Exhaled Volatile Organic Compounds Are Able to Discriminate between Neutrophilic and Eosinophilic Asthma
Exhaled Volatile Organic Compounds Are Able to Discriminate between Neutrophilic and Eosinophilic Asthma
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DOI：
10.1164/rccm.201811-2210oc
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发表时间：
2019-08-15
影响因子：
24.7
通讯作者：
Louis, Renaud
中科院分区：
文献类型：
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作者：
Schleich, Florence N.;Zanella, Delphine;Louis, Renaud
原理：利用内源性挥发性有机化合物（VOCs）分析呼出气体的哮喘表型，为无创诊断和治疗监测提供了可能。诱导痰确实没有广泛使用，中性粒细胞哮喘的标志物仍然缺乏。目的：确定使用内源性挥发性有机化合物分析呼出气体是否可以作为识别痰炎表型的替代标志物。方法：我们对从列日大学哮喘诊所招募的521例哮喘患者进行了前瞻性研究。患者接受挥发性有机化合物（VOC）测定、呼出一氧化氮（FENO）肺活量测定、痰诱导，并进行血样采集。根据痰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：在这项发现研究中，276名哮喘患者的训练队列中，通过气相色谱-质谱分析突出了7种潜在的生物标志物。在重复研究（n = 245）中，我们使用综合二维气相色谱法和高分辨率飞行时间质谱法确认了四种感兴趣的挥发性有机化合物，以区分哮喘炎症表型。正己烷和2-己酮被认为是在嗜酸性哮喘中具有最高分类性能的化合物，其准确性与血液嗜酸性粒细胞和FENO相当。此外，结合FENO、血嗜酸性粒细胞和VOCs对嗜酸性粒细胞哮喘有很好的预测作用（受试者工作特征曲线下面积为0.9）。对于嗜中性粒细胞哮喘，壬醛、1-丙醇和己烷的组合在嗜酸性哮喘中的分类性能类似于FENO或血嗜酸性粒细胞。这些化合物在嗜中性粒细胞哮喘中含量较高。结论：我们的研究首次尝试根据大量哮喘患者的痰粒细胞谱来表征挥发性有机化合物，并为中性粒细胞哮喘提供替代标志物。
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.