Management of the patient with incomplete response to PPI therapy

Proton pump inhibitors (PPIs) remove most of the acid from the gastroesophageal refluxate. However, PPIs do not eliminate reflux and the response of specific GERD symptoms to PPI therapy depends on the degree to which acid drives those symptoms. PPIs are progressively less effective for heartburn, regurgitation, chest pain and extra-oesophageal symptoms. Hence, with an incomplete PPI response, obtaining an accurate history, detailing which symptoms are ‘refractory’ and exactly what evidence exists linking these symptoms to GERD is paramount. Reflux can continue to cause symptoms despite PPI therapy because of persistent acid reflux or weakly acidic reflux. Given these possibilities, diagnostic testing (pH or pH-impedance monitoring) becomes essential. Antireflux surgery is an alternative in patients if a clear relationship is established between persistent symptoms, particularly regurgitation, and reflux. Treating visceral hypersensitivity may also benefit the subset of GERD patients whose symptoms are driven by this mechanism.     

Short and long-term PPI treatment for GERD. Do we need more-potent anti-secretory drugs?

Because the reflux of the acidic gastric content into the esophagus plays a major role in the pathogenesis of symptoms of GERD and lesions of erosive esophagitis, acid suppression with a proton pump inhibitor (PPI) is currently the mainstay of anti-reflux therapy. There is a strong correlation between the degree of acid suppression provided by a given drug and its efficacy. The superiority of PPIs over other drugs (antacids, prokinetics and H(2)-receptor antagonists) has now been established beyond doubt, both for short- and long-term treatment. However, there are still some unmet therapeutic needs in GERD; hence, patients with non-erosive reflux disease (NERD) are less responsive to PPIs than those with erosive esophagitis. Moreover, the efficacy of PPIs in patients with atypical symptoms is frequently limited to the relief of associated heartburn or regurgitation. With respect to safety, although most studies on short- and long-term PPI use have provided reassuring data, recent reports have drawn attention to potential side effects or drug-drug interference. Better healing rates in the most severe forms of esophagitis, or a faster onset of symptom relief, may require optimization of acid suppressive therapy with regard to the daily course of acid secretion, especially during the night. Different pharmacological approaches can be considered, with the ultimate goals of achieving faster, stronger and more-sustained acid inhibition. How a better pharmacological profile may translate into clinical benefit should now be tested in appropriate, controlled studies.     

Proton Pump Inhibitor-Related Gastric Mucosal Changes

Proton pump inhibitors (PPIs) are used worldwide to treat of acid-related disorders such as peptic ulcer and gastroesophageal reflux disease and to prevent gastroduodenal injuries due to nonsteroidal anti-inflammatory drugs. PPIs are the most potent inhibitors of gastric acid secretion currently available, and they are one of the most commonly prescribed classes of drugs because of their high efficacy and low toxicity. However, long-term PPI use causes histopathological changes such as parietal cell protrusion into the gland lumen, cystic dilation of gastric fundic glands, and foveolar epithelial hyperplasia. These changes can manifest on endoscopic examination as fundic gland polyps, hyperplastic polyps, multiple white and flat elevated lesions, cobblestone-like mucosa, or black spots. Clinicians must be aware of PPI-induced endoscopic features in patients with chronic long-term PPI use. Conversely, identifying patients with long-term PPI use based on their endoscopic findings is important. Recently, potassium-competitive acid blockers (P-CABs), a new class of acid suppressants that inhibit gastric acid secretion more strongly than PPIs, have recently been introduced clinically. Further long-term prospective studies on these gastric mucosal lesions in patients with either PPI or P-CAB use are required to investigate their association with histopathological changes and to establish the clinical significance of these findings. (Gut Liver 2021;15:-652)     

Proton pump inhibitor resistance,the real challenge in gastro-esophageal reflux disease

Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.     

Management strategies for gastroesophageal reflux disease

Abstract   In the treatment of gastroesophageal reflux disease (GERD), the most effective treatment option is the use of proton pump inhibitor (PPI), which minimizes the effect of gastric acid on the distal esophagus. Both the step-up and step-down treatment strategies have advantages and disadvantages. Most physicians would like to choose the step-down therapy rather than the step-up therapy. The 'No-step' PPI therapy (i.e. continuous PPI therapy) is another relevant option. After an initial remission, long-term PPI therapy is an appropriate form of maintenance therapy in many patients.
As a treatment plan for non-erosive reflux disease, a standard dose of PPI for 4–8 weeks followed by either the step-down strategy or the on-demand treatment strategy is acceptable. When treating erosive esophagitis, PPI is better than H₂ receptor blockers in healing mucosal breaks and relieving symptoms. Long-term maintenance PPI therapy is reported to be very effective in maintaining the remission of reflux esophagitis for up to 5 years. On-demand PPI is also another good option for a maintenance therapy in erosive esophagitis. In Barrett's esophagus, symptoms seem to be well-controlled with PPIs. Unfortunately, however, PPIs have no effect on the shortening of Barrett's esophagus or in preventing the progression to dysplasia and adenocarcinoma.
In summary, after reviewing existing guidelines a rather simple guideline on the management of GERD is suggested – PPI should be given for 4–8 weeks followed by either on-demand or maintenance PPI therapy according to the clinical severity.     

Acid suppression therapy: where do we go from here?

The dramatic success of pharmacological acid suppression in healing peptic ulcers and managing patients with gastroesophageal reflux disease (GERD) has been reflected in the virtual abolition of elective surgery for ulcer disease, a reduction in nonsteroidal anti-inflammatory drug (NSAID)-associated gastropathy and the decision by most patients with reflux symptoms to continue medical therapy rather than undergo surgical intervention. However, a number of challenges remain in the management of acid-related disorders. These include management of patients with gastroesophageal symptoms who do not respond adequately to proton pump inhibitor (PPI) therapy, treatment of patients with nonvariceal upper gastrointestinal bleeding, prevention of stress-related mucosal bleeding, optimal treatment and prevention of NSAID-related gastrointestinal injury, and optimal combination of antisecretory and antibiotic therapy for the eradication of Helicobacter pylori infection. A number of new drugs are currently being investigated to provide a significant advance on current treatments. Some of them (namely potassium-competitive acid blockers (P-CABs) and CCK2-receptor antagonists) have already reached clinical testing while some others (like the antigastrin vaccine, H3-receptor ligands or gastrin-releasing peptide receptor antagonists) are still in preclinical development and need the proof of concept in human beings. Of the current approaches to reduce acid secretion, P-CABs and CCK2-receptor antagonists hold the greatest promise, with several compounds already in clinical trials. Although the quick onset of action of P-CABs (i.e. a full effect from the first dose) is appealing, the results of phase II studies with one such agent (namely AZD0865) did not show any advantages over esomeprazole. Thanks to their limited efficacy and the development of tolerance it is unlikely that CCK2 antagonists will be used alone as antisecretory compounds but, rather, their combination with PPIs will be attempted with the aim of reducing the long-term consequences of hypergastrinemia. While H2-receptor antagonists (especially soluble or over-the-counter formulations) will become the 'antacids of the third millennium' and will be particularly useful for on-demand symptom relief, clinicians will continue to rely on PPIs to control acid secretion in GERD and other acid-related diseases. In this connection, several new PPI formulations have been developed and two novel drugs (namely ilaprazole and tenatoprazole) are being studied in humans. The recently introduced immediate-release (IR) omeprazole formulation (currently available only in the USA) quickly increases intragastric pH and, given at bedtime, seems to achieve a better control of nocturnal acidity. IR formulations of other PPIs (including the investigational ones) will probably be available in the future and will enlarge our therapeutic armamentarium. Amongst the novel PPIs, tenatoprazole appears to be a true advance in the acid suppression therapy. Its long half-life (the longest among the available compounds) and longer duration of antisecretory action, with no difference between day and night, will allow the drug to go beyond the intrinsic limitations of currently available PPIs. Thanks to its favorable pharmacokinetics, the sodium salt of S-tenatoprazole is being developed and the preliminary results indicate that this drug has the potential to address unmet clinical needs. Although some decades have elapsed since the introduction of effective and safe antisecretory drugs in clinical practice and their use has stood the test of time, the ongoing research will further provide the clinician with more effective means of controlling acid secretion.     

Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: A meta-analysis

AIM: To investigate the efficacy of adding prokinetics to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD).METHODS: PubMed, Cochrane Library, and Web of Knowledge databases (prior to October 2013) were systematically searched for randomized controlled trials (RCTs) that compared therapeutic efficacy of PPI alone (single therapy) or PPI plus prokinetics (combined therapy) for GERD. The primary outcome of those selected trials was complete or partial relief of non-erosive reflux disease symptoms or mucosal healing in erosive reflux esophagitis. Using the test of heterogeneity, we established a fixed or random effects model where the risk ratio was the primary readout for measuring efficacy.RESULTS: Twelve RCTs including 2403 patients in total were enrolled in this study. Combined therapy was not associated with significant relief of symptoms or alterations in endoscopic response relative to single therapy (95%CI: 1.0-1.2, P = 0.05; 95%CI: 0.66-2.61, P = 0.44). However, combined therapy was associated with a greater symptom score change (95%CI: 2.14-3.02, P < 0.00001). Although there was a reduction in the number of reflux episodes in GERD [95%CI: -5.96-(-1.78), P = 0.0003] with the combined therapy, there was no significant effect on acid exposure time (95%CI: -0.37-0.60, P = 0.65). The proportion of patients with adverse effects undergoing combined therapy was significantly higher than for PPI therapy alone (95%CI: 1.06-1.36, P = 0.005) when the difference between 5-HT receptor agonist and PPI combined therapy and single therapy (95%CI: 0.84-1.39, P = 0.53) was excluded.CONCLUSION: Combined therapy may partially improve patient quality of life, but has no significant effect on symptom or endoscopic response of GERD.     

Maintenance therapy of gastroesophageal reflux disease

The aims of treatment of gastroesophageal reflux disease (GERD) are to cure mucosal breaks, control symptoms, and prevent complications (e.g. stricture, Barrett’s esophagus, and esophageal adenocarcinoma). Proton pump inhibitors (PPIs) are known to be the best drugs to cure esophagitis; however, a highrecurrence rate of about 80% was described after the completion of initial therapy. Regretfully, not so many physicians perform maintenance therapy in clinical practice. Histamine H2 receptor antagonists have an insufficient effect in maintenance therapy compared with PPIs; therefore, they could be prescribed for mild reflux esophagitis. Several clinical trials have been conducted to investigate the efficacy of continuous PPI administration maintenance therapy for GERD. Among these trials, recent large-scale studies showed that esomeprazole was equal to or superior to other kinds of PPIs. On the other hand, on-demand PPI studies have been conducted, mainly in patients with nonerosive reflux disease or uninvestigated GERD;however, this strategy was less effective than continuous therapy in many studies. Because on-demand therapy is less expensive, it is worth confirming this strategy in further studies. Studies of maintenance therapy with investigations conducted for as long a period as 5 years have described that PPI maintenance therapy could be considered as effective, safe, and well tolerated.     

Positive predictors for gastroesophageal reflux disease and the therapeutic response to proton-pump inhibitors

AIM:To identify objective and subjective predictors for the reliable diagnosis of gastroesophageal reflux disease(GERD)and the response to proton pump inhibitor(PPI)therapy.METHODS:Retrospectively,683 consecutive patients suspected for GERD who underwent pH-metry/impedance measurement(pH/MII)were analyzed.All patients had previously undergone standard PPI treatment(e.g.,pantoprazole 40 mg/d or comparable).Four hundred sixty patients were at least 10 d off PPIs(group A),whereas 223 patients were analyzed during their ongoing PPI therapy(group B).In addition,all patients completed a standardized symptom-and lifestyle-based questionnaire,including the therapeutic response to previous PPI trials on a 10-point scale.Uniand multivariance analyses were performed to identify criteria associated with positive therapeutic response to PPIs.RESULTS:In group A,positive predictors(PPs)for response in empirical PPI trials were typical GERD symptoms(heartburn and regurgitation),a positive symptom index(SI)and pathological results in pH/MII,along with atypical symptoms,including hoarseness and fullness.In group B,regular alcohol consumption was associated with the therapeutic response.The PPs for pathological results in pH/MII in group A included positive SI,male gender,obesity,heartburn and regurgitation.In group B,the PPs were positive SI and vomiting.Analyzing for positive SI,the PPs were pathological pH and/or MII,heartburn regurgitation,fullness,nausea and vomiting in group A and pathological pH and/or MII in group B.CONCLUSION:Anamnestic parameters(gender,obesity,alcohol)can predict PPI responses.In non-obese,female patients with non-typical reflux symptoms,pH/MII should be considered instead of empirical PPIs.     

New pharmacological agents for the treatment of gastroesophageal reflux disease

Proton pump inhibitors (PPIs) are currently the most effective and most widely used agents for gastroesophageal reflux disease (GERD). Despite the efficacy of these agents in healing and symptom relief, a substantial proportion of patients require twice-daily therapy with PPIs, and break-through symptoms cause others to use over-the-counter antacids and histamine 2-receptor antagonists to supplement their PPI therapy. Major strategies that are being pursued include the development of agents that have a faster onset of action for on-demand therapy; have better control of acid secretion, resulting in improved healing in advanced grades of esophagitis and better symptom control; and agents that decrease transient lower esophageal sphincter relaxations (TLESRs), thereby reducing distal acid exposure and weakly acidic refluxate. A number of new pharmaceutical agents are currently undergoing clinical evaluation for the treatment of GERD. These include agents that reduce TLESRs, serotonergic agents/ prokinetics, long-acting PPIs, mucosal protectants, and antigastrin agents. One or more of these agents may be the future of GERD therapy.     

Twice‐daily proton pump inhibitor therapy does not decrease the frequency of reflux episodes during nocturnal recumbency in patients with refractory GERD: analysis of 200 patients using multichannel intraluminal impedance–pH testing

Over half of patients with gastroesophageal reflux disease (GERD) report nocturnal symptoms. Proton pump inhibitors (PPIs) are the main medications used to treat GERD. Multichannel intraluminal impedance with pH (MII‐pH) monitoring is the most sensitive method for detection and characterization of GERD. The aim of this study was to assess and compare reflux frequency in patients with refractory GERD symptoms on and off PPI therapy during the nocturnal recumbent period, as assessed by MII‐pH testing. We analyzed 24‐hour MII‐pH studies performed in 200 patients monitored either on twice‐daily (n = 100) or off (n = 100) PPI therapy. Demographic analysis of the on‐therapy group revealed a mean age of 52 years (24–78 years) with 37% males, and the off‐therapy group revealed a mean age of 49 years (18–84 years) with 40% males. All studies were interpreted to assess and characterize the number of acid and nonacid reflux episodes in the nocturnal recumbent period identified by each patient on an overnight recorder (Zephyr, Sandhill Scientific, Inc., Highlands Ranch, CO, USA). The nocturnal recumbent period was the period documented by patients during which they lie in the recumbent period at night to sleep with average periods lasting 456 and 453 minutes for patients on and off PPI therapy. There were more mean recumbent reflux episodes in the on‐therapy group in comparison with the off‐therapy group (3.76 mean reflux episodes [mre] per patient in the recumbent vs. 2.82 mre); the difference was not statistically significant (P = 0.187). When the reflux events are classified into acid and non‐acid reflux episodes, the relative occurrence of acid reflux events is less in the on‐therapy group (P = 0.047), while the off‐therapy group have fewer nonacid reflux episodes (P = 0.003). PPIs decrease the acidity of esophageal refluxate but do not decrease the relative frequency of reflux episodes in the recumbent position in patients with refractory GERD despite twice‐a‐day treatment with PPI therapy. The explanation for the finding of numerically increased, although not statistically significant, amount of reflux episodes in the PPI treatment group in this study, and previous studies is unclear and warrants further evaluation.     

Yield of 24-Hour Esophageal pH and Bilitec Monitoring in Patients with Persisting Symptoms on PPI Therapy

Current management algorithms propose pH monitoring under proton pump inhibitors (PPIs) in suspected gastroesophageal reflux disease (GERD) with insufficient treatment response, but recent observations challenge this approach because of its low yield. AIM: To perform an audit of the outcomes of pH monitoring under PPI therapy in our unit, and to study the yield of additional nonacid reflux monitoring. METHODS: All pH monitoring studies under antireflux therapy since 1997, with or without simultaneous Bilitec monitoring, were analyzed. RESULTS: From 1997 to 2003, 347 patients (157 men, mean age 49.4 +/- 0.8 years) underwent pH studies on PPI therapy (28% half-, 67% full-, and 5% double-dose PPI) for persisting typical (53%) or atypical (75%) symptoms. In 184 patients, simultaneous Bilitec monitoring was performed. Esophageal pH monitoring on PPI was pathological in 105 (30%) patients. Pathological pH monitoring on PPI was associated with typical reflux symptoms (64 versus 52%, P = 0.03), and a higher prevalence of persisting esophagitis (54 versus 36%, P < 0.005) and of hiatal hernia (58 versus 27%, P < 0.005). Bilitec monitoring on PPI therapy was pathological in 114 (62%) patients, of which 74 (40%) had normal pH monitoring. Adding Bilitec increased the rate of abnormal results over pH monitoring alone, from 38% to 69% on half-dose, from 27% to 69% on full-dose, and from 0% to 38% on double-dose PPI. CONCLUSIONS: The rate of abnormal pH monitoring in symptomatic GERD patients while on PPI therapy is relatively low, especially in those on double-dose PPI. Combined pH and Bilitec monitoring significantly increased the rate of ongoing pathological reflux compared to pH alone in refractory to PPI therapy GERD patients.     

Proton pump inhibitors in gastroesophageal reflux disease: "a custom-tailored therapeutic regimen"

The Montreal Definition and Classification divides Gastroesophageal Reflux Disease (GERD) into esophageal symptomatic syndromes (and with mucosal damage) and extraesophageal syndromes (with acid established association and proposed association). In typical GERD symptoms, an 8-week treatment with PPIs is satisfactory in most cases (> 90%). Response rates to PPIs in GERD are highly variable, as they also rely on an appropriate clinical diagnosis of the disease; endoscopy differentiates the macroscopic GERD phenotype. The non-erosive variety (50-70% prevalence) has a different symptomatic response rate, as gastric acid is not the sole etiology of symptoms. The possible explanations of treatment failure include treatment adherence, PPI metabolism alterations and characteristics, and inadequate diagnosis. Refractory symptoms are related to gastric content neutralization by the chronic use of PPIs.Extraesophageal manifestations are associated with other pathophysiological mechanisms where an autonomic nervous system disturbance gives rise to symptoms. In these clinical entities, the relationship between symptoms and acid needs to be established in order to determine the use of PPIs, or consider other drugs. In other words, so as to "custom-tailor the best-fitting therapy" we need to answer the questions for whom, for what, how and for how long. Finally, PPI safety and tolerability are factors to be considered in elderly patients requiring chronic PPI use, who usually have chronic concomitant illnesses.     

Effect of Antisecretory Therapy on Atypical Symptoms in Gastroesophageal Reflux Disease

The effect of proton pump inhibitor (PPI) therapy on extraesophageal or atypical manifestations of gastroesophageal reflux disease (GERD) remains unclear. This study aimed to evaluate the prevalence of atypical manifestations in patients with acid reflux disease and the effect of PPI treatment. Patients with symptoms and signs suggestive of reflux were enrolled. Erosive esophagitis was stratified using the Los Angeles classification. Demographic data and symptoms were assessed using a questionnaire and included typical symptoms (heartburn, regurgitation, dysphagia, odynophagia), and atypical symptoms (e.g., chest pain, sialorrhea, hoarseness, globus sensation, chronic coughing, episodic bronchospasm, hiccup, eructations, laryngitis, and pharyngitis). Symptoms were reassessed after a 3-month course of b.i.d. PPI therapy. A total of 266 patients with a first diagnosis of GERD (erosive, 166; non-erosive, 100) were entered in the study. Presentation with atypical symptoms was approximately equal in those with erosive GERD and with non-erosive GERD, 72% vs 79% (P = 0.18). None of the study variables showed a significant association with the body mass index. PPI therapy resulted in complete symptom resolution in 69% (162/237) of the participants, 12% (28) had improved symptoms, and 20% (47) had minimal or no improvement. We conclude that atypical symptoms are frequent in patients with GERD. A trial of PPI therapy should be considered prior to referring these patients to specialists.     

Pharmacologic management of gastroesophageal reflux disease

The burden of gastroesophageal reflux disease (GERD) results from its widespread prevalence and the unfavorable impact of its symptoms on well-being and quality of life. Whereas abnormalities of the antireflux barrier (lower esophageal sphincter) are important in the pathophysiology of GERD, pharmacologic therapy for GERD is based on suppression of acid, which is responsible for the majority of the symptoms and for epithelial damage. Proton pump inhibitors (PPIs) are the agents of choice for achieving the goals of medical therapy in GERD, which include symptom relief, improvement in quality of life, and healing and prevention of mucosal injury. As a class, these drugs are extremely safe. The newest PPI, esomeprazole, brings a statistically significant increase in healing of mucosal injury and symptom relief in patients with erosive esophagitis, compared with omeprazole and lansoprazole. This article reviews the role of medical therapy in the short-and long-term management of symptomatic patients with or without erosive esophagitis, including extraesophageal presentations, GERD during pregnancy, and Barrett’s esophagus. Management of refractory patients is addressed.     

Endoscopic therapy for GERD: Does it have a future?

Approximately 20% of patients with gastroesophageal reflux disease (GERD) have symptoms refractory to long-term proton pump inhibitor (PPI) therapy. Furthermore, PPI therapy is expensive. Fundoplication is considered the gold standard of GERD therapy in terms of normalization of esophageal acid exposure and symptom control; however, this exposes the patient to the risks of surgery and anesthesia. Therefore, an endoscopic approach to treating GERD that obviates the need for PPIs and avoids surgical morbidity is desirable. Several endoscopic methods have been used, including radiofrequency ablation, implantation of foreign substances as bulking agents, and various tissue apposition strategies. The emerging field of GERD endotherapy is promising, but more rigorous, sham-controlled, long-term studies are required to elucidate its exact role in clinical practice. This review discusses the evolution of these concepts, describes specific endoscopic devices that have been developed, and explores the future of endotherapies as viable treatment alternatives for GERD.     

Gastroesophageal reflux symptoms not responding to proton pump inhibitor: GERD,NERD, NARD,esophageal hypersensitivity or dyspepsia?

Gastroesophageal reflux (GER) is a common gastrointestinal process that can generate symptoms of heartburn and chest pain. Proton pump inhibitors (PPIs) are the gold standard for the treatment of GER; however, a substantial group of GER patients fail to respond to PPIs. In the past, it was believed that acid reflux into the esophagus causes all, or at least the majority, of symptoms attributed to GER, with both erosive esophagitis and nonerosive outcomes. However, with modern testing techniques it has been shown that, in addition to acid reflux, the reflux of nonacid gastric and duodenal contents into the esophagus may also induce GER symptoms. It remains unknown how weakly acidic or alkaline refluxate with a pH similar to a normal diet induces GER symptoms. Esophageal hypersensitivity or functional dyspepsia with superimposed heartburn may be other mechanisms of symptom generation, often completely unrelated to GER. Detailed studies investigating the pathophysiology of esophageal hypersensitivity are not conclusive, and definitions of the various disease states may overlap and are often confusing. The authors aim to clarify the pathophysiology, definition, diagnostic techniques and medical treatment of patients with heartburn symptoms who fail PPI therapy.     

Extra-esophageal gastroesophageal reflux disease and asthma: understanding this interplay

Gastroesophageal reflux disease (GERD) is a condition that develops when there is reflux of stomach contents, which typically manifests as heartburn and regurgitation. These esophageal symptoms are well recognized; however, there are extra-esophageal manifestations of GERD, which include asthma, chronic cough, laryngitis and sinusitis. With the rising incidence of asthma, there is increasing interest in identifying how GERD impacts asthma development and therapy. Due to the poor sensitivity of endoscopy and pH monitoring, empiric therapy with proton pump inhibitors (PPIs) is now considered the initial diagnostic step in patients suspected of having GERD-related symptoms. If unresponsive, diagnostic testing with pH monitoring off therapy and/or impedance/pH monitoring on therapy, may be reasonable in order to assess for baseline presence of reflux with the former and exclude continued acid or weakly acid reflux with the latter tests. PPI-unresponsive asthmatics, without overt regurgitation, usually have either no reflux or causes other than GERD. In this group, PPI therapy should be discontinued. In those with GERD as a contributing factor acid suppressive therapy should be continued as well as optimally treating other etiologies requiring concomitant treatment. Surgical fundoplication is rarely needed but in those with a large hiatal hernia, moderate-to-severe reflux by pH monitoring surgery might be helpful in eliminating the need for high-dose acid suppressive therapy.     

Laparoscopic fundoplication for gastroesophageal reflux disease

Gastroesophageal reflux disease(GERD) is a condition that develops when the reflux of gastric contents into the esophagus leads to troublesome symptoms and/or complications. Heartburn is the cardinal symptom, often associated with regurgitation. In patients with endoscopy-negative heartburn refractory to proton pump inhibitor(PPI) therapy and when the diagnosis of GERD is in question, direct reflux testing by impedance-pH monitoring is warranted. Laparoscopic fundoplication is the standard surgical treatment for GERD. It is highly effective in curing GERD with a 80% success rate at 20-year follow-up. The Nissen fundoplication, consisting of a total(360°) wrap, is the most commonly performed antireflux operation. To reduce postoperative dysphagia and gas bloating, partial fundoplications are also used, including the posterior(Toupet) fundoplication, and the anterior(Dor) fundoplication. Currently, there is consensus to advise laparoscopic fundoplication in PPI-responsive GERD only for those patients who develop untoward side-effects or complications from PPI therapy. PPI resistance is the real challenge in GERD. There is consensus that carefully selected GERD patients refractory to PPI therapy are eligible for laparoscopic fundoplication, provided that objective evidence of reflux as the cause of ongoing symptoms has been obtained. For this purpose, impedance-pH monitoring is regarded as the diagnostic gold standard.