Molecular breath analysis supports altered amino acid metabolism in idiopathic pulmonary fibrosis
Molecular breath analysis supports altered amino acid metabolism in idiopathic pulmonary fibrosis
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DOI：
10.1111/resp.13465
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发表时间：
2019-05-01
期刊：
影响因子：
6.9
通讯作者：
Kohler, Malcolm
中科院分区：
文献类型：
--
作者：
Gaugg, Martin Thomas;Engler, Anna;Kohler, Malcolm
背景与目的特发性肺纤维化（IPF）诊断复杂，发病机制尚不清楚。最近的研究结果表明，IPF患者肺组织中脯氨酸和其他氨基酸水平升高，这也可能具有诊断价值。根据这些发现，我们假设这种改变的代谢谱将反映在呼出气中，因此可以在真实的时间内无创地捕获。方法我们的目的是验证这些结果，使用实时呼出气分析二次电喷雾电离质谱，它可以提供一个非侵入性的，无痛的和快速的洞察代谢。在一项匹配的1：1病例对照研究中进行了呼吸分析，该研究涉及21例IPF患者和21例对照受试者。结果IPF患者呼气中脯氨酸、4-羟脯氨酸、丙氨酸、缬氨酸、亮氨酸/异亮氨酸和丙氨酸水平显著升高（P < 0.05），而焦谷氨酸和苯丙氨酸水平无显著性差异。这与肺组织中氨基酸的丰度一致，表明我们的观察反映了纤维化的进展。此外，氨基酸水平在受试者之间相关，进一步支持共同的潜在途径。我们能够获得0.86的交叉验证曲线下面积，表明呼出气中这些增加的氨基酸水平有可能用作IPF的生物标志物。结论我们可以验证先前发现的IPF患者肺组织氨基酸水平升高，并表明在线呼吸分析可能是快速筛查IPF的实用工具。
Background and objective Diagnosis of idiopathic pulmonary fibrosis (IPF) is complex and its pathogenesis is poorly understood. Recent findings indicate elevated levels of proline and other amino acids in lung tissue of IPF patients which may also be of diagnostic value. Following these findings, we hypothesized that such altered metabolic profiles would be mirrored in exhaled breath and could therefore be captured non-invasively in real time. Methods We aimed to validate these results using real-time exhaled breath analysis by secondary electrospray ionization-mass spectrometry, which can provide a non-invasive, painless and fast insight into the metabolism. Breath analysis was performed in a matched 1:1 case-control study involving 21 patients with IPF and 21 control subjects. Results We found significantly (P < 0.05) elevated levels of proline, 4-hydroxyproline, alanine, valine, leucine/isoleucine and allysine in breath of IPF patients, whereas pyroglutamic acid and phenylalanine did not show significant differences. This coincides with the amino acid's abundance in pulmonary tissue indicating that our observations reflect progressing fibrosis. In addition, amino acid levels correlated across subjects, further supporting a common underlying pathway. We were able to obtain a cross-validated area under the curve of 0.86, suggesting that these increased amino acid levels in exhaled breath have the potential to be used as biomarkers for IPF. Conclusion We could validate previous findings of elevated lung tissue amino acid levels in IPF and show that online breath analysis might be a practical tool for a rapid screening for IPF.