Functional heartburnWord文件下载.docx

1、Functional heartburn has more in common with functional dyspepsia than with non-erosive reflux diseaseE Savarino1, D Pohl2, P Zentilin1, P Dulbecco1, G Sammito1, L Sconfienza1, S Vigneri3, G Camerini4, R Tutuian2, V Savarino1 1 Division of Gastroenterology, Department of Internal Medicine, Universit

2、y of Genoa, Genoa, Italy2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital Zurich, Zurich, Switzerland3 Division of Gastroenterology, Department of Internal Medicine, University of Palermo, Palermo, Italy4 Division of Surgery, Department of Internal M

3、edicine, University of Genoa, Genoa, Italy Correspondence to:Correspondence to Dr E Savarino, Cattedra di Gastroenterologia, Universit di Genova, Viale Benedetto XV, 16100 Genova, Italy; edoardo.savarinounige.it Revised version received 6 April 2009 Accepted 16 April 2009ABSTRACT TOPABSTRACTMethodsR

4、esultsDiscussionREFERENCESIntroduction: Functional dyspepsia and non-erosive reflux disease （NERD） are prevalent gastrointestinal conditions with accumulating evidence regarding an overlap between the two. Still, patients with NERD represent a very heterogeneous group and limited data on dyspeptic s

5、ymptoms in various subgroups of NERD are available. Aim: To evaluate the prevalence of dyspeptic symptoms in patients with NERD subclassified by using 24 h impedance-pH monitoring （MII-pH）. Methods: Patients with typical reflux symptoms and normal endoscopy underwent impedance-pH monitoring off prot

6、on pump inhibitor treatment. Oesophageal acid exposure time （AET）, type of acid and non-acid reflux episodes, and symptom association probability （SAP） were calculated. A validated dyspepsia questionnaire was used to quantify dyspeptic symptoms prior to reflux monitoring. Results: Of 200 patients wi

7、th NERD （105 female; median age, 48 years）, 81 （41%） had an abnormal oesophageal AET （NERD pH-POS）, 65 （32%） had normal oesophageal AET and positive SAP for acid and/or non-acid reflux （hypersensitive oesophagus）, and 54 （27%） had normal oesophageal AET and negative SAP （functional heartburn）. Patie

8、nts with functional heartburn had more frequent （p0.01） postprandial fullness, bloating, early satiety and nausea compared to patients with NERD pH-POS and hypersensitive oesophagus. Conclusion: The increased prevalence of dyspeptic symptoms in patients with functional heartburn reinforces the conce

9、pt that functional gastrointestinal disorders extend beyond the boundaries suggested by the anatomical location of symptoms. This should be regarded as a further argument to test patients with symptoms of gastro-oesophageal reflux disease in order to separate patients with functional heartburn from

10、patients with NERD in whom symptoms are associated with gastro-oesophageal reflux. Gastro-oesophageal reflux disease （GORD） is one of the most common chronic gastrointestinal diseases in Western countries.1 2 Recent studies documented that up to 70% of reflux patients have typical reflux symptoms （i

11、e, heartburn and/or regurgitation） in the absence of endoscopically visible oesophageal mucosal injuries, making non-erosive reflux disease （NERD） the more common form of GORD.3 4 The NERD patient group incorporates subgroups which differ significantly in terms of presentation, pathophysiology and m

12、anagement. Patients experiencing typical reflux symptoms without evidence of oesophagitis on upper endoscopy are classified on the basis of oesophageal pH monitoring results and symptom association analysis as suffering either from NERD, when excessive acid reflux or a positive symptom association w

13、ith acid reflux is demonstrated, or from functional heartburn （FH）, when, in agreement with Rome III criteria, distal oesophageal acid exposure is normal and a negative response to acid suppression is found.5 6 Recognising that stimuli other than acid can evoke typical reflux symptoms,7 our group pr

14、eviously proposed subclassifying patients with typical reflux symptoms and normal upper gastrointestinal endoscopy as follows: （1） NERD pH-POS patients with normal endoscopy and abnormal distal oesophageal acid exposure; （2） hypersensitive oesophagus patients with normal endoscopy, normal distal oes

15、ophageal acid exposure and positive symptom association for either acid or non-acid reflux; and （3） functional heartburn patients with normal endoscopy, normal distal oesophageal acid exposure and negative symptom association for acid and non-acid reflux.8 Patients with GORD, both with erosive oesop

16、hagitis and NERD, frequently report dyspeptic symptoms.9 Epidemiological studies investigating the prevalence of dyspeptic and oesophageal symptoms have reported a higher prevalence of dyspeptic symptoms in patients with GORD, suggesting that the degree of overlap is greater than could be predicted

17、by chance alone.10 Moreover, it was recently demonstrated that patients with functional heartburn and poor response to acid suppressive therapy are more likely to have psychopathology similarly to patients with functional dyspepsia.11 Last, but not least, abdominal symptoms appear to be independent

18、predictors of the severity of reflux symptoms in patients with NERD when compared to normal controls.12 Given previous reports indicating an inverse relationship between dyspeptic symptoms and the objective criteria for GORD we hypothesised that in patients with functional heartburn dyspeptic sympto

19、ms should be more prevalent compared to the rest of NERD patients. To test this hypothesis, we evaluated the prevalence of dyspeptic symptoms in patients with NERD subclassified into three distinct groups by using 24 h MII-pH monitoring. Methods Study subjectsBetween June 2004 and September 2008, pa

20、tients presenting to the outpatient motility centre at the University of Genoa with predominant typical GORD symptoms （ie, heartburn and regurgitation） lasting for more than 6 months and occurring at least three times weekly, were prospectively enrolled in the study. All subjects who agreed to parti

21、cipate in our investigation underwent careful history taking physical and clinical examination, upper gastrointestinal endoscopy to assess the presence or not of oesophageal mucosal injury, routine biochemistry, and upper abdominal ultrasound. The medical history included information on treatment wi

22、th acid suppressive medication （in particular proton pump inhibitors （PPIs） and symptomatic response to PPI therapy. Patients reporting 50% symptom improvement were considered responders to PPI therapy. Patients treated with antisecretory drugs were asked to discontinue acid suppressive therapy at l

23、east 30 days before the endoscopic examination. During the washout period, patients were allowed to use an oral antacid or alginate on an as-needed basis for the relief of heartburn. Based on the results of upper endoscopy, patients were then subdivided into three major groups Barretts oesophagus, e

24、rosive oesophagitis and NERD in cases where the typical symptoms of GORD were present, and where visible oesophageal mucosal injury was absent. Patients with Barretts oesophagus and erosive oesophagitis were not included in the present study. Within 15 days （median 3 days） from the upper endoscopy,

25、patients with NERD underwent ambulatory combined impedance-pH monitoring. Exclusion criteria were: history of thoracic, oesophageal or gastric surgery; primary or secondary severe oesophageal motility disorders （eg, achalasia, scleroderma, diabetes mellitus, autonomic or peripheral neuropathy, myopa

26、thy）; underlying psychiatric illness; use of non-steroidal anti-inflammatory drugs （NSAIDs） and aspirin; presence of peptic stricture and duodenal or gastric ulcer on upper endoscopy, evidence of erosive oesophagitis at previous （25 years） endoscopy, presence of dyspeptic symptoms as major symptoms.

27、 In women of childbearing age, pregnancy was excluded by urine analysis. During upper gastrointestinal endoscopy, biopsies were taken from the antrum and the corpus for assessing the presence of Helicobacter pylori. Patients were asked to discontinue any medication that would influence oesophageal m

28、otor function at least 1 week before administering the questionnaires and performing tests of oesophageal function. All participants gave written informed consent before entering the study. Symptom questionnaireBefore the 24 h pH-impedance study, each patient completed a functional dyspepsia questio

29、nnaire as reported and validated previously.13 This questionnaire included questions on the presence and intensity （range, 03; where 0 = absent, 1 = mild, 2 = moderate, and 3 = severe, interfering with daily activities） of epigastric pain, bloating, postprandial fullness, early satiety, nausea, vomi

30、ting, excessive belching and epigastric burning. Also, typical GORD symptoms （ie, heartburn and regurgitation） were evaluated using the same questionnaire （0 = absent, 1 = mild, 2 = moderate, and 3 = severe）. A second investigator completed a structured interview with the patient including a careful

31、 medical history （including height and weight）, current medication, tobacco use and alcohol consumption. Oesophageal multichannel intraluminal impedance and pH monitoringOesophageal impedance-pH monitoring was performed using an ambulatory multichannel intraluminal impedance and pH （MII-pH） monitori

32、ng system （Sleuth; Sandhill Scientific, Highland Ranch, Colorado, USA）. The system included a portable data logger and a catheter with one antimony pH electrode and eight impedance electrodes at 2, 4, 6, 8, 10, 14, 16 and 18 cm from the tip of the catheter. Each pair of adjacent electrodes represented an impedance-measuring segment （2 cm length） corresponding to one recording channel. The six impedance and one pH signals were recorded at 50 Hz on a 128 MB