| Popis: |
The aims of the present study were to: 1) evaluate a self-administered questionnaire for the assessment of gastroesophageal reflux disease (GERD); 2) compare clinical and pathophysiological features, and the response of symptoms to acid challenge and acid-suppressive therapy in patients with active reflux disease, with or without esophagitis; 3) investigate factors that may affect short-term response of symptoms to acid-suppressive therapy and risk of relapse of esophagitis during long-term treatment; and 4) evaluate if H. pylori infection influences the response to acid-suppressive therapy in GERD.Methods: The diagnostic validity of the questionnaire was tested against endoscopy and 24-hour intra-esophageal pH monitoring. A further evaluation was undertaken in patients with symptoms suggestive of GERD and in patients with non-ulcer dyspepsia in order to identify factors that might predict symptom relief during short-term treatment with omeprazole. The efficacy of acid-suppressive therapy in the relief of heartburn in patients without esophagitis was investigated in a placebo-controlled study in 509 patients, and compared to patients with esophagitis in another study comprising 538 patients. The integrity of the esophageal epithelium in patients with active GERD, with or without esophagitis, was assessed by potential difference (PD) measurements during acid perfusion, and compared to healthy controls. Data from 1154 patients with reflux esophagitis were evaluated in order to identify factors predicting relapse of esophagitis during maintenance therapy. The influence of H. pylori infection on the short and long-term response to treatment with omeprazole was evaluated in 858 patients with reflux esophagitis and 230 patients with endoscopy-negative GERD.Results: Using endoscopic signs of esophagitis and 24-hour pH data as the gold standard , the questionnaire had a sensitivity of 92%, but a very low specificity of 19%. Heartburn, described as a burning feeling rising from the stomach or lower chest up towards the neck , and relief from antacids , predicted relief of symptoms during treatment with omeprazole. Complete relief of dyspeptic symptoms in non-ulcer dyspepsia was confined to the subgroup of patients who identified their main discomfort as heartburn, as described above. Fewer endoscopy-negative patients responded to treatment with omeprazole than those with esophagitis. Symptom relief was achieved more frequently in endoscopy-negative patients with increased pre-treatment esophageal acid reflux. Absence of heartburn, described as above, and a high abdominal pain score before treatment were associated with failure to respond. After cessation of treatment, symptomatic relapse was rapid and frequent in both endoscopy-positive and endoscopy-negative patients. Patients with active GERD, regardless of the presence or absence of esophagitis, responded to acid stress with symptoms and more lumen negative peak PD values, reflecting a greater degree of epithelial permeability to hydrogen ions. The greater epithelial permeability appeared to diminish or resolve with effective medical or surgical therapy. H. pylori infection affected the short-term clinical response to acid-suppressive therapy only marginally, and had no impact on symptomatic relapse after cessation of therapy. During maintenance therapy, the risk of relapse was lower in H. pylori infected patients and in older patients, whereas severe esophagitis before treatment predicted a higher risk of relapse. Symptom relief was highly predictive for the maintenance of healing.Conclusions: The present questionnaire, which uses a descriptive language, seems to be a useful tool to identify heartburn in patients presenting with upper abdominal symptoms. The presence of this symptom predicts symptom resolution during treatment with omeprazole. The lower response rate to treatment with omeprazole in endoscopy-negative patients is probably due to misinterpretation of symptoms of another origin as being due to reflux disease. Epithelial defects associated with reflux disease are partly reversible with effective treatment, but the effectiveness of barrier restoration is precarious as judged by the rapidity of relapse in patients with GERD. Determining the severity of esophagitis and H. pylori status is important in the management of GERD with acid-suppressive therapy, as these are important prognostic factors for efficacy. This suggests that troublesome reflux is best evaluated once by a pre-treatment endoscopy, and that then further management is guided primarily by symptom response in patients with uncomplicated GERD. |
