Northwestern University, Feinberg School of Medicine, Division of Gastroenterology and Hepatology, Department of Medicine, 676 N St Clair Street, Chicago, IL 60611, USA.
Gut. 2012 Oct;61(10):1501-9. doi: 10.1136/gutjnl-2011-301898. Epub 2012 Jun 8.
Treatment modalities for gastro-oesophageal reflux disease (GORD) mirror the pathophysiology of the disease. Since acid plays a key role in GORD-associated mucosal lesions, proton pump inhibitors (PPIs) are the dominant GORD treatment, being the most potent inhibitors of acid secretion available. However, the clinical effectiveness of PPIs varies with the specific symptoms being treated; they are more effective for heartburn than for regurgitation than for extra-oesophageal symptoms. An alternative therapeutic approach to GORD is to prevent the most fundamental cause of reflux symptoms, reflux itself, which most commonly occurs by transient lower oesophageal sphincter relaxation (TLOSR). Among potential pharmaceutical agents developed to target TLOSRs, the most advanced are GABA(B) (γ-aminobutyric acid) agonists, which experimentally reduce the occurrence of TLOSRs by about 40% in both animal and human studies. However, the effectiveness of GABA(B) agonists in clinical trials of patients with GORD with an incomplete response to PPI treatment has been modest. In part, this is probably attributable to the difficult problem of patient selection in these trials. Identifying patients by partial response to PPI treatment results in a heterogeneous population, including those with persistent weakly acidic reflux, patients with visceral hypersensitivity and those with functional heartburn, dyspepsia, or chest pain. From the clinical data available, the best treatment results and, hence, the patients most likely to benefit from reflux inhibitors, are those with persistent reflux, most commonly manifest as persistent regurgitation despite PPI treatment.
胃食管反流病（GORD）的治疗方式反映了疾病的病理生理学。由于酸在 GORD 相关黏膜损伤中起关键作用，质子泵抑制剂（PPIs）是 GORD 的主要治疗方法，是目前可用的最强胃酸分泌抑制剂。然而，PPIs 的临床疗效因治疗的具体症状而异；它们对烧心比反流更有效，对食管外症状则效果较差。GORD 的另一种治疗方法是预防反流症状的最根本原因，即反流本身，这主要是通过短暂性食管下括约肌松弛（TLOSR）发生的。在针对 TLOSRs 开发的潜在药物中，最先进的是 GABA(B)（γ-氨基丁酸）激动剂，在动物和人体研究中，这些激动剂可将 TLOSRs 的发生减少约 40%。然而，GABA(B) 激动剂在对 PPI 治疗反应不完全的 GORD 患者临床试验中的有效性并不显著。部分原因可能是这些试验中患者选择存在困难。通过 PPI 治疗的部分反应来识别患者会导致人群异质性，包括持续弱酸性反流的患者、内脏高敏感的患者以及功能性烧心、消化不良或胸痛的患者。根据现有临床数据，最好的治疗效果，因此最有可能从反流抑制剂中受益的患者，是那些有持续反流的患者，最常见的表现是尽管接受 PPI 治疗仍持续反流。
