Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, South Carolina, USA.
Am J Gastroenterol. 2011 May;106(5):844-50. doi: 10.1038/ajg.2010.476. Epub 2010 Dec 21.
Refractory heartburn despite acid suppression may be explained by ongoing gastroesophageal reflux disease (GERD) or functional heartburn (FH), i.e., symptoms without evidence of GERD. Impedance-pH monitoring (impedance-pH) detects acid and nonacid reflux and is useful for evaluating acid-suppressed, refractory patients. Intercellular space diameter (ISD) of esophageal epithelium measured by transmission electron microscopy (TEM) is a marker of epithelial damage present in both erosive and nonerosive reflux disease. ISD has not been used to study refractory heartburn or FH. Our aim was to compare ISD in healthy controls and refractory heartburn patients with GERD and FH.
In refractory heartburn patients (heartburn more than twice/week for at least 2 months despite proton pump inhibitor (PPI) b.i.d.), erosive esophagitis and/or abnormal impedance-pH (increased acid exposure or positive symptom index) defined GERD; normal esophagogastroduodenoscopy (EGD)/impedance-pH defined FH. Asymptomatic, healthy controls had normal EGD and pH-metry. Mean ISD in each subject, determined by blinded TEM of esophageal biopsies, was the average of 100 measurements (10 measurements in each of 10 micrographs).
In all, 11 healthy controls, 11 FH, and 15 GERD patients were studied. Mean ISD was significantly higher in GERD compared with controls (0.87 vs. 0.32 μm, P=0.003) and FH (0.87 vs. 0.42 μm, P=0.012). Mean ISD was similar in FH and controls (0.42 vs. 0.32 μm, P=0.1). The proportion of patients with abnormal ISD was significantly higher for GERD compared with FH (60 vs. 9%, P=0.014).
ISD is increased in refractory heartburn patients with GERD but not those with FH. Our findings suggest that measurement of ISD by TEM might be a useful tool to distinguish GERD from FH in patients with refractory heartburn.
尽管进行了抑酸治疗，但仍存在难治性烧心，这可能是由胃食管反流病（GERD）或功能性烧心（FH）引起的，即存在烧心症状而无 GERD 的证据。阻抗-pH 监测（impedance-pH）可检测酸反流和非酸反流，有助于评估抑酸治疗后仍存在烧心的患者。透射电子显微镜（TEM）测量的食管上皮细胞间隙直径（ISD）是糜烂性和非糜烂性反流病中存在的上皮损伤的标志物。目前尚未将 ISD 用于研究难治性烧心或 FH。我们的目的是比较健康对照组和 GERD 及 FH 相关难治性烧心患者的 ISD。
在难治性烧心患者（质子泵抑制剂（PPI）bid 治疗至少 2 个月，每周烧心超过 2 次）中，存在糜烂性食管炎和/或阻抗-pH 异常（酸暴露增加或阳性症状指数）定义为 GERD；正常食管胃十二指肠镜（EGD）/阻抗-pH 定义为 FH。无症状的健康对照组 EGD 和 pH 监测正常。通过食管活检的 TEM 进行盲法分析，得出每位患者的平均 ISD，由 10 张显微镜照片中的 10 个测量值（每个测量值 10 次）的平均值计算得出。
共纳入 11 名健康对照组、11 名 FH 患者和 15 名 GERD 患者。GERD 组的平均 ISD 明显高于对照组（0.87μm 比 0.32μm，P=0.003）和 FH 组（0.87μm 比 0.42μm，P=0.012）。FH 组和对照组的平均 ISD 相似（0.42μm 比 0.32μm，P=0.1）。GERD 组异常 ISD 患者的比例明显高于 FH 组（60%比 9%，P=0.014）。
GERD 相关难治性烧心患者的 ISD 增加，但 FH 相关难治性烧心患者的 ISD 无增加。我们的研究结果表明，TEM 测量 ISD 可能是一种有用的工具，可用于区分难治性烧心患者的 GERD 和 FH。
