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Savarino EV, Lechien JR, Bertin L. Pathophysiology of Laryngopharyngeal Reflux Disease: The Reflux vs Reflex Theory. Otolaryngol Clin North Am 2025:S0030-6665(25)00001-5. [PMID: 40148171 DOI: 10.1016/j.otc.2025.01.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
Laryngopharyngeal reflux (LPR) involves the reflux of stomach contents into the upper aerodigestive tract, causing symptoms through both direct injury and reflex-mediated mechanisms. While traditional reflux and reflex theories provide insights into LPR pathogenesis, they do not fully encompass its clinical spectrum. Emerging evidence highlights the role of hypersensitivity-both peripheral and central-in LPR, with significant implications for treatment responses and the impact of psychological factors on symptom severity. Understanding these complex interactions is crucial for developing more effective management strategies for LPR.
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Affiliation(s)
- Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università Padova, Padua, Italy.
| | - Jérôme René Lechien
- Department of Otorhinolaryngology and Head and Neck Surgery, CHU de Bruxelles, CHU Saint-Pierre, School of Medicine, Brussels, Belgium; Department of Laryngology and Broncho-Esophagology (Anatomy Department), EpiCURA Hospital, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium; Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, Paris Saclay University, Research Committee of Young-Otolaryngologists of the International Federations of Oto-Rhino-Laryngological Societies (YO-IFOS), Paris, France; Department of Otorhinolaryngology and Head and Neck Surgery, Polyclinic of Poitiers, Poitiers, France
| | - Luisa Bertin
- Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; Gastroenterology Unit, Azienda Ospedale Università Padova, Padua, Italy. https://twitter.com/dr_luisa_bertin
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Liu CP, Jiang AY, Chen F, Wu J, Wang SY, Cao L, Liao T, Zheng YQ. Predictive Value of Laryngeal Mucosa Pepsin in Therapeutic Response of Laryngopharyngeal Reflux. J Voice 2024; 38:1412-1418. [PMID: 35760633 DOI: 10.1016/j.jvoice.2022.05.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 05/19/2022] [Accepted: 05/20/2022] [Indexed: 11/24/2022]
Abstract
OBJECTIVES/HYPOTHESIS To investigate the predictive capability of pepsin level in the laryngeal mucosa to the therapeutic effect of proton-pump inhibitors in patients with suspected laryngopharyngeal reflux (LPR), so as to verify whether it can be referred to as a biomarker of LPR. STUDY DESIGN Prospective case study. METHODS Sixty patients with clinical empiric LPR were enrolled, with an reflux symptom index (RSI) ≥ 13 and an reflux finding score (RFS) > 7 as screening criteria. Biopsy specimens from the interarytenoid mucosa were obtained under topical anesthesia for pepsin immunohistochemical staining. Two parameters were observed in these patients with different pepsin levels after the administration of esomeprazole for 12 weeks: the RSI and the RFS. RESULTS Among the 60 cases, 35 cases were negative or weakly positive for pepsin (Pepsin(-) group), and 25 cases were moderately positive or strongly positive for pepsin (Pepsin(+) group). After therapy, the RSI significantly decreased from 17.00 (15.00, 19.00) to 6.00 (5.00, 11.00) in the Pepsin(+) group (Z = -4.38, P < 0.01), but no difference was found in the RFS (T = 1.48, P > 0.05). No significant difference was observed in the RSI (T = 2.01, P > 0.05) or the RFS (T = 2.01, P > 0.05) in the Pepsin(-) group either before or after therapy. An improvement in the RSI ≥ 50% was taken as the standard of effective therapy. The effective rate in the Pepsin(+) group was 72.0% (18/25), while it was 14.3% (5/35) in the Pepsin(-) group. There was a significant difference in the effective rate between the two groups (χ2 = 20.55, P < 0.01). CONCLUSIONS Proton-pump inhibitors exhibited better effects in patients with higher pepsin levels in the laryngeal mucosa. Laryngeal mucosa pepsin may serve as an ideal indicator to screen patients suitable for proton-pump inhibitor therapy and a reliable biomarker to identify patients with LPR.
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Affiliation(s)
- Cai-Peng Liu
- Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Ai-Yun Jiang
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Fang Chen
- Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Jian Wu
- Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Shu-Yue Wang
- Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Lei Cao
- Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Tao Liao
- Department of Otorhinolaryngology Head and Neck Surgery, Guangzhou Red Cross Hospital of Jinan University, Guangzhou, China
| | - Yi-Qing Zheng
- Department of Otorhinolaryngology Head and Neck Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China; Department of Otorhinolaryngology Head and Neck Surgery, Sun Yat-sen Memorial Hospital of Sun Yatsen University, Guangzhou, China.
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Fernandez AM, Chan WW. Update on extraesophageal manifestations of gastroesophageal reflux. Curr Opin Gastroenterol 2024; 40:305-313. [PMID: 38662405 DOI: 10.1097/mog.0000000000001037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/26/2024]
Abstract
PURPOSE OF REVIEW 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. RECENT FINDINGS 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. SUMMARY 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.
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Affiliation(s)
- Annel M Fernandez
- Department of Medicine, Brigham and Women's Hospital
- Harvard Medical School
| | - Walter W Chan
- Department of Medicine, Brigham and Women's Hospital
- Harvard Medical School
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Boston, Massachusetts, USA
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Yun JM, Kim KW, Kim S, So YK. Salivary pepsin as an independent predictor of treatment response for laryngopharyngeal reflux: prospective cohort study with multivariate analysis. Sci Rep 2023; 13:22893. [PMID: 38129481 PMCID: PMC10739976 DOI: 10.1038/s41598-023-50014-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 12/14/2023] [Indexed: 12/23/2023] Open
Abstract
To analyze the predictive value of salivary pepsin for treatment outcomes in laryngopharyngeal reflux (LPR) using multivariate analysis that includes various associated factors. This prospective cohort study was conducted between August 2020 and August 2022. Patients with LPR who had symptoms lasting more than 1 month and a reflux symptom index (RSI) of 14 or higher were enrolled. The participants received a 2-month regimen of proton pump inhibitors (PPIs) treatment and lifestyle modification. Salivary pepsin was checked using fasting saliva before treatment. Salivary pepsin was detected more frequently in the good treatment response group (61.1%), compared to 14.3% in the poor response group. Similarly, patients with higher compliance to lifestyle modifications (> 90%) had a higher chance of a good response (91.7%) compared to those with lower compliance, who had a 53.8% chance of a good response. Other clinical factors have no significant association with treatment response. In multivariate analysis, both pretreatment salivary pepsin and higher compliance with lifestyle modification were found to be independent factors for treatment response (OR 14.457, CI 1.075 ~ 194.37 for both). This study found that positive salivary pepsin and strict lifestyle modification are independent predictors of treatment outcomes in LPR.
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Affiliation(s)
- Ji Min Yun
- Department of Otorhinolaryngology-Head and Neck Surgery, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang-si, Gyeonggi-do, 10380, Republic of Korea
- Department of Otorhinolaryngology-Head and Neck Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Ki Won Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang-si, Gyeonggi-do, 10380, Republic of Korea
| | - Suji Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang-si, Gyeonggi-do, 10380, Republic of Korea
| | - Yoon Kyoung So
- Department of Otorhinolaryngology-Head and Neck Surgery, Ilsan Paik Hospital, Inje University College of Medicine, 170 Juhwa-ro, Ilsanseo-gu, Goyang-si, Gyeonggi-do, 10380, Republic of Korea.
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Laracca M, Miele G, Podestà L, Sangiovanni S. A Non-Invasive Technique for Long-Term Monitoring of Gastroesophageal Reflux-A Pilot Study. SENSORS (BASEL, SWITZERLAND) 2023; 23:9459. [PMID: 38067832 PMCID: PMC10708781 DOI: 10.3390/s23239459] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 09/27/2023] [Revised: 11/17/2023] [Accepted: 11/24/2023] [Indexed: 12/18/2023]
Abstract
Many people suffer from gastric or gastroesophageal reflux disorder (GERD) due to a malfunction of the cardia, the valve between the esophagus and the stomach. GERD is a syndrome caused by the ascent of gastric juices and bile from the stomach. This article proposes a non-invasive impedance measurement method and demonstrates the correlation between GERD and impedance variation between appropriately chosen points on the patient's chest. This method is presented as an alternative to the most widely accepted diagnostic techniques for reflux, such as pH-metry, pH-impedance measurement, and esophageal manometry, which are invasive because they use a probe that is inserted through a nostril and reaches down to the esophagus.
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Affiliation(s)
- Marco Laracca
- Department of Astronautics, Electrical and Energetics Engineering (DIAEE), Sapienza University of Rome, Via Eudossiana 18, 00184 Rome, Italy; (M.L.); (L.P.)
| | - Gianfranco Miele
- Department of Electrical and Information Engineering, University of Cassino and Southern Lazio, 03043 Cassino, Italy;
| | - Luca Podestà
- Department of Astronautics, Electrical and Energetics Engineering (DIAEE), Sapienza University of Rome, Via Eudossiana 18, 00184 Rome, Italy; (M.L.); (L.P.)
| | - Silvia Sangiovanni
- Department of Astronautics, Electrical and Energetics Engineering (DIAEE), Sapienza University of Rome, Via Eudossiana 18, 00184 Rome, Italy; (M.L.); (L.P.)
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Vance D, Park J, Alnouri G, Turner RR, Daggumati S, Ferster APO, Ahmad A, Lyons K, Ross J, Russell K, Wu W, Sataloff RT. Diagnosing Laryngopharyngeal Reflux: A Comparison between 24-hour pH-Impedance Testing and Pharyngeal Probe (Restech) Testing, with Introduction of the Sataloff Score. J Voice 2023; 37:737-747. [PMID: 34092465 DOI: 10.1016/j.jvoice.2021.04.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Revised: 04/07/2021] [Accepted: 04/07/2021] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The purpose of this study was to compare the diagnostic utility of pH monitoring using 24-hour esophageal pH-Impedance (HEMII-pH) testing versus pharyngeal pH (Restech) testing (Respiratory Technology Corporation, Houston, Texas) for diagnosing laryngopharyngeal reflux (LPR). METHODS Retrospectively, patients were reviewed who had completed a Reflux Symptom Index (RSI) survey and stroboscopy within 60 days before or after undergoing simultaneous esophageal pH-Impedance monitoring and Restech testing. Reflux Finding Score (RFS) was determined by 4 blinded observers. 80.45% of patients were on anti-reflux medications at the time of study and had incomplete response to treatment for reflux. Improvement on reflux treatment was determined by evaluating presenting pre-pH monitoring RFS, post treatment RFS, and improvement of symptoms. Pearson correlation coefficients were calculated to assess relationships among RSI, RFS, and test results from HEMII-pH and Restech tests. RESULTS Eighty-seven patients were included in the analysis. The inter-rater reliability of the RFS determination was 74.57%, and the intra-rater reliability was 67.00%. Subjects who had a positive RYAN Score had a significant correlation with RFS (r of 0.222 and p-value of 0.0492). There was no correlation between RFS and number or percent time of reflux events, longest event, total number of events, or percent of time at alkaline pH for either HEMII-PH or Restech test. RSI correlated better with HEMII-pH test than with Restech for percent time spent in both upright (r of 0.226 and p-value of 0.029) and supine position (r of 0.261 and a p-value of 0.032). Restech correlated better with total patient symptom Scores including cough, heartburn, burping, and throat clearing, with a r of 0.242 and a p-value of 0.048. Restech detected more percent time in reflux for total reflux, supine reflux, and upright reflux (p-value less than 0.0001). Restech also detected longer event times than Impedance (p-value of less than 0.0001). When diagnosis of LPR is based on the definition of CRC, the Sataloff Score test had 70.45% sensitivity and 80.95% specificity. The RYAN Score had a sensitivity of 72%, and a specificity of 56.45%, and the Wu Score had a sensitivity of 62.16%, and specificity of 54.05%. When the Sataloff and Wu Score were used together, the sensitivity was 71.45%, specificity 100%, positive predictive value of 100%, and a negative predictive value of 59.46%. CONCLUSION The amount of time of reflux events correlates with symptoms better than the number of events. The HEMII-pH test was able to detect more events of pH<4 than Restech, possibly because there might have been more acid events below than above the upper esophageal sphincter, while Restech detected more total events. Restech recorded longer event times than HEMII-pH test. Since length of time correlates with RFS (probably reflecting laryngeal inflammation), and since laryngeal clearance of acid is more similar to pharyngeal than esophageal clearance, this finding might prove valuable clinically. The Sataloff Score has a sensitivity of 70.45%, and a specificity of 80.95% and appears useful clinically to detect mild to moderate that is missed by the RYAN Score. A combination of Sataloff Score and Wu Score may be clinically valuable to identify LPR with an increased sensitivity of 71.45% and increased specificity of 100%. The Wu Score is not yet available for the general clinical use, but the Sataloff Score is.
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Affiliation(s)
| | - Jin Park
- Drexel University College of Medicine
| | - Ghiath Alnouri
- Department of Otolaryngology, Head and Neck Surgery, Drexel University College of Medicine
| | | | - Srihari Daggumati
- Department of Otolaryngology, Head and Neck Surgery, Virginia Commonwealth University
| | | | - Asyia Ahmad
- Division of Gastroenterology, Drexel University College of Medicine
| | - Karen Lyons
- Department of Otolaryngology, Head and Neck Surgery, Drexel University College of Medicine
| | - Justin Ross
- Department of Otolaryngology, Head and Neck Surgery, Philadelphia College of Osteopathic Medicine
| | - Karissa Russell
- Division of Gastroenterology, Drexel University College of Medicine
| | - Wei Wu
- Department of Otorhinolaryngology, Head and Neck Surgery, PLA Strategic Support Force Characteristic Medical Center; Director of the State Environmental Protection Key Laboratory of Environmental Sense Organ Stress and Health, China
| | - Robert T Sataloff
- Department of Otolaryngology, Head and Neck Surgery, Senior Associate Dean for Clinical Academic Specialties, Drexel University College of Medicine; Director of Otolaryngology and Communication Sciences Research, Lankenau Institute for Medical Research; Drexel University College of Medicine.
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Chen JW, Vela MF, Peterson KA, Carlson DA. AGA Clinical Practice Update on the Diagnosis and Management of Extraesophageal Gastroesophageal Reflux Disease: Expert Review. Clin Gastroenterol Hepatol 2023; 21:1414-1421.e3. [PMID: 37061897 DOI: 10.1016/j.cgh.2023.01.040] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 12/23/2022] [Accepted: 01/02/2023] [Indexed: 04/17/2023]
Abstract
DESCRIPTION The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available evidence and expert advice regarding the clinical management of patients with suspected extraesophageal gastroesophageal reflux disease. METHODS This article provides practical advice based on the available published evidence including that identified from recently published reviews from leading investigators in the field, prospective and population studies, clinical trials, and recent clinical guidelines and technical reviews. This best practice document is not based on a formal systematic review. The best practice advice as presented in this document applies to patients with symptoms or conditions suspected to be related to extraesophageal reflux (EER). This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. These Best Practice Advice (BPA) statements were drawn from a review of the published literature and from expert opinion. Because systematic reviews were not performed, these BPA statements do not carry formal ratings of the quality of evidence or strength of the presented considerations. BEST PRACTICE ADVICE 1: Gastroenterologists should be aware of potential extraesophageal manifestations of gastroesophageal reflux disease (GERD) and should inquire about such disorders including laryngitis, chronic cough, asthma, and dental erosions in GERD patients to determine whether GERD may be a contributing factor to these conditions. BEST PRACTICE ADVICE 2: Development of a multidisciplinary approach to extraesophageal (EER) manifestations is an important consideration because the conditions are often multifactorial, requiring input from non-gastroenterology (GI) specialties. Results from diagnostic testing (ie, bronchoscopy, thoracic imaging, laryngoscopy, etc) from non-GI disciplines should be taken into consideration when gastroesophageal reflux (GER) is considered as a cause for extraesophageal symptoms. BEST PRACTICE ADVICE 3: Currently, there is no single diagnostic tool that can conclusively identify GER as the cause of EER symptoms. Determination of the contribution of GER to EER symptoms should be based on the global clinical impression derived from patients' symptoms, response to GER therapy, and results of endoscopy and reflux testing. BEST PRACTICE ADVICE 4: Consideration should be given toward diagnostic testing for reflux before initiation of proton pump inhibitor (PPI) therapy in patients with potential extraesophageal manifestations of GERD, but without typical GERD symptoms. Initial single-dose PPI trial, titrating up to twice daily in those with typical GERD symptoms, is reasonable. BEST PRACTICE ADVICE 5: Symptom improvement of EER manifestations while on PPI therapy may result from mechanisms of action other than acid suppression and should not be regarded as confirmation for GERD. BEST PRACTICE ADVICE 6: In patients with suspected extraesophageal manifestation of GERD who have failed one trial (up to 12 weeks) of PPI therapy, one should consider objective testing for pathologic GER, because additional trials of different PPIs are low yield. BEST PRACTICE ADVICE 7: Initial testing to evaluate for reflux should be tailored to patients' clinical presentation and can include upper endoscopy and ambulatory reflux monitoring studies of acid suppressive therapy. BEST PRACTICE ADVICE 8: Testing can be considered for those with an established objective diagnosis of GERD who do not respond to high doses of acid suppression. Testing can include pH-impedance monitoring while on acid suppression to evaluate the role of ongoing acid or non-acid reflux. BEST PRACTICE ADVICE 9: Alternative treatment methods to acid suppressive therapy (eg, lifestyle modifications, alginate-containing antacids, external upper esophageal sphincter compression device, cognitive-behavioral therapy, neuromodulators) may serve a role in management of EER symptoms. BEST PRACTICE ADVICE 10: Shared decision-making should be performed before referral for anti-reflux surgery for EER when the patient has clear, objectively defined evidence of GERD. However, a lack of response to PPI therapy predicts lack of response to anti-reflux surgery and should be incorporated into the decision process.
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Affiliation(s)
- Joan W Chen
- Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, Michigan.
| | - Marcelo F Vela
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona
| | | | - Dustin A Carlson
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Lien HC, Lee PH, Wang CC. Diagnosis of Laryngopharyngeal Reflux: Past, Present, and Future-A Mini-Review. Diagnostics (Basel) 2023; 13:diagnostics13091643. [PMID: 37175034 PMCID: PMC10177910 DOI: 10.3390/diagnostics13091643] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 04/19/2023] [Accepted: 05/05/2023] [Indexed: 05/15/2023] Open
Abstract
Laryngopharyngeal reflux (LPR) is a variant of gastroesophageal reflux disease (GERD) in which gastric refluxate irritates the lining of the aerodigestive tract and causes troublesome airway symptoms or complications. LPR is a prevalent disease that creates a significant socioeconomic burden due to its negative impact on quality of life, tremendous medical expense, and possible cancer risk. Although treatment modalities are similar between LPR and GERD, the diagnosis of LPR is more challenging than GERD due to its non-specific symptoms/signs. Due to the lack of pathognomonic features of endoscopy, mounting evidence focused on physiological diagnostic testing. Two decades ago, a dual pH probe was considered the gold standard for detecting pharyngeal acidic reflux episodes. Despite an association with LPR, the dual pH was unable to predict the treatment response in clinical practice, presumably due to frequently encountered artifacts. Currently, hypopharygneal multichannel intraluminal impedance-pH catheters incorporating two trans-upper esophageal sphincter impedance sensors enable to differentiate pharyngeal refluxes from swallows. The validation of pharyngeal acid reflux episodes that are relevant to anti-reflux treatment is, therefore, crucial. Given no diagnostic gold standard of LPR, this review article aimed to discuss the evolution of objective diagnostic testing and its predictive role of treatment response.
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Affiliation(s)
- Han-Chung Lien
- Division of Gastroenterology, Taichung Veterans General Hospital, Taichung 407219, Taiwan
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, Taiwan
| | - Ping-Huan Lee
- Division of Gastroenterology, Taichung Veterans General Hospital, Taichung 407219, Taiwan
| | - Chen-Chi Wang
- School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung 402, Taiwan
- Department of Otolaryngology, Taichung Veterans General Hospital, Taichung 407219, Taiwan
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Sintusek P, Mutalib M, Thapar N. Gastroesophageal reflux disease in children: What’s new right now? World J Gastrointest Endosc 2023; 15:84-102. [PMID: 37034973 PMCID: PMC10080553 DOI: 10.4253/wjge.v15.i3.84] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2022] [Revised: 01/15/2023] [Accepted: 02/08/2023] [Indexed: 03/16/2023] Open
Abstract
Gastroesophageal reflux (GER) in children is very common and refers to the involuntary passage of gastric contents into the esophagus. This is often physiological and managed conservatively. In contrast, GER disease (GERD) is a less common pathologic process causing troublesome symptoms, which may need medical management. Apart from abnormal transient relaxations of the lower esophageal sphincter, other factors that play a role in the pathogenesis of GERD include defects in esophageal mucosal defense, impaired esophageal and gastric motility and clearance, as well as anatomical defects of the lower esophageal reflux barrier such as hiatal hernia. The clinical manifestations of GERD in young children are varied and nonspecific prompting the necessity for careful diagnostic evaluation. Management should be targeted to the underlying aetiopathogenesis and to limit complications of GERD. The following review focuses on up-to-date information regarding of the pathogenesis, diagnostic evaluation and management of GERD in children.
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Affiliation(s)
- Palittiya Sintusek
- Thai Pediatric Gastroenterology, Hepatology and Immunology Research Unit (TPGHAI), Division of Gastroenterology, Department of Pediatrics, King Chulalongkorn Memorial Hospital and Thai Red Cross, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Bangkok, Thailand
| | - Mohamed Mutalib
- Department of Paediatric Gastroenterology, Pediatric and Gastroenterology Services, Evelina London Children’s Hospital, London SE1 7EH, United Kingdom
| | - Nikhil Thapar
- Department of Gastroenterology, Hepatology and Liver Transplant, Queensland Children’s Hospital, Brisbane, Queensland 4101, Australia
- School of Medicine, University of Queensland, Brisbane, Queensland 4006, Australia
- Woolworths Centre for Child Nutrition Research, Queensland University of Technology, Brisbane, Queensland 4101, Australia
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Kouki S, Viitanen SJ, Koho N, Laurila HP, Lilja‐Maula L, Holopainen S, Neuvonen M, Niemi M, Fastrès A, Clercx C, Rajamäki MM. Extraesophageal reflux and reflux aspiration in dogs with respiratory diseases and in healthy dogs. Vet Med (Auckl) 2023; 37:268-276. [PMID: 36655626 PMCID: PMC9889628 DOI: 10.1111/jvim.16622] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Accepted: 12/15/2022] [Indexed: 01/20/2023]
Abstract
BACKGROUND Salivary bile acids are used to diagnose extraesophageal reflux (EER) and to evaluate the risk of reflux aspiration that is associated with respiratory diseases in dogs. OBJECTIVES To study total bile acid (TBA) concentrations in saliva and in bronchoalveolar lavage fluid (BALF) to investigate EER and reflux aspiration in dogs with respiratory diseases and in healthy dogs. ANIMALS Thirty-one West Highland White Terriers (WHWTs) with idiopathic pulmonary fibrosis (IPF), 12 dogs with inflammatory airway disease (IAD), 6 dogs with recurrent pneumonia (RP), 26 brachycephalic dogs (BD), 27 healthy WHWTs (HW), 52 healthy dogs (HD). All privately-owned dogs. METHODS Saliva and BALF were collected from dogs in each group. RESULTS Salivary TBA concentrations were higher in IPF (median 0.1692 μM, interquartile range [IQR] 0.1115-0.2925 μM, Cohen's d 3.4, 95% confidence interval [CI] 2.2-4.0, P < .001) and BD (0.0256 μM, IQR 0.0086-0.0417 μM, d 0.5, CI -0.1 to 1.1, P = .003) compared to HD (0 μM, IQR not quantifiable [n.q.]-0.0131 μM). Bronchoalveolar lavage fluid TBA concentrations were higher in IPF (0.0117 μM, IQR 0.0048-0.0361 μM, d 0.5, CI 0-1.1, P < .001) compared to HD (0 μM, IQR n.q.-0.0074 μM). CONCLUSION AND CLINICAL IMPORTANCE Extraesophageal reflux and reflux aspiration occur in healthy dogs and those with respiratory diseases.
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Affiliation(s)
- Sirkku Kouki
- Department of Equine and Small Animal Medicine, Faculty of Veterinary MedicineUniversity of HelsinkiHelsinkiFinland
| | - Sanna J. Viitanen
- Department of Equine and Small Animal Medicine, Faculty of Veterinary MedicineUniversity of HelsinkiHelsinkiFinland
| | - Ninna Koho
- Department of Equine and Small Animal Medicine, Faculty of Veterinary MedicineUniversity of HelsinkiHelsinkiFinland
| | - Henna P. Laurila
- Department of Equine and Small Animal Medicine, Faculty of Veterinary MedicineUniversity of HelsinkiHelsinkiFinland
| | - Liisa Lilja‐Maula
- Department of Equine and Small Animal Medicine, Faculty of Veterinary MedicineUniversity of HelsinkiHelsinkiFinland
| | - Saila Holopainen
- Department of Equine and Small Animal Medicine, Faculty of Veterinary MedicineUniversity of HelsinkiHelsinkiFinland
| | - Mikko Neuvonen
- Department of Clinical Pharmacology, Faculty of MedicineUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Mikko Niemi
- Department of Clinical Pharmacology, Faculty of MedicineUniversity of Helsinki and Helsinki University HospitalHelsinkiFinland
| | - Aline Fastrès
- Department of Clinical Sciences, Faculty of Veterinary MedicineUniversity of LiègeLiègeBelgium
| | - Cécile Clercx
- Department of Clinical Sciences, Faculty of Veterinary MedicineUniversity of LiègeLiègeBelgium
| | - Minna M. Rajamäki
- Department of Equine and Small Animal Medicine, Faculty of Veterinary MedicineUniversity of HelsinkiHelsinkiFinland
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11
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Bobin F, Lechien JR. The role of pH-impedance monitoring in swallowing disorders. Curr Opin Otolaryngol Head Neck Surg 2022; 30:406-416. [PMID: 36004789 DOI: 10.1097/moo.0000000000000841] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW To review the current evidence about the usefulness and the place of pH study in the management of patients with swallowing disorders. RECENT FINDINGS Gastroesophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) are found in approximately 30% of patients with esophageal or oropharyngeal dysphagia. Patients with suspected GERD may benefit from gastrointestinal endoscopy and proton pump inhibitors according to guidelines. The diagnosis of LPR in patients with oropharyngeal dysphagia is more controversial because there are no gold standard and diagnostic guidelines. The clinical diagnosis based on empirical therapeutic trial is a reasonable first-line strategy, but many dysphagic patients should not respond to treatment. These patients require hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH), which is the most effective examination providing important information on GERD and LPR features. At the HEMII-pH, GERD patients often report upright (daytime) and supine (nighttime) liquid acid esophageal events with significant esophageal distal acid exposure time. LPR patients have more frequently upright (daytime) gaseous weakly acid or nonacid pharyngeal reflux events without distal esophageal acid exposure abnormalities in many times. The features of reflux at the HEMII-pH may indicate a personalized treatment for dysphagic patients combining proton pump inhibitors, alginate/magaldrate or gastroprokinetic in cases of esophageal dysmotility. SUMMARY GERD and LPR are prevalent causes of dysphagia. The large number of reflux patients who do not respond to empirical treatment makes important the awareness of otolaryngologists about pH-impedance monitoring indication, features, and interpretation.
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Affiliation(s)
- Francois Bobin
- Polyclinic of Poitiers, Elsan Hospital, Poitiers, France
| | - Jerome R Lechien
- Polyclinic of Poitiers, Elsan Hospital, Poitiers, France
- Department of Anatomy and Experimental Oncology, Mons School of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons
- Department of Otolaryngology-Head and Neck Surgery, EpiCURA Hospital, Baudour, Belgium
- Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, Paris Saclay University, Paris, France
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Wu J, Ma Y, Chen Y. GERD-related chronic cough: Possible mechanism, diagnosis and treatment. Front Physiol 2022; 13:1005404. [PMID: 36338479 PMCID: PMC9630749 DOI: 10.3389/fphys.2022.1005404] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 10/07/2022] [Indexed: 11/04/2023] Open
Abstract
GERD, or gastroesophageal reflux disease, is a prevalent medical condition that affects millions of individuals throughout the world. Chronic cough is often caused by GERD, and chronic cough caused by GER is defined as GERD-related chronic cough (GERC). It is still unclear what the underlying molecular mechanism behind GERC is. Reflux theory, reflex theory, airway allergies, and the novel mechanism of esophageal motility disorders are all assumed to be linked to GERC. Multichannel intraluminal impedance combined with pH monitoring remains the gold standard for the diagnosis of GERC, but is not well tolerated by patients due to its invasive nature. Recent discoveries of new impedance markers and new techniques (mucosal impedance testing, salivary pepsin, real-time MRI and narrow band imaging) show promises in the diagnosis of GERD, but the role in GERC needs further investigation. Advances in pharmacological treatment include potassium-competitive acid blockers and neuromodulators (such as Baclofen and Gabapentin), prokinetics and herbal medicines, as well as non-pharmacological treatments (such as lifestyle changes and respiratory exercises). More options have been provided for the treatment of GERC other than acid suppression therapy and anti-reflux surgery. In this review, we attempt to review recent advances in GERC mechanism, diagnosis, and subsequent treatment options, so as to provide guidance for management of GERC.
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Affiliation(s)
| | - Yiming Ma
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yan Chen
- Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
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13
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Diagnostic utility of salivary pepsin in laryngopharyngeal reflux: a systematic review and meta-analysis. Braz J Otorhinolaryngol 2022; 89:339-347. [PMID: 36347787 PMCID: PMC10071530 DOI: 10.1016/j.bjorl.2022.10.050] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Revised: 09/14/2022] [Accepted: 10/14/2022] [Indexed: 11/22/2022] Open
Abstract
OBJECTIVES Salivary pepsin has emerged as a biomarker for Laryngopharyngeal Reflux (LPR), which, however, has been questioned for its efficacy due to a lack of supporting medical data. Therefore, this study analyzed the diagnostic value of salivary pepsin for LPR and assessed a better cutoff value. METHODS Studies were searched in PubMed, Embase, and Cochrane Library from their receptions to October 1, 2021. Then, RevMan 5.3 and Stata 14.0 were utilized to summarize the diagnostic indexes for further meta-analysis. Data were separately extracted by two reviewers according to the trial data extraction form of the Cochrane Handbook. The risk of bias in Randomized Control Trials (RCTs) was evaluated with the Cochrane Risk of Bias Tool. RESULTS A total of 16 studies matched the criteria and were subjected to meta-analysis. The results revealed a pooled sensitivity of 61% (95% CI 50%-71%), a pooled specificity of 67% (95% CI 48%-81%), a positive likelihood ratio of 2 (95% CI 1.2-2.8), a negative likelihood ratio of 0.58 (95% CI 0.47‒0.72), and the area under the receiver operating characteristic curve of 0.67 (95% CI 0.63‒0.71). Subgroup analyses indicated that the cutoff value of pepsin at 50 ng/mL had a higher degree of diagnostic accuracy than that of pepsin at 16 ng/mL in cohort studies. CONCLUSION The review demonstrated low diagnostic performance of salivary pepsin for LPR and that the cutoff value of 50 ng/mL pepsin had superior diagnostic accuracy. Nevertheless, the diagnostic value may vary dependent on the utilized diagnostic criteria. Therefore, additional research is needed on the improved way of identifying salivary pepsin in the diagnosis of LPR, and also longer-term and more rigorous RCTs are warranted to further assess the effectiveness of salivary pepsin.
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14
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Zhang J, Wang X, Wang J, Zhao J, Zhang C, Liu Z, Li J. Optimal Timing of the Salivary Pepsin Test for the Diagnosis of Laryngopharyngeal Reflux. Laryngoscope 2022. [PMID: 36149876 DOI: 10.1002/lary.30408] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/13/2022] [Accepted: 08/29/2022] [Indexed: 11/11/2022]
Abstract
OBJECTIVE To investigate the optimal time point for diagnosing laryngopharyngeal reflux (LPR) through combining 24-h hypopharyngeal-esophageal multichannel intraluminal impedance-pH (24-h HEMII-pH) monitoring and the multi-time point salivary pepsin test (MTPSPT). STUDY DESIGN Prospective uncontrolled trial. METHOD Patients with and without LPR symptoms were included as the test group and the control group, respectively. The patients in the test group underwent 24-h HEMII-pH and MTPSPT. The results of 24-h HEMII-pH were used as a diagnostic criterion for LPR, and the diagnostic value of salivary pepsin tests performed at different time points was compared by receiver operating characteristic (ROC) analysis. RESULTS A total of 153 patients were included. Based on 24-h HEMII-pH, the positive rate of LPR in the test group of patients was 84.00%. In the control group, only one person (3.57%) had a positive salivary pepsin test result. The area under the curve (AUC) of the MTPSPT was 0.827. In addition, we separately calculated the AUC of the combined salivary pepsin test at different time points, and found good diagnostic value (AUC = 0.799) when the test was combined with the waking, 1 and 2 h after breakfast and lunch, and 1 h after dinner tests. However, when the number of tests were further increased, the diagnostic value did not improve significantly. CONCLUSION Salivary pepsin testing combined with waking, 1 h and 2 h after breakfast and lunch, and 1 h after dinner has almost the same diagnostic value as MTPSPT, and testing at these time points can be an effective method for diagnosing LPR. LEVEL OF EVIDENCE 3 Laryngoscope, 2022.
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Affiliation(s)
- Jinhong Zhang
- Department of Otolaryngology, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China.,Department of Otolaryngology, School of Medicine, South China University of Technology, Guangzhou, China
| | - Xiaoyu Wang
- Department of Otolaryngology, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China
| | - Jiasen Wang
- Department of Otolaryngology, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China
| | - Jing Zhao
- Department of Otolaryngology, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China
| | - Chun Zhang
- Department of Otolaryngology, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China.,Department of Otolaryngology, School of Medicine, South China University of Technology, Guangzhou, China
| | - Zhi Liu
- Department of Otolaryngology, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China
| | - Jinrang Li
- Department of Otolaryngology, The Sixth Medical Center of PLA General Hospital of Beijing, Beijing, China.,Department of Otolaryngology, School of Medicine, South China University of Technology, Guangzhou, China
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15
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Lechien JR. Clinical Update Findings about pH-Impedance Monitoring Features in Laryngopharyngeal Reflux Patients. J Clin Med 2022; 11:3158. [PMID: 35683545 PMCID: PMC9181144 DOI: 10.3390/jcm11113158] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 05/27/2022] [Accepted: 05/30/2022] [Indexed: 02/01/2023] Open
Abstract
Purpose: The diagnosis of laryngopharyngeal reflux (LPR) is commonly based on non-specific symptoms and findings and a positive response to an empirical therapeutic trial. The therapeutic response is, however, unpredictable, and many patients need pH-impedance monitoring to confirm the diagnosis. Methods: A review of the recent literature was conducted in PubMED, Scopus, and Embase about the pH-study features of LPR patients. A summary of last evidence was proposed. Results: The awareness of otolaryngologists about indications and interpretation of pH-impedance monitoring is low. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) is the most reliable examination determining the type and composition of hypopharyngeal reflux events (HRE) and the LPR features. The use of HEMII-pH is important to confirm the diagnosis in selected patients because non-specificity of symptoms and findings. There are no international consensus guidelines for the LPR diagnosis at the HEMII-pH. However, most studies supported the occurrence of >1 acid/weakly acid/nonacid HRE as diagnostic threshold. HREs are more frequently gaseous, weakly/nonacid compared with reflux events of gastroesophageal reflux. HREs occurred as daytime and upright, which does not support the value of double proton pump inhibitors or bedtime alginate. Oropharyngeal pH-monitoring is another approach reporting different sensitivity and specificity outcomes from HEMII-pH. The use of Ryan score for the LPR diagnosis at the oropharyngeal pH monitoring may be controversial regarding the low consideration of alkaline HREs. Conclusions: The awareness of otolaryngologists about HEMII-pH indication, features, and interpretation is an important issue regarding the high prevalence of LPR in outpatients consulting in otolaryngology. The HEMII-pH findings may indicate a more personalized treatment considering type and occurrence time of HREs.
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Affiliation(s)
- Jerome R. Lechien
- Polyclinic of Poitiers, Elsan Hospital, 86000 Poitiers, France;
- Department of Anatomy and Experimental Oncology, Mons School of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), 7000 Mons, Belgium
- Department of Otolaryngology-Head and Neck Surgery, EpiCURA Hospital, 7301 Baudour, Belgium
- Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, Paris Saclay University, 92150 Paris, France
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Finding relief for the self-conscious esophagus: laparoscopic anti-reflux surgery and the esophageal hypersensitivity and anxiety scale. Surg Endosc 2022; 36:7656-7663. [PMID: 35182218 DOI: 10.1007/s00464-022-09081-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2021] [Accepted: 01/25/2022] [Indexed: 01/06/2023]
Abstract
INTRODUCTION Measures of mood and effective coping strategies have notable correlations with quality of life and treatment responses. There is evidence that patients with previously diagnosed anxiety disorders have less improvement in patient-reported outcome measures (PROMs) after laparoscopic anti-reflux surgery (LARS) and that objective pathology does not correlate well with symptom severity. We were interested in investigating whether anxiety and hypervigilance, as measured preoperatively with the esophageal hypervigilance anxiety scale (EHAS), is associated with the improvement in GERD-specific PROMs and EHAS scores 6 months after LARS. METHODS We performed a retrospective cohort study of 102 adult patients (31% men, average age 64) who underwent LARS. In the preoperative evaluation, baseline gastroesophageal reflux disease-health-related quality of life (GERD-HRQL), laryngopharyngeal reflux symptom index (LPR-RSI) and EHAS scores were collected in addition to the standard reflux workup, including endoscopy, manometry, barium swallow, and pH study. For all three surveys, a higher score represents worse symptom severity. At 6 months postoperatively, 70 patients completed repeat GERD-HRQL, LPR-RSI, and EHAS surveys. We then analyzed for surgical and patient-related factors associated with improvement in the 6-month postoperative GERD-HRQL and LPR-RSI scores. RESULTS There was a statistically significant decrease in the GERD-HRQL (25 vs. 2, p < 0.001), LPR-RSI (17 vs. 3, p < 0.001) and EHAS (34 vs. 15, p < 0.001) 6 months after LARS. On multivariable linear regression, a higher baseline EHAS score was independently associated with a greater improvement in GERD-HRQL (β 0.35, p < 0.001) and LPR-RSI (β 0.19, p = 0.03) 6-months after LARS. Additionally, the degree of improvement in EHAS, GERD-HRQL, and LPR-RSI was not influenced by the type of LARS performed or by the severity of disease. CONCLUSION These findings are consistent with literature suggesting that measures of psychoemotional health correlate better with symptom intensity than objective pathology. We found that patients with a higher EHAS score have greater symptom severity and lower quality of life at baseline. Novel findings to this study are that patients with a higher preoperative EHAS, a measure of psychoemotional health, actually benefitted more from surgery and not less, which has been the traditional view in the literature. Future studies are warranted to establish directionality and explore the role of preoperative cognitive behavioral therapy with LARS for patients with significant symptoms of hypervigilance and anxiety.
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ACG Clinical Guideline for the Diagnosis and Management of Gastroesophageal Reflux Disease. Am J Gastroenterol 2022; 117:27-56. [PMID: 34807007 PMCID: PMC8754510 DOI: 10.14309/ajg.0000000000001538] [Citation(s) in RCA: 396] [Impact Index Per Article: 132.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Accepted: 08/30/2021] [Indexed: 01/30/2023]
Abstract
Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that as of this writing do not have sufficient evidence to grade are also provided.
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Abstract
Gastroesophageal reflux disease (GERD) continues to be among the most common diseases seen by gastroenterologists, surgeons, and primary care physicians. Our understanding of the varied presentations of GERD, enhancements in diagnostic testing, and approach to patient management have evolved. During this time, scrutiny of proton pump inhibitors (PPIs) has increased considerably. Although PPIs remain the medical treatment of choice for GERD, multiple publications have raised questions about adverse events, raising doubts about the safety of long-term use and increasing concern about overprescribing of PPIs. New data regarding the potential for surgical and endoscopic interventions have emerged. In this new document, we provide updated, evidence-based recommendations and practical guidance for the evaluation and management of GERD, including pharmacologic, lifestyle, surgical, and endoscopic management. The Grading of Recommendations, Assessment, Development, and Evaluation system was used to evaluate the evidence and the strength of recommendations. Key concepts and suggestions that as of this writing do not have sufficient evidence to grade are also provided.
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Li Y, Xu G, Zhou B, Tang Y, Liu X, Wu Y, Wang Y, Kong J, Xu T, He C, Zhu S, Wang X, Zhang J. Effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases: physiopathology and therapeutic targets. Eur Arch Otorhinolaryngol 2021; 279:2743-2752. [PMID: 34860271 PMCID: PMC9072476 DOI: 10.1007/s00405-021-07201-w] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Accepted: 11/23/2021] [Indexed: 12/18/2022]
Abstract
PURPOSE Laryngopharyngeal reflux disease (LPRD) is a general term for the reflux of gastroduodenal contents into the laryngopharynx, oropharynx and even the nasopharynx, causing a series of symptoms and signs. Currently, little is known regarding the physiopathology of LPRD, and proton pump inhibitors (PPIs) are the drugs of choice for treatment. Although acid reflux plays a critical role in LPRD, PPIs fail to relieve symptoms in up to 40% of patients with LPRD. The influence of other reflux substances on LPRD, including pepsin, bile acid, and trypsin, has received increasing attention. Clarification of the substances involved in LPRD is the basis for LPRD treatment. METHODS A review of the effects of acids, pepsin, bile acids, and trypsin on laryngopharyngeal reflux diseases was conducted in PubMed. RESULTS Different reflux substances have different effects on LPRD, which will cause various symptoms, inflammatory diseases and neoplastic diseases of the laryngopharynx. For LPRD caused by different reflux substances, 24-h multichannel intraluminal impedance combined with pH-metry (MII-pH), salivary pepsin, bile acid and other tests should be established so that different drugs and treatment courses can be used to provide patients with more personalized treatment plans. CONCLUSION This article summarizes the research progress of different reflux substances on the pathogenesis, detection index and treatment of LPRD and lays a theoretical foundation to develop target drugs and clinical diagnosis and treatment.
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Affiliation(s)
- Yading Li
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Gaofan Xu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Bingduo Zhou
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Yishuang Tang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Xiaowen Liu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Yue Wu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Yi Wang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Jing Kong
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Tingting Xu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Cong He
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Shengliang Zhu
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Xiaosu Wang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
| | - Jianning Zhang
- Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, 110 Ganhe Road, Hongkou District, Shanghai, 200437 China
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Zhang J, Li J, Zhang Y, Nie Q, Zhang R, Wang X, Jiang X, Wu Y, Wu R, Bi X, Cui X, Song H, Ran T, Li L. Multitime point pepsin testing can double the rate of the diagnosis of laryngopharyngeal reflux. Laryngoscope Investig Otolaryngol 2021; 6:1389-1394. [PMID: 34938879 PMCID: PMC8665477 DOI: 10.1002/lio2.700] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2021] [Revised: 10/26/2021] [Accepted: 11/10/2021] [Indexed: 12/14/2022] Open
Abstract
OBJECTIVE To study the value of multitime point salivary pepsin testing (MTPSPT) for the diagnosis of laryngopharyngeal reflux (LPR). STUDY DESIGN Prospective noncontrolled. METHODS For patients who met the enrollment criteria, the reflux symptom index (RSI) and reflux finding score (RFS) were calculated and salivary pepsin testing was performed. The pepsin test was performed every hour from 7:00 a.m. to 6:00 p.m. by collecting fresh saliva samples. A single positive test result was needed for the diagnosis of LPR. The consistency in the diagnosis of LPR between the two methods was compared with the weighted Cohen's kappa statistic. RESULTS A total of 204 patients were included. The kappa value between the two methods was 0.566 (p = .00). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of MTPSPT were 76.43%, 85.94%, 92.24%, and 62.5%, respectively. We also compared a single pepsin measure at 7 a.m. with the screening results based on the RSI and RFS, and found a much lower kappa agreement value (0.223, p = .00). The sensitivity, specificity, PPV, NPV, and false-negative rate of pepsin testing at 7 a.m. (fasting) were 37.86%, 92.18%, 91.38%, 40.41%, and 58.57%, respectively. CONCLUSION The use of the result of a single salivary pepsin test in the morning yields a relatively higher rate of missed diagnosis of LPR, and multitime point testing through a day increased the accuracy and sensitivity of detection of LPR twofold compared to a single morning fasting sample. LEVEL OF EVIDENCE 3.
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Affiliation(s)
- Jinhong Zhang
- Department of OtolaryngologySchool of Medicine, South China University of TechnologyGuangzhouChina
- Department of OtolaryngologyThe Sixth Medical Center of PLA General Hospital of BeijingBeijingChina
| | - Jinrang Li
- Department of OtolaryngologySchool of Medicine, South China University of TechnologyGuangzhouChina
- Department of OtolaryngologyThe Sixth Medical Center of PLA General Hospital of BeijingBeijingChina
| | - Yanping Zhang
- Department of OtolaryngologyThe Eighth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Qian Nie
- Department of OtolaryngologyThe Sixth Medical Center of PLA General Hospital of BeijingBeijingChina
| | - Ran Zhang
- Department of OtolaryngologyThe Sixth Medical Center of PLA General Hospital of BeijingBeijingChina
| | - Xiaoyu Wang
- Department of OtolaryngologyThe Sixth Medical Center of PLA General Hospital of BeijingBeijingChina
| | - Xingwang Jiang
- Department of OtolaryngologyThe Eighth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Yingying Wu
- Department of OtolaryngologyThe Eighth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Runze Wu
- Department of OtolaryngologyThe Eighth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Xinxin Bi
- Department of OtolaryngologyThe Eighth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Xiaohuan Cui
- Department of OtolaryngologyThe Eighth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Hui Song
- Department of OtolaryngologyThe Eighth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Taotao Ran
- Department of OtolaryngologyThe Eighth Medical Center of Chinese PLA General HospitalBeijingChina
| | - Lina Li
- Department of OtolaryngologyThe Eighth Medical Center of Chinese PLA General HospitalBeijingChina
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张 青, 谢 萌, 郭 瑞, 马 思, 刘 小, 杨 敏, 李 娜, 刘 海, 任 晓, 罗 花. [Effect of proton pump inhibitort on salivary pepsin concentration in patients with laryngopharyngeal reflux]. LIN CHUANG ER BI YAN HOU TOU JING WAI KE ZA ZHI = JOURNAL OF CLINICAL OTORHINOLARYNGOLOGY, HEAD, AND NECK SURGERY 2021; 35:965-970. [PMID: 34886597 PMCID: PMC10128359 DOI: 10.13201/j.issn.2096-7993.2021.11.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Indexed: 06/13/2023]
Abstract
Objective:To investigate the effect of proton pump inhibitor（PPI） treatment on salivary pepsin concentration in laryngopharyngeal reflux（LPR）. Methods:152 patients with suspected LPR complaining non-specific symptoms such as foreign body sensation, dry throat, phlegm and other non-specific symptoms were enrolled， in the Second Affiliated Hospital of Xi'an Jiaotong University from August 2019 to December 2020. According to the scores of reflux symptom index（RSI） and reflux finding score（RFS）, all the patients were divided into LPR （+） group and LPR （-） group, RSI （+） group and RSI （-） group, RFS （+） group and RFS （-） group . Patients in the LPR （+） group were reassessed after 1 month of PPI treatment. Saliva samples were collected from all the patients at initial diagnosis and follow-up diagnosis after treatment. The salivary pepsin concentration was determined by enzyme linked immunosorbent assay （ELISA）. The differences of RSI, RFS scores and salivary pepsin concentrations before and after treatment were compared. Results:The median concentration of salivary pepsin in LPR （+） group was significantly higher than that in LPR （-） group, and （73.01 ng/mL vs 25.66 ng/mL, P<0.01）, the median concentration of salivary pepsin in RFS （+） group were significantly higher than that in RFS （-） group（78.00 ng/mL vs 35.79 ng/mL, P<0.01） Furthermore, the median scores of RSI （11.00 vs 7.00, P<0.05） and RFS （9.00 vs 7.00, P<0.01） of LPR （+） patients notably decreased after PPI treatment for 1 month, and the salivary pepsin median concentration was memorably lower than that before treatment（53.60 ng/mL vs 46.49 ng/mL, P<0.05）. Meanwhile, the scores of symptoms such as pharyngeal paraesthesia, heartburn, chest pain, stomachache, and the scores of signs such as false vocal fold, erythema or congestion, vocal fold edema, posterior commissure hypertrophy and thick endolaryngeal mucus were conspicuously lower after treatment than those before treatment（P<0.05）. Conclusion:After 1 month of PPI treatment, the scores of partial symptoms and signs, and the salivary pepsin concentrations of LPR patients decreased significantly, suggesting that pepsin plays an important role in the pathogenesis of LPR, and pepsin may be closely related to the symptoms and signs such as pharyngeal paraesthesia and vocal fold edema.
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Affiliation(s)
- 青青 张
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - 萌 谢
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - 瑞昕 郭
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - 思敬 马
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - 小红 刘
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - 敏娟 杨
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - 娜 李
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - 海琴 刘
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - 晓勇 任
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
| | - 花南 罗
- 西安交通大学第二附属医院耳鼻咽喉头颈外科病院(西安，710004)Department of Otolaryngology Head and Neck Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, China
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Guo Z, Jiang J, Wu H, Zhu J, Zhang S, Zhang C. Salivary peptest for laryngopharyngeal reflux and gastroesophageal reflux disease: A systemic review and meta-analysis. Medicine (Baltimore) 2021; 100:e26756. [PMID: 34397878 PMCID: PMC8360476 DOI: 10.1097/md.0000000000026756] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Accepted: 07/06/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND A rapid lateral flow test (Peptest) to detect pepsin in saliva/sputum has been considered as a valuable method for diagnosing laryngopharyngeal reflux (LPR) and gastroesophageal reflux disease (GERD). The aim of this meta-analysis is to analyze the utility of Peptest for diagnosis of LPR and GERD. METHODS PubMed, EMBASE, and the Cochran Library (from January 1980 to 26 January 2020) were searched for pepsin in saliva for LPR/GERD diagnosis. Sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve data were summarized to examine the accuracy. RESULTS A total of 16 articles that included 2401 patients and 897 controls were analyzed. The pooled sensitivity and specificity for the diagnosis of GERD/LPR with Peptest were 62% (95% confidence interval [CI] 49%-73%) and 74% (95% CI 50%-90%), respectively. The summarized diagnostic odds ratio and area under the curve were 5.0 (95% CI 2-19) and 0.70 (95% CI 0.66-0.74), respectively. CONCLUSION Peptest shows moderate diagnostic value for LPR and GERD. More studies with standard protocols should be done to verify its usefulness.
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Affiliation(s)
- Zihao Guo
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China
| | - Jiali Jiang
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China
| | - Hao Wu
- Department of Cardiovascular diseases, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China
| | - Jinxia Zhu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
- National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing, China
- Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
| | - Chuan Zhang
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China
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Fass R, Boeckxstaens GE, El-Serag H, Rosen R, Sifrim D, Vaezi MF. Gastro-oesophageal reflux disease. Nat Rev Dis Primers 2021; 7:55. [PMID: 34326345 DOI: 10.1038/s41572-021-00287-w] [Citation(s) in RCA: 90] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/22/2021] [Indexed: 02/07/2023]
Abstract
Gastro-oesophageal reflux disease (GERD) is a common disorder in adults and children. The global prevalence of GERD is high and increasing. Non-erosive reflux disease is the most common phenotype of GERD. Heartburn and regurgitation are considered classic symptoms but GERD may present with various atypical and extra-oesophageal manifestations. The pathophysiology of GERD is multifactorial and different mechanisms may result in GERD symptoms, including gastric composition and motility, anti-reflux barrier, refluxate characteristics, clearance mechanisms, mucosal integrity and symptom perception. In clinical practice, the diagnosis of GERD is commonly established on the basis of response to anti-reflux treatment; however, a more accurate diagnosis requires testing that includes upper gastrointestinal tract endoscopy and reflux monitoring. New techniques and new reflux testing parameters help to better phenotype the condition. In children, the diagnosis of GERD is primarily based on history and physical examination and treatment vary with age. Treatment in adults includes a combination of lifestyle modifications with pharmacological, endoscopic or surgical intervention. In refractory GERD, optimization of proton-pump inhibitor treatment should be attempted before a series of diagnostic tests to assess the patient's phenotype.
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Affiliation(s)
- Ronnie Fass
- The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical System, Case Western Reserve University, Cleveland, OH, USA.
| | - Guy E Boeckxstaens
- Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
| | - Hashem El-Serag
- Department of Medicine, Baylor College of Medicine, Houston, TX, USA
| | - Rachel Rosen
- Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA
| | - Daniel Sifrim
- Wingate Institute of Neurogastroenterology, Royal London Hospital, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Michael F Vaezi
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
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24
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Lechien JR, Chan WW, Akst LM, Hoppo T, Jobe BA, Chiesa-Estomba CM, Muls V, Bobin F, Saussez S, Carroll TL, Vaezi MF, Bock JM. Normative Ambulatory Reflux Monitoring Metrics for Laryngopharyngeal Reflux: A Systematic Review of 720 Healthy Individuals. Otolaryngol Head Neck Surg 2021; 166:802-819. [PMID: 34313507 DOI: 10.1177/01945998211029831] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To review the normative data for acid, weakly acid, and nonacid proximal esophageal (PRE) and hypopharyngeal reflux (HRE) events in diagnosing laryngopharyngeal reflux (LPR) using ambulatory reflux monitoring. DATA SOURCES PubMed, Cochrane Library, and Scopus. REVIEW METHODS A literature search was conducted about the normative data for PRE and HRE on multichannel intraluminal impedance-pH monitoring (MII-pH), hypopharyngeal-esophageal MII-pH (HEMII-pH), or oropharyngeal pH monitoring using PICOTS (population, intervention, comparison, outcome, timing, and setting) and PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statements. Outcomes reviewed included device characteristics, impedance/pH sensor placements, study duration, number/average and percentiles of PRE or HRE occurrence, and the event characteristics (pH, composition, and position). RESULTS Of 154 identified studies, 18 met criteria for analysis, including 720 healthy individuals. HEMII-pH, MII-pH, and oropharyngeal pH monitoring were used in 7, 6, and 5 studies, respectively. The definition and inclusion/exclusion criteria of healthy individuals varied substantially across studies, with 6 studies considering only digestive symptoms to exclude potential LPR patients. Substantial heterogeneity across studies was noted, including impedance/pH sensor placements/configurations and definitions of composition (liquid, gas, mixed) and type (acid, weakly acid, nonacid) of PRE/HRE. The 95th percentile thresholds were 10 to 73 events for PRE, 0 to 10 events for HRE on HEMII-pH, and 40 to 128 for events with pH <6.0 on oropharyngeal pH monitoring. Most HREs were nonacid and occurred upright. The mean HRE among healthy individuals was 1. CONCLUSION The low number of studies and the heterogeneity in inclusion criteria, definitions, and characterization of PRE and HRE limit the establishment of consensual normative criteria for LPR on ambulatory reflux monitoring. Future large multicenter studies are needed.
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Affiliation(s)
- Jerome R Lechien
- Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, School of Medicine, University Paris Saclay, Paris, France.,Department of Otolaryngology-Head and Neck Surgery, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium.,Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium
| | - Walter W Chan
- Division of Gastroenterology, Hepatology and Endoscopy, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Lee M Akst
- Department of Otolaryngology-Head Neck Surgery, Johns Hopkins Hospital, Baltimore, MA, USA
| | - Toshitaka Hoppo
- Esophageal Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA
| | - Blair A Jobe
- Esophageal Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA
| | - Carlos M Chiesa-Estomba
- Department of Otorhinolaryngology-Head & Neck Surgery, Hospital Universitario Donostia, San Sebastian, Spain
| | - Vinciane Muls
- Department of Gastroenterology, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium
| | | | - Sven Saussez
- Department of Otolaryngology-Head and Neck Surgery, CHU Saint-Pierre, Université Libre de Bruxelles, Brussels, Belgium.,Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium
| | - Thomas L Carroll
- Department of Otolaryngology-Head Neck Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | - Michael F Vaezi
- Division of Gastroenterology, Hepatology, and Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jonathan M Bock
- Department of Otorhinolaryngology-Head & Neck Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
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25
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Diagnostic Value of the Peptest TM in Detecting Laryngopharyngeal Reflux. J Clin Med 2021; 10:jcm10132996. [PMID: 34279479 PMCID: PMC8268930 DOI: 10.3390/jcm10132996] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Revised: 06/29/2021] [Accepted: 07/01/2021] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The PeptestTM is a non-invasive diagnostic test for measuring the pepsin concentration in saliva, which is thought to correlate with laryngopharyngeal reflux (LPR). The aim of this study was to investigate the diagnostic value of the Peptest in detecting LPR based on 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring using several hypopharyngeal reflux episodes as criterion for LPR. METHODS Patients with suspected LPR were examined with the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), fasting Peptest, and MII-pH monitoring. We calculated the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the Peptest, RSI, and RFS based on the threshold of one and six hypopharyngeal reflux episodes. RESULTS Altogether, the data from 46 patients were analyzed. When one hypopharyngeal reflux episode was used as a diagnostic threshold for LPR, the accuracy, sensitivity, specificity, PPV, and NPV were, respectively, as follows: 35%, 33%, 100%, 100%, and 3%, for the Peptest; 39%, 40%, 0%, 95%, and 0%, for the RSI; and 57%, 58%, 0%, 96%, and 0%, for the RFS. The accuracy, sensitivity, specificity, PPV, and NPV of the Peptest for diagnosing gastroesophageal reflux disease (GERD) were 46%, 27%, 63%, 40.0%, and 48%, respectively. CONCLUSIONS A positive Peptest is highly supportive of a pathological LPR diagnosis. However, a negative test could not exclude LPR.
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26
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Babic B, Müller DT, Gebauer F, Schiffmann LM, Datta RR, Schröder W, Bruns CJ, Leers JM, Fuchs HF. Gastrointestinal function testing model using a new laryngopharyngeal pH probe (Restech) in patients after Ivor-Lewis esophagectomy. World J Gastrointest Oncol 2021; 13:612-624. [PMID: 34163577 PMCID: PMC8204358 DOI: 10.4251/wjgo.v13.i6.612] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2020] [Revised: 02/11/2021] [Accepted: 05/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND There is no established correlation between 24-h esophageal pH-metry (Eso-pH) and the new laryngopharyngeal pH-monitoring system (Restech) as only small case series exist. Eso-pH was not designed to detect laryngopharyngeal reflux (LPR) and Restech may detect LPR better. We have previously published a dataset using the two techniques in a large patient collective with gastroesophageal reflux disease. Anatomically, patients after esophagectomy were reported to represent an ideal human reflux model as no reflux barrier exists. AIM To use a human reflux model to examine our previously published correlation in these patients. METHODS Patients after Ivor Lewis esophagectomy underwent our routine follow-up program with surveillance endoscopies, computed tomography scans and further exams following surgery. Only patients with a complete check-up program and reflux symptoms were offered inclusion into this prospective study and evaluated using Restech and simultaneous Eso-pH. Subsequently, the relationship between the two techniques was evaluated. RESULTS A total of 43 patients from May 2016 - November 2018 were included. All patients presented with mainly typical reflux symptoms such as heartburn (74%), regurgitation (84%), chest pain (58%), and dysphagia (47%). Extraesophageal symptoms such as cough, hoarseness, asthma symptoms, and globus sensation were also present. Esophageal 24-hour pH-metry was abnormal in 88% of patients with a mean DeMeester Score of 229.45 [range 26.4-319.5]. Restech evaluation was abnormal in 61% of cases in this highly selective patient cohort. All patients with abnormal supine LPR were also abnormal for supine esophageal reflux measured by conventional Eso-pH. CONCLUSION Patients following esophagectomy and reconstruction with gastric interposition can ideally serve as a human reflux model. Interestingly, laryngopharyngeal reflux phases occur mainly in the upright position. In this human volume-reflux model, results of simultaneous esophageal and laryngopharyngeal (Restech) pH-metry showed 100% correlation as being explicable by one of our reflux scenarios.
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Affiliation(s)
- Benjamin Babic
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne 50931, Germany
| | - Dolores T Müller
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne 50931, Germany
| | - Florian Gebauer
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne 50931, Germany
| | - Lars Mortimer Schiffmann
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne 50931, Germany
| | - Rabi R Datta
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne 50931, Germany
| | - Wolfgang Schröder
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne 50931, Germany
| | - Christiane J Bruns
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne 50931, Germany
| | - Jessica M Leers
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne 50931, Germany
| | - Hans F Fuchs
- Department of General, Visceral, Cancer and Transplant Surgery, University of Cologne, Cologne 50931, Germany
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Yadlapati R, Kaizer A, Greytak M, Ezekewe E, Simon V, Wani S. Diagnostic performance of salivary pepsin for gastroesophageal reflux disease. Dis Esophagus 2021; 34:5974938. [PMID: 33180095 PMCID: PMC9989599 DOI: 10.1093/dote/doaa117] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2020] [Accepted: 10/07/2020] [Indexed: 12/11/2022]
Abstract
Uncertain diagnostic performance has limited clinical adoption of salivary pepsin, a noninvasive diagnostic tool for gastroesophageal reflux disease (GERD). This study aimed to assess diagnostic performance of salivary pepsin, and test validity of thresholds in an external cohort of patients with or without GERD. This two-phase prospective study conducted at two centers enrolled adult asymptomatic volunteers, patients with symptoms of GERD undergoing reflux monitoring, and patients with Barrett's esophagus (BE). Fasting saliva samples were processed for pepsin concentration using Peptest. Phase 1 compared pepsin concentration between No GERD (volunteers/functional heartburn) and GERD (erosive reflux disease/nonerosive reflux disease (NERD)/BE). Phase 2 tested validity of the diagnostic thresholds identified from Phase 1 among external functional heartburn and NERD cohorts. Of 243 enrolled subjects, 156 met inclusion criteria. Phase 1 (n = 114): Pepsin concentrations were significantly higher in GERD (n = 84) versus No GERD (n = 30) (73.8 ng/mL vs. 21.1 ng/mL; P < 0.001). Area under the curve for pepsin concentration was 0.74 (95% CI 0.65, 0.83). A salivary pepsin threshold of 24.9 ng/mL optimized the true negative rate and 100.0 ng/mL optimized the true positive rate. Phase 2 (n = 42): Pepsin concentrations were significantly higher in NERD (n = 22) versus Functional Heartburn (n = 20) (176.0 ng/mL vs. 53.3 ng/mL, P < 0.001). Applying Phase 1 thresholds in this external cohort, salivary pepsin 24.9 ng/mL was 86% sensitive (64%, 97%) and 100.0 ng/mL was 72% specific for distinguishing NERD from functional heartburn. Given modest sensitivity and specificity for GERD, salivary pepsin may have clinical utility as a noninvasive office based diagnostic screening tool for GERD.
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Affiliation(s)
- Rena Yadlapati
- Division of Gastroenterology, University of California, San Diego School of Medicine, La Jolla, CA, USA
| | - Alexander Kaizer
- University of Colorado, Anschutz Medical Campus, Colorado School of Public Health, Department of Biostatistics and Informatics, Aurora, CO, USA
| | - Madeline Greytak
- Division of Gastroenterology, University of California, San Diego School of Medicine, La Jolla, CA, USA
| | - Eze Ezekewe
- Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Violette Simon
- Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
| | - Sachin Wani
- Division of Gastroenterology & Hepatology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
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Abstract
Globus is the sensation of a foreign body in the throat. Investigation and management of patients with globus is widely variable. Most investigations yield negative results yet incur varying patient morbidity and healthcare costs, while malignancy is vanishingly rare in the absence of red flag symptoms and ear, nose and throat examination findings. History taking is key and can help to identify possible causative pathology, directing further investigations and management if necessary. Treatment of globus mainly centres on patient reassurance and counselling, and may include reflux management, neuromodulation, or speech therapy in selected cases, and treatment of any identified cause.
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Affiliation(s)
- Richard Siau
- Ear, Nose and Throat Department, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Andrew Kinshuck
- Ear, Nose and Throat Department, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
| | - Lisa Houghton
- Speech and Language Therapy Department, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK
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Abstract
PURPOSE OF REVIEW This review explores the recent evidence and established scientific literature surrounding proton pump inhibitors in the context of laryngology. RECENT FINDINGS Proton pump inhibitors are often associated with gastroenterology; however, they also have a place in laryngology. Several laryngopharyngeal disorders are treated with proton pump inhibitors, though limited evidence regarding effectiveness, dosing and length of treatment exists. With the recent influx of articles reporting possible adverse effects of proton pump inhibitors, the appropriate prescribing of them has come under scrutiny. These reported risks include cancer, stroke, myocardial infarction, kidney disease and cognitive decline. It should be noted though that many of these studies by nature, are fraught with potential confounding. Regardless, clinicians ought to be aware of any risks associated with treatment regimens and prescribe the optimal dosage and duration. SUMMARY Proton pump inhibitor treatment should be dose-appropriate and for a limited duration. Concerning potential adverse effects, the limitations of retrospective cohort studies must be taken into consideration when reviewing the evidence.
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30
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Failed Swallows on High-Resolution Manometry Independently Correlates With Severity of LPR Symptoms. J Voice 2020; 36:832-837. [DOI: 10.1016/j.jvoice.2020.09.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 09/07/2020] [Accepted: 09/10/2020] [Indexed: 11/23/2022]
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Abstract
Esophageal symptoms are common and may indicate the presence of gastroesophageal reflux disease (GERD), structural processes, motor dysfunction, behavioral conditions, or functional disorders. Esophageal physiologic tests are often performed when initial endoscopic evaluation is unrevealing, especially when symptoms persist despite empiric management. Commonly used esophageal physiologic tests include esophageal manometry, ambulatory reflux monitoring, and barium esophagram. Functional lumen imaging probe (FLIP) has recently been approved for the evaluation of esophageal pressure and dimensions using volumetric distension of a catheter-mounted balloon and as an adjunctive test for the evaluation of symptoms suggestive of motor dysfunction. Targeted utilization of esophageal physiologic tests can lead to definitive diagnosis of esophageal disorders but can also help rule out organic disorders while making a diagnosis of functional esophageal disorders. Esophageal physiologic tests can evaluate obstructive symptoms (dysphagia and regurgitation), typical and atypical GERD symptoms, and behavioral symptoms (belching and rumination). Certain parameters from esophageal physiologic tests can help guide the management of GERD and predict outcomes. In this ACG clinical guideline, we used the Grading of Recommendations Assessment, Development and Evaluation process to describe performance characteristics and clinical value of esophageal physiologic tests and provide recommendations for their utilization in routine clinical practice.
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Yin CY, Zhang SS, Zhong JT, Zhou SH. Pepsin and Laryngeal and Hypopharyngeal Carcinomas. Clin Exp Otorhinolaryngol 2020; 14:159-168. [PMID: 32734742 PMCID: PMC8111387 DOI: 10.21053/ceo.2020.00465] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Accepted: 07/17/2020] [Indexed: 02/08/2023] Open
Abstract
Laryngeal and hypopharyngeal carcinomas are common malignant tumors of the head and neck, and the incidence of both is increasing. Laryngopharyngeal reflux refers to the retrograde flow of gastric contents into the larynx, oropharynx, and/or nasopharynx. It remains controversial whether laryngopharyngeal reflux is a risk factor for laryngeal and hypopharyngeal cancers. The refluxing substances mainly include hydrochloric acid, pepsin, and occasionally bile acids and bile salts, as well as bacteria that colonize the gastrointestinal tract. Loss of epithelium in the mucous membrane of the larynx and hypopharynx is thought to be caused by pepsin. Here, we review the relationships between laryngopharyngeal reflux and both laryngeal and hypopharyngeal carcinomas, as well as the significance of pepsin, methods of clinical detection, and the mechanism of carcinogenesis.
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Affiliation(s)
- Cheng-Yi Yin
- Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.,Department of Otolaryngology, The First People's Hospital of Huzhou City, Zhejiang, China
| | - Sha-Sha Zhang
- Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Jiang-Tao Zhong
- Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Shui-Hong Zhou
- Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
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Clinical utility of salivary pepsin measurement in patients with proton pump inhibitor-refractory gastroesophageal reflux disease symptoms: a prospective comparative study. Esophagus 2020; 17:339-347. [PMID: 31982992 DOI: 10.1007/s10388-020-00714-z] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Accepted: 01/12/2020] [Indexed: 02/03/2023]
Abstract
BACKGROUND Salivary pepsin measurement has been reported to be useful for diagnosing gastroesophageal reflux disease (GERD). This study aimed to clarify the usefulness of salivary pepsin measurement in patients with proton pump inhibitor (PPI)-refractory GERD symptoms without erosive esophagitis. METHODS One hundred and two patients were included. Over seven days after terminating PPI treatment, all patients underwent a 24-h pH-impedance test and salivary pepsin measurement. In patients whose main symptoms included laryngopharyngeal symptoms, a hypopharyngeal multichannel intraluminal impedance (HMII) test was performed, whereas in other patients, a conventional combined multichannel intraluminal impedance-pH (MII-pH) test was performed. In the HMII tests, patients were divided into abnormal proximal exposure (APE) and non-APE groups. Salivary pepsin concentrations were compared according to acid exposure time (AET) values and were also compared between the APE and non-APE groups. RESULTS The median salivary pepsin concentration in patients with AET > 6% was significantly higher than that in patients with AET ≤ 6% (345.0 [170.0-469.3] ng/mL vs. 120.0 [97.0-290.1] ng/mL, p < 0.01). The sensitivity, specificity, positive predictive value, and negative predictive value of a positive test (> 109 ng/mL) to diagnose patients with AET > 6% were 75.0%, 51.3%, 32.1%, and 86.9%, respectively. There was no significant difference between concentrations in the APE group and concentrations in the non-APE group. CONCLUSIONS In patients with PPI-refractory nonerosive reflux disease, salivary pepsin measurement may help diagnose patients who have conclusive evidence of reflux, whereas it is not adequate for identifying patients with APE.
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Bozzani A, Grattagliano I, Pellegatta G, Furnari M, Galeone C, Savarino V, Savarino E, De Bastiani R. Usefulness of Pep-Test for Laryngo-Pharyngeal Reflux: A Pilot Study in Primary Care. Korean J Fam Med 2020; 41:250-255. [PMID: 32460472 PMCID: PMC7385291 DOI: 10.4082/kjfm.18.0207] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2018] [Accepted: 04/22/2019] [Indexed: 12/13/2022] Open
Abstract
Background Gastroesophageal reflux disease is a digestive disorder characterized by nausea, regurgitation, and heartburn. Gastroesophageal reflux is the primary cause of laryngeal symptoms, especially chronic posterior laryngitis. The best diagnostic test for this disease is esophageal impedance-pH monitoring; however, it is poorly employed owing to its high cost and invasiveness. Salivary pepsin measured using a lateral flow device (Pep-test) has been suggested as an indirect marker of laryngopharyngeal reflux (LPR). The present study tested the reliability of Pep-test in diagnosing LPR in uninvestigated primary care attenders presenting with chronic laryngeal symptoms, and evaluated the raw pepsin concentration in patients with LPR. Methods A multicenter, non-interventional pilot study was conducted on 86 suspected patients with LPR and 59 asymptomatic subjects as controls in three Italian primary care settings. A reflux symptom index questionnaire was used to differentiate patients with LPR (score >13) from controls (score <5). Two saliva samples were collected, and comparisons between the groups were performed using two-sided statistical tests, according to variable distributions. Results There was no statistical difference in the salivary pepsin positivity between LPR patients and controls, whereas the pepsin intensity value was higher in controls than in LPR patients. Conclusion A high prevalence of pepsin positivity was observed in asymptomatic controls. Pepsin measurement should not be considered as a diagnostic test for LPR in primary care patients.
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Affiliation(s)
- Alberto Bozzani
- GIGA-CP (Italian Group for Primary Care Gastroenterology), Milan, Italy
| | | | | | | | - Carlotta Galeone
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | | | | | - Rudi De Bastiani
- GIGA-CP (Italian Group for Primary Care Gastroenterology), Milan, Italy
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Wang YJ, Lang XQ, Wu D, He YQ, Lan CH, Xiao X, Wang B, Zou DW, Wu JM, Zhao YB, Dettmar PW, Chen DF, Yang M. Salivary Pepsin as an Intrinsic Marker for Diagnosis of Sub-types of Gastroesophageal Reflux Disease and Gastroesophageal Reflux Disease-related Disorders. J Neurogastroenterol Motil 2020; 26:74-84. [PMID: 31650768 PMCID: PMC6955190 DOI: 10.5056/jnm19032] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 06/14/2019] [Accepted: 07/23/2019] [Indexed: 12/13/2022] Open
Abstract
Background/Aims To determine the value of salivary pepsin in discriminating sub-types of gastroesophageal reflux disease (GERD) and GERD-related disorders. Methods Overall, 322 patients with different sub-types of GERD and 45 healthy controls (HC) were studied. All patients took Gastroesophageal Reflux Disease Questionnaire (GerdQ) and underwent endoscopy and 24-hour esophageal pH monitoring and manometry. Salivary pepsin concentration (SPC) was detected by using colloidal gold double-antibody immunological sandwich assay. Oral esomeprazole treatment was administrated in the patients with non-erosive reflux disease (NERD) and extra-esophageal symptoms (EES). Results Compared to HC, patients with erosive esophagitis, NERD, EES, EES plus typical GERD symptoms, or Barrett’s esophagus had a higher prevalence of saliva and SPC (all P < 0.001). There was no significant difference in the positive rate for pepsin in patients with functional heartburn or GERD with anxiety and depression, compared to HC. After esomeprazole treatment, the positive rate and SPC were significantly reduced in NERD (both P < 0.001) and in EES (P = 0.001 and P = 0.002, respectively). Of the 64 NERD patients, 71.9% (n = 46) were positive for salivary pepsin, which was significantly higher than the rate (43.8%, n = 28) of pathological acid reflux as detected by 24-hour esophageal pH monitoring (P = 0.002). Conclusions Salivary pepsin has an important significance for the diagnosis of GERD and GERD-related disorders. Salivary pepsin and 24-hour esophageal pH monitoring may complement with each other to improve the diagnostic efficiency.
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Affiliation(s)
- Yan-Jun Wang
- Department of Gastroenterology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China
| | - Xiu-Qiong Lang
- Department of Gastroenterology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China
| | - Dan Wu
- Department of Gastroenterology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China
| | - Yu-Qin He
- Department of Gastroenterology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China
| | - Chun-Hui Lan
- Department of Gastroenterology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China
| | - Xiao Xiao
- Department of Gastroenterology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China
| | - Bin Wang
- Department of Gastroenterology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China
| | - Duo-Wu Zou
- Department of Gastroenterology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Ji-Min Wu
- Department of Gastroenterology, Department of Gastroesophageal Reflux Disease, PLA Rocket Force General Hospital, Beijing, China
| | - Yong-Bin Zhao
- Department of Gastroenterology, Xinqiao Hospital, Chongqing, China
| | | | - Dong-Feng Chen
- Department of Gastroenterology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China
| | - Min Yang
- Department of Gastroenterology, Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, China
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Utilidad clínica de la determinación de pepsina en saliva en pacientes con tos crónica asociada a refujo. OPEN RESPIRATORY ARCHIVES 2020. [DOI: 10.1016/j.opresp.2019.12.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Klimara MJ, Samuels TL, Johnston N, Chun RH, McCormick ME. Detection of Pepsin in Oral Secretions of Infants with and without Laryngomalacia. Ann Otol Rhinol Laryngol 2019; 129:224-229. [DOI: 10.1177/0003489419884332] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Objectives: Laryngomalacia is a common cause of stridor in infants and is associated with laryngopharyngeal reflux (LPR). Although pepsin in operative supraglottic lavage specimens is associated with severe laryngomalacia, detection of pepsin in oral secretions has not been demonstrated in an outpatient setting. Methods: Children <2 years old with laryngomalacia diagnosed by flexible laryngoscopy and children without stridor were selected. Oral secretion samples were obtained in clinic from all subjects. Pepsin, IL-1β, and IL-8 enzyme-linked immunosorbent assays were performed to determine presence of LPR. Results: Sixteen laryngomalacia and sixteen controls were enrolled. Pepsin was detected more frequently in oral secretions of patients with laryngomalacia (13/16) than in controls (2/16; P < .001). Four patients with laryngomalacia developed symptoms requiring supraglottoplasty. Presence and level of salivary pepsin was not significantly associated with need for surgical management, nor were the levels or presence of IL-1β or IL-8 significantly associated with presence or level of pepsin, diagnosis of laryngomalacia, or need for operative management. Conclusion: Pepsin in saliva appears to be associated with laryngomalacia, suggesting a role for salivary pepsin as a noninvasive marker of LPR in patients with laryngomalacia. Future studies will determine the utility of this test in laryngomalacia.
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Affiliation(s)
- Miles J. Klimara
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Tina L. Samuels
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Nikki Johnston
- Department of Otolaryngology and Communication Sciences and Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA
| | - Robert H. Chun
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA
- Division of Pediatric Otolaryngology, Children’s Hospital of Wisconsin, Milwaukee, WI, USA
| | - Michael E. McCormick
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, USA
- Division of Pediatric Otolaryngology, Children’s Hospital of Wisconsin, Milwaukee, WI, USA
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Yu Y, Wen S, Wang S, Shi C, Ding H, Qiu Z, Xu X, Yu L. Reflux characteristics in patients with gastroesophageal reflux-related chronic cough complicated by laryngopharyngeal reflux. ANNALS OF TRANSLATIONAL MEDICINE 2019; 7:529. [PMID: 31807511 DOI: 10.21037/atm.2019.09.162] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background This study aimed to investigate the reflux characteristics in patients with gastroesophageal reflux-related chronic cough (GERC) complicated by laryngopharyngeal reflux (LPR). Methods Patients with chronic cough were recruited. Reflux symptom index (RSI) scoring, cough symptom scoring, assessment of capsaicin cough sensitivity, and multichannel intraluminal impedance and pH monitoring (MII-pH) were performed. Results RSI score in GERC patients was significantly higher than that in patients with atopic cough (AC), cough variant asthma, eosinophilic bronchitis (EB), and upper airway cough syndrome (UACS) (P<0.05). The RSI score in non-acid GERC patients was significantly higher than that in acid GERC patients (P=0.003). The cut-off value of the RSI score was defined as 19 during diagnosis of non-acid GERC. In the RSI ≥19 group, there was more proximal reflux and more significant gas and non-acid reflux, and the efficacy of a combined use of baclofen or gabapentin was better than that of the RSI <19 group (P<0.05). The efficacy of proton pump inhibitor (PPI) at a routine dosage together with prokinetic agents in the RSI <19 group was better than that in the RSI ≥19 group (P=0.009). Conclusions LPR overlaps with GERC in part. GERC patients with higher RSI scores may present more proximal reflux, non-acid reflux, and gas reflux, and get better efficacy with neuromodulators (gabapentin or baclofen) used as an add-on therapy.
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Affiliation(s)
- Yiming Yu
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China.,Department of Pulmonary and Critical Care Medicine, Tongren Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200336, China
| | - Siwan Wen
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Shengyuan Wang
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Cuiqin Shi
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Hongmei Ding
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Zhongmin Qiu
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Xianghuai Xu
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
| | - Li Yu
- Department of Pulmonary and Critical Care Medicine, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
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Ghisa M, Della Coletta M, Barbuscio I, Marabotto E, Barberio B, Frazzoni M, De Bortoli N, Zentilin P, Tolone S, Ottonello A, Lorenzon G, Savarino V, Savarino E. Updates in the field of non-esophageal gastroesophageal reflux disorder. Expert Rev Gastroenterol Hepatol 2019; 13:827-838. [PMID: 31322443 DOI: 10.1080/17474124.2019.1645593] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Introduction: Gastroesophageal reflux disease (GERD) is one of the most prevalent conditions in Western Countries, normally presenting with heartburn and regurgitation. Extra-esophageal (EE) GERD manifestations, such as asthma, laryngitis, chronic cough and dental erosion, represent the most challenging aspects from diagnostic and therapeutic points of view because of their multifactorial pathogenesis and low response to proton pump inhibitors (PPIs). In fact, in the case of EE, other causes must by preventively excluded, but instrumental methods, such as upper gastrointestinal endoscopy and laryngoscopy, have low specificity and sensitivity as diagnostic tools. In the absence of alarm signs and symptoms, empirical therapy with a double-dose of PPIs is recommended as a first diagnostic approach. Subsequently, impedance-pH monitoring could help to define whether the symptoms are GERD-related. Areas covered: This article reviews the current literature regarding established and proposed EE-GERD, reporting on all available options for its correct diagnosis and therapeutic management. Expert opinion: MII-pH could help to identify a hidden GERD that causes EE. Unfortunately, standard MII-pH analysis results are often unable to define this association. New parameters such as the mean nocturnal baseline impedance and post-reflux swallow-induced peristaltic wave index may have an improved diagnostic yield, but prospective studies using impedance-pH are needed.
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Affiliation(s)
- Matteo Ghisa
- Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua , Italy
| | - Marco Della Coletta
- Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua , Italy
| | - Ilenia Barbuscio
- Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua , Italy
| | - Elisa Marabotto
- Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties, University of Genoa , Genoa , Italy
| | - Brigida Barberio
- Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua , Italy
| | | | - Nicola De Bortoli
- Gastrointestinal Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa , Pisa , Italy
| | - Patrizia Zentilin
- Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties, University of Genoa , Genoa , Italy
| | - Salvatore Tolone
- Surgery Unit, Department of Surgery, University of Campania Luigi Vanvitelli , Caserta , Italy
| | - Andrea Ottonello
- Department of Surgical Science and Integrated Diagnostics, University of Genoa , Genoa , Italy
| | - Greta Lorenzon
- Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua , Italy
| | - Vincenzo Savarino
- Gastrointestinal Unit, Department of Internal Medicine and Medical Specialties, University of Genoa , Genoa , Italy
| | - Edoardo Savarino
- Gastrointestinal Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua , Padua , Italy
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Klimara MJ, Johnston N, Samuels TL, Visotcky AM, Poetker DM, Loehrl TA, Blumin JH, Bock JM. Correlation of salivary and nasal lavage pepsin with MII-pH testing. Laryngoscope 2019; 130:961-966. [PMID: 31329290 DOI: 10.1002/lary.28182] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2019] [Revised: 06/10/2019] [Accepted: 06/24/2019] [Indexed: 11/12/2022]
Abstract
OBJECTIVES Laryngopharyngeal reflux (LPR) is a common upper airway disease. Salivary pepsin is a proposed marker for LPR; however, the optimal time for collection of specimens for pepsin detection and pepsin's presence in the oral and nasal secretions relative to concurrent multichannel intraluminal impedance-pH (MII-pH) monitoring are unknown. STUDY DESIGN Prospective case-control study with an experimental design. METHODS Patients undergoing MII-pH testing for evaluation of LPR and asymptomatic control subjects were selected. Nasal lavage and saliva samples were collected in the clinic prior to MII-pH probe placement. Additional saliva samples were obtained an hour after each meal and upon waking the following morning. Nasal lavage and salivary pepsin were measured by ELISA. RESULTS Twenty-six patients undergoing MII-pH testing and 13 reflux-free control patients were enrolled. Salivary pepsin was detected in 11 of 26 patients with suspected LPR and 0 of 13 controls. Pepsin was most frequently detected in the specimen provided upon waking at an average concentration of 186.9 ng/mL. A significant correlation was observed between salivary pepsin in waking samples to MII-pH measurements, including reflux bolus duration, and proximal and distal recumbent reflux episodes (P < 0.05). A significant correlation was also observed between salivary pepsin upon waking or sinus lavage and reflux symptom index (P < 0.05). CONCLUSION Pepsin in salivary and nasal lavage samples demonstrated an association with MII-pH-documented LPR. Pepsin detection was most frequent in morning samples, supporting use of morning salivary pepsin levels as a potential noninvasive technique for LPR diagnosis. LEVEL OF EVIDENCE 2 Laryngoscope, 130:961-966, 2020.
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Affiliation(s)
- Miles J Klimara
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - Nikki Johnston
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - Tina L Samuels
- Institute for Health and Equity, Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - Alexis M Visotcky
- Institute for Health and Equity, Division of Biostatistics, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - David M Poetker
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - Todd A Loehrl
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - Joel H Blumin
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
| | - Jonathan M Bock
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, U.S.A
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Duricek M, Banovcin P, Halickova T, Hyrdel R, Kollarik M. Acidic Pharyngeal Reflux Does Not Correlate with Symptoms and Laryngeal Injury Attributed to Laryngopharyngeal Reflux. Dig Dis Sci 2019; 64:1270-1280. [PMID: 30430298 PMCID: PMC10694844 DOI: 10.1007/s10620-018-5372-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2018] [Accepted: 11/08/2018] [Indexed: 12/15/2022]
Abstract
BACKGROUND Laryngopharyngeal reflux (LPR) is suspected when the symptoms are attributed to the penetration of acidic gastroesophageal reflux (GER) into the larynx. However, the relationships between the intensity of LPR and symptoms and laryngeal injury have not been elucidated. Several factors confound the study of LPR, namely pH is monitored in the pharynx (pharyngeal reflux) but the pharyngeal acidity (pH) required to induce laryngeal injury is unknown, the GER origin of pharyngeal acid is not always established, and a recent treatment with proton pump inhibitors (PPI) confounds the analysis. AIMS We aimed to limit these confounding factors to analyze the relationship between LPR and symptoms and laryngeal injury. METHODS We used dual pharyngeal and distal esophageal 24-h pH/impedance monitoring to establish GER origin of pharyngeal reflux, we used an unbiased approach to analysis by evaluating a whole range of acidity (pH < 6, pH < 5.5, pH < 5.0, pH < 4.5 and pH < 4.0) in patients with suspected LPR without PPI for > 30 days. RESULTS Pharyngeal reflux was (median[IQR]) 14[8-20.5] and 4[1.5-6.5] pharyngeal reflux episodes with pH < 6.0 and pH < 5.5, respectively. Pharyngeal reflux with pH < 5.0 was rare. Comprehensive analysis did not reveal any correlation between symptoms (reflux symptom index) or laryngeal injury (reflux finding score) and the number of pharyngeal reflux episodes or duration of pharyngeal acid exposure at any pH level. CONCLUSION Unbiased comprehensive approach did not reveal any relationship between acidic pharyngeal reflux and the symptoms or laryngeal injury attributed to LPR. Limited clinical usefulness of pharyngeal monitoring reported by others is unlikely due to confounding factors.
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Affiliation(s)
- Martin Duricek
- Gastroenterology Clinic JFM CU, Jessenius Faculty of Medicine in Martin (JFM CU), Comenius University in Bratislava, Kollárova 2, 03659, Martin, Slovakia
| | - Peter Banovcin
- Gastroenterology Clinic JFM CU, Jessenius Faculty of Medicine in Martin (JFM CU), Comenius University in Bratislava, Kollárova 2, 03659, Martin, Slovakia.
| | - Tatiana Halickova
- Clinic of ENT and Head and Neck Surgery, Central Military and Faculty Hospital in Ružomberok, Považská 1380/2, 034 01, Ružomberok, Slovakia
| | - Rudolf Hyrdel
- Gastroenterology Clinic JFM CU, Jessenius Faculty of Medicine in Martin (JFM CU), Comenius University in Bratislava, Kollárova 2, 03659, Martin, Slovakia
| | - Marian Kollarik
- Department of Pathophysiology JFM CU, Jessenius Faculty of Medicine in Martin (JFM CU), Comenius University in Bratislava, Ružomberok, Slovakia
- Department of Molecular Pharmacology & Physiology, University of South Florida, Tampa, FL, USA
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Race C, Chowdry J, Russell JM, Corfe BM, Riley SA. Studies of salivary pepsin in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2019; 49:1173-1180. [PMID: 30977177 DOI: 10.1111/apt.15138] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 10/24/2018] [Accepted: 12/20/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastro-oesophageal reflux disease (GERD) is difficult to diagnose without invasive testing. Peptest (RD Biomed, Hull, UK) is a recently marketed diagnostic tool which aims to quantify salivary pepsin as a marker of reflux, providing a rapid alternative to invasive procedures. AIM To evaluate optimal timing for sampling, and to evaluate the accuracy of Peptest against an independent measure. METHODS Thirty diagnosed GERD patients (12 female, mean age 49 [range 20-72]) and 20 asymptomatic subjects (14 female, mean age 56 [range 21-56]) were subject to diurnal saliva sampling, with additional samples for 60 minutes following self-reported reflux symptoms and triggering of a proximal reflux alarm. Saliva samples were split and were analysed by both Peptest and ELISA with operators for each blinded to sample identity. RESULTS Salivary pepsin was detectable in most patients and most volunteers. Peptest scores were significantly lower for patients than controls (P < 0.005). ELISA scores showed no difference between patients and controls. There was no effect of diurnal sampling time (P = 0.75) or time after symptoms (P = 0.76) on Peptest readout. There was no correlation between Peptest and Pepsin ELISA (P = 0.55); Bland-Altman analysis suggested no agreement between the tests (P = 0.414). Receiver-operator curve suggests that neither Peptest (P = 0.3328) nor pepsin (P = 0.4476) is useful for predicting GERD. CONCLUSION Salivary pepsin is not a reliable tool for the diagnosis of GERD.
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Affiliation(s)
- Caroline Race
- Department of Gastroenterology, Northern General Hospital, Sheffield, UK
| | - Joanna Chowdry
- Molecular Gastroenterology Research Group, Academic Unit of Surgical Oncology, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK
| | - Jean M Russell
- Department of Corporate Information and Computer Services, University of Sheffield, Sheffield, UK
| | - Bernard M Corfe
- Molecular Gastroenterology Research Group, Academic Unit of Surgical Oncology, Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK.,Insigneo Institute, University of Sheffield, Sheffield, UK
| | - Stuart A Riley
- Department of Gastroenterology, Northern General Hospital, Sheffield, UK.,Insigneo Institute, University of Sheffield, Sheffield, UK
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Evaluation of Important Analytical Parameters of the Peptest Immunoassay that Limit its Use in Diagnosing Gastroesophageal Reflux Disease. J Clin Gastroenterol 2019; 53:355-360. [PMID: 29863588 DOI: 10.1097/mcg.0000000000001066] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
GOAL To evaluate the analytical parameters of a lateral flow (LF) pepsin immunoassay (Peptest) and assess its suitability in the diagnostics of gastroesophageal reflux disease (GERD). BACKGROUND Peptest is a noninvasive assay to analyze pepsin in saliva, intended for use in GERD diagnostics. Although commercialized, fundamental studies on its performance are missing. The assay therefore requires basic analytical parameter evaluation to assess its suitability in clinical practice. STUDY Assay reaction's time dependence, reader device repeatability, and individual LF devices and longitudinal pepsin concentration reproducibility in individual subjects was evaluated. Salivary pepsin was analyzed in 32 GERD patients with extraesophageal reflux symptoms and 13 healthy individuals. RESULTS The assay's signal increase is not completed at the recommend readout time and continues to increase for another 25 minutes. The relative standard deviation of measurement was good when using the same LF device, ranging from 2.3% to 12.9%, but the reproducibility of 10 different individual LF devices was poor. The random error when analyzing the same saliva sample on 10 LF devices was as high as 36 ng/mL and this value is thus suggested as the positivity cut-off. Pepsin concentration in individual subjects during a 10-day period varied significantly. The sensitivity of the Peptest was 36.8% in the group with acid reflux and 23.1% in the group with weakly acid reflux. The specificity was 61.5%. CONCLUSIONS The Peptest assay's sensitivity and specificity is low, the results are highly variable and it should not be used as a near-patient diagnostic method in primary care.
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Jung AR, Kwon OE, Park JM, Dong SH, Jung SY, Lee YC, Eun YG. Association Between Pepsin in the Saliva and the Subjective Symptoms in Patients With Laryngopharyngeal Reflux. J Voice 2019; 33:150-154. [DOI: 10.1016/j.jvoice.2017.10.015] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2017] [Revised: 09/08/2017] [Accepted: 10/18/2017] [Indexed: 12/12/2022]
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Naik RD, Evers L, Vaezi MF. Advances in the Diagnosis and Treatment of GERD: New Tricks for an Old Disease. ACTA ACUST UNITED AC 2019; 17:1-17. [DOI: 10.1007/s11938-019-00213-w] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
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Guo Z, Wu H, Jiang J, Zhang C. Pepsin in Saliva as a Diagnostic Marker for Gastroesophageal Reflux Disease: A Meta-Analysis. Med Sci Monit 2018; 24:9509-9516. [PMID: 30596632 PMCID: PMC6324865 DOI: 10.12659/msm.913978] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is very common. Salivary pepsin detection has previously been considered as a method for GERD diagnosis. We performed a meta-analysis to investigate the utility of salivary pepsin assay as a diagnostic tool of GERD. MATERIAL AND METHODS PubMed, Web of Science, the Cochran Library, and EMBASE (from January 1980 to 23 October 2018) were searched for pepsin in saliva for GERD diagnosis. We summarized the retrieved specificity, sensitivity, negative likelihood ratio (NLR), positive likelihood ratio (PLR), diagnostic odds ratio (DOR), and receiver operating characteristic (ROC) curves data in the meta-analysis. RESULTS In final analysis, a total of 5 studies were included. The summary sensitivity, specificity, NLR, and PLR were 0.60 (95% CI 0.41-0.76), 0.71 (95% CI 0.51-0.86), 0.56 (95% CI 0.34-0.93), and 2.1 (95% CI 1.1-4.1), respectively. The pooled DOR was 4 (95% CI 1.0-11.0) and area under the ROC was 0.70 (95% CI 0.66-0.74). CONCLUSIONS The meta-analysis showed that pepsin in saliva has moderate diagnostic value for GERD, and is not as helpful as previously thought.
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Affiliation(s)
- Zihao Guo
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China (mainland)
| | - Hao Wu
- Department of Cardiovascular, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China (mainland)
| | - Jiali Jiang
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China (mainland)
| | - Chuan Zhang
- Department of Gastroenterology, Beijing Tong Ren Hospital, Capital Medical University, Beijing, China (mainland)
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Yadlapati R, Craft J, Adkins CJ, Pandolfino JE. The Upper Esophageal Sphincter Assist Device Is Associated With Symptom Response in Reflux-Associated Laryngeal Symptoms. Clin Gastroenterol Hepatol 2018; 16:1670-1672. [PMID: 29408585 PMCID: PMC6067982 DOI: 10.1016/j.cgh.2018.01.031] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/22/2017] [Revised: 01/16/2018] [Accepted: 01/21/2018] [Indexed: 02/07/2023]
Abstract
Reflux-associated laryngeal symptoms (RALS) is the process in which chronic laryngeal symptoms are related to gastroesophagopharyngeal reflux.1 Impairment of upper esophageal sphincter (UES) reflexes may predispose to esophagopharyngeal reflux.1 The novel noninvasive nonpharmacologic UES assist device (UESAD) applies external cricoid pressure to augment intraluminal UES pressure by 20 to 30 mm Hg and reduce esophagopharyngeal reflux events.2 This study aimed to assess the therapeutic efficacy of the UESAD in a pragmatic clinical setting, and to identify factors associated with symptom response among patients with suspected RALS.
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Affiliation(s)
- Rena Yadlapati
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
| | - Jenna Craft
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | | | - John E. Pandolfino
- Department of Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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Wang CP, Wang CC, Lien HC, Lin WJ, Wu SH, Liang KL, Liu SA. Saliva Pepsin Detection and Proton Pump Inhibitor Response in Suspected Laryngopharyngeal Reflux. Laryngoscope 2018; 129:709-714. [PMID: 30247754 DOI: 10.1002/lary.27502] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/12/2018] [Indexed: 12/13/2022]
Abstract
OBJECTIVES/HYPOTHESIS To evaluate the prediction value of saliva pepsin detection for an 8-week proton pump inhibitor (PPI) response in patients with a Reflux Symptoms Index (RSI) score ≥13, which indicates possible laryngopharyngeal reflux. STUDY DESIGN Prospective individual single-cohort study. METHODS Patients were recruited who had experienced chronic laryngopharyngeal symptoms (RSI score ≥13) for more than 3 months after excluding other etiologies. The patients received PPI (40 mg of esomeprazole once daily) treatment for 8 weeks. Prior to treatment, the patients submitted saliva/sputum samples that were collected during the time symptoms were observed. The samples were taken for pepsin detection, and performed using the commercially available Peptest lateral flow device. The association of the Peptest results and PPI response were statistically analyzed with the χ2 test. RESULTS Seventy-four patients completed the study, and upon completion of PPI treatment, the mean RSI score was significantly reduced from 19.22 ± 5.18 to 8.99 ± 5.69. Forty-four (59.5%) patients exhibited a good response as defined by an RSI score reduction ≥50%. The results of the Peptest were semiquantitatively graded as 0, 1, 2, 3 (negative, weak positive, moderate positive and strong positive, respectively) based upon the visual intensity of the test sample line as compared to the control line. Twenty-four patients (32.4%) exhibited grade 3 strong positive results. The Peptest strong positive results (P < .05) were significantly associated with a good PPI response, with the positive predictive value being 79.2%. CONCLUSIONS Analysis of strong positive results for pepsin detection in saliva/sputum samples may be a useful, noninvasive method for predicting better PPI response in patients with suspected reflux induced chronic laryngopharyngeal symptoms. LEVEL OF EVIDENCE 2 Laryngoscope, 129:709-714, 2019.
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Affiliation(s)
- Ching-Ping Wang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Speech Language Pathology and Audiology, Chung Shan Medical University, Taichung, Taiwan.,Department of Otolaryngology-Head and Neck Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chen-Chi Wang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Speech Language Pathology and Audiology, Chung Shan Medical University, Taichung, Taiwan.,Department of Otolaryngology-Head and Neck Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Han-Chung Lien
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Wen-Jiun Lin
- Department of Otolaryngology-Head and Neck Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Shang-Heng Wu
- Department of Otolaryngology-Head and Neck Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Kai-Li Liang
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Otolaryngology-Head and Neck Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.,College of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Shih-An Liu
- School of Medicine, National Yang-Ming University, Taipei, Taiwan.,Department of Otolaryngology-Head and Neck Surgery, Taichung Veterans General Hospital, Taichung, Taiwan
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Vaezi MF, Katzka D, Zerbib F. Extraesophageal Symptoms and Diseases Attributed to GERD: Where is the Pendulum Swinging Now? Clin Gastroenterol Hepatol 2018; 16:1018-1029. [PMID: 29427733 DOI: 10.1016/j.cgh.2018.02.001] [Citation(s) in RCA: 67] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2017] [Revised: 01/31/2018] [Accepted: 02/02/2018] [Indexed: 02/07/2023]
Abstract
The purpose of this review is to outline the recent developments in the field of extraesophageal reflux disease and provide clinically relevant recommendations. The recommendations outlined in this review are based on expert opinion and on relevant publications from PubMed and EMbase. The Clinical Practice Updates Committee of the American Gastroenterological Association proposes the following recommendations: Best Practice Advice 1: The role of a gastroenterologist in patients referred for evaluation of suspected extra esophageal symptom is to assess for gastroesophageal etiologies that could contribute to the presenting symptoms. Best Practice Advice 2: Non-GI evaluations by ENT, pulmonary and/or allergy are essential and often should be performed initially in most patients as the cause of the extraesophageal symptom is commonly multifactorial or not esophageal in origin. Best Practice Advice 3: Empiric therapy with aggressive acid suppression for 6-8 weeks with special focus on response of the extraesophageal symptoms can help in assessing association between reflux and extraesophageal symptoms. Best Practice Advice 4: No single testing methodology exists to definitively identify reflux as the etiology for the suspected extra esophageal symptoms. Best Practice Advice 5: Constellation of patient presentation, diagnostic test results and response to therapy should be employed in the determination of reflux as a possible etiology in extra esophageal symptoms. Best Practice Advice 6: Testing may need to be off or on proton pump inhibitor (PPI) therapy depending on patients' presenting demographics and symptoms in assessing the likelihood of abnormal gastroesophageal reflux. A. On therapy testing may be considered in those with high probability of baseline reflux (those with previous esophagitis, Barrett's esophagus or abnormal pH). B. Off therapy testing may be considered in those with low probability of baseline reflux with the goal of identifying moderate to severe reflux at baseline. Best Practice Advice 7: Lack of response to aggressive acid suppressive therapy combined with normal pH testing off therapy or impedance-pH testing on therapy significantly reduces the likelihood that reflux is a contributing etiology in presenting extraesophageal symptoms. Best Practice Advice 8: Surgical fundoplication is discouraged in those with extra esophageal reflux symptoms unresponsive to aggressive PPI therapy. Best Practice Advice 9: Fundoplication should only be considered in those with a mechanical defect (e.g., hiatal hernia), moderate to severe reflux at baseline off PPI therapy who have continued reflux despite PPI therapy and have failed more conservative non-GI treatments.
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Affiliation(s)
- Michael F Vaezi
- Division of Gastroenterology, Hepatology, Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee.
| | - David Katzka
- Department of Gastroenterology, Mayo Clinic, Rochester, Minnesota
| | - Frank Zerbib
- CHU Bordeaux, Department of Gastroenterology, Hepatology and Digestive Oncology, University of Bordeaux, Bordeaux, France
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