Department of Respiratory Sciences and.
Department of Chemistry, University of Leicester, Leicester, United Kingdom.
Am J Respir Crit Care Med. 2024 Nov 1;210(9):1101-1112. doi: 10.1164/rccm.202310-1759OC.
Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker signature to predict sputum eosinophilia in asthma. VOCs emitted into the space above sputum samples (headspace) from patients with severe asthma ( = 36) were collected onto sorbent tubes and analyzed using thermal desorption gas chromatography-mass spectrometry (GC-MS). Elastic net regression identified stable VOCs associated with sputum eosinophilia ⩾ 3% and generated a volatile biomarker signature. This VOC signature was validated in breath samples from: ) patients with acute asthma according to blood eosinophilia ⩾0.3 × 10cells/L or sputum eosinophilia of ⩾3% in the UK EMBER (East Midlands Breathomics Pathology Node) consortium ( = 65) and ) U-BIOPRED-IMI (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes Innovative Medicines Initiative) consortium ( = 42). Breath samples were collected onto sorbent tubes (EMBER) or Tedlar bags (U-BIOPRED) and analyzed by GC-MS (GC × GC-MS for EMBER or GC-MS for U-BIOPRED). The headspace identified 19 VOCs associated with sputum eosinophilia, and the derived VOC signature yielded good diagnostic accuracy for sputum eosinophilia ⩾3% in headspace (area under the receiver operating characteristic curve [AUROC] 0.90; 95% confidence interval [CI], 0.80-0.99; < 0.0001), correlated inversely with sputum eosinophil percentage ( = -0.71; < 0.0001), and outperformed fractional exhaled nitric oxide (AUROC 0.61; 95% CI, 0.35-0.86). Analysis of exhaled breath in replication cohorts yielded a VOC signature AUROC (95% CI) for acute asthma exacerbations of 0.89 (0.76-1.0) (EMBER cohort) with sputum eosinophilia and 0.90 (0.75-1.0) in U-BIOPRED, again outperforming fractional exhaled nitric oxide in U-BIOPRED (0.62 [0.33-0.90]). We have discovered and provided early-stage clinical validation of a volatile biomarker signature associated with eosinophilic airway inflammation. Further work is needed to translate our discovery using point-of-care clinical sensors.
哮喘患者呼出气中的挥发性有机化合物（VOCs）可能与痰中嗜酸性粒细胞增多有关。我们开发了一种挥发性生物标志物特征，以预测哮喘患者的痰嗜酸性粒细胞增多。从严重哮喘患者（ = 36 人）的痰样本上方空间（顶空）收集到的 VOCs 被收集到吸附管中，并使用热解吸气相色谱-质谱法（GC-MS）进行分析。弹性网络回归确定了与痰嗜酸性粒细胞增多 ⩾ 3%相关的稳定 VOCs，并生成了挥发性生物标志物特征。该 VOC 特征在英国 EMBER（东米德兰呼吸组学病理节点）联盟中根据血液嗜酸性粒细胞计数 ⩾0.3 × 10cells/L 或痰嗜酸性粒细胞计数 ⩾3%的急性哮喘患者（ = 65 人）和 U-BIOPRED-IMI（预测呼吸道疾病结果的无偏生物标志物创新药物倡议）联盟（ = 42 人）的呼吸样本中得到了验证。呼吸样本被收集到吸附管（EMBER）或 Tedlar 袋（U-BIOPRED）中，并通过 GC-MS（EMBER 为 GC-×-GC-MS，U-BIOPRED 为 GC-MS）进行分析。顶空分析确定了 19 种与痰嗜酸性粒细胞增多相关的 VOCs，衍生的 VOC 特征对头空间中痰嗜酸性粒细胞增多 ⩾3%具有良好的诊断准确性（接受者操作特征曲线下面积 [AUROC] 0.90；95%置信区间 [CI]，0.80-0.99； < 0.0001），与痰嗜酸性粒细胞百分比呈负相关（ = -0.71； < 0.0001），并优于呼出气一氧化氮分数（AUROC 0.61；95% CI，0.35-0.86）。在复制队列中分析呼气样本得到了急性哮喘发作时的 VOC 特征 AUROC（95% CI），对于 EMBER 队列中存在痰嗜酸性粒细胞增多的患者为 0.89（0.76-1.0），对于 U-BIOPRED 为 0.90（0.75-1.0），再次在 U-BIOPRED 中优于呼出气一氧化氮分数（0.62 [0.33-0.90]）。我们已经发现并提供了一种与嗜酸性气道炎症相关的挥发性生物标志物特征的早期临床验证。需要进一步的工作来使用即时护理临床传感器来转化我们的发现。
