7或更低，62%（7568名患者中的4680名）患者的FEV1低于预测值的80%，89%（3968名患者中的3519名）患者至少有一个活跃的疾病领域。尽管79%（13453名患者中的10632名）患者接受了生物治疗，但超过66%（3968名患者中的2621名）患者仍至少有两个活跃的疾病领域。尽管广泛使用生物治疗和维持性口服皮质类固醇治疗，2型生物标志物升高的情况仍然存在（89%[3153名患者中的2806名]至少有一种生物标志物升高）。一部分未接受过生物治疗的患者（35%；3018名患者中的1069名）在不到10年的时间内疾病负担迅速累积，提示可能存在加速进展轨迹。
解读：这项泛欧洲重度哮喘分析显示，尽管采用了先进的治疗方法，但仍存在显著的临床异质性和巨大的疾病负担，凸显了2型炎症的持续性、现有治疗方法下当前缓解策略可能的不足，以及早期识别高危患者的必要性。
（中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校）
（Lancet Respir Med. 2026 Jun 24:S2213-2600(26)00141-4. doi: 10.1016/S2213-2600(26)00141-4.）
Severe asthma and remission prospects in Europe (SHARP): insights from a multicentre observational study based on the European Severe Asthma Registry
Evangelia Fouka, Aruna T Bansal, Kjell Erik Julius Håkansson, Fabienne Jaun, Renaud Louis, Shane Hanon, Guy Brusselle, Stéphanie Ziant, Virginie Paulus, Sanja Popović-Grle, Gordana Pavlisa, Marina Lampalo, Mirna Vergles, Eugenija Basioli Kasap, Vratislav Sedlak, Marianne Søndergaard, Susanne Hansen, Svetlana Sergejeva, Jeanne-Marie Perotin, Camille Taillé, Gilles Devouassoux, Caroline Giboin, Eve Klising, Candice Estellat, Dounya Metdaoui, Eckard Hamelmann, Konstantinos Samitas, Konstantinos Porpodis, Eleftherios Zervas, Mina Gaga, Zsuzsanna Csoma, Ildiko Horvath, Dóra Lúdvíksdóttir, Kristín Dóra Sigurdardóttir, Giorgio Walter Canonica, Enrico Heffler, Cristina Cardini, Anna Alloni, Iveta Kroiča, Dace Matisa, Kristina Bieksiene, Jolita Palacionyte, Nils Christian, Romain Tching, Ilse Boudewijn, Jacob K Sont, Simone Hashimoto, Piotr Kuna, Maria Morawska, Claudia Chaves Loureiro, João A Fonseca, Diogo Canhoto, Hadassa Santos, Ana Mendes, Inês Belchior, Carlos Lopes, Florin Mihaltan, Sanja Hromis, Mihailo Stjepanovic, Vojislav Cupurdija, Vesna Tomic-Spiric, Sabina Skrgat, Peter Kopac, David Ramos-Barbon, Luis Pérez de Llano, Victor Lozoya Garcia, David Morenos Martos, Barbro Dahlén, Valentyna Yasinska, Oksana Tenselius, Christer Janson, Arne Egesten, Jens Richter, Össur Ingi Emilsson, Joerg Leuppi, Bilun Gemicioglu, Gulfem Celik, Ebru Damadoglu, Ozlem Goksel, Liam Heaney, John Busby, Charlene Redmond, Matthew Masoli, Rekha Chaudhuri, Patrick Dennison, Simon Doe, Ramesh Kurukulaaratchy, Elisabeth Bel, Ratko Djukanovic, Arnaud Bourdin, Anneke Ten Brinke, Florence Schleich, Celeste Porsbjerg, Apostolos Bossios
Abstract
Background: Severe asthma affects a minority of patients with asthma; however, it substantially impacts morbidity, health-care use, and systemic corticosteroid-related harm. Despite the increasing use of biological treatments, achievement of severe asthma remission remains elusive. Notably, real-world data on the disease burden and remission potential of severe asthma in Europe remain limited. We aimed to close this knowledge gap, offering insights with global relevance.
Methods: Using data from 13 455 adults with severe asthma enrolled in the European Severe Heterogeneous Asthma Registry, Patient-centred Clinical Research Collaboration (SHARP CRC), this cross-sectional observational study evaluated the burden of severe asthma and remission-related clinical domains (exacerbations, asthma control, airflow limitation, and maintenance oral corticosteroid use) across Europe and examined their relationship with disease duration, biological therapy, and type 2 biomarkers (blood eosinophils, fractional exhaled nitric oxide [FeNO], and total IgE). Patients with severe asthma had been enrolled in national registries according to local principles and guidelines and in accordance with the European Respiratory Society/American Thoracic Society guidelines; 3% (430 of 13 885) of patients were excluded due to no consent for the international study and/or missing medication data.
Findings: Patients were predominantly female (59%; 7999 of 13 453), with adult-onset asthma (82%; 8751 of 10 711), and a median disease duration of 23 years (95% CI 20-26 years). 59% (4148 of 7006) of patients had FEV1/FVC of 0·7 or less, 62% (4680 of 7568) had FEV1 lower than 80% predicted, and 89% (3519 of 3968) had at least one active disease domain. Despite 79% (10 632 of 13 453) receiving biological therapy, more than 66% (2621 of 3968) still had at least two active domains. Elevation of type 2 biomarkers persisted (89% [2806 of 3153] with at least one elevated biomarker) despite widespread biological and maintenance oral corticosteroid treatment. A subset of biologic-naive patients (35%; 1069 of 3018) exhibited a rapid accumulation of disease burden within less than 10 years, suggesting a potentially accelerated progression trajectory.
Interpretation: This pan-European analysis of severe asthma revealed significant clinical heterogeneity and a substantial disease burden despite advanced therapies, highlighting the enduring nature of type 2 inflammation, the potential inadequacy of current remission strategies with available therapeutic approaches, and the necessity for early identification of high-risk patients.
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度普利尤单抗对持续性哮喘患者气道炎症的影响
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特泽利尤单抗在2型（T2）与非2型重症哮喘表型中的真实世界疗效：一项西班牙多中心队列研究
