Nuovo Ospedale S. Agostino, Modena, Italy.
Aliment Pharmacol Ther. 2011 Mar;33(5):601-6. doi: 10.1111/j.1365-2036.2010.04550.x. Epub 2010 Dec 29.
In patients with heartburn that persists despite proton pump inhibitor (PPI) therapy, reflux oesophagitis is found rarely, and its pathogenesis has been scarcely studied.
To assess reflux parameters by impedance-pH monitoring in PPI-resistant reflux oesophagitis.
Impedance-pH monitoring was performed on PPI therapy in patients with symptomatic reflux oesophagitis detected despite standard or high-dose PPI therapy of at least 8-week duration.
Twenty patients, ten on once daily and ten on twice daily PPI regimens, were studied. The gastric acid exposure time (per cent time pH <4) ranged from 10% to 81% and was >30% in 70% of cases, but the oesophageal acid exposure time (per cent time pH <4) was abnormal in 20% of patients only. The number of acid, weakly acidic and weakly alkaline refluxes was abnormal in 25%, 100% and 15% of patients, respectively.
Weakly acidic refluxes were above the normal range in all cases, whereas acid reflux parameters and weakly alkaline refluxes were normal in the vast majority of cases. Gastric acid secretion, with consequent intra-gastric pepsins activation, persists despite ongoing PPI therapy and activated pepsins may well be present in weakly acidic refluxes. As activated pepsins maintain their proteolytic activity in a weakly acidic environment, they may be responsible for mucosal damage. We conclude that weakly acidic refluxes have a major role in the pathogenesis of PPI-resistant reflux oesophagitis. Therapeutic interventions in patients with PPI-resistant reflux oesophagitis should be tailored on the basis of impedance-pH-monitoring results.
尽管质子泵抑制剂 (PPI) 治疗，但仍存在胃灼热的患者，发现反流性食管炎很少见，其发病机制尚未得到充分研究。
通过阻抗-pH 监测评估 PPI 抵抗性反流性食管炎的反流参数。
对标准或高剂量 PPI 治疗至少 8 周后仍存在症状性反流性食管炎的患者进行 PPI 治疗时进行阻抗-pH 监测。
研究了 20 名患者，其中 10 名每天一次服用 PPI，10 名每天两次服用 PPI。胃酸暴露时间（pH <4 的时间百分比）范围为 10%至 81%，70%的病例胃酸暴露时间>30%，但只有 20%的患者食管酸暴露时间（pH <4 的时间百分比）异常。酸、弱酸性和弱碱性反流的次数分别在 25%、100%和 15%的患者中异常。
所有病例的弱酸性反流均高于正常范围，而酸反流参数和弱碱性反流在绝大多数病例中均正常。尽管持续进行 PPI 治疗，但胃泌酸仍持续存在，继而胃蛋白酶激活，激活的胃蛋白酶可能存在于弱酸性反流中。由于激活的胃蛋白酶在弱酸性环境中保持其蛋白水解活性，它们可能是黏膜损伤的原因。我们得出结论，弱酸性反流在 PPI 抵抗性反流性食管炎的发病机制中起主要作用。PPI 抵抗性反流性食管炎患者的治疗干预应根据阻抗-pH 监测结果进行调整。
