Abstract：
BACKGROUND: Bronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma. Although multiple trials have demonstrated clinical improvement after BT, optimal patient selection remains a challenge and the mechanism of action is incompletely understood. The aim of this study was to examine whether exhaled breath analysis can contribute to discriminate between BT-responders and non-responders at baseline and to explore pathophysiological insights of BT.
METHODS: Exhaled breath was collected from patients at baseline and six months post-BT. Patients were defined as responders or non-responders based on a half point increase in asthma quality of life questionnaire scores. Gas chromatography-mass spectrometry was used for volatile organic compounds (VOCs) detection and analyses. Analytical workflow consisted of: 1) detection of VOCs that differentiate between responders and non-responders and those that differ between baseline and six months post-BT, 2) identification of VOCs of interest and 3) explore correlations between clinical biomarkers and VOCs.
RESULTS: Data was available from 14 patients. Nonanal, 2-ethylhexanol and 3-thujol showed a significant difference in intensity between responders and non-responders at baseline (p = 0.04, p = 0.01 and p = 0.03, respectively). After BT, no difference was found in the compound intensity of these VOCs. A negative correlation was observed between nonanal and IgE and BALF eosinophils (r = -0.68, p < 0.01 and r = -0.61, p = 0.02 respectively) and 3-thujol with BALF neutrophils (r = -0.54, p = 0.04).
CONCLUSIONS: This explorative study identified discriminative VOCs in exhaled breath between BT responders and non-responders at baseline. Additionally, correlations were found between VOC\'s and inflammatory BALF cells. Once validated, these findings encourage research in breath analysis as a non-invasive easy to apply technique for identifying airway inflammatory profiles and eligibility for BT or immunotherapies in severe asthma.
METHODS: Exhaled breath was collected from patients at baseline and six months post-BT. Patients were defined as responders or non-responders based on a half point increase in asthma quality of life questionnaire scores. Gas chromatography-mass spectrometry was used for volatile organic compounds (VOCs) detection and analyses. Analytical workflow consisted of: 1) detection of VOCs that differentiate between responders and non-responders and those that differ between baseline and six months post-BT, 2) identification of VOCs of interest and 3) explore correlations between clinical biomarkers and VOCs.
RESULTS: Data was available from 14 patients. Nonanal, 2-ethylhexanol and 3-thujol showed a significant difference in intensity between responders and non-responders at baseline (p = 0.04, p = 0.01 and p = 0.03, respectively). After BT, no difference was found in the compound intensity of these VOCs. A negative correlation was observed between nonanal and IgE and BALF eosinophils (r = -0.68, p < 0.01 and r = -0.61, p = 0.02 respectively) and 3-thujol with BALF neutrophils (r = -0.54, p = 0.04).
CONCLUSIONS: This explorative study identified discriminative VOCs in exhaled breath between BT responders and non-responders at baseline. Additionally, correlations were found between VOC\'s and inflammatory BALF cells. Once validated, these findings encourage research in breath analysis as a non-invasive easy to apply technique for identifying airway inflammatory profiles and eligibility for BT or immunotherapies in severe asthma.
摘要：
背景：支气管热成形术（BT）是一种用于重度哮喘的支气管镜治疗方法。尽管多项试验已证明BT后的临床改善，最佳患者选择仍然是一个挑战,作用机制尚不完全清楚.这项研究的目的是检查呼出气分析是否有助于在基线时区分BT应答者和非应答者，并探索BT的病理生理学见解。
方法：在基线和BT后6个月采集患者的呼气。根据哮喘生活质量问卷得分增加半个百分点，将患者定义为应答者或非应答者。气相色谱-质谱法用于挥发性有机化合物（VOC）的检测和分析。分析工作流程包括：1）检测VOCs，以区分响应者和非响应者以及基线和BT后六个月之间的差异，2）鉴定感兴趣的VOC，3）探索临床生物标志物与VOC之间的相关性。
结果：数据来自14例患者。非肛门，2-乙基己醇和3-thujol在基线时在响应者和非响应者之间显示出强度的显着差异（分别为p=0.04，p=0.01和p=0.03）。BT之后,这些VOC的复合强度没有发现差异。观察到nonanal，IgE和BALF嗜酸性粒细胞（r=-0.68，p<0.01和r=-0.61，p=0.02）和3-thujol与BALF中性粒细胞（r=-0.54，p=0.04）之间呈负相关。
结论：这项探索性研究确定了基线时BT反应者和非反应者的呼气中的区别VOCs。此外,发现VOC与炎性BALF细胞之间存在相关性。一旦验证，这些研究结果鼓励呼吸分析作为一种易于应用的非侵入性技术进行研究,用于确定气道炎症谱和接受重症哮喘的BT或免疫治疗的资格.
方法：在基线和BT后6个月采集患者的呼气。根据哮喘生活质量问卷得分增加半个百分点，将患者定义为应答者或非应答者。气相色谱-质谱法用于挥发性有机化合物（VOC）的检测和分析。分析工作流程包括：1）检测VOCs，以区分响应者和非响应者以及基线和BT后六个月之间的差异，2）鉴定感兴趣的VOC，3）探索临床生物标志物与VOC之间的相关性。
结果：数据来自14例患者。非肛门，2-乙基己醇和3-thujol在基线时在响应者和非响应者之间显示出强度的显着差异（分别为p=0.04，p=0.01和p=0.03）。BT之后,这些VOC的复合强度没有发现差异。观察到nonanal，IgE和BALF嗜酸性粒细胞（r=-0.68，p<0.01和r=-0.61，p=0.02）和3-thujol与BALF中性粒细胞（r=-0.54，p=0.04）之间呈负相关。
结论：这项探索性研究确定了基线时BT反应者和非反应者的呼气中的区别VOCs。此外,发现VOC与炎性BALF细胞之间存在相关性。一旦验证，这些研究结果鼓励呼吸分析作为一种易于应用的非侵入性技术进行研究,用于确定气道炎症谱和接受重症哮喘的BT或免疫治疗的资格.
