Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness.
Visualization of exhaled breath metabolites reveals distinct diagnostic signatures for acute cardiorespiratory breathlessness.
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呼气代谢物的可视化显示急性心肺呼吸困难的独特诊断特征。
DOI：
10.1126/scitranslmed.abl5849
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发表时间：
2022-11-16
影响因子：
17.1
通讯作者：
Shaw JA
中科院分区：
文献类型：
--
作者：
Ibrahim W;Wilde MJ;Cordell RL;Richardson M;Salman D;Free RC;Zhao B;Singapuri A;Hargadon B;Gaillard EA;Suzuki T;Ng LL;Coats T;Thomas P;Monks PS;Brightling CE;Greening NJ;Siddiqui S;EMBER Consortium;Munton R;Le Quesne J;Goodall AH;Pandya HC;Reynolds JC;Clokie MRJ;Samani NJ;Barer MR;Shaw JA
急性心肺呼吸困难占所有急诊住院病例的八分之一。早期的非侵入性诊断测试是临床上的优先事项，可以进行快速分诊和治疗。在这里，我们试图发现和复制急性心肺疾病的呼吸挥发性有机化合物(VOC)生物标志物，了解呼吸代谢网络在急性疾病中的丰富，以期获得对呼吸生化紊乱的机制认识。我们收集并分析了277名表现为急性心肺疾病恶化的参与者和年龄匹配的健康志愿者的呼气样本。拓扑数据分析(TDA)表型区分急性疾病与健康和急性心肺疾病加重亚型[急性心力衰竭、急性哮喘、急性慢性阻塞性肺疾病(COPD)和社区获得性肺炎]。多生物标记物评分(10 1个呼吸生物标记物)在发现和复制两组中均显示出良好的诊断敏感性和特异性(≥80%)，并与2年后的全因死亡率相关。此外，VOC生物标记物评分可区分心肺疾病恶化的代谢亚组。结合代谢物浓缩和相似性评估的Louvain VOCs聚类法揭示了所有急性疾病亚组中高度特异的浓缩模式，例如心力衰竭时相关C5-7碳氢化合物和C3-5羰基的选择性浓缩，以及急性哮喘中相关醛的选择性耗竭。这项研究确定了区分急性心肺疾病恶化的呼吸VOCs以及与疾病相关的VOCs亚型和代谢簇。
Acute cardiorespiratory breathlessness accounts for 1 in 8 of all emergency hospitalisations. Early, non-invasive diagnostic testing is a clinical priority that allows rapid triage and treatment. Here, we sought to discover and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements. We collected and analysed exhaled breath samples from 277 participants presenting with acute cardiorespiratory exacerbations and aged matched healthy volunteers. Topological data analysis (TDA) phenotypes differentiated acute disease from health and acute cardiorespiratory exacerbation subtypes [acute heart failure, acute asthma, acute Chronic Obstructive Pulmonary Disease (COPD) and community-acquired pneumonia]. A multi-biomarker score (101 breath biomarkers) demonstrated good diagnostic sensitivity and specificity (≥ 80%) in both discovery and replication sets and was associated with all-cause mortality at 2 years. In addition, VOC biomarker scores differentiated metabolic subgroups of cardiorespiratory exacerbation. Louvain clustering of VOCs coupled with metabolite enrichment and similarity assessment revealed highly specific enrichment patterns in all acute disease subgroups, for example selective enrichment of correlated C5-7 hydrocarbons and C3-5 carbonyls in heart failure and selective depletion of correlated aldehydes in acute asthma. This study identified breath VOCs that differentiate acute cardiorespiratory exacerbations and associated subtypes and metabolic clusters of disease-associated VOCs.
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影响因子：
2.9
作者：
Ibrahim, Wadah;Wilde, Michael;Siddiqui, Salman
通讯作者：
Siddiqui, Salman
LabPipe：可扩展的生物信息学工具包，用于管理实验数据和元数据。
影响因子：
3
作者：
Zhao B;Bryant L;Cordell R;Wilde M;Salman D;Ruszkiewicz D;Ibrahim W;Singapuri A;Coats T;Gaillard E;Beardsmore C;Suzuki T;Ng L;Greening N;Thomas P;Monks P;Brightling C;Siddiqui S;Free RC
通讯作者：
Free RC
影响因子：
3.8
作者：
Phan, Joann;Meinardi, Simone;Whiteson, Katrine
通讯作者：
Whiteson, Katrine
影响因子：
3.8
作者：
Pizzini, Alex;Filipiak, Wojciech;Bellmann-Weiler, Rosa
通讯作者：
Bellmann-Weiler, Rosa
影响因子：
3.1
作者：
Hutchinson A;Pickering A;Williams P;Bland JM;Johnson MJ
通讯作者：
Johnson MJ