Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus, OH, USA.
Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Respir Med. 2022 Jan;191:106687. doi: 10.1016/j.rmed.2021.106687. Epub 2021 Nov 23.
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.
囊性纤维化（CF）患者的肺部功能会突然出现不可预测的下降，这与肺部恶化（PEx）有关，可能需要住院治疗。PEx 的症状因缺乏用于诊断和治疗反应的通用诊断标准而在 CF 患者中有所不同。
我们对因 PEx 而住院接受静脉（IV）抗生素治疗的 CF 患者进行了 IV 抗生素治疗前后的汗液代谢组学分析，以确定其可行性，并确定 IV 抗生素治疗 PEx 时的生物学变化。
从诊所招募了因 PEx 需要住院接受 IV 抗生素治疗的 CF 患者。在开始 IV 抗生素治疗前和完成 IV 抗生素治疗前在入院时使用 Macroduct®汗液采集系统采集汗液样本。使用超高效液相色谱/串联精确质量质谱法分析样本中的代谢物变化。
29 名住院 CF 患者中有 26 名完成了整个研究。在汗液样本中检测到 326 种已知身份的化合物。在检测到的代谢物中，有 147 种在因 PEx 接受 IV 抗生素治疗前和治疗完成后的差异有统计学意义（平均治疗 14 天）。全球汗液代谢组在接受 IV 抗生素治疗前后发生了变化。我们发现了与 PEx 状态相关的特定代谢物特征以及与 PEx 相关的富集生物学途径。然而，在未能恢复到基线肺功能的和那些恢复到基线肺功能的 CF 患者中，代谢组学变化相似。
我们的研究结果表明，非侵入性汗液代谢组学分析在 CF 患者中是可行的，并且汗液代谢组学有可能成为一种前瞻性的诊断和研究工具，以进一步深入了解 CF 患者的 PEx。
