基于哮喘内因型个体化治疗(ADEPT)寻找哮喘临床特征与生物标志物
2015/12/29
研究背景:哮喘是一种异质性疾病,需要了解其病理生理亚型,从而研发新的治疗方法。ADEPT(针对气道疾病内因型的个体化治疗 )研究目的是通过分析哮喘来探讨其临床特征和生物标记物与分子特征之间的关联。
研究方法:研究纳入不同严重程度的哮喘患者和非特应性体质的健康对照者。随访哮喘患者12月。评估其哮喘病史、患者问卷调查、肺功能、气道对乙酸甲胆碱的反应性、呼出气一氧化氮(FeNO)以及诱导痰、血和支气管镜检标本中生物标志物检测。所有研究对象均进行诱导痰检测,有30例行支气管镜检查。
研究结果:纳入对象均来自北美和西欧,其中根据严重程度哮喘组分为轻度52例,中度55例和重度51例三组,健康对照组30例。研究发现患者气流受限程度、支气管扩张反应及气道高反应性随着哮喘严重程度增高而加重,重度哮喘组的用力肺活量(FVC)下降。哮喘严重程度越重,哮喘控制调查问卷-7(ACQ-7)评分相应越差。尽管其个体差异较大,哮喘患者临床及生物标志物特征在随访12个月期间保持稳定。FENO和血嗜酸性粒细胞与哮喘的严重程度无关。轻度哮喘患者其诱导痰嗜酸性粒细胞而非中性粒细胞数量较中、重度哮喘患者低。
研究结论:ADEPT研究成功纳入不同严重程度的哮喘患者及非特应性健康对照者。研究发现患者临床特点与哮喘严重程度相关,基本上哮喘特征如肺功能在跟踪12个月期间是稳定的。ADEPT研究数据有利于界定生物学亚型,从而促进个体化治疗的实施。
评论:ADEPT研究评估了诱导痰、支气管镜检标本以及生物标志物。纳入了预计数量的不同严重程度哮喘患者及非特应性健康对照组。研究过程中安全地完成痰诱导实验和纤支镜检查。同预期一致,不同严重程度的哮喘患者临床特点与生物标志物有差异。未来研究的方向将覆盖不同严重程度哮喘患者的气道标本基因表达谱和其他指标的检测;另外,利用聚类分析法将研究对象分组并明确不同的生物学特点。ADEPT研究将建立一个丰富的数据库,有助于明确患者的生物表型从而促进哮喘个体化治疗的发展。
Silkoff, P.E., et al., Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study. Respir Res, 2015. 16: p. 142.
Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study
Background: Asthma is a heterogeneous disease and development of novel therapeutics requires an understanding of pathophysiologic phenotypes. The purpose of the ADEPT study was to correlate clinical features and biomarkers with molecular characteristics, by profiling asthma (NCT01274507). This report presents for the first time the study design, and characteristics of the recruited subjects.
Methods: Patients with a range of asthma severity and healthy non-atopic controls were enrolled. The asthmatic subjects were followed for 12 months. Assessments included history, patient questionnaires, spirometry, airway hyper-responsiveness to methacholine, fractional exhaled nitric oxide (FENO), and biomarkers measured in induced sputum, blood, and bronchoscopy samples. All subjects underwent sputum induction and 30 subjects/cohort had bronchoscopy.
Results: Mild (n = 52), moderate (n = 55), severe (n = 51) asthma cohorts and 30 healthy controls were enrolled from North America and Western Europe. Airflow obstruction, bronchodilator response and airways hyperresponsiveness increased with asthma severity, and severe asthma subjects had reduced forced vital capacity. Asthma control questionnaire-7 (ACQ7) scores worsened with asthma severity. In the asthmatics, mean values for all clinical and biomarker characteristics were stable over 12 months although individual variability was evident. FENO and blood eosinophils did not differ by asthma severity. Induced sputum eosinophils but not neutrophils were lower in mild compared to the moderate and severe asthma cohorts.
Conclusions: The ADEPT study successfully enrolled asthmatics across a spectrum of severity and non-atopic controls. Clinical characteristics were related to asthma severity and in general asthma characteristics e.g. lung function, were stable over 12 months. Use of the ADEPT data should prove useful in defining biological phenotypes to facilitate personalized therapeutic approaches.
Silkoff, P.E., et al., Asthma characteristics and biomarkers from the Airways Disease Endotyping for Personalized Therapeutics (ADEPT) longitudinal profiling study. Respir Res, 2015. 16: p. 142.
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屋尘螨激发后加重无哮喘症状的持续变应性鼻炎患者气道炎症和气道高反应性
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不同成人哮喘表型证实可以反映痰嗜酸粒细胞炎症的生物标志物