Empirical Acid Suppression Research Articles

Update on extraesophageal manifestations of gastroesophageal reflux.

Symptoms/complications related to extraesophageal reflux (EER) are increasingly prevalent presentations and pose significant challenges for clinicians. We summarize and discuss clinical advances and developments in pathophysiology, testing and treatment algorithms of upper/lower airway manifestations of EER. Growing evidence supports likely multifactorial causes of laryngeal symptoms, including EER, oropharyngeal pathologies, allergic conditions, and cognitive-affective processes (brain-larynx interaction). Diagnostic paradigm for laryngopharyngeal reflux (LPR) is shifting towards a personalized approach with noninvasive strategies/prediction tools to risk-stratify patients for upfront reflux testing over empiric acid suppression trials. Management should be multipronged to include antireflux therapies and treatments targeting other causes. Lower airway complications of EER may result in lung dysfunction and poor transplant outcomes. Esophageal symptoms are often absent and routine esophageal/reflux testing to guide timely antireflux therapies may lead to improved outcomes. Modalities that leverage impedance technology may be important, given the potential role of nonacidic reflux. Novel impedance-based metrics such as mean nocturnal baseline impedance and postreflux swallow-induced peristaltic wave index may provide adjunctive diagnostic values. Standardized approach to diagnosis/management of EER should include multidisciplinary care teams and consider different phenotypes, nonreflux contributors, and the complex gut-airway relationships. Prompt antireflux therapies after careful candidate selection may improve outcomes of these airway complications.

Up-Front Endoscopy Maximizes Cost-Effectiveness and Cost-Satisfaction in Uninvestigated Dyspepsia

Practice guidelines promote a routine noninvasive, non-endoscopic initial approach to investigating dyspepsia without alarm features in young patients, yet many patients undergo prompt upper endoscopy. We aimed to assess tradeoffs among costs, patient satisfaction, and clinical outcomes to inform discrepancy between guidelines and practice. We constructed a decision-analytic model and performed cost-effectiveness/cost-satisfaction analysis over a 1-year time horizon on patients with uninvestigated dyspepsia without alarm features referred to gastroenterology. A RAND/UCLA expert panel informed model design. Four competing diagnostic/management strategies were evaluated: prompt endoscopy, testing for Helicobacter pylori and eradicating if present (test-and-treat), testing for H pylori and performing endoscopy if present (test-and-scope), and empiric acid suppression. Outcomes were derived from systematic reviews of clinical trials. Costs were informed by prospective observational cohort studies and national commercial/federal cost databases. Health gains were represented using quality-adjusted life years. From the patient perspective, costs and outcomes were similar for all strategies (maximum out-of-pocket difference of $30 and <0.01 quality-adjusted life years gained/year regardless of strategy). Prompt endoscopy maximized cost-satisfaction and health system reimbursement. Test-and-scope maximized cost-effectiveness from insurer and patient perspectives. Results remained robust on multiple one-way sensitivity analyses on model inputs and across most willingness-to-pay thresholds. Noninvasive management strategies appear to result in inferior cost-effectiveness and patient satisfaction outcomes compared with strategies promoting up-front endoscopy. Therefore, additional studies are needed to evaluate the drivers of patient satisfaction to facilitate inclusion in value-based healthcare transformation efforts.

Effectiveness of management strategies for uninvestigated dyspepsia: systematic review and network meta-analysis

ObjectiveTo determine the effectiveness of management strategies for uninvestigated dyspepsia.DesignSystematic review and network meta-analysis.Data sourcesMedline, Embase, Embase Classic, the Cochrane Central Register of Controlled Trials, and clinicaltrials.gov from inception to...

Dual pH Probes Without Proximal Esophageal and Pharyngeal Impedance May Be Deficient in Diagnosing LPR

Laryngopharyngeal reflux (LPR) is commonly treated with empiric acid suppression. More evidence points to pepsin in the pathophysiology of LPR. Previous studies have evaluated esophageal impedance in patients who had previously failed high dose proton pump inhibitor (PPI) using older catheters without proximal esophageal (just under the upper esophageal sphincter) and pharyngeal impedance sensors. The aim of this study was to compare what traditional diagnostic tools, used for esophageal reflux, would detect and diagnose compared with what a combined hypopharyngeal-esophageal MII catheter with dual pH (HEMII-pH) can detect in the esophagus and pharynx in patients with suspected LPR. Forty-two subjects with presumed LPR were referred for HEMII-pH testing. The number of distal and proximal esophageal impedance events, number of pharyngeal impedance events, symptom correlation, and event acidity were recorded. Previous normative values (>1 pharyngeal impedance events every 24 hours) were used to designate what was pathological LPR on HEMII-pH. Forty-two total subjects had pharyngeal impedance sensor data recorded. Twelve (28.6%) of the subjects were tested while taking high-dose PPI therapy. The mean number of proximal esophageal events was 23.3. The mean number of pharyngeal impedance events was 10. Thirty-four subjects (81%) tested positive for pharyngeal reflux. All patients who tested positive using traditional proximal impedance criteria also tested positive using pharyngeal criteria. Of patients who tested negative using traditional criteria, 72% were positive based on pharyngeal criteria. HEMII-pH catheters should be considered in patients with LPR symptoms. Traditional criteria used for diagnosing esophageal reflux may not translate into LPR.

Infantile Gastroesophageal Reflux: Adherence to Treatment Guidelines in the Hospital Setting.

Recent guidelines defined and differentiated the management of gastroesophageal reflux (GER) and gastroesophageal reflux disease (GERD). The guidelines recommend against using empiric acid suppression therapy for infantile GER. The primary objective of this study was to assess inpatient guideline adherence regarding management of infantile GER through the perspective of pharmacists. Secondary objectives included assessing pharmacist comfort level with differentiation between GER and GERD, observing current trends in practice relating to the primary objective, and determining the availability of institution-specific guidelines that address the management of infantile GER. An institutional review board-approved, national, online survey of pharmacists with inpatient pediatric experience was conducted. Pediatric pharmacy membership directories were used to create the listserv of eligible pharmacists. The 2009 NASPGHAN/ESPGHAN (North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Gastroenterology, Hepatology, and Nutrition) Pediatric Gastroesophageal Reflux Clinical Practice Guideline was used to develop the survey and to define both GER and GERD. Demographic data was also collected regarding the institutional setting and pharmacists responding. The overall response rate was 14.8% (n = 149). Although 29.7% of pharmacists stated empiric acid suppression trials were not used for infantile GER at their institution, 44.6% responded that these trials are initiated 1 to 2 times per week in their hospitals. In addition, 19.6% responded that these empiric trials were initiated 3 to 5 times per week. A smaller percentage of responders reported even higher frequencies per week at their institutions. From the results of the survey, infants continue to receive empiric acid suppression trials for GER in the inpatient setting, which is not adherent to the current guideline recommendation.

What is the place of empirical proton pump inhibitor testing in the diagnosis of gastroesophageal reflux disease? (Description, duration, and dosage).

Empirical acid suppression tests that are performed with proton pump inhibitors (PPI) are used to detect both the presence of acid-related gastrointestinal symptoms and gastroesophageal reflux disease (GERD). In comparison to other diagnostic methods, it is non-invasive, easily applicable, and cost-effective in the diagnosis of GERD. In addition to typical reflux symptoms, it can also be used for diagnostic purposes in patients with non-cardiac chest pain (NCCP). If the symptom response is 50% and above when obtained using the PPI test in patients with NCCP, it can be considered as positive and the treatment should be continued sensitivity of the PPI test in patients with typical symptoms of GERD is 27%-89%, while its specificity is 35%-83%. Although there are differences related to the duration and dosage of the PPI test, a significant difference has not been found according to the type of PPI. When PPI test sensitivity and specificity were calculated by cumulatively evaluating the data regarding the PPI test in the literature, a sensitivity of 82.3% and specificity of 51.5% was obtained. It has been found that high doses of PPI were mostly used in studies, and the duration of the median test was 14 days. As a result, the sensitivity of PPI trial test is good, but the specificity is low in the diagnosis of GERD in patients with typical reflux symptoms.

A Large Spontaneous Esophageal Perforation Treated With Endoscopic Stent Placement

Esophageal perforations are extremely rare, with an incidence of 3.1 per 1,000,000 annually. About 15% are spontaneous, usually referred to as Boerhaave's syndrome, which occurs due to increased intraluminal pressure with inability of upper esophageal sphincter to relax during retching. However, a spontaneous perforation without such an inciting event is even more infrequent. An 88 year-old male with no prior medical history presented with chest pain, dyspnea and worsening acid reflux. Preliminary workup was concerning for a cardiac event, for which he underwent a cardiac catherization with stent placement. However, he continued to have chest pain, thus a CTA chest/abdomen/pelvis was performed, and revealed a likely hiatal hernia with significant reflux, however otherwise normal. Three days later a CXR showed a left pleural effusion, and eventually a CT chest revealed oral contrast in the left thorax with significant pneumomediastinum, suspicious for an esophageal perforation. He was transferred to the surgical ICU, kept NPO, started on empiric antibiotic, antifungal, and acid suppression therapy. The cardiothoracic surgical team placed two chest tubes. He then had an esophagram, showing a large esophageal defect with free extravasation of contrast into the mediastinum. Given that he was deemed a poor surgical candidate, he was taken to the OR for endoscopic stent placement. EGD revealed a large, 5cm perforation in the distal esophagus. No esophagitis or tumor was seen. Successful placement of two fully covered metal stents achieved adequate closure of the defect. Taking into account the lack of typical symptoms, typical inciting events, and overall patient tolerance of such a large perforation, this is a highly unusual case and suggests a possibly chronic underlying defect. Diagnosis of spontaneous esophageal perforation is often delayed as the classic triad of vomiting, chest pain and subcutaneous or mediastinal air, is only described in 50% of cases. Esophageal stents are an alternative to surgical treatment of perforations. Although esophageal stent placement successfully sealed the majority of our patients' perforation, a defect of this size will likely require surgical repair. This case emphasizes the importance of prompt recognition of a suspected esophageal perforation, the importance and diagnostic accuracy of CT scan with PO contrast and the potential role of fully covered metal stents as a therapeutic alternative to emergent surgery. Watch the video: https://goo.gl/fhkDGTFigure: CT chest/abdomen with IV and PO contrast demonstrating pneumomediastinum and oral contrast in the mediastinum.Figure: Fluoroscopic images from gastrograffin esophagram revealing large area of extravasation into the left mediastinum.

Challenging surgical dogma in the management of proximal esophageal atresia with distal tracheoesophageal fistula: Outcomes from the Midwest Pediatric Surgery Consortium

PurposePerioperative management of infants with esophageal atresia and tracheoesophageal fistula (EA/TEF) is frequently based on surgeon experience and dogma rather than evidence-based guidelines. This study examines whether commonly perceived important aspects of practice affect outcome in a contemporary multi-institutional cohort of patients undergoing primary repair for the most common type of esophageal atresia anomaly, proximal EA with distal TEF. MethodsThe Midwest Pediatric Surgery Consortium conducted a multicenter, retrospective study examining selected outcomes on infants diagnosed with proximal EA with distal TEF who underwent primary repair over a 5-year period (2009–2014), with a minimum 1-year follow up, across 11 centers. Results292 patients with proximal EA and distal TEF who underwent primary repair were reviewed. The overall mortality was 6% and was significantly associated with the presence of congenital heart disease (OR 4.82, p=0.005). Postoperative complications occurred in 181 (62%) infants, including: anastomotic stricture requiring intervention (n=127; 43%); anastomotic leak (n=54; 18%); recurrent fistula (n=15; 5%); vocal cord paralysis/paresis (n=14; 5%); and esophageal dehiscence (n=5; 2%). Placement of a transanastomotic tube was associated with an increase in esophageal stricture formation (OR 2.2, p=0.01). Acid suppression was not associated with altered rates of stricture, leak or pneumonia (all p>0.1). Placement of interposing prosthetic material between the esophageal and tracheal suture lines was associated with an increased leak rate (OR 4.7, p<0.001), but no difference in the incidence of recurrent fistula (p=0.3). Empiric postoperative antibiotics for >24h were used in 193 patients (66%) with no difference in rates of infection, shock or death when compared to antibiotic use ≤24h (all p>0.3). Hospital volume was not associated with postoperative complication rates (p>0.08). Routine postoperative esophagram obtained on day 5 resulted in no delayed/missed anastomotic leaks or a difference in anastomotic leak rate as compared to esophagrams obtained on day 7. ConclusionMorbidity after primary repair of proximal EA and distal TEF patients is substantial, and many common practices do not appear to reduce complications. Specifically, this large retrospective series does not support the use of prophylactic antibiotics beyond 24h and empiric acid suppression may not prevent complications. Use of a transanastomotic tube was associated with higher rates of stricture, and interposition of prosthetic material was associated with higher leak rates. Routine postoperative esophagram can be safely obtained on day 5 resulting in earlier initiation of oral feeds. Study typeTreatment study. Level of evidenceIII.

Role of Gastric Acid in Dyspepsia

Functional dyspepsia is a clinical syndrome in which there is an absence of underlying organic disease to explain the symptoms. Empiric acid suppression is one among the many options available in the therapeutic armamentarium to treat this common condition. However the response to acid suppression is not always a consistent one. It is because of the heterogeneous nature of the pathophysiologic mechanisms involving gastric acid in this scenario. This variation in the role of the gastric acids is determined possibly by the genetic constitution and it is influenced by the factors like H. pylori infection, irritants, allergens and diet. All these events primarily lead to visceral hypersensitivity. Finally, it is the degree of affection, whether gastric or duodenal, decides its clinical presentation. If it is a predominant gastric visceral hypersensitivity, presentation would be of Rome III-EPS type, whereas duodenal sensitisation would present as Rome III-PDS.

Supraesophageal reflux disease: A review of the literature

Supraesophageal reflux disease (SERD), defined as reflux proximal to the upper esophageal sphincter, is a common cause of morbidity of the upper aerodigestive tract, including rhinitis, laryngitis, cough, postnasal drip, and throat clearing. Although SERD has a high prevalence, the ideal means of diagnosing and treating the disease remain poorly defined. Evolving pH monitoring technology and a body of literature with conflicting reports regarding the best means for measuring and interpreting supraesophageal acidic reflux complicates the diagnosis of SERD. Treatment options include empiric acid suppression therapy, lifestyle modification, and surgery. However, limited data regarding the effectiveness of these strategies vary between studies and patient populations. It is the goal of this article to summarize the presentation and pathogenesis of SERD and to integrate the evolving body of literature pertaining to diagnostic and treatment strategies.

Are there risks associated with empiric acid suppression treatment of infants and children suspected of having gastroesophageal reflux disease?

It has become common practice to empirically treat infants and children who have suspected gastroesophageal reflux disease by using acid-suppressive medications. However, evidence to support the effectiveness of these medications in the pediatric population is limited. With multiple studies in adult patients indicating increased risk of infection, we reviewed the literature to determine the association between acid-suppressive medications and serious adverse effects in infants and children. We conducted a PubMed search on the adverse effects of H2 antagonists and proton pump inhibitors in pediatric patients. The studies selected were original research and systematic reviews with control groups and study objectives evaluating the relationship between acid-suppressive medications and serious adverse effects (namely, infections). Fourteen studies met our inclusion criteria. The majority of studies found a significant association between acid-suppressive medications and the risk of necrotizing enterocolitis, sepsis/bacteremia, pneumonia, and gastrointestinal infections in infants and children. Given the questionable efficacy of H2 antagonists and proton pump inhibitors and the growing evidence of increased risk of serious infections, acid-suppressive medications should be used cautiously in infants and children suspected of having gastroesophageal reflux disease.

The Efficacy of the Upright Position on Gastro-Esophageal Reflux and Reflux-Related Respiratory Symptoms in Infants With Chronic Respiratory Symptoms

PurposeGastro-esophageal reflux (GER), particularly non-acid reflux, is common in infants and is a known cause of chronic respiratory symptoms in infancy. Recent guidelines recommended empirical acid suppression therapy and the head-up position in patients with suspected GER. However, the efficacy of the upright position in relieving GER and reflux-related respiratory symptoms in infants is unclear. We conducted this study to investigate the efficacy of the upright position on GER and reflux-related respiratory symptoms in infants with chronic respiratory symptoms.MethodsThirty-two infants (21 male; median age, 5 months; range, 0 to 19 months) with unexplained chronic respiratory symptoms underwent multi-channel intraluminal esophageal impedance and pH monitoring. We retrospectively compared the frequencies of GER and reflux-related symptoms according to body position.ResultsA mean of 3.30 episodes of reflux per hour was detected. Overall, refluxes were more frequent during the postprandial period than the emptying period (3.77 vs. 2.79 episodes/hour, respectively; P=0.01). Although there was no significant difference in the total refluxes per hour between the upright and recumbent positions (6.12 vs. 3.77 episodes, P=0.10), reflux-related respiratory symptoms per reflux were significantly fewer in infants kept in an upright position than in a recumbent position during the postprandial period (3.07% vs. 14.75%, P=0.016). Non-acid reflux was the predominant type of reflux in infants, regardless of body position or meal time.ConclusionsThe upright position may reduce reflux-related respiratory symptoms, rather than reflux frequency. Thus, it may be a useful non-pharmacological treatment for infantile GER disease resistant to acid suppressants.

Practices in Peptic Ulcer Bleeding Controversies among University- Versus Nonuniversity-Affiliated Gastroenterologists

Practices relating to acute peptic ulcer bleeding (APUB) outside of guideline recommendations are unknown. To evaluate the practices of university-affiliated (UA) versus nonuniversity-affiliated (non-UA) gastroenterologists in controversial APUB issues. Gastroenterologists in Canada were mailed an anonymous questionnaire (January 2008) regarding APUB management. Responses were received for 281 of the 530 questionnaires mailed (53%). There were no differences between the UA versus non-UA gastroenterologists regarding acid suppression medication and route of administration pre- and postendoscopy (all P>0.05). There were no differences in endoscopic practices between groups regarding large versus small volume injection, endoclip versus combination injection plus coagulation, endoclip versus endoclip plus injection, and management of adherent clots (all P>0.05). There was variability within each group regarding optimal empirical acid suppression pre- and postendoscopy, volume of injection therapy and endoclip use. The non-UA group had longer delays before restarting acetylsalicyclic acid (P=0.08) and warfarin (P=0.02) post-APUB. UA and non-UA gastroenterologists have similar practices in acid suppression and endoscopic therapy for controversial APUB issues; however, non-UA gastroenterologists appear more cautious in restarting acetylsalicylic acid and warfarin. Further studies are needed to address the optimal empirical acid suppression pre- and postendoscopy, injection therapy volume, endoclip use, and timing of restarting antiplatelet and anticoagulation therapy.

Managing dyspepsia

The prevalence of dyspepsia in the general population is as high as 40%, and its management represents a considerable financial burden to the health care system. Causes of dyspepsia amenable to medical therapy include peptic ulcer and functional dyspepsia, and testing for Helicobacter pylori and treating positive individuals is beneficial in both conditions. Individuals presenting for the first time with uninvestigated dyspepsia, age greater than 50 years, or alarm features require upper gastrointestinal (GI) endoscopy to exclude gastroesophageal malignancy. Upper GI endoscopy for younger individuals without alarm features is not cost-effective compared with the "test and treat" approach. Test and treat and empirical acid-suppression using a proton pump inhibitor (PPI) have similar costs and effects. Recent evidence suggests that empirical acid suppression commencing with antacids is as effective as PPI. Screening and treatment of H. pylori in PPI users and the community may reduce the costs of managing dyspepsia.

Should we step‑up or step‑down in the treatment of new‑onset dyspepsia in primary care?

Dyspepsia is common in the community, and the condition represents a considerable burden to the health service. Individuals over the age of 50 to 55 years consulting with new-onset dyspepsia and those with alarming features, such as dysphagia and weight loss, require urgent endoscopy to exclude gastro-esophageal malignancy. For younger individuals without alarm features prompt endoscopy and "test and scope" are not cost-effective initial management strategies. "Test and treat" or empirical acid suppression therapy should be preferred, depending on patient and physician choice, as well as local prevalence of Helicobacter pylori. If empirical acid suppression therapy is favored, a recent primary care-based trial from the Netherlands suggests the choice of initial acid suppressant (antacid or proton pump inhibitor [PPI]) has little effect on the likelihood of remaining symptomatic, and that stepping-up from antacid to PPI is more cost-effective than stepping-down from PPI, when current prices of branded drugs were considered.

Clinical trial: a randomized trial of early endoscopy, Helicobacter pylori testing and empirical therapy for the management of dyspepsia in primary care

Early endoscopy, Helicobacter pylori eradication and empirical acid suppression are commonly used dyspepsia management strategies in primary care but have not been directly compared in a single trial. To compare endoscopy, H. pylori test and refer, H. pylori test and treat and empirical acid suppression for dyspepsia in primary care. Patients presenting to their general practitioner with dyspepsia were randomized to endoscopy, H. pylori'test and treat', H. pylori test and endoscope positives, or empirical therapy with symptoms, patient satisfaction, healthcare costs and cost effectiveness at 12 months being the outcomes. At 2 months, the proportion of patients reporting no or minimal dyspeptic symptoms ranged from 74% for those having early endoscopy to 55% for those on empirical therapy (P = 0.009), but at 1 year, there was little difference among the four strategies. Early endoscopy was associated with fewer subsequent consultations for dyspepsia (P = 0.003). 'Test and treat' resulted in fewer endoscopies overall and was most cost-effective over a range of cost assumptions. Empirical therapy resulted in the lowest initial costs, but the highest rate of subsequent endoscopy. Gastro-oesophageal cancers were found in four patients randomized to the H. pylori testing strategies. While early endoscopy offered some advantages 'Test and treat' was the most cost-effective strategy. In older patients, early endoscopy may be an appropriate strategy in view of the greater risk of malignant disease.

Meta‐analysis: Helicobacter pylori‘test and treat’ compared with empirical acid suppression for managing dyspepsia

Which of Helicobacter pylori'test and treat' or empirical acid suppression should be preferred for the initial management of uncomplicated dyspepsia is controversial. Aim To conduct an individual patient data meta-analysis of randomized controlled trials (RCTs) of 'test and treat' vs. empirical acid suppression in adults with uncomplicated dyspepsia in primary care. Investigators provided original data sets for analysis. Effect of management strategy on symptom status and dyspepsia-related resource use at 12-month follow-up was examined by pooling symptom and cost data to obtain relative risk (RR) of remaining symptomatic at 12 months and weighted mean difference (WMD) in costs between the two strategies with 95% confidence intervals (CI). We identified three eligible RCTs containing 1547 patients, 791 (51%) of whom were assigned to 'test and treat'. There was no difference detected in symptom-cure at 12 months (RR = 0.99; 95% CI: 0.95-1.03). There was a nonsignificant trend towards cost-savings with 'test and treat' (WMD in costs = - 28.91 pound; 95% CI: - 68.48 pound to 10.65 pound). There was little difference in symptom-resolution or costs between the two strategies. A combination of patient and physician preference should determine the initial approach to the management of uncomplicated dyspepsia.

Helicobacter pylori test and treat versus proton pump inhibitor in initial management of dyspepsia in primary care: multicentre randomised controlled trial (MRC-CUBE trial)

Objective To determine the cost effectiveness of Helicobacter pylori “test and treat” compared with empirical acid suppression in the initial management of patients with dyspepsia in primary care.Design Randomised controlled...

A Second-Order Simulation Model of the Cost-Effectiveness of Managing Dyspepsia in the United States

The "gold-standard'' evidence of effectiveness for a clinical practice guideline is the randomized controlled trial (RCT), although RCTs have a limited ability to explore potential management strategies for a chronic disease where these interact over time. Modeling can be used to fill this gap, and models have become increasingly complex, with both dynamic sampling and representation of second-order uncertainty to provide more precise estimates. However, both simulation modeling and probabilistic sensitivity analysis are rarely used together. The objective of this study was to explore uncertainty in controversial areas of the 2005 American Gastroenterology Association position statement on the management of dyspepsia. Individual sampling model, incorporating a second-order probabilistic sensitivity analysis. US adult patients presenting in primary care with dyspepsia. Interventions compared: empirical acid suppression, test and treat for Helicobacter pylori, initial endoscopy, acid suppression then endoscopy, test and treat then proton pump inhibitor (PPI) then endoscopy. Cost-effectiveness, quality-adjusted life years, and costs in US dollars from a societal perspective, measured over a 5-year period. mainly Cochrane meta-analyses. Endoscopy was dominated at all ages by other strategies. PPI therapy was the most cost-effective strategy in 30-year-olds with a low prevalence of H. pylori. In 60-year-olds, H. pylori test and treat was the most cost-effective option. Acid suppression alone was more cost-effective than either endoscopy or H. pylori test and treat in younger dyspepsia patients with a low prevalence of infection.

Symptom Assessment

Gastroesophageal reflux disease (GERD) presents symptomatically and the main aim of treatment is to reduce or abolish these reflux-related symptoms. Objective tests such as endoscopy, esophageal pH monitoring, and esophageal histology, identify a high proportion of patients who have reflux-related esophageal injury but they identify a smaller proportion of patients with reflux symptoms and, probably, a yet smaller proportion with atypical, chest pain symptoms. The usefulness of objective tests for determining the role of gastroesophageal reflux in the etiology of extraesophageal respiratory, oropharyngeal and otorhinologic syndromes are even more limited. Symptom assessment is, therefore, crucial for the management of reflux disease. However, the symptomatic manifestations of GERD are protean and, although typical symptoms of heartburn and regurgitation are associated with GERD in a high proportion of individuals, there is no single symptom or combination of symptoms that is diagnostic of GERD, particularly when the esophageal and extraesophageal syndromes are considered. Symptom-based questionnaires developed for the diagnosis of GERD are not, therefore, adequate for the identification of all individuals with GERD although their diagnostic accuracy can be improved by combining them with other diagnostic tests and applying, for example, latent class analysis or Bayesian analysis. Symptom assessment is also crucial in evaluating the effect of therapy in individuals who have a diagnosis, confirmed or presumptive, of GERD. In clinical practice, treatment-induced symptom resolution is generally associated with an improvement in the patient's quality of life and is predictive of an improvement in esophageal injury syndromes; in clinical trials, it is necessary to know that an improvement in symptoms is actually indicative of an improvement in the manifestations of GERD. The need for a validated, symptom-based, evaluative instrument to assess GERD symptoms and their response to therapy has been addressed by the development of a new tool-the ReQuest questionnaire. ReQuest has now been validated in patients with erosive esophagitis, patients with nonerosive reflux disease, and in individuals who do not have reflux disease and it provides an instrument that may be used in clinical research and regulatory studies to document treatment efficacy. In the future, it may also be combined with empiric acid suppression therapy, for example with a proton pump inhibitor, to provide a GERD diagnosis ex juantibus, without the need for supplementary expensive or invasive investigations.