Sweat metabolomics before and after intravenous antibiotics for pulmonary exacerbation in people with cystic fibrosis.
Sweat metabolomics before and after intravenous antibiotics for pulmonary exacerbation in people with cystic fibrosis.
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DOI：
10.1016/j.rmed.2021.106687
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发表时间：
2022-01
影响因子：
4.3
通讯作者：
Hayes D Jr
中科院分区：
文献类型：
--
作者：
Woodley FW;Gecili E;Szczesniak RD;Shrestha CL;Nemastil CJ;Kopp BT;Hayes D Jr
囊性纤维化(PWCF)患者患有急性不可预测的肺功能下降，与肺恶化(PEX)相关，可能需要住院治疗。Pex症状在没有通用诊断标准的PWCF和对治疗的反应之间存在差异。我们研究了静脉(IV)抗生素治疗PEX前后PWCF患者汗液代谢的变化，以确定静脉注射抗生素治疗PEX的可行性和生物学改变。临床病例均为因静脉注射抗生素需住院治疗的Pex患者。在入院时、开始静脉注射抗生素前和出院前完成后，使用Macroducts®汗液收集系统采集汗液样本。使用超高效液相色谱/串联准确质谱仪分析样品中代谢物的变化。29名住院的PWCF中有26人完成了整个研究。在汗液样本中共检测到326种已知身份的化合物。在检测到的代谢物中，147个在开始静脉注射抗生素之前和完成Pex后(平均治疗14天)之间有显著差异。静脉注射抗生素治疗前后的全球汗液代谢发生了变化。我们发现了预测PEX状态的特定代谢物特征，以及与PEX相关的丰富的生物途径。然而，未恢复到基线肺功能的PWCF患者和未恢复到基线肺功能患者的代谢变化相似。我们的研究结果证明了非侵入性汗液代谢图谱在PWCF中的可行性，以及汗液代谢组学作为一种前瞻性的诊断和研究工具的潜力，以进一步促进我们对PWCF中PEX的理解。
People with cystic fibrosis (PWCF) suffer from acute unpredictable reductions in pulmonary function associated with a pulmonary exacerbation (PEx) that may require hospitalization. PEx symptoms vary between PWCF without universal diagnostic criteria for diagnosis and response to treatment. We characterized sweat metabolomes before and after intravenous (IV) antibiotics in PWCF hospitalized for PEx to determine feasibility and define biological alterations by IV antibiotics for PEx. PWCF with PEx requiring hospitalization for IV antibiotics were recruited from clinic. Sweat samples were collected using the Macroduct® Sweat Collection System at admission prior to initiation of IV antibiotics and after completion prior to discharge. Samples were analyzed for metabolite changes using ultra-high-performance liquid chromatography/tandem accurate mass spectrometry. Twenty-six of 29 hospitalized PWCF completed the entire study. A total of 326 compounds of known identity were detected in sweat samples. Of detected metabolites, 147 were significantly different between pre-initiation and post-completion of IV antibiotics for PEx (average treatment 14 days). Global sweat metabolomes changed from before and after IV antibiotic treatment. We discovered specific metabolite profiles predictive of PEx status as well as enriched biologic pathways associated with PEx. However, metabolomic changes were similar in PWCF who failed to return to baseline pulmonary function and those who did not. Our findings demonstrate the feasibility of non-invasive sweat metabolomic profiling in PWCF and the potential for sweat metabolomics as a prospective diagnostic and research tool to further advance our understanding of PEx in PWCF.
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