呼出气挥发性有机化合物能够区分中性粒细胞性哮喘和嗜酸性粒细胞性哮喘
2019/04/19
摘要
依据：利用内生挥发性有机化合物(VOCs)分析呼出气对哮喘表型的影响，为无创性诊断和治疗监测提供可能。诱导痰技术未完全普及，依然缺乏对中性粒细胞性哮喘的标志物的研究。
方法：我们对来自列日大学哮喘门诊的521名哮喘患者进行前瞻性研究。对患者进行VOC测定、呼出一氧化氮(FeNO)及肺功能测定、诱导痰及血样检测。根据哮喘患 者痰中粒细胞计数将其分为三种炎症表型。
结果：在这项研究中，276名哮喘患者的训练集中，发现有7种潜在的生物标志物能被GC-MS高度强调。在复制研究中(n=245)，我们利用GC×GC-HRTOFMS技术证实了4种VOCs能够鉴别哮喘炎症表型。己烷和2-己酮被认定为在嗜酸性粒细胞性哮喘中具有最高分类性能的化合物，其准确度与血液嗜酸性粒细胞和FeNO相当。此外，FeNO、血嗜酸性粒细胞和VOCs联合使用对嗜酸性哮喘有很好的预测作用(AUROC: 0.9)。对于中性粒细胞性哮喘，壬醛、1-丙醇和己烷的组合具有与嗜酸性粒细胞性哮喘中FeNO或外周血嗜酸性粒细胞类似的分类价值。发现在中性粒细胞性哮喘这些化合物含量较高。
结论：我们的研究是首次尝试根据大量哮喘患者的痰粒细胞特征描述VOCs，并为中性粒细胞性哮喘提供替代指标。
Exhaled Volatile Organic Compounds are Able to Discriminate between Neutrophilic and Eosinophilic Asthma.
Schleich FN, Zanella D, Stefanuto PH, Bessonov K, Smolinska A, Dallinga JW, Henket M, Paulus V, Guissard F, Graff S, Moermans C, Wouters EFM, Van Steen K, van Schooten FJ, Focant JF, Louis R.
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.
METHODS: We conducted a prospective study on 521 asthmatics recruited from the University Asthma Clinic of Liege. Patient underwent VOC measurement, fraction of exhaled nitric oxide (FeNO) spirometry, sputum induction and gave a blood sample. Asthmatics were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.
RESULTS: In the discovery study, seven potential biomarkers were highlighted by GC-MS in a training cohort of 276 asthmatics. In the replication study (n=245), we confirmed 4 VOCs of interest to discriminate between asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC×GC-HRTOFMS). Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to the one of blood eosinophils and FeNO. Moreover the combination of FeNO, blood eosinophils and VOCs gave a very good prediction of eosinophilic asthma (AUROC: 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.
CONCLUSION: Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of asthmatics and provide surrogate markers for neutrophilic asthma.
依据：利用内生挥发性有机化合物(VOCs)分析呼出气对哮喘表型的影响，为无创性诊断和治疗监测提供可能。诱导痰技术未完全普及，依然缺乏对中性粒细胞性哮喘的标志物的研究。
方法：我们对来自列日大学哮喘门诊的521名哮喘患者进行前瞻性研究。对患者进行VOC测定、呼出一氧化氮(FeNO)及肺功能测定、诱导痰及血样检测。根据哮喘患 者痰中粒细胞计数将其分为三种炎症表型。
结果：在这项研究中，276名哮喘患者的训练集中，发现有7种潜在的生物标志物能被GC-MS高度强调。在复制研究中(n=245)，我们利用GC×GC-HRTOFMS技术证实了4种VOCs能够鉴别哮喘炎症表型。己烷和2-己酮被认定为在嗜酸性粒细胞性哮喘中具有最高分类性能的化合物，其准确度与血液嗜酸性粒细胞和FeNO相当。此外，FeNO、血嗜酸性粒细胞和VOCs联合使用对嗜酸性哮喘有很好的预测作用(AUROC: 0.9)。对于中性粒细胞性哮喘，壬醛、1-丙醇和己烷的组合具有与嗜酸性粒细胞性哮喘中FeNO或外周血嗜酸性粒细胞类似的分类价值。发现在中性粒细胞性哮喘这些化合物含量较高。
结论：我们的研究是首次尝试根据大量哮喘患者的痰粒细胞特征描述VOCs，并为中性粒细胞性哮喘提供替代指标。
（中日友好医院呼吸与危重症医学科 张鑫 摘译林江涛 审校）
（Am J Respir Crit Care Med. 2019 Apr 11. doi: 10.1164/rccm.201811-2210OC.）
（Am J Respir Crit Care Med. 2019 Apr 11. doi: 10.1164/rccm.201811-2210OC.）
Exhaled Volatile Organic Compounds are Able to Discriminate between Neutrophilic and Eosinophilic Asthma.
Schleich FN, Zanella D, Stefanuto PH, Bessonov K, Smolinska A, Dallinga JW, Henket M, Paulus V, Guissard F, Graff S, Moermans C, Wouters EFM, Van Steen K, van Schooten FJ, Focant JF, Louis R.
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.
METHODS: We conducted a prospective study on 521 asthmatics recruited from the University Asthma Clinic of Liege. Patient underwent VOC measurement, fraction of exhaled nitric oxide (FeNO) spirometry, sputum induction and gave a blood sample. Asthmatics were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.
RESULTS: In the discovery study, seven potential biomarkers were highlighted by GC-MS in a training cohort of 276 asthmatics. In the replication study (n=245), we confirmed 4 VOCs of interest to discriminate between asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry (GC×GC-HRTOFMS). Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to the one of blood eosinophils and FeNO. Moreover the combination of FeNO, blood eosinophils and VOCs gave a very good prediction of eosinophilic asthma (AUROC: 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.
CONCLUSION: Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of asthmatics and provide surrogate markers for neutrophilic asthma.
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哮喘患者气道不同部位诱导型一氧化氮合酶基因表达的比较及与一氧化氮参数的关系
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探索哮喘小气道功能障碍的相关性和程度(ATLANTIS)：一项前瞻性队列研究的基线数据
