Lack of improvement of impaired chemical clearance characterizes PPI-refractory reflux-related heartburn
Lack of improvement of impaired chemical clearance characterizes PPI-refractory reflux-related heartburn
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DOI：
10.1038/s41395-018-0044-5
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发表时间：
2018-05-01
影响因子：
9.8
通讯作者：
Savarino, Edoardo
中科院分区：
文献类型：
--
作者：
Frazzoni, Marzio;Frazzoni, Leonardo;Savarino, Edoardo
目的：胃灼热是反流性疾病最特异性的症状，对质子泵抑制剂（PPI）治疗反应强烈。一些患者对质子泵抑制剂没有反应，但其难治性的机制尚未完全阐明。阻抗- ph监测，允许对反流进行全面的治疗评估，是研究PPI难治性的一个有价值的测试。方法：前瞻性多中心研究，比较内窥镜阴性的ppi难治性和ppi反应性胃灼热患者。通过非ppi阻抗- ph监测证实了反流疾病，并通过非ppi阻抗- ph监测研究了顽固性机制。阻抗- ph示踪的评估包括常规参数、反流后吞咽诱发蠕动波（PSPW）指数和平均夜间基线阻抗（MNBI）。结果：64例患者进入研究，其中32例为ppi难治性胃灼热，32例为ppi反应性胃灼热。在PPI方面，两组间胃酸和食管酸暴露时间和反酸次数的中位数百分比无差异；相反，ppi难治性病例的总酸返流数和弱酸性返流数以及丸内暴露百分比显著较高，而PSPW指数和MNBI显著较低。多因素logistic回归分析显示，PSPW指数是PPI难治性的唯一独立危险因素（OR 1.082, 95% CI 1.022-1.146, P = 0.007）。比较关闭和打开ppi参数，ppi难治性患者的中位PSPW指数没有变化（24%对26%，P = 0.327），但ppi反应性患者的中位PSPW指数显著增加（29%对46%，P < 0.001）。结论：受损的化学清除缺乏改善是PPI难治性的主要决定因素。及时的反流后唾液吞咽是ppi难治性反流相关胃灼热的关键防御机制和未来治疗方式的潜在目标。
Objective: Heartburn is the most specific symptom of reflux disease and is highly responsive to proton pump inhibitor (PPI) therapy. Some patients do not respond to PPIs, but mechanisms of refractoriness have not yet been fully elucidated. Impedance-pH monitoring, allowing comprehensive on-therapy assessment of reflux, represents a valuable test to investigate PPI refractoriness.Methods: Prospective multicenter study comparing endoscopy-negative patients with PPI-refractory and PPI-responsive heartburn. Reflux disease was demonstrated by off-PPI impedance-pH monitoring and mechanisms of refractoriness were studied with on-PPI impedance-pH monitoring. Assessment of impedance-pH tracings comprised conventional parameters, post-reflux swallow-induced peristaltic wave (PSPW) index, and mean nocturnal baseline impedance (MNBI).Results : Sixty-four patients entered the study, 32 with PPI-refractory and 32 with PPI-responsive heartburn. On PPI, median percentage gastric and esophageal acid exposure time and number of acid refluxes did not differ between the two groups; conversely, number of total and weakly acidic refluxes and percentage bolus exposure were significantly higher while PSPW index and MNBI were significantly lower in PPI-refractory cases. At multivariate logistic regression analysis, PSPW index was the sole independent risk factor for PPI refractoriness (OR 1.082, 95% CI 1.022-1.146, P = 0.007). Comparing off-and on-PPI parameters, median PSPW index did not change in PPI-refractory patients (24% vs. 26%, P = 0.327) but increased significantly in PPI-responsive cases (29% vs. 46%, P < 0.001).Conclusions: Lack of improvement of impaired chemical clearance is a major determinant of PPI refractoriness. Timely post-reflux salivary swallowing represents a key defensive mechanism and a potential target for future treatment modalities in PPI-refractory reflux-related heartburn.