ChiCTR2600126336 版本V1.0 版本创建时间2026/06/08 10:02:54 中国临床试验注册中心

审核状态：

Project audit state：

通过审核

Successful

注册号：

Registration number：

 ChiCTR2600126336 

最近更新日期：

Date of Last Refreshed on：

 2026-06-08 10:02:43 

注册时间：

Date of Registration：

 2026-06-08 00:00:00 

注册号状态：

预注册

Registration Status：

Prospective registration

注册题目：

人工智能辅助重度哮喘精准分型研究

Public title：

Artificial intelligence-assisted precise classification of severe asthma

注册题目简写：

English Acronym：

研究课题的正式科学名称：

基于人工智能构建重度哮喘精准分型体系

Scientific title：

Construction of a precise classification system for severe asthma based on artificial intelligence

研究课题代号(代码)：

Study subject ID：

在二级注册机构或其它机构的注册号：

The registration number of the Partner Registry or other register：

申请注册联系人：

张旻 

研究负责人：

张旻 

Applicant：

Min Zhang 

Study leader：

Min Zhang 

申请注册联系人电话：

Applicant telephone：

 +86 13482345145

研究负责人电话：

Study leader's
telephone：

+86 21 6324 0090

申请注册联系人传真 ：

Applicant Fax：

研究负责人传真：

Study leader's fax：

申请注册联系人电子邮件：

Applicant E-mail：

 zhangmin@sjtu.edu.cn

研究负责人电子邮件：

Study leader's E-mail：

 13482345145@163.com

申请单位网址(自愿提供)：

Applicant website(voluntary supply)：

研究负责人网址(自愿提供)：

Study leader's website(voluntary supply)：

申请注册联系人通讯地址：

上海市虹口区武进路85号

研究负责人通讯地址：

上海市虹口区武进路85号

Applicant address：

85 Wujin Road, Hongkou District, Shanghai, China

Study leader's address：

85 Wujin Road, Hongkou District, Shanghai, China

申请注册联系人邮政编码：

Applicant postcode：

研究负责人邮政编码：

Study leader's postcode：

申请人所在单位：

上海市第一人民医院

Applicant's institution：

Shanghai General Hospital

研究负责人所在单位：

上海市第一人民医院

Affiliation of the Leader：

Shanghai General Hospital

是否获伦理委员会批准：

是

Approved by ethic committee：

Yes

伦理委员会批件文号：

Approved No. of ethic committee：

 院伦快【2026】191号

伦理委员会批件附件：

Approved file of Ethical Committee：

 查看附件View

批准本研究的伦理委员会名称：

上海市第一人民医院人体试验伦理审查委员会

Name of the ethic committee：

Ethics Committee for Human Trials of Shanghai General Hospital

伦理委员会批准日期：

Date of approved by ethic committee：

 2026-03-26 00:00:00

伦理委员会联系人：

耿雯倩

Contact Name of the ethic committee：

Geng Wenqian

伦理委员会联系地址：

上海市虹口区武进路85号

Contact Address of the ethic committee：

85 Wujin Road, Hongkou District, Shanghai, China

伦理委员会联系人电话：

Contact phone of the ethic committee：

 +86 21 36126254

伦理委员会联系人邮箱：

Contact email of the ethic committee：

 13262983906@163.com

研究实施负责（组长）单位：

上海市第一人民医院

Primary sponsor：

Shanghai General Hospital

研究实施负责（组长）单位地址：

上海市虹口区武进路85号

Primary sponsor's address：

85 Wujin Road, Hongkou District, Shanghai, China

试验主办单位(项目批准或申办者)：

Secondary sponsor：

国家：

中国

省(直辖市)：

上海市

市(区县)：

Country：

China

Province：

Shanghai

City：

单位(医院)：

上海市第一人民医院

具体地址：

上海市虹口区武进路85号

Institution
hospital：

Shanghai General Hospital

Address：

85 Wujin Road, Hongkou District, Shanghai, China

经费或物资来源：

癌症、心脑血管、呼吸和代谢性疾病防治研究国家科技重大专项

Source(s) of funding：

Major National Science and Technology Project for Research on Prevention and Treatment of Cancer

研究疾病：

重度哮喘；重度哮喘急性发作  

Target disease：

Severe asthma; Acute exacerbation of severe asthma

研究疾病代码：

Target disease code：

研究类型：

观察性研究

Study type：

Observational study

研究所处阶段：

 其它 

Study phase：

N/A

研究设计：

病例对照研究 

Study design：

Case-Control study 

研究目的：

1. 基于多模态临床数据与多组学数据，利用人工智能机器学习算法构建并验证重度哮喘高分辨率分型模型。 2. 基于影像组学和呼气组学数据研发重度哮喘无创精准分型技术。 3. 基于纵向多模态数据，构建并验证重度哮喘急性发作精准分型模型。  

Objectives of Study：

1. Based on multimodal clinical data and multi-omics data, use artificial intelligence and machine learning algorithms to construct and validate a high-resolution classification model for severe asthma. 2. Develop non-invasive precision classification technology for severe asthma based on radiomics and exhalomics data. 3. Based on longitudinal multimodal data, construct and validate a precise classification model for acute exacerbations of severe asthma.

药物成份或治疗方案详述：

 

Description for medicine or protocol of treatment in detail：

 

纳入标准：

1.静态分型队列，哮喘患者入选标准： 1)受试者必须自愿参加此项研究及遵守研究规定，了解并遵守、能够配合完成临床数据采集、生物样本（外周血、诱导痰等）采集、影像学检查（胸部CT，可接受入组前3个月内胸部CT）及呼出气样本采集，遵守用药剂量、随访计划，并自愿签署书面知情同意书。 2)受试者年龄≥18岁，并≤80岁，不限男女和种族。 3)符合《支气管哮喘防治指南（2024 版）》哮喘诊断标准，且满足以下轻、中度或重度哮喘定义。 轻度哮喘：通过第1级、第2级治疗能达到良好控制者，即按需使用低剂量吸入糖皮质激素（ICS）联合快速起效的长效β?受体激动剂（LABA）（如布地奈德-福莫特罗）（优选方案）、低剂量ICS维持治疗联合按需SABA或ICS-SABA复方制剂可实现良好控制的哮喘（备选方案）。 中度哮喘：低、中剂量吸入糖皮质激素维持治疗可实现良好控制。 重度哮喘：连续3个月及以上规范使用中高剂量ICS- LABA治疗，并且针对共患疾病和环境因素等进行处理后仍未控制，或者在高剂量ICS-LABA治疗方案降级时出现加重的哮喘。 4)育龄期女性在试验期间采取有效的避孕措施。
2.静态分型队列，健康受试者入选标准： 1)受试者必须自愿参加此项研究及遵守研究规定，了解并遵守、配合相应检查，遵守随访计划，并自愿签署书面知情同意书。 2)年龄≥18 岁且≤80 岁，不限性别、种族，自愿签署书面知情同意书。 3)无哮喘及其他慢性呼吸系统疾病（如 COPD、间质性肺炎）病史及相关症状（喘息、咳嗽、胸闷等）。 4)肺功能检查（FEV?、FEV?/FVC）在正常参考值范围内，支气管舒张试验阴性。 5)呼出气一氧化氮（FeNO）检测结果正常，血常规（含嗜酸性粒细胞）无异常。 6)既往未使用哮喘相关药物（如 ICS、LABA、SABA 等）及生物靶向制剂。 7)能够配合完成临床数据采集、生物样本（外周血）采集、胸部 CT（入组前3个月内） 及呼出气样本采集。 8)育龄期女性在试验期间采取有效的避孕措施。
3.急性发作队列入选标准： 1)受试者必须自愿参加此项研究及遵守研究规定，了解并遵守、能够配合完成急性发作期及缓解期（急性发作控制后2-4周、3个月）的临床数据采集、生物样本（外周血、痰液、呼出气等）采集及影像学检查，遵守用药剂量、随访计划，并自愿签署书面知情同意书。 2)受试者年龄≥18岁，并≤80岁，不限男女和种族。 3)符合《支气管哮喘防治指南（2024版）》哮喘诊断标准。 4)因哮喘急性发作就诊（门急诊或住院），符合重度哮喘急性发作诊断标准：因哮喘急性发作急诊/住院治疗且需全身糖皮质激素治疗≥3天。 5)育龄期女性在试验期间采取有效的避孕措施。

Inclusion criteria

1. Eligibility Criteria for Asthma Patients in the Static Phenotyping Cohort: (1) Participants must voluntarily participate in this study, abide by study regulations, understand and cooperate with the collection of clinical data, biological samples (peripheral blood, induced sputum, etc.), imaging examinations (chest CT, and chest CT completed within 3 months prior to enrollment is acceptable) and exhaled breath samples, adhere to medication dosages and follow-up schedules, and voluntarily sign the written informed consent form. (2) Participants are aged >= 18 years and <= 80 years, with no restrictions on gender or race. (3) Participants shall meet the diagnostic criteria for bronchial asthma in the *Guidelines for the Prevention and Treatment of Bronchial Asthma (2024 Edition)*, and conform to the definitions of mild, moderate or severe asthma as follows: Mild asthma refers to asthma well controlled with Step 1 or Step 2 treatment, namely asthma well controlled with on-demand low-dose inhaled corticosteroid (ICS) combined with fast-acting long-acting beta2-agonist (LABA) (e.g., budesonide-formoterol) as the preferred regimen, or with maintenance low-dose ICS plus on-demand short-acting beta2-agonist (SABA) or ICS-SABA combination preparation as alternative regimens. Moderate asthma refers to asthma well controlled with maintenance treatment of low-to-medium dose ICS. Severe asthma refers to asthma that remains uncontrolled after standardized treatment with medium-to-high dose ICS-LABA for 3 consecutive months or longer and targeted management of comorbidities and environmental factors, or asthma that exacerbates when the high-dose ICS-LABA regimen is de-escalated. (4) Women of childbearing potential shall adopt effective contraceptive measures during the study period. 2. Eligibility Criteria for Healthy Subjects in the Static Phenotyping Cohort: (1) Participants must voluntarily participate in this study, comply with study regulations, understand and cooperate with relevant examinations and follow-up schedules, and voluntarily sign the written informed consent form. (2) Participants are aged >= 18 years and <= 80 years with no restrictions on gender or race, and shall sign the written informed consent form voluntarily. (3) Participants have no history of asthma or other chronic respiratory diseases such as COPD and interstitial pneumonia, and present no associated symptoms including wheezing, cough and chest tightness. (4) Pulmonary function tests (FEV1, FEV1/FVC) are within the normal reference range, and the bronchodilator test is negative. (5) The level of fractional exhaled nitric oxide (FeNO) is normal, and routine blood tests including eosinophil count show no abnormalities. (6) Participants have never used asthma-related medications such as ICS, LABA and SABA, or biologic targeted agents in the past. (7) Participants are capable of cooperating with the collection of clinical data, biological samples (peripheral blood), chest CT scan (conducted within 3 months prior to enrollment) and exhaled breath samples. (8) Women of childbearing potential shall adopt effective contraceptive measures during the study period. 3. Eligibility Criteria for Acute Exacerbation Cohort: (1) Participants must voluntarily participate in this study, comply with relevant regulations, and be able to cooperate with clinical data collection, biological sample collection (peripheral blood, sputum, exhaled breath, etc.) and imaging examinations during the acute exacerbation stage and remission stage (2-4 weeks and 3 months after the acute exacerbation is controlled), follow the prescribed medication doses and follow-up plans, and voluntarily sign the written informed consent form. (2) Participants are aged >= 18 years and <= 80 years, regardless of gender and race. (3) Participants shall meet the diagnostic criteria for bronchial asthma in the *Guidelines for the Prevention and Treatment of Bronchial Asthma (2024 Edition)*. (4) Participants seek medical treatment at outpatient, emergency or inpatient departments due to acute asthma exacerbation and meet the diagnostic criteria for severe acute asthma exacerbation, namely receiving emergency or inpatient treatment for acute asthma exacerbation with systemic glucocorticoid therapy for no less than 3 days. (5) Women of childbearing potential shall take effective contraceptive measures during the study period.

排除标准：

1.静态分型队列哮喘患者排除标准： 1)不能配合哮喘诊断的相关检查或其他原因不能合作者。 2)伴有除哮喘以外的临床重大肺部疾病（如活动性肺部感染、慢性阻塞性肺疾病（研究者判断）、支气管扩张症、肺纤维化、囊性纤维化、与肥胖相关的低通气综合征、肺癌、α1抗胰蛋白酶缺乏症和原发性纤毛运动障碍）或伴有除哮喘之外导致外周血嗜酸性粒细胞计数升高的全身疾病（如嗜酸性肉芽肿性多血管炎、嗜酸性粒细胞增多综合征、嗜酸性食管炎等）。 3)既往或伴有自身免疫性疾病（如类风湿性关节炎、炎症性肠病、原发性胆汁性肝硬化、系统性红斑狼疮、多发性硬化等）。 4)筛选前4周内至随机前出现具有临床意义的感染且需要全身性抗生素或抗病毒药物治疗，如上呼吸道感染、下呼吸道感染等，及筛选期出现血常规除嗜酸性粒细胞以外的明显异常。 5)筛选前6个月内患有蠕虫寄生虫感染，且未接受标准治疗或标准治疗无效。 6)筛选前5年内有任何恶性肿瘤病史，已治愈（如基底细胞癌、皮肤鳞状细胞癌、低危/极低危局限性前列腺癌、甲状腺乳头状癌等）或已根治性切除的原位癌（如乳腺导管内原位癌、子宫颈原位癌等）除外。 7)伴有严重、进展性或无法控制的中枢神经系统、心血管系统、消化系统、内分泌系统、呼吸系统、泌尿系统、血液系统等系统性疾病者，经研究者评估可能影响受试者安全或研究结果等不适合参加本临床研究的情况。 8)筛选前1年内有长期酗酒或吸毒/药物滥用史。 9)筛选前1年内患有活动性结核病史。 10)筛选前 8 周内进行过大手术或计划在试验期间进行需要全身麻醉或住院治疗＞1天的手术。 11)筛选前2周内接受过T细胞2（Th2）细胞因子抑制剂甲磺司特。 12)筛选前4周内接受过免疫球蛋白或血液制品。 13)首次给药前4周内和试验期间接种减毒活疫苗。 14)既往使用过生物靶向制剂（包括但不限于抗IL-4Rα、抗IL-5、抗IL-5Rα、抗TSLP、抗IgE等生物制剂）控制的哮喘患者。 15)首次给药前3个月内接受过系统性免疫抑制剂/免疫调节药物（如甲氨蝶呤、环孢素等），用于哮喘/哮喘急性加重治疗的OCS除外。 16)筛选前12个月内接受过支气管热成型术。 17)筛选期出现以下病毒学检查异常：乙型肝炎病毒表面抗原（HbsAg）阳性且乙肝病毒脱氧核糖核酸（HBV DNA）阳性、丙型肝炎病毒抗体（HCV-Ab）阳性且丙型肝炎病毒核糖核酸（HCV RNA）阳性、人免疫缺陷病毒抗体（Anti-HIV）检查阳性、梅毒螺旋体特异性抗体阳性（特异性抗体检测阳性，非特异性抗体检测阴性且结合临床判断确证为非活动期感染者除外）。 18)筛选期肝功能异常并伴随以下结果：丙氨酸氨基转移酶（ALT）和/或天门冬氨酸氨基转移酶（AST）和/或碱性磷酸酶（ALP）＞2×ULN导入期出现任何除哮喘以外的其他有临床意义的异常发现，经研究者评估受试者参加本研究获益＜风险，或可能影响研究结果，或可能影响受试者依从性的情况。 19)孕妇或哺乳期女性，或筛选期/D1的血妊娠检测结果为阳性。 20)研究者认为受试者存在不适合入组的其他情况；
2.静态分型队列健康受试者排除标准： 1)不能配合哮喘诊断的相关检查或其他原因不能合作者。 2)合并心血管、代谢、免疫、神经等系统严重疾患，或影响研究的其他疾病。 3)酗酒或麻醉药物滥用史，或具有精神病史、对抗性格、不良动机、多疑或其他情感或智力问题等可能影响参与此研究的知情有效性的情况。 4)妊娠或哺乳期女性。 5)存在诱导痰采集、胸部CT检查或呼出气样本采集禁忌。 6)正在参加其他药物临床试验项目。
3.急性发作队列哮喘患者排除标准： 1)不能配合哮喘诊断的相关检查或其他原因不能合作者。 2)伴有除哮喘以外的临床重大肺部疾病（如活动性肺部感染、慢性阻塞性肺疾病（研究者判断）、支气管扩张症、肺纤维化、囊性纤维化、与肥胖相关的低通气综合征、肺癌、α1抗胰蛋白酶缺乏症和原发性纤毛运动障碍）或伴有除哮喘之外导致外周血嗜酸性粒细胞计数升高的全身疾病（如嗜酸性肉芽肿性多血管炎、嗜酸性粒细胞增多综合征、嗜酸性食管炎等）。 3)既往或伴有自身免疫性疾病（如类风湿性关节炎、炎症性肠病、原发性胆汁性肝硬化、系统性红斑狼疮、多发性硬化等）。 4)筛选前4周内至随机前出现具有临床意义的感染且需要全身性抗生素或抗病毒药物治疗，如上呼吸道感染、下呼吸道感染等。 5)筛选前6个月内患有蠕虫寄生虫感染，且未接受标准治疗或标准治疗无效。 6)筛选前5年内有任何恶性肿瘤病史，已治愈（如基底细胞癌、皮肤鳞状细胞癌、低危/极低危局限性前列腺癌、甲状腺乳头状癌等）或已根治性切除的原位癌（如乳腺导管内原位癌、子宫颈原位癌等）除外。 7)伴有严重、进展性或无法控制的中枢神经系统、心血管系统、消化系统、内分泌系统、呼吸系统、泌尿系统、血液系统等系统性疾病者，经研究者评估可能影响受试者安全或研究结果等不适合参加本临床研究的情况。 8)筛选前1年内有长期酗酒或吸毒/药物滥用史。 9)筛选前1年内患有活动性结核病史。 10)筛选前 8 周内进行过大手术或计划在试验期间进行需要全身麻醉或住院治疗＞1天的手术。 11)筛选前2周内接受过T细胞2（Th2）细胞因子抑制剂甲磺司特。 12)筛选前4周内接受过免疫球蛋白或血液制品。 13)首次给药前4周内和试验期间接种减毒活疫苗。 14)既往使用过生物靶向制剂（包括但不限于抗IL-4Rα、抗IL-5、抗IL-5Rα、抗TSLP、抗IgE等生物制剂）控制的哮喘患者。 15)首次给药前3个月内接受过系统性免疫抑制剂/免疫调节药物（如甲氨蝶呤、环孢素等），用于哮喘/哮喘急性加重治疗的OCS除外。 16)筛选前12个月内接受过支气管热成型术。 17)筛选期出现以下病毒学检查异常：乙型肝炎病毒表面抗原（HbsAg）阳性且乙肝病毒脱氧核糖核酸（HBV DNA）阳性、丙型肝炎病毒抗体（HCV-Ab）阳性且丙型肝炎病毒核糖核酸（HCV RNA）阳性、人免疫缺陷病毒抗体（Anti-HIV）检查阳性、梅毒螺旋体特异性抗体阳性（特异性抗体检测阳性，非特异性抗体检测阴性且结合临床判断确证为非活动期感染者除外）。 18)筛选期肝功能异常并伴随以下结果：丙氨酸氨基转移酶（ALT）和/或天门冬氨酸氨基转移酶（AST）和/或碱性磷酸酶（ALP）＞2×ULN导入期出现任何除哮喘以外的其他有临床意义的异常发现，经研究者评估受试者参加本研究获益＜风险，或可能影响研究结果，或可能影响受试者依从性的情况。 19)孕妇或哺乳期女性，或筛选期/D1的血妊娠检测结果为阳性。 20)研究者认为受试者存在不适合入组的其他情况；

Exclusion criteria：

1. Exclusion Criteria for Asthma Patients in the Static Phenotyping Cohort: (1) Subjects who are unable to cooperate with examinations for asthma diagnosis or fail to cooperate for other reasons. (2) Subjects with clinically significant major pulmonary diseases other than asthma (e.g., active pulmonary infection, chronic obstructive pulmonary disease as judged by the investigator, bronchiectasis, pulmonary fibrosis, cystic fibrosis, obesity hypoventilation syndrome, lung cancer, alpha-1 antitrypsin deficiency, primary ciliary dyskinesia), or systemic diseases other than asthma that cause elevated peripheral blood eosinophil counts (e.g., eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, eosinophilic esophagitis). (3) Subjects with a history of or concomitant autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cholangitis, systemic lupus erythematosus, multiple sclerosis). (4) Subjects who developed clinically significant infections requiring systemic antibiotics or antiviral therapy such as upper and lower respiratory tract infections from 4 weeks prior to screening to randomization, or presented with marked abnormalities in routine blood tests excluding eosinophils during the screening period. (5) Subjects with helminthic infection within 6 months prior to screening who have not received standard treatment or failed to respond to standard treatment. (6) Subjects with any history of malignant tumors within 5 years prior to screening, excluding cured malignancies such as basal cell carcinoma, cutaneous squamous cell carcinoma, low-risk or very low-risk localized prostate cancer, papillary thyroid carcinoma, and radically resected carcinoma in situ including ductal carcinoma in situ of the breast and cervical carcinoma in situ. (7) Subjects with severe, progressive or uncontrolled systemic diseases involving the central nervous system, cardiovascular system, digestive system, endocrine system, respiratory system, urinary system, hematological system and other systems, or those deemed ineligible for this clinical trial by the investigator due to potential risks to subject safety or interference with study results. (8) Subjects with a history of chronic alcohol abuse or drug/substance abuse within 1 year prior to screening. (9) Subjects with a history of active tuberculosis within 1 year prior to screening. (10) Subjects who underwent major surgery within 8 weeks prior to screening or plan to receive surgery requiring general anesthesia or hospitalization for more than 1 day during the trial. (11) Subjects who received suplatast tosilate, a T helper 2 (Th2) cytokine inhibitor, within 2 weeks prior to screening. (12) Subjects who received immunoglobulins or blood products within 4 weeks prior to screening. (13) Subjects who received live attenuated vaccines within 4 weeks before the first study drug administration or during the trial period. (14) Asthma patients previously treated with biologic targeted agents, including but not limited to anti-IL-4Rα, anti-IL-5, anti-IL-5Rα, anti-TSLP and anti-IgE monoclonal antibodies. (15) Subjects who received systemic immunosuppressants or immunomodulatory agents such as methotrexate and cyclosporine within 3 months before the first study drug administration, excluding oral corticosteroids (OCS) used for the treatment of asthma or acute asthma exacerbations. (16) Subjects who underwent bronchial thermoplasty within 12 months prior to screening. (17) Subjects with abnormal virological test results during the screening period, including positive hepatitis B surface antigen (HBsAg) combined with positive hepatitis B virus deoxyribonucleic acid (HBV DNA), positive hepatitis C virus antibody (HCV-Ab) combined with positive hepatitis C virus ribonucleic acid (HCV RNA), positive human immunodeficiency virus antibody (Anti-HIV), and positive treponema pallidum specific antibody, excluding those with positive specific antibody, negative non-specific antibody and confirmed inactive infection based on clinical assessment. (18) Subjects with liver function abnormalities during the screening period with alanine transaminase (ALT), and/or aspartate transaminase (AST), and/or alkaline phosphatase (ALP) levels exceeding 2 times the upper limit of normal (ULN); or those with any other clinically significant abnormal findings unrelated to asthma during the run-in phase, where the investigator determines that the risks of participation outweigh the benefits, or the conditions may interfere with study results or subject compliance. (19) Pregnant or lactating women, or those with a positive serum pregnancy test at screening or on Day 1 (D1). (20) Subjects with any other conditions deemed inappropriate for enrollment by the investigator. 2. Exclusion Criteria for Healthy Subjects in the Static Phenotyping Cohort: (1) Individuals who cannot cooperate with examinations for asthma diagnosis or are uncooperative for other reasons. (2) Individuals with severe diseases involving the cardiovascular, metabolic, immune, nervous and other systems, or other conditions that may interfere with the study. (3) Individuals with a history of alcohol abuse or narcotic drug abuse, or those with psychiatric disorders, defiant attitude, improper motives, suspicious mentality or other emotional and intellectual problems that may compromise the validity of informed consent for study participation. (4) Pregnant or lactating women. (5) Individuals with contraindications to induced sputum collection, chest CT scanning or exhaled breath sample collection. (6) Individuals currently participating in other clinical drug trials. 3. Exclusion Criteria for Asthma Patients in the Acute Exacerbation Cohort: (1) Subjects who fail to cooperate with examinations for asthma diagnosis or are uncooperative for other reasons. (2) Subjects with clinically significant major pulmonary diseases other than asthma (e.g., active pulmonary infection, chronic obstructive pulmonary disease as assessed by the investigator, bronchiectasis, pulmonary fibrosis, cystic fibrosis, obesity hypoventilation syndrome, lung cancer, alpha-1 antitrypsin deficiency, primary ciliary dyskinesia), or systemic diseases other than asthma that cause elevated peripheral blood eosinophil counts (e.g., eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, eosinophilic esophagitis). (3) Subjects with a history of or concurrent autoimmune diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, primary biliary cholangitis, systemic lupus erythematosus, multiple sclerosis). (4) Subjects who developed clinically significant infections requiring systemic antibiotics or antiviral therapy, such as upper and lower respiratory tract infections, from 4 weeks prior to screening until randomization. (5) Subjects with helminthic infection within 6 months prior to screening who have not received standard treatment or showed no response to standard treatment. (6) Subjects with any history of malignant tumors within 5 years prior to screening, excluding cured cases such as basal cell carcinoma, cutaneous squamous cell carcinoma, low-risk or very low-risk localized prostate cancer, papillary thyroid carcinoma, and radically resected carcinoma in situ including ductal carcinoma in situ of the breast and cervical carcinoma in situ. (7) Subjects with severe, progressive or uncontrolled systemic diseases involving the central nervous system, cardiovascular system, digestive system, endocrine system, respiratory system, urinary system, hematological system and other systems, or those judged ineligible for this clinical trial by the investigator due to potential risks to subject safety or interference with study results. (8) Subjects with a history of chronic alcohol abuse or drug abuse within 1 year prior to screening. (9) Subjects with a history of active tuberculosis within 1 year prior to screening. (10) Subjects who underwent major surgery within 8 weeks prior to screening or plan to receive surgery requiring general anesthesia or hospitalization for more than one day during the trial. (11) Subjects who received suplatast tosilate, a Th2 cytokine inhibitor, within 2 weeks prior to screening. (12) Subjects who received immunoglobulins or blood products within 4 weeks prior to screening. (13) Subjects who received live attenuated vaccines within 4 weeks before the first study drug administration or during the trial period. (14) Asthma patients previously treated with biologic targeted agents, including but not limited to anti-IL-4Rα, anti-IL-5, anti-IL-5Rα, anti-TSLP and anti-IgE biologics. (15) Subjects who received systemic immunosuppressants or immunomodulatory agents such as methotrexate and cyclosporine within 3 months before the first study drug administration, excluding oral corticosteroids (OCS) used for the treatment of asthma or acute asthma exacerbations. (16) Subjects who underwent bronchial thermoplasty within 12 months prior to screening. (17) Subjects with abnormal virological test results during the screening period: positive hepatitis B surface antigen (HBsAg) combined with positive HBV DNA, positive HCV-Ab combined with positive HCV RNA, positive Anti-HIV, or positive treponema pallidum specific antibody, excluding subjects with positive specific antibody, negative non-specific antibody and clinically confirmed inactive infection. (18) Subjects with liver function abnormalities during the screening period where alanine transaminase (ALT), and/or aspartate transaminase (AST), and/or alkaline phosphatase (ALP) levels exceed 2 x ULN; or those with any other clinically significant abnormalities unrelated to asthma during the run-in phase, for whom the investigator determines that the risks of participation outweigh the benefits, or whose conditions may affect study results or subject compliance. (19) Pregnant or lactating women, or those with a positive serum pregnancy test at screening or on Day 1 (D1). (20) Subjects with any other conditions deemed unsuitable for enrollment by the investigator.

研究实施时间：

Study execute time：

从 From 2026-03-01 00:00:00至 To 2030-02-28 00:00:00  

征募观察对象时间：

Recruiting time：

从 From 2026-06-10 00:00:00 至 To 2030-02-28 00:00:00

干预措施：

Interventions：

组别：

轻中度哮喘

样本量：

 600

Group：

Mild to Moderate Asthma

Sample size：

干预措施：

无

干预措施代码：

Intervention：

None

Intervention code：

组别：

急性发作队列

样本量：

 150

Group：

Acute Exacerbation

Sample size：

干预措施：

无

干预措施代码：

Intervention：

None

Intervention code：

组别：

健康参与者

样本量：

 100

Group：

Healthy Participants

Sample size：

干预措施：

无

干预措施代码：

Intervention：

None

Intervention code：

组别：

重度哮喘

样本量：

 600

Group：

Severe Asthma

Sample size：

干预措施：

无

干预措施代码：

Intervention：

None

Intervention code：

研究实施地点：

Countries of recruitment and research settings：

国家：

 中国

省(直辖市)：

 上海市 

市(区县)：

  

Country：

China

Province：

Shanghai

City：

单位(医院)：

 上海市第一人民医院 

单位级别：

 三级甲等 

Institution
hospital：

Shanghai General Hospital

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 四川省 

市(区县)：

  

Country：

China

Province：

Sichuan

City：

单位(医院)：

 四川大学华西医院 

单位级别：

 三级甲等 

Institution
hospital：

West China Hospital, Sichuan University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 北京市 

市(区县)：

  

Country：

China

Province：

Beijing

City：

单位(医院)：

 北京邮电大学 

单位级别：

 大学 

Institution
hospital：

Beijing University of Posts and Telecommunications

Level of the institution：

University

国家：

 中国

省(直辖市)：

 广东省 

市(区县)：

  

Country：

China

Province：

Guangdong

City：

单位(医院)：

 广州医科大学附属第二医院 

单位级别：

 三级甲等 

Institution
hospital：

The Second Affiliated Hospital of Guangzhou Medical University

Level of the institution：

Tertiary A

国家：

 中国

省(直辖市)：

 广东省 

市(区县)：

  

Country：

China

Province：

Guangdong

City：

单位(医院)：

 南方医科大学南方医院 

单位级别：

 三级甲等 

Institution
hospital：

Nanfang Hospital Southern Medical University

Level of the institution：

Tertiary A

测量指标：

Outcomes：

指标中文名：

胸部CT影像灰度均值

指标类型：

次要指标

Outcome：

Mean（First-order Mean）

Type：

Secondary indicator

测量时间点：

基线入组时、末次访视

测量方法：

采集胸部CT平扫影像，采用U?Net算法分割肺实质与气道结构，通过3D Swin Transformer提取高维影像特征，经重采样与灰度归一化后，使用LightGBM与LASSO回归筛选影像组学标签。

Measure time point of outcome：

Baseline、the final visit

Measure method：

Chest CT plain scan images are acquired. Lung parenchyma and airway structures are segmented using U?Net. High?dimensional radiomic features are extracted by 3D Swin Transformer. After resampling and gray?level normalization, radiomic signatures are selected using LightGBM and LASSO regression.

指标中文名：

年化急性发作次数

指标类型：

主要指标

Outcome：

Annualized number of acute exacerbations

Type：

Primary indicator

测量时间点：

基线入组时，急性发作期、临床缓解期，随访1年结束时

测量方法：

通过电子病例报告表（eCRF）回顾性采集，并在不同访视期进行统计，同时采集参与者人口学特征、哮喘病史、用药史（吸入激素、生物制剂使用情况）、合并症及 ACT/ACQ 症状评分。

Measure time point of outcome：

Baseline, exacerbation, remission, and 1-year follow-up

Measure method：

Data were retrospectively collected via electronic case report forms (eCRF) and counted at different visit periods. Meanwhile, demographic characteristics, asthma history, medication history (including inhaled corticosteroids and biological agents), comorbidities, as well as ACT and ACQ symptom scores of participants were collected.

指标中文名：

诱导痰炎症细胞计数

指标类型：

主要指标

Outcome：

Induced sputum inflammatory cell count

Type：

Primary indicator

测量时间点：

基线入组时，急性发作期，末次访视

测量方法：

采集诱导痰样本进行嗜酸性粒细胞百分比等炎症细胞计数，用于识别重度哮喘的分子内型，构建高分辨率精准分型模型。

Measure time point of outcome：

Baseline, exacerbation, and the final visit

Measure method：

Induced sputum samples were collected for inflammatory cell counting including eosinophil percentage to identify molecular endotypes of severe asthma and construct a high-resolution precise subtyping model.

指标中文名：

第1秒用力呼气容积

指标类型：

主要指标

Outcome：

Forced Expiratory Volume in one second

Type：

Primary indicator

测量时间点：

基线入组时，急性发作期、临床缓解期，随访1年结束时

测量方法：

通过电子病例报告表（eCRF）采集以下信息：完成肺功能检测采集第1秒用力呼气容积及其他肺功能指标（FVC、FEV1/FVC、PEF以及小气道功能参数等）、脉冲振荡（IOS）检测（R5、R20等）、FeNO检测及炎症指标（嗜酸性粒细胞计数、IgE、CRP等）检测。

Measure time point of outcome：

Baseline, exacerbation, remission, and 1-year follow-up

Measure method：

Data were collected via electronic case report forms (eCRF), including pulmonary function parameters from spirometry: forced expiratory volume in one second (FEV?), FVC, FEV?/FVC ratio, PEF and small airway function indicators; impulse oscillometry (IOS) indices such as R5 and R20; FeNO measurement; and inflammatory biomarkers including eosinophil count, serum IgE and CRP.

指标中文名：

痰微生物丰度

指标类型：

次要指标

Outcome：

Sputum microbiota abundance

Type：

Secondary indicator

测量时间点：

基线入组时

测量方法：

留取诱导痰样本，微生物组测序分析气道菌群构成。

Measure time point of outcome：

Baseline

Measure method：

Induced sputum samples were collected and subjected to microbiome sequencing to analyze the composition of airway microbiota.

指标中文名：

外周血嗜酸性粒细胞

指标类型：

主要指标

Outcome：

Peripheral blood eosinophil

Type：

Primary indicator

测量时间点：

基线入组时，急性发作期，末次访视

测量方法：

采集外周血样本进行嗜酸性粒细胞百分比等炎症细胞计数，用于识别重度哮喘的分子内型，构建高分辨率精准分型模型。

Measure time point of outcome：

Baseline, exacerbation, and the final visit

Measure method：

Peripheral blood samples were collected to perform inflammatory cell counts including eosinophil percentage, so as to identify molecular endotypes of severe asthma and establish a high-resolution precise subtyping model.

指标中文名：

呼出气挥发性有机物浓度

指标类型：

次要指标

Outcome：

Concentration of exhaled VOCs

Type：

Secondary indicator

测量时间点：

基线入组时

测量方法：

收集VOCs标本，进行代谢组学定量检测，用于识别重度哮喘的分子内型，构建高分辨率精准分型模型。

Measure time point of outcome：

Baseline

Measure method：

VOCs samples were collected and quantified via metabolomic assays to identify molecular endotypes of severe asthma and develop a high-resolution precise subtyping model.

采集人体标本：

Collecting sample(s)
from participants：

标本中文名：

血

组织：

Sample Name：

Blood

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

标本中文名：

诱导痰

组织：

Sample Name：

Induced Sputum

Tissue：

人体标本去向

 使用后保存  

说明

Fate of sample：

Preservation after use  

Note：

征募研究对象情况：

Recruiting status：

尚未开始

Not yet recruiting

年龄范围：

Participant age：
最小 Min age 18 岁 years
最大 Max age 80 岁 years

性别：

男女均可

Gender：

Both

随机方法（请说明由何人用什么方法产生随机序列）：

无

Randomization Procedure (please state who generates the random number sequence and by what method)：

None

是否公开试验完成后的统计结果:

Calculated Results after the Study Completed public access:

不公开/Private

盲法：

无

Blinding：

None

是否共享原始数据：

IPD sharing

是Yes

共享原始数据的方式（说明：请填入公开原始数据日期和方式，如采用网络平台，需填该网络平台名称和网址）：

论文发表后半年内，国家人口健康科学数据中心，https://www.ncmi.cn/index.html

The way of sharing IPD”(include metadata and protocol, If use web-based public database, please provide the url)：

Within six months after the paper is published,National Population Health Science Data Center, https://www.ncmi.cn/index.html

数据采集和管理（说明：数据采集和管理由两部分组成，一为病例记录表(Case Record Form, CRF)，二为电子采集和管理系统(Electronic Data Capture, EDC)，如ResMan即为一种基于互联网的EDC：

本研究采用电子数据采集（EDC）系统建立电子病例报告表（eCRF）进行数据管理。数据管理员根据研究方案要求建立相应的eCRF，确保表格设计逻辑清晰、易于理解，并预设合理的数据验证规则和格式要求。研究者或临床研究协调员通过分配的账号和密码登录EDC系统进行数据录入，对每位研究参与者在研究中的所有相关资料均及时、真实、完整地记录在eCRF中。 数据管理员和统计人员对录入数据进行实时质量监控，重点关注数据完整性、逻辑一致性、异常值识别和缺失数据模式。EDC系统自动执行预设的质量检查规则，包括日期逻辑性检查、纳入排除标准一致性验证、数值范围合理性检查和必填字段完整性检查等，系统自动发出数据疑问涉及日期逻辑、入组标准、排除标准、脱落、缺失值等关键信息。对统计分析的重要指标，系统利用计算机程序进行详细检查，及时发现问题并生成疑问。 当系统发现数据问题时，研究者可直接在线查看并解答疑问，数据管理员实时审核答疑结果并督促及时处理。对于复杂疑问，监查员可下载数据疑问表，由研究者对疑问表中的问题进行书面解答并签名后，统一由数据录入人员进行数据修改。研究者应尽快对系统疑问予以解答，答疑后数据必要时可再次触发质量检查并发出新的疑问，确保数据质量持续改进。 所有数据疑问解决后，数据管理人员将"清洁"数据从EDC系统导出，生成数据质量报告并检查数据完整性和一致性。随后组织数据审核会议，由主要研究者、统计分析人员、数据管理人员共同对数据进行全面审核，评估数据收集完整性、主要变量质量、缺失数据影响并制定异常值处理决策。各方代表签署数据审核决议后，数据管理人员执行数据库锁定操作，建立数据版本控制记录，并将锁定后的最终分析数据集提交统计师进行统计分析。 数据库锁定后的任何数据变更都必须遵循严格的变更控制程序，需要有充分的科学依据，并获得主要研究者、统计学家和数据管理员共同签署的同意书，同时详细记录变更原因、内容和时间，保留完整的审计轨迹。EDC系统将建立分级访问权限体系，定期审查用户权限，记录所有数据访问和修改日志，并采用安全的数据存储和传输方式，对个人身份信息进行去标识化处理，确保数据安全与保密。

Data collection and Management (A standard data collection and management system include a CRF and an electronic data capture：

This study adopts an Electronic Data Capture (EDC) system to establish electronic Case Report Forms (eCRFs) for data management. Data managers establish corresponding eCRFs according to the requirements of the research protocol, ensuring that the form design is logically clear and easy to understand, and preset reasonable data validation rules and format requirements. Researchers or clinical research coordinators log in to the EDC system with assigned accounts and passwords to enter data, and record all relevant information of each study participant in the eCRF in a timely, truthful and complete manner. Data managers and statisticians conduct real-time quality monitoring of the entered data, focusing on data integrity, logical consistency, outlier identification and missing data patterns. The EDC system automatically executes preset quality check rules, including date logic check, consistency verification of inclusion and exclusion criteria, rationality check of numerical ranges and completeness check of required fields, and automatically generates data queries involving key information such as date logic, inclusion criteria, exclusion criteria, dropout and missing values. For important indicators for statistical analysis, the system conducts detailed inspections using computer programs to promptly identify problems and generate queries. When the system detects data problems, researchers can directly view and answer queries online, and data managers review the answers in real time and urge timely processing. For complex queries, monitors can download the data query form, and after researchers provide written answers to the questions in the form and sign them, data entry personnel will uniformly make data modifications. Researchers should answer system queries as soon as possible, and after answering, the data may trigger quality checks again and generate new queries if necessary to ensure continuous improvement of data quality. After all data queries are resolved, data managers export the "clean" data from the EDC system, generate a data quality report and check data integrity and consistency. Subsequently, a data review meeting is organized, where the principal investigator, statistical analysts and data managers conduct a comprehensive review of the data, evaluate the completeness of data collection, the quality of key variables, the impact of missing data and formulate decisions on outlier handling. After representatives of all parties sign the data review resolution, data managers perform the database lock operation, establish data version control records, and submit the locked final analysis dataset to statisticians for statistical analysis. Any data modification after database lock must follow strict change control procedures, require sufficient scientific basis, and obtain a consent form jointly signed by the principal investigator, statistician and data manager, while recording the reason, content and time of the modification in detail and retaining a complete audit trail. The EDC system will establish a hierarchical access control system, regularly review user permissions, record all data access and modification logs, adopt secure data storage and transmission methods, and de-identify personal identifiable information to ensure data security and confidentiality.

数据与安全监察委员会：

Data and Safety Monitoring Committee：

有/Yes

注册人：

Name of Registration：

  2026-06-08 10:02:43