不同亚型胃食管反流病患者呼气中挥发性标志物的筛选

Screening and Diagnostic Value of Volatile Markers in Exhaled Breath of Patients with Gastroesophageal Reflux Disease

目的筛选胃食管反流病(GERD)及不同亚型GERD呼出气体中挥发性有机化合物(VOCs),评价其在诊断GERD中的价值。方法2019年11月至2020年10于新疆维吾尔自治区人民医院住院治疗的GERD患者及健康体检的人群作为研究对象。以内镜及食管24 h pH监测结果为标准,收集不同亚型GERD及非GERD呼气标本共126例。利用固相微萃取联用气相色谱-质谱分析样本中的VOCs,通过MPP软件分析并筛选出GERD及GERD亚型的特异性VOCs标志物,并采用受试者工作特征曲线(ROC)评价其在诊断GERD中的价值。结果不同亚型GERD患者的体质量,体质量指数与对照组比较有统计学差异(P<0.05),而平均年龄无差异(P>0.05)。GC-MS结果显示,GERD组与非GERD组比较筛选出了正十二烷、正十六烷、5-甲基-十一烷、5-乙基癸烷等4种差异性VOCs;不同亚型GERD分别与对照比较,糜烂性食管炎伴病理性酸反流筛选出正十四烷、正十六烷、5-甲基-十一烷和5-丙基壬烷等4种差异性VOCs;非糜烂性反流病筛选出邻三氟甲基苯甲酸,2-甲基-十一烷及正十二烷等3种差异性VOCs;糜烂性食管炎伴生理性酸反流筛选出5-甲基-十一烷、5-乙基癸烷、5-丙基壬烷等3种差异性VOCs。ROC曲线显示,5-乙基癸烷诊断GERD的灵敏度80.90%,特异度47.61%(P>0.05),无参考价值。5-甲基-十一烷灵敏度88.40%,特异度48.40%。正十二烷灵敏度91.20%,特异度53.85%。正十六烷灵敏度91.20%,特异度53.86%。结论5-甲基-十一烷、正十二烷和正十六烷可作为筛选GERD和非GERD人群的标志性VOCs,其中正十二烷可能作为早期诊断GERD的新参考指标。

Objective To screen out specific VOCs associated with GERD and different phenotypes of GERD and further evaluate their value in the diagnosis of GERD.Methods The study subjects were grouped based on endoscopic findings and esophageal 24 h pH monitoring results.Breath specimens from GERD patients and healthy control patients were collected,and VOCs in the samples were analyzed by combined SPEM/GC-MS technique,and VOCs markers of GERD and GERD subtypes were screened by comparison with MPP software,and their value in the diagnosis of GERD was evaluated by ROC curve.Results There were significant differences in body weight and BMI between different subtypes of GERD and control group(P<0.05),but no difference in age(P>0.05);Four VOCs with significant differences,including n-dodecane,n-hexadecane,5-methyl-undecane and 5-ethyldecane,were screened in GERD compared with the control group.N-tetradecane,n-hexadecane,5-methyl-undecane and 5-propylnonane were screened in EE+pH+group.O-trifluoromethylbenzoic acid,2-methyl-undecane and n-dodecane,were screened in NERD.5-methyl-undecane,5-ethyl-decane and 5-propyl-nonane were screened in EE+pH-.By making ROC curves,we found that the sensitivity of 5-ethyl-decane for the diagnosis of GERD was 80.90%,specificity 47.61%(P>0.05),but no reference value.5-methyl-undecane had 88.40%sensitivity and 48.40%specificity.The sensitivity of n-dodecane was 91.20%and the specificity was 53.85%.The sensitivity of n-hexadecane was 91.20%and the specificity was 53.86%.Conclusion 5-methyl-undecane,n-dodecane and n-hexadecane can be used as landmark VOCs for early discri mination between GERD patients and healthy populations,among which n-dodecane may serve as a new reference indicator for early diagnosis of GERD.