呼出的挥发性有机化合物能够区分嗜中性粒细胞和嗜酸性哮喘
2020/02/11
摘要
原理：利用内生挥发性有机化合物(VOCs)对哮喘表型进行呼出的气体的分析，为无创诊断和治疗监测提供了可能。诱导痰确实不容易广泛的获得，而且中性粒细胞性哮喘的标志物仍然缺乏。
目的:确定利用内生VOCs分析呼出气体是否可以作为识别痰液炎症表型的替代标记。
方法:我们对来自列日大学哮喘诊所的521名哮喘患者进行了前瞻性研究。患者接受VOC测定、呼出一氧化氮(FeNO)肺活量测定比例、痰液诱导、血样测定。根据痰中粒细胞计数将哮喘患者分为三种炎症表型。测量和主要结果:在探索的研究中，通过气相色谱-质谱联用技术对试验组中276名哮喘患者重点强调了7个潜在的生物标志物。在验证研究中(n = 245)，我们确认了四种利用综合二维气相色谱结合高分辨率飞行时间质谱来鉴别哮喘炎症表型有意义的VOCs。己烷和2-己酮被认为是在嗜酸性哮喘中分类性能最高的化合物，其准确性可与血液嗜酸性粒细胞和FeNO相媲美。此外，FeNO、血嗜酸细胞和VOCs的组合对嗜酸细胞性哮喘有很好的预测作用(受体工作特性曲线下面积0.9)。对于中性粒细胞性哮喘，壬醛、1-丙醇和己烷的组合的分类性能，与在嗜酸性哮喘中的FeNO或血嗜酸细胞的的分类性能相似。这些化合物在嗜中性哮喘中含量较高。
结论:我们的研究首次尝试根据大量哮喘患者的痰中性粒细胞的分布来描述挥发性有机化合物的特点，并为中性粒细胞性哮喘提供替代标记。
Exhaled Volatile Organic Compounds Are Able to Discriminate between Neutrophilic and Eosinophilic Asthma.
Schleich FN, et al. Am J Respir Crit Care Med. 2019 Aug 15.
Abstract
Rationale: Analysis of exhaled breath for asthma phenotyping using endogenously generated volatile organic compounds (VOCs) offers the possibility of noninvasive diagnosis and therapeutic monitoring. Induced sputum is indeed not widely available and markers of neutrophilic asthma are still lacking.
Objectives: To determine whether analysis of exhaled breath using endogenously generated VOCs can be a surrogate marker for recognition of sputum inflammatory phenotypes.
Methods: We conducted a prospective study on 521 patients with asthma recruited from the University Asthma Clinic of Liege. Patients underwent VOC measurement, fraction of exhaled nitric oxide (FeNO) spirometry, sputum induction, and gave a blood sample. Subjects with asthma were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.Measurements and Main Results: In the discovery study, seven potential biomarkers were highlighted by gas chromatography-mass spectrometry in a training cohort of 276 patients with asthma. In the replication study (n = 245), we confirmed four VOCs of interest to discriminate among asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry. Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to that of blood eosinophils and FeNO. Moreover, the combination of FeNO, blood eosinophils, and VOCs gave a very good prediction of eosinophilic asthma (area under the receiver operating characteristic curve, 0.9). For neutrophilic asthma, the combination of nonanal, 1-propanol, and hexane had a classification performance similar to FeNO or blood eosinophils in eosinophilic asthma. Those compounds were found in higher levels in neutrophilic asthma.
Conclusions: Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of patients with asthma and provide surrogate markers for neutrophilic asthma.
原理：利用内生挥发性有机化合物(VOCs)对哮喘表型进行呼出的气体的分析，为无创诊断和治疗监测提供了可能。诱导痰确实不容易广泛的获得，而且中性粒细胞性哮喘的标志物仍然缺乏。
目的:确定利用内生VOCs分析呼出气体是否可以作为识别痰液炎症表型的替代标记。
方法:我们对来自列日大学哮喘诊所的521名哮喘患者进行了前瞻性研究。患者接受VOC测定、呼出一氧化氮(FeNO)肺活量测定比例、痰液诱导、血样测定。根据痰中粒细胞计数将哮喘患者分为三种炎症表型。测量和主要结果:在探索的研究中，通过气相色谱-质谱联用技术对试验组中276名哮喘患者重点强调了7个潜在的生物标志物。在验证研究中(n = 245)，我们确认了四种利用综合二维气相色谱结合高分辨率飞行时间质谱来鉴别哮喘炎症表型有意义的VOCs。己烷和2-己酮被认为是在嗜酸性哮喘中分类性能最高的化合物，其准确性可与血液嗜酸性粒细胞和FeNO相媲美。此外，FeNO、血嗜酸细胞和VOCs的组合对嗜酸细胞性哮喘有很好的预测作用(受体工作特性曲线下面积0.9)。对于中性粒细胞性哮喘，壬醛、1-丙醇和己烷的组合的分类性能，与在嗜酸性哮喘中的FeNO或血嗜酸细胞的的分类性能相似。这些化合物在嗜中性哮喘中含量较高。
结论:我们的研究首次尝试根据大量哮喘患者的痰中性粒细胞的分布来描述挥发性有机化合物的特点，并为中性粒细胞性哮喘提供替代标记。
（中国医科大学附属第一医院 李文扬 摘译 杨冬 审校）
（Schleich FN, et al. Am J Respir Crit Care Med. 2019 Aug 15.）
（Schleich FN, et al. Am J Respir Crit Care Med. 2019 Aug 15.）
Exhaled Volatile Organic Compounds Are Able to Discriminate between Neutrophilic and Eosinophilic Asthma.
Schleich FN, et al. Am J Respir Crit Care Med. 2019 Aug 15.
Abstract
Rationale: Analysis of exhaled breath for asthma phenotyping using endogenously generated volatile organic compounds (VOCs) offers the possibility of noninvasive diagnosis and therapeutic monitoring. Induced sputum is indeed not widely available and markers of neutrophilic asthma are still lacking.
Objectives: To determine whether analysis of exhaled breath using endogenously generated VOCs can be a surrogate marker for recognition of sputum inflammatory phenotypes.
Methods: We conducted a prospective study on 521 patients with asthma recruited from the University Asthma Clinic of Liege. Patients underwent VOC measurement, fraction of exhaled nitric oxide (FeNO) spirometry, sputum induction, and gave a blood sample. Subjects with asthma were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.Measurements and Main Results: In the discovery study, seven potential biomarkers were highlighted by gas chromatography-mass spectrometry in a training cohort of 276 patients with asthma. In the replication study (n = 245), we confirmed four VOCs of interest to discriminate among asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry. Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to that of blood eosinophils and FeNO. Moreover, the combination of FeNO, blood eosinophils, and VOCs gave a very good prediction of eosinophilic asthma (area under the receiver operating characteristic curve, 0.9). For neutrophilic asthma, the combination of nonanal, 1-propanol, and hexane had a classification performance similar to FeNO or blood eosinophils in eosinophilic asthma. Those compounds were found in higher levels in neutrophilic asthma.
Conclusions: Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of patients with asthma and provide surrogate markers for neutrophilic asthma.
上一篇：
高度中性粒细胞性哮喘患者血清IgE升高，OCS依赖性和IL-17/22表达升高
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肺功能统计的第一印象至关重要：一年就可以改变哮喘预后
