Evaluation of Patients With Symptoms of Gastroesophageal Reflux -- Role of Reflux Monitoring
Philip O. Katz, MD
Introduction
Gastroesophageal reflux disease (GERD) is a common problem in gastroenterologic practice. In the vast majority of clinical scenarios, the diagnosis is suspected on the basis of patient history and a therapeutic trial of antisecretory therapy initiated to confirm the relationship between the presenting symptoms and acid. Patients who fail to respond to therapy or have complicated disease or unusual symptoms require further evaluation. In many cases, prolonged monitoring either for acid reflux (measurement of pH) or nonacid reflux may be required to determine whether the symptoms are indeed due to GERD. In addition, an endoscopic evaluation may be needed to assess for the presence or absence of mucosal disease.
Two New technologies recently available for prolonged reflux monitoring are the wireless pH monitoring system (Bravo; Medtronic; Minneapolis, Minnesota) and multichannel intraluminal impedance (Sleuth; Sandhill Scientific, Inc.; Highlands Ranch, Colorado). Wireless pH monitoring, which uses a "telemetry capsule"-based monitoring system, allows sampling for 48 hours and can be placed such that no catheter is required. This advancement in patient comfort and acceptance has progressed our knowledge of GERD and our ability to determine the relationship between acid and symptoms. Multichannel intraluminal impedance technology (MII/pH) has allowed us to characterize a bolus independent of the presence of acid. This combined MII/pH monitoring allows us to assess the patient for the presence of acid or nonacid (pH > 4) reflux using a single catheter. This so-called "nonacid reflux" has been a source of controversy because it has been difficult to determine whether refluxate with a pH > 4 is responsible for symptoms. During this year's meeting of the American College of Gastroenterology, several studies addressed the use of these technologies in the evaluation of patients with suspected GERD and are the focus of this report.
Catheter-Based Reflux Monitoring
Utility in the Diagnosis of Refractory GERD Symptoms?
Maqbool and colleagues[1] evaluated combined MII/pH monitoring to assess the clinical utility of this technology in patients with refractory GERD symptoms. In this prospective study involving 42 patients, 15 with atypical symptoms (hoarseness, throat clearing, sore throat, cough, chest pain, and globus) and 27 with predominantly typical symptoms (heartburn and regurgitation) on twice-daily proton-pump inhibitor therapy (PPI) were evaluated. MII/pH monitoring was performed by placing the catheter transnasally such that the impedance measuring segments were 3, 5, 7, 9, 15, and 17 cm above the lower esophageal sphincter (LES), with a simultaneous pH sensor at 5 cm above the LES. The study authors reviewed the tracings for the presence of distal and proximal reflux events. They found that all patients with purely atypical symptoms (n = 15) had a normal MII/pH study. In contrast, 9 of 27 (33%) with typical symptoms had abnormal MII/pH findings (P < .02). The predominant symptom in this latter group was regurgitation (7 of 9; 78%). Although not part of the original study, the investigators commented that 5 of 9 patients with abnormal MII/pH studies, 4 of whom had regurgitation, underwent surgical fundoplication and had complete symptom resolution in the early postoperative period. Their conclusion that MII/pH monitoring is rarely useful in patients with atypical symptoms refractory to aggressive acid suppression is similar to other preliminary observations.[2] However, the findings in patients with typical symptoms, particularly regurgitation, suggest the usefulness of this New technology in this patient population. Surgical success in a small group of patients with nonacid reflux and a positive symptom association were reported in another preliminary study.[3]
Evaluation of Gastroesophageal Reflux After Fundoplication
A small study by Kaul and Krauze[4] attempted to characterize the frequency and composition of gastroesophageal reflux after fundoplication in children using impedance technology (MII/pH). The authors performed 24 studies in children ranging from age 10 months to 11.5 years. The catheter was placed after endoscopy under general anesthesia and position verified by chest x-ray. They found: a trend towards a decrease in total number of reflux episodes after fundoplication; that gas reflux was more frequent than liquid reflux; and that few patients had evidence of esophagitis, including by microscopic examination. The study authors concluded that this technology was tolerated by the children and would provide useful results if reflux monitoring was required.
GERD in Patients With Pulmonary Symptoms
Ferguson and colleagues[5] presented the results of a study assessing the utility of MII/pH technology in patients with pulmonary diseases and complaints. The study involved 17 patients with pulmonary diseases/complaints as follows: idiopathic pulmonary fibrosis (n = 6), chronic obstructive pulmonary disease (n = 5), chronic cough (n = 3), and 1 patient each with restrictive bronchiolitis, asthma, and pulmonary hypertension. Overall, 10 of 17 (58%) patients had evidence of abnormal reflux, with 6 of 17 demonstrating normal pH testing but abnormal nonacid reflux. Four of 17 had abnormal acid reflux (2 on twice-daily PPI therapy and 2 off acid-suppressing therapy). Although no therapy was given to patients with nonacid reflux, nor any outcomes reported, the utility of pH testing with impedance in assessing this patient population for nonacid reflux was confirmed, and the frequency of nonacid reflux was found to be similar to that reported in earlier studies.[2,3]
Symptomatology Among GERD Patients on PPI Therapy
Jazrawi and colleagues[6] retrospectively evaluated 30 patients who had undergone MII/pH monitoring while on PPI therapy. They calculated the symptom association probability (positive if greater than 95%) and the symptom index (positive if greater than 50%), 2 ways of documenting the relationship between symptoms and reflux, with the goal of determining whether one strategy was more helpful in patient assessment. Their findings were similar to those discussed above, in that heartburn, regurgitation, and cough were the symptoms most likely to have a positive symptom association probability. Most important, however, the authors found a poor concordance for the symptom association probability and symptom index for both acidic and nonacidic reflux (33.3% and 42.8%, respectively). These study findings underscore that although MII/pH technology can detect nonacid reflux, correlating the presence of nonacid reflux and symptoms remains a clinical challenge using the current measures of symptom association probability and index.
Frequencies of Acid and Nonacid Reflux After Treatment
A small study by Vela and Richter[7] presented preliminary data on the use of MII/pH technology to assess the efficacy of pharmacologic interventions in patients with GERD. Six patients underwent separate 24-hour ambulatory MII/pH studies, the first after 2 weeks of baclofen* (gamma aminobutyric acid receptor type B agonist that inhibits transient LES relaxations) 20 mg 3 times per day, and the second after 2 weeks of therapy with esomeprazole 40 mg once daily. Adequate technical tracings were available for all 12 studies, and revealed that a similar number of reflux episodes were detected regardless of therapeutic intervention, with reflux on baclofen being predominantly acid and on esomeprazole being predominantly nonacid. This study reinforces the potential utility of baclofen-like drugs in the treatment of reflux, particularly postprandial symptoms in patients on acid-suppression therapy. Drugs with a better safety profile are awaited.
Wireless pH Monitoring
Concordance of Data Between First and Second 24-Hour Recording Periods
A group from the Mayo Clinic in Scottsdale, Arizona,[8] assessed intrasession variability and reproducibility of wireless pH studies in patients who had the capsule placed while either sedated or unsedated. Eighty-seven patients were studied, with approximately half comprising each group. The study authors evaluated the concordance of data between the two 24-hour periods in sedated vs unsedated patients, assessing intergroup differences in pH parameters. Overall, 85 of 87 (98%) of patients completed the full 48-hour study period. Significant correlations were found between the two 24-hour recording periods for both groups; however, variability was higher and correlations (reproducibility) lower in the sedated group compared with the unsedated group. Although these differences were not statistically significant, additional study is required to determine the optimal approach to placement of this device.
Does Wireless pH Capsule Placement Affect Esophageal Motor Function?
In a very straightforward study, Zhang and colleagues[9] evaluated the effect of the attachment of the wireless pH capsule on esophageal motility. Ten subjects were evaluated with a solid-state manometry assembly with 36 circumferential sensors spaced 1 cm apart, positioned to record from the hypopharynx to the stomach. Manometry studies were performed before and 12 or more hours after capsule placement. Two barium-swallow studies were also performed in 6 subjects under fluoroscopy, synchronized with manometric recordings. Overall, there was no change in basal LES pressure, LES relaxation, or peristaltic function. It is interesting to note that there was a noticeable 1.5-cm high pressure focus during peristalsis at the location of the capsule during fluoroscopy. Additionally, 5 of the 10 subjects reported foreign-body sensation and/or chest pain. Although the median pressure at the attachment site was increased in the 5 subjects with symptoms, it did not reach statistical significance compared with those without symptoms. These findings suggest that this short area of increased peristaltic amplitude may have a bearing on the genesis of symptoms in patients while the capsule is in place.
pH Testing in Patients With Noncardiac Chest Pain
Persistent noncardiac chest pain in patients on PPI therapy remains a clinical challenge. The optimal evaluation of these patients has still not been determined, and what additional diagnostic information pH monitoring may offer in this population remains to be assessed. Achem and colleagues[10] reviewed their experience with prolonged pH testing in a large cohort of patients with noncardiac chest pain. One hundred and thirty patients were evaluated, 80 of whom were on PPI therapy, with 59 agreeing to pH monitoring. In the group evaluated on PPI therapy, only 5 of 59 (8.4%) had continued acid reflux. Perhaps of equal interest, only 18 of 59 (30.5%) subjects studied while off PPI therapy had abnormal pH studies.
Findings from this retrospective observational study reinforce that the presence of abnormal gastroesophageal reflux in patients with noncardiac chest pain may not be as frequent as reported, and that an important minority of patients on PPI therapy continue to reflux acid. Most important, careful evaluation of these patients is required to make an accurate diagnosis of reflux.
Concluding Remarks
Our approach to the evaluation of patients with symptoms suspected to be due to GERD despite PPI therapy continues to evolve. As MII/pH technology has been studied further, we have come to understand that an important minority of patients continue to have nonacid reflux and symptoms associated with these events. It is possible that a select group of patients, probably those with regurgitation as the primary symptom, have a clear relationship between symptoms and reflux. The association of nonacid reflux with atypical symptoms, including chest pain and ear-nose-throat symptoms, remains a subject of debate, and requires additional study. Further developments in prolonged monitoring with capsule-based technology promise to add much to our understanding and management of this difficult patient group. We await these enhancements and the future research in this difficult patient group.
*The US Food and Drug Administration has not approved this medication for this use.
Saludos Cordiales
Dr. José Manuel Ferrer Guerra
Introduction
Gastroesophageal reflux disease (GERD) is a common problem in gastroenterologic practice. In the vast majority of clinical scenarios, the diagnosis is suspected on the basis of patient history and a therapeutic trial of antisecretory therapy initiated to confirm the relationship between the presenting symptoms and acid. Patients who fail to respond to therapy or have complicated disease or unusual symptoms require further evaluation. In many cases, prolonged monitoring either for acid reflux (measurement of pH) or nonacid reflux may be required to determine whether the symptoms are indeed due to GERD. In addition, an endoscopic evaluation may be needed to assess for the presence or absence of mucosal disease.
Two New technologies recently available for prolonged reflux monitoring are the wireless pH monitoring system (Bravo; Medtronic; Minneapolis, Minnesota) and multichannel intraluminal impedance (Sleuth; Sandhill Scientific, Inc.; Highlands Ranch, Colorado). Wireless pH monitoring, which uses a "telemetry capsule"-based monitoring system, allows sampling for 48 hours and can be placed such that no catheter is required. This advancement in patient comfort and acceptance has progressed our knowledge of GERD and our ability to determine the relationship between acid and symptoms. Multichannel intraluminal impedance technology (MII/pH) has allowed us to characterize a bolus independent of the presence of acid. This combined MII/pH monitoring allows us to assess the patient for the presence of acid or nonacid (pH > 4) reflux using a single catheter. This so-called "nonacid reflux" has been a source of controversy because it has been difficult to determine whether refluxate with a pH > 4 is responsible for symptoms. During this year's meeting of the American College of Gastroenterology, several studies addressed the use of these technologies in the evaluation of patients with suspected GERD and are the focus of this report.
Catheter-Based Reflux Monitoring
Utility in the Diagnosis of Refractory GERD Symptoms?
Maqbool and colleagues[1] evaluated combined MII/pH monitoring to assess the clinical utility of this technology in patients with refractory GERD symptoms. In this prospective study involving 42 patients, 15 with atypical symptoms (hoarseness, throat clearing, sore throat, cough, chest pain, and globus) and 27 with predominantly typical symptoms (heartburn and regurgitation) on twice-daily proton-pump inhibitor therapy (PPI) were evaluated. MII/pH monitoring was performed by placing the catheter transnasally such that the impedance measuring segments were 3, 5, 7, 9, 15, and 17 cm above the lower esophageal sphincter (LES), with a simultaneous pH sensor at 5 cm above the LES. The study authors reviewed the tracings for the presence of distal and proximal reflux events. They found that all patients with purely atypical symptoms (n = 15) had a normal MII/pH study. In contrast, 9 of 27 (33%) with typical symptoms had abnormal MII/pH findings (P < .02). The predominant symptom in this latter group was regurgitation (7 of 9; 78%). Although not part of the original study, the investigators commented that 5 of 9 patients with abnormal MII/pH studies, 4 of whom had regurgitation, underwent surgical fundoplication and had complete symptom resolution in the early postoperative period. Their conclusion that MII/pH monitoring is rarely useful in patients with atypical symptoms refractory to aggressive acid suppression is similar to other preliminary observations.[2] However, the findings in patients with typical symptoms, particularly regurgitation, suggest the usefulness of this New technology in this patient population. Surgical success in a small group of patients with nonacid reflux and a positive symptom association were reported in another preliminary study.[3]
Evaluation of Gastroesophageal Reflux After Fundoplication
A small study by Kaul and Krauze[4] attempted to characterize the frequency and composition of gastroesophageal reflux after fundoplication in children using impedance technology (MII/pH). The authors performed 24 studies in children ranging from age 10 months to 11.5 years. The catheter was placed after endoscopy under general anesthesia and position verified by chest x-ray. They found: a trend towards a decrease in total number of reflux episodes after fundoplication; that gas reflux was more frequent than liquid reflux; and that few patients had evidence of esophagitis, including by microscopic examination. The study authors concluded that this technology was tolerated by the children and would provide useful results if reflux monitoring was required.
GERD in Patients With Pulmonary Symptoms
Ferguson and colleagues[5] presented the results of a study assessing the utility of MII/pH technology in patients with pulmonary diseases and complaints. The study involved 17 patients with pulmonary diseases/complaints as follows: idiopathic pulmonary fibrosis (n = 6), chronic obstructive pulmonary disease (n = 5), chronic cough (n = 3), and 1 patient each with restrictive bronchiolitis, asthma, and pulmonary hypertension. Overall, 10 of 17 (58%) patients had evidence of abnormal reflux, with 6 of 17 demonstrating normal pH testing but abnormal nonacid reflux. Four of 17 had abnormal acid reflux (2 on twice-daily PPI therapy and 2 off acid-suppressing therapy). Although no therapy was given to patients with nonacid reflux, nor any outcomes reported, the utility of pH testing with impedance in assessing this patient population for nonacid reflux was confirmed, and the frequency of nonacid reflux was found to be similar to that reported in earlier studies.[2,3]
Symptomatology Among GERD Patients on PPI Therapy
Jazrawi and colleagues[6] retrospectively evaluated 30 patients who had undergone MII/pH monitoring while on PPI therapy. They calculated the symptom association probability (positive if greater than 95%) and the symptom index (positive if greater than 50%), 2 ways of documenting the relationship between symptoms and reflux, with the goal of determining whether one strategy was more helpful in patient assessment. Their findings were similar to those discussed above, in that heartburn, regurgitation, and cough were the symptoms most likely to have a positive symptom association probability. Most important, however, the authors found a poor concordance for the symptom association probability and symptom index for both acidic and nonacidic reflux (33.3% and 42.8%, respectively). These study findings underscore that although MII/pH technology can detect nonacid reflux, correlating the presence of nonacid reflux and symptoms remains a clinical challenge using the current measures of symptom association probability and index.
Frequencies of Acid and Nonacid Reflux After Treatment
A small study by Vela and Richter[7] presented preliminary data on the use of MII/pH technology to assess the efficacy of pharmacologic interventions in patients with GERD. Six patients underwent separate 24-hour ambulatory MII/pH studies, the first after 2 weeks of baclofen* (gamma aminobutyric acid receptor type B agonist that inhibits transient LES relaxations) 20 mg 3 times per day, and the second after 2 weeks of therapy with esomeprazole 40 mg once daily. Adequate technical tracings were available for all 12 studies, and revealed that a similar number of reflux episodes were detected regardless of therapeutic intervention, with reflux on baclofen being predominantly acid and on esomeprazole being predominantly nonacid. This study reinforces the potential utility of baclofen-like drugs in the treatment of reflux, particularly postprandial symptoms in patients on acid-suppression therapy. Drugs with a better safety profile are awaited.
Wireless pH Monitoring
Concordance of Data Between First and Second 24-Hour Recording Periods
A group from the Mayo Clinic in Scottsdale, Arizona,[8] assessed intrasession variability and reproducibility of wireless pH studies in patients who had the capsule placed while either sedated or unsedated. Eighty-seven patients were studied, with approximately half comprising each group. The study authors evaluated the concordance of data between the two 24-hour periods in sedated vs unsedated patients, assessing intergroup differences in pH parameters. Overall, 85 of 87 (98%) of patients completed the full 48-hour study period. Significant correlations were found between the two 24-hour recording periods for both groups; however, variability was higher and correlations (reproducibility) lower in the sedated group compared with the unsedated group. Although these differences were not statistically significant, additional study is required to determine the optimal approach to placement of this device.
Does Wireless pH Capsule Placement Affect Esophageal Motor Function?
In a very straightforward study, Zhang and colleagues[9] evaluated the effect of the attachment of the wireless pH capsule on esophageal motility. Ten subjects were evaluated with a solid-state manometry assembly with 36 circumferential sensors spaced 1 cm apart, positioned to record from the hypopharynx to the stomach. Manometry studies were performed before and 12 or more hours after capsule placement. Two barium-swallow studies were also performed in 6 subjects under fluoroscopy, synchronized with manometric recordings. Overall, there was no change in basal LES pressure, LES relaxation, or peristaltic function. It is interesting to note that there was a noticeable 1.5-cm high pressure focus during peristalsis at the location of the capsule during fluoroscopy. Additionally, 5 of the 10 subjects reported foreign-body sensation and/or chest pain. Although the median pressure at the attachment site was increased in the 5 subjects with symptoms, it did not reach statistical significance compared with those without symptoms. These findings suggest that this short area of increased peristaltic amplitude may have a bearing on the genesis of symptoms in patients while the capsule is in place.
pH Testing in Patients With Noncardiac Chest Pain
Persistent noncardiac chest pain in patients on PPI therapy remains a clinical challenge. The optimal evaluation of these patients has still not been determined, and what additional diagnostic information pH monitoring may offer in this population remains to be assessed. Achem and colleagues[10] reviewed their experience with prolonged pH testing in a large cohort of patients with noncardiac chest pain. One hundred and thirty patients were evaluated, 80 of whom were on PPI therapy, with 59 agreeing to pH monitoring. In the group evaluated on PPI therapy, only 5 of 59 (8.4%) had continued acid reflux. Perhaps of equal interest, only 18 of 59 (30.5%) subjects studied while off PPI therapy had abnormal pH studies.
Findings from this retrospective observational study reinforce that the presence of abnormal gastroesophageal reflux in patients with noncardiac chest pain may not be as frequent as reported, and that an important minority of patients on PPI therapy continue to reflux acid. Most important, careful evaluation of these patients is required to make an accurate diagnosis of reflux.
Concluding Remarks
Our approach to the evaluation of patients with symptoms suspected to be due to GERD despite PPI therapy continues to evolve. As MII/pH technology has been studied further, we have come to understand that an important minority of patients continue to have nonacid reflux and symptoms associated with these events. It is possible that a select group of patients, probably those with regurgitation as the primary symptom, have a clear relationship between symptoms and reflux. The association of nonacid reflux with atypical symptoms, including chest pain and ear-nose-throat symptoms, remains a subject of debate, and requires additional study. Further developments in prolonged monitoring with capsule-based technology promise to add much to our understanding and management of this difficult patient group. We await these enhancements and the future research in this difficult patient group.
*The US Food and Drug Administration has not approved this medication for this use.
Saludos Cordiales
Dr. José Manuel Ferrer Guerra
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