疑似哮喘患者接受间接支气管挑战后呼气中挥发性有机化合物的变化
2023/08/28
摘要
背景：吸入甘露醇可通过炎症细胞渗透性脱颗粒过程中释放的介质引起支气管收缩，因此是一种有用的哮喘诊断测试和急性发作模型。我们假设，甘露醇挑战会引发呼出的挥发性有机化合物（VOCs）发生变化，从而产生候选生物标志物，并对其来源有新的认识。
方法：招募了临床诊断为哮喘或正在接受疑似哮喘检查的参与者。对支气管高反应性（BHR）患者进行吸入甘露醇挑战，2 周后进行模拟挑战。在挑战前后收集了呼出的挥发性有机化合物（VOCs），并使用气相色谱-质谱联用进行了分析。
结果：共有46名患者（平均年龄52岁，标准差16岁）完成了甘露醇挑战，其中16人（35%）呈阳性，其中15人完成了模拟挑战。在甘露醇挑战后，有16种在51种已确认的VOCs中的数量发生了变化（p<0.05），其中11种为多变量稀疏偏最小二乘判别分析模型做出了贡献，分类错误率为13.8%。在这16种VOCs中，有5种在模拟挑战后数量也发生了变化（p<0.05），此外还有4种其他VOCs。在具有对甘露醇的支气管高反应性的患者中，与模拟挑战后相比，观察到了不同的挑战后VOC特征。
结论：吸入甘露醇与呼出VOCs的变化相关，并且在具有BHR的人群中，与模拟挑战相比，呼出的气息特征呈现出明显的差异。这些差异表达的VOCs可能与急性气道炎症和/或支气管收缩有关，并值得进一步研究作为哮喘潜在生物标志物。
Changes in exhaled volatile organic compounds following indirect bronchial challenge in suspected asthma
Peel A, Wang R, Ahmed W, White I, Wilkinson M, Loke YK, Wilson AM, Fowler SJ.
Abstract
Background:Inhaled mannitol provokes bronchoconstriction via mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that the mannitol challenge would trigger changes in exhaled volatile organic compounds (VOCs), generating both candidate biomarkers and novel insights into their origin.
Methods:Participants with a clinical diagnosis of asthma, or undergoing investigation for suspected asthma, were recruited. Inhaled mannitol challenges were performed, followed by a sham challenge after 2 weeks in participants with bronchial hyper-responsiveness (BHR). VOCs were collected before and after challenges and analysed using gas chromatography-mass spectrometry.
Results:Forty-six patients (mean (SD) age 52 (16) years) completed a mannitol challenge, of which 16 (35%) were positive, and 15 of these completed a sham challenge. Quantities of 16 of 51 identified VOCs changed following mannitol challenge (p<0.05), of which 11 contributed to a multivariate sparse partial least square discriminative analysis model, with a classification error rate of 13.8%. Five of these 16 VOCs also changed (p<0.05) in quantity following the sham challenge, along with four further VOCs. In patients with BHR to mannitol distinct postchallenge VOC signatures were observed compared with post-sham challenge.
Conclusion:Inhalation of mannitol was associated with changes in breath VOCs, and in people with BHR resulted in a distinct exhaled breath profile when compared with a sham challenge. These differentially expressed VOCs are likely associated with acute airway inflammation and/or bronchoconstriction and merit further investigation as potential biomarkers in asthma.
背景：吸入甘露醇可通过炎症细胞渗透性脱颗粒过程中释放的介质引起支气管收缩，因此是一种有用的哮喘诊断测试和急性发作模型。我们假设，甘露醇挑战会引发呼出的挥发性有机化合物（VOCs）发生变化，从而产生候选生物标志物，并对其来源有新的认识。
方法：招募了临床诊断为哮喘或正在接受疑似哮喘检查的参与者。对支气管高反应性（BHR）患者进行吸入甘露醇挑战，2 周后进行模拟挑战。在挑战前后收集了呼出的挥发性有机化合物（VOCs），并使用气相色谱-质谱联用进行了分析。
结果：共有46名患者（平均年龄52岁，标准差16岁）完成了甘露醇挑战，其中16人（35%）呈阳性，其中15人完成了模拟挑战。在甘露醇挑战后，有16种在51种已确认的VOCs中的数量发生了变化（p<0.05），其中11种为多变量稀疏偏最小二乘判别分析模型做出了贡献，分类错误率为13.8%。在这16种VOCs中，有5种在模拟挑战后数量也发生了变化（p<0.05），此外还有4种其他VOCs。在具有对甘露醇的支气管高反应性的患者中，与模拟挑战后相比，观察到了不同的挑战后VOC特征。
结论：吸入甘露醇与呼出VOCs的变化相关，并且在具有BHR的人群中，与模拟挑战相比，呼出的气息特征呈现出明显的差异。这些差异表达的VOCs可能与急性气道炎症和/或支气管收缩有关，并值得进一步研究作为哮喘潜在生物标志物。
(中日友好医院呼吸与危重症医学科 沈焜路 摘译 林江涛 审校)
(Thorax. 2023 Jul 26; DOI:10.1136/thorax-2022-219708)
(Thorax. 2023 Jul 26; DOI:10.1136/thorax-2022-219708)
Changes in exhaled volatile organic compounds following indirect bronchial challenge in suspected asthma
Peel A, Wang R, Ahmed W, White I, Wilkinson M, Loke YK, Wilson AM, Fowler SJ.
Abstract
Background:Inhaled mannitol provokes bronchoconstriction via mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that the mannitol challenge would trigger changes in exhaled volatile organic compounds (VOCs), generating both candidate biomarkers and novel insights into their origin.
Methods:Participants with a clinical diagnosis of asthma, or undergoing investigation for suspected asthma, were recruited. Inhaled mannitol challenges were performed, followed by a sham challenge after 2 weeks in participants with bronchial hyper-responsiveness (BHR). VOCs were collected before and after challenges and analysed using gas chromatography-mass spectrometry.
Results:Forty-six patients (mean (SD) age 52 (16) years) completed a mannitol challenge, of which 16 (35%) were positive, and 15 of these completed a sham challenge. Quantities of 16 of 51 identified VOCs changed following mannitol challenge (p<0.05), of which 11 contributed to a multivariate sparse partial least square discriminative analysis model, with a classification error rate of 13.8%. Five of these 16 VOCs also changed (p<0.05) in quantity following the sham challenge, along with four further VOCs. In patients with BHR to mannitol distinct postchallenge VOC signatures were observed compared with post-sham challenge.
Conclusion:Inhalation of mannitol was associated with changes in breath VOCs, and in people with BHR resulted in a distinct exhaled breath profile when compared with a sham challenge. These differentially expressed VOCs are likely associated with acute airway inflammation and/or bronchoconstriction and merit further investigation as potential biomarkers in asthma.
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支气管扩张剂反应性的患病率、诊断实用性及相关特征
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数字化用药依从性和肺功能测量在指导未控制哮喘治疗中的应用（INCA Sun）：一项多中心、单盲、随机临床试验
