Orlando Roy C
Department of Medicine, Tulane University Medical School, New Orleans, Louisiana 70112, USA.
Drugs. 2006;66 Suppl 1:1-5; discussion 29-33. doi: 10.2165/00003495-200666001-00002.
Gastro-oesophageal reflux disease (GERD) covers a broad range of signs and symptoms arising from the orad movement of gastric contents into the oesophagus, oropharynx, larynx or airway. Most commonly, contact with and damage to the oesophageal epithelium by acidic refluxate causes micro or macroscopic defects leading to the symptom of heartburn. However, GERD can also give rise to extra-oesophageal manifestations such as pharyngitis, laryngitis, asthma and other disorders, identifiable as acid-mediated events by a favorable response to acid suppression. Only one-third of individuals with heartburn have endoscopic evidence of erosive oesophagitis; the remainder have endoscopy-negative or non-erosive reflux disease (NERD). Improved investigative technologies are increasing our understanding of the pathophysiology of NERD. For example, although a number of microscopic abnormalities have been identified, oesophageal damage in NERD has been shown to be characterized by the presence of 'dilated intercellular spaces' within oesophageal stratified squamous epithelium. Dilated intercellular spaces that reflect damage to the intercellular junctions enable levels of acidity that would be considered innocuous when present in the oesophageal lumen to initiate pathological responses within oesophageal nociceptors when present within the intercellular spaces. This effectively gives rise to the symptom of heartburn. Excessive acidity within the intercellular spaces in NERD also presages its evolution to erosive disease, the latter through inflammation-mediated disruption of the antireflux and luminal clearance mechanisms. Support for this scenario is evident by the ability of effective acid control with proton pump inhibitors both to control symptoms, and lead to resolution of dilated intercellular spaces in patients with both erosive and non-erosive disease. This article examines these concepts and how they shape our current understanding of GERD.
胃食管反流病（GERD）涵盖了一系列因胃内容物向食管、口咽、喉或气道的逆蠕动而产生的体征和症状。最常见的情况是，酸性反流物与食管上皮接触并造成损伤，导致微观或宏观上的缺损，进而引发烧心症状。然而，GERD也可能引发食管外表现，如咽炎、喉炎、哮喘和其他疾病，通过对抑酸治疗的良好反应可将这些表现识别为酸介导的事件。只有三分之一有烧心症状的个体在内镜检查时有糜烂性食管炎的证据；其余患者则为内镜检查阴性或非糜烂性反流病（NERD）。改进后的检查技术正在加深我们对NERD病理生理学的理解。例如，尽管已经发现了一些微观异常，但NERD中的食管损伤表现为食管复层鳞状上皮内存在“细胞间间隙增宽”。反映细胞间连接受损的细胞间间隙增宽，使得当存在于食管腔内时被认为无害的酸度水平，在存在于细胞间间隙时能够引发食管伤害感受器内的病理反应。这实际上就引发了烧心症状。NERD中细胞间间隙内的过度酸度也预示着其向糜烂性疾病的演变，后者是通过炎症介导的抗反流和管腔清除机制的破坏。质子泵抑制剂有效控制胃酸能够同时控制症状，并使糜烂性和非糜烂性疾病患者的细胞间间隙增宽得到缓解，这一现象证明了上述情况。本文探讨了这些概念以及它们如何塑造了我们目前对GERD的理解。
