放射性肺损伤是治疗胸腔癌症的放疗的后果。研究报告称，接受放疗的患者中高达80%会出现CT可检测的间质性肺异常，而限制放射性肺损伤的策略可能会降低放疗治疗癌症的效果。我们实验室和其他一些实验室报道称，患有特发性肺纤维化的患者的肺组织存在代谢缺陷，包括增加的糖酵解和乳酸生产。在这里，我们假设患有放射性肺损伤的患者将展现与纤维化发生率有关的明显肺代谢变化。利用液相色谱/串联质谱鉴定代谢化合物，我们分析了经CT确认肺部损伤的肺癌放疗受试者的呼出气冷凝物（EBC），并将其与健康受试者、吸烟者和尚未接受放疗的肺癌患者进行比较。纤维化病例组的肺代谢组学特征与3个对照组明显不同。除了乳酸水平的增加外，通路富集分析揭示病例患者的EBC表现出脂肪酸氧化和谷氨酸通路的上调。由于辐射引起的有氧糖酵解和乳酸产生驱动肌成纤维细胞分化，我们的结果支持此假设——将丙酮酸优选转化为乳酸会减少三羧酸循环的一个关键输入，需要上调代替能量输入以满足慢性创伤修复的代谢需求。以Noninvasive方式探究肺疾病的“组学”方法有助于未来的机理研究和新型治疗靶点的开发。

Radiation-induced lung injury is a consequence of therapeutic irradiation (TR) for thoracic cancers. Studies report that up to 80% of patients who undergo TR will have CT-detectable interstitial lung abnormalities, and strategies to limit the risk of RILI may make radiotherapy less effective at treating cancer. Our lab and others have reported that lung tissue from patients with idiopathic pulmonary fibrosis exhibit metabolic defects including increased glycolysis and lactate production. Here, we hypothesized that patients with radiation-induced lung damage will exhibit distinct changes in lung metabolism that may be associated with incidence of fibrosis. Using liquid chromatography/tandem mass spectrometry to identify metabolic compounds, we analyzed exhaled breath condensate (EBC) in subjects with CT-confirmed lung lesions after TR for lung cancer, compared to healthy subjects, smokers, and cancer patients who had not yet received TR. The lung metabolomic profile of the fibrosis case group was significantly different from the 3 control groups. Along with increased levels of lactate, pathway enrichment analysis revealed that EBC from the case patients exhibited upregulations of the fatty acid oxidation and glutamate pathways. As radiation induces aerobic glycolysis and production of lactate which drives myofibroblast differentiation, our results support the hypothesis that preferential conversion of pyruvate to lactate deprives the tricarboxylic acid cycle of a key input, requiring compensatory upregulation of alternative energy inputs to meet the metabolic demands of chronic wound repair. Utilizing an 'omics' approach to probe lung disease in a non-invasive manner could inform future mechanistic investigations and development of novel therapeutic targets.