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Hránková V, Balner T, Gubová P, Staníková L, Zeleník K, Komínek P. Narrative review of relationship between chronic cough and laryngopharyngeal reflux. Front Med (Lausanne) 2024; 11:1348985. [PMID: 38707186 PMCID: PMC11066273 DOI: 10.3389/fmed.2024.1348985] [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: 12/03/2023] [Accepted: 04/08/2024] [Indexed: 05/07/2024] Open
Abstract
Gastroesophageal reflux disease (GERD) as a possible cause of chronic cough is known for decades. However, more than 75% of patients with extraoesophageal symptoms do not suffer from typical symptoms of GERD like pyrosis and regurgitations and have negative upper gastrointestinal endoscopy. For such a condition term laryngopharyngeal reflux (LPR) was introduced and is used for more than two decades. Since the comprehensive information on relationship between chronic cough and LPR is missing the aim of this paper is to summarize current knowledge based on review of published information during last 13 years. Laryngopharyngeal reflux is found in 20% of patients with chronic cough. The main and recognized diagnostic method for LPR is 24-h multichannel intraluminal impedance-pH (MII-pH) monitoring, revealing reflux episodes irritating the upper and lower respiratory tract mucosa. The treatment of LPR should be initiated with dietary and lifestyle measures, followed by proton pump inhibitor (PPI) therapy and other measures. Despite progress, more research is needed for accurate diagnosis and targeted therapies. Key areas for exploration include biomarkers for diagnosis, the impact of non-acid reflux on symptom development, and the efficacy of new drugs. Further studies with a focused population, excluding other causes like asthma, and using new diagnostic criteria for LPR are essential. It's crucial to consider LPR as a potential cause of unexplained chronic cough and to approach diagnosis and treatment with a multidisciplinary perspective.
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Affiliation(s)
- Viktória Hránková
- Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Ostrava, Ostrava, Czechia
- Department of Craniofacial Surgery, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
| | - Tomáš Balner
- Department of Allergology and Clinical Immunology, University Hospital of Ostrava, Ostrava, Czechia
- Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
| | - Patrícia Gubová
- Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Ostrava, Ostrava, Czechia
| | - Lucia Staníková
- Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Ostrava, Ostrava, Czechia
- Department of Craniofacial Surgery, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
| | - Karol Zeleník
- Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Ostrava, Ostrava, Czechia
- Department of Craniofacial Surgery, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
| | - Pavel Komínek
- Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital of Ostrava, Ostrava, Czechia
- Department of Craniofacial Surgery, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
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Fossmark R, Ness-Jensen E, Sørdal Ø. Is empiric proton pump inhibition in patients with symptoms of extraesophageal gastroesophageal reflux justified? BMC Gastroenterol 2023; 23:303. [PMID: 37674110 PMCID: PMC10483799 DOI: 10.1186/s12876-023-02945-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2023] [Accepted: 09/04/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND The prevalence of gastroesophageal reflux disease (GERD) has had a marked increase in Western countries with a paralleling interest in extraesophageal (EE) manifestations of GERD, including laryngopharyngeal reflux (LPR). There are considerable differences in clinical practice between gastroenterologists, otolaryngologists and pulmonologists. METHODS In this narrative review we address some of these controversies concerning EE manifestations of GERD and LPR. RESULTS It is disputed whether there is causal relationship between reflux and the numerous symptoms and conditions suggested to be EE manifestations of GERD. Similarly, the pathophysiology is uncertain and there are disagreements concerning diagnostic criteria. Consequently, it is challenging to provide evidence-based treatment recommendations. A significant number of patients are given a trial course with a proton pump inhibitor (PPI) for several months before symptoms are evaluated. In randomized controlled trials (RCTs) and meta-analyses of RCTs PPI treatment does not seem to be advantageous over placebo, and the evidence supporting that patients without verified GERD have any benefit of PPI treatment is negligible. There is a large increase in both over the counter and prescribed PPI use in several countries and a significant proportion of this use is without any symptomatic benefit for the patients. Whereas short-term treatment has few side effects, there is concern about side-effects after long-term use. Although empiric PPI treatment for suspected EE manifestations of GERD instead of prior esophageal 24-hour pH and impedance monitoring is included in several guidelines by various societies, this practice contributes to overtreatment with PPI. CONCLUSION We argue that the current knowledge suggests that diagnostic testing with pH and impedance monitoring rather than empiric PPI treatment should be chosen in a higher proportion of patients presenting with symptoms possibly attributable to EE reflux.
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Affiliation(s)
- Reidar Fossmark
- Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Prinsesse Kristinas gate 1, Trondheim, 7030, Norway.
- Medicus Endoscopy, Trondheim, Norway.
| | - Eivind Ness-Jensen
- HUNT Research Center, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway
- Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway
- Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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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: 1] [Impact Index Per Article: 0.5] [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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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: 423] [Impact Index Per Article: 141.0] [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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Vandenplas Y, Kindt S. Gastroesophageal Reflux. TEXTBOOK OF PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND NUTRITION 2022:125-155. [DOI: 10.1007/978-3-030-80068-0_10] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Lechien JR, Mouawad F, Bobin F, Bartaire E, Crevier-Buchman L, Saussez S. Review of management of laryngopharyngeal reflux disease. Eur Ann Otorhinolaryngol Head Neck Dis 2021; 138:257-267. [DOI: 10.1016/j.anorl.2020.11.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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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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Park JS, Burton L, Van der Wall H, Falk GL. Modified Reflux Scintigraphy Detects Pulmonary Microaspiration in Severe Gastro-Esophageal and Laryngopharyngeal Reflux Disease. Lung 2021; 199:139-145. [PMID: 33751204 DOI: 10.1007/s00408-021-00432-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 02/22/2021] [Indexed: 12/29/2022]
Abstract
INTRODUCTION Previously described methodologies for detecting laryngopharyngeal reflux (LPR) have limitations. Symptoms alone are non-diagnostic, and pH-impedance studies have poor sensitivity. Pulmonary micro-aspiration is under-recognised in LPR and gastro-esophageal reflux disease (GERD). The present study aimed to describe the results of a modified technique for scintigraphic reflux studies in two groups with severe reflux: those with typical reflux symptoms and those with laryngopharyngeal manifestations of reflux. METHODS A prospective database of severely symptomatic, treatment-resistant reflux patients was grouped based upon predominant symptom profile of typical GERD or LPR. All patients underwent reflux scintigraphy. Results were obtained for early scintigraphic reflux contamination of the pharynx and proximal esophagus, and delayed contamination of the pharynx and lungs after 2 h. RESULTS 187 patients were studied (82 GERD, 105 LPR). The LPR patients were predominantly female (70.5% vs. 56.1%; p = 0.042) and older than the GERD group (median age 60 years vs. 55.5 years; p = 0.002). Early scintigraphic reflux was seen at the pharynx in 89.2% (GERD 87.7%, LPR 90.4%; p = 0.133), and at the proximal esophagus in 89.7% (GERD 88.9%, LPR 90.4%; p = 0.147). Delayed contamination of the pharynx was seen in 95.2% (GERD 93.9%, LPR 96.2%; p = 0.468). Delayed pulmonary aspiration was seen in 46% (GERD 36.6%, LPR 53.3%; p = 0.023). CONCLUSION Reflux scintigraphy demonstrated a high rate of reflux-related pulmonary aspiration. Contamination of the proximal esophagus and pharynx was observed frequently in both groups of severe disease. The likelihood of pulmonary aspiration and potential pulmonary disease needs to be entertained in severe GERD and LPR.
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Affiliation(s)
- Jin-Soo Park
- Department of Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia. .,School of Medicine, University of Notre Dame, Sydney, NSW, Australia.
| | - Leticia Burton
- School of Medicine, University of Notre Dame, Sydney, NSW, Australia.,CNI Meadowbank, Sydney, NSW, Australia
| | - Hans Van der Wall
- School of Medicine, University of Notre Dame, Sydney, NSW, Australia.,CNI Meadowbank, Sydney, NSW, Australia
| | - Gregory Leighton Falk
- Department of Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia.,University of Sydney, Sydney, NSW, Australia
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Park JS, Khoma O, Burton L, Van der Wall H, Falk GL. A new diagnostic paradigm for laryngopharyngeal reflux disease: correlation of impedance-pH monitoring and digital reflux scintigraphy results. Eur Arch Otorhinolaryngol 2021; 278:1917-1926. [PMID: 33582850 DOI: 10.1007/s00405-021-06658-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 01/28/2021] [Indexed: 01/02/2023]
Abstract
PURPOSE No gold-standard investigation exists for laryngopharyngeal reflux (LPR). Multichannel intraluminal impedance (MII)-pH testing has uncertain utility in LPR. Meanwhile, reflux scintigraphy allows immediate and delayed visualisation of tracer reflux in the esophagus, pharynx, and lungs. The present study aimed to correlate MII-pH and scintigraphic reflux results in patients with primary LPR. METHODS Consecutive patients with LPR underwent MII-pH and scintigraphic reflux studies. Abnormal values for MII-pH results were defined from existing literature. MII-pH and scintigraphic data were correlated. RESULTS 105 patients with LPR [31 males (29.5%), median age 60 years (range 20-87)] were studied. Immediate scintigraphic reflux was seen in the pharynx in 94 (90.4%), and in the proximal esophagus in 94 (90.4%). Delayed scintigraphic contamination of the pharynx was seen in 101 patients (96.2%) and in the lungs of 56 patients (53.3%). For MII-pH, abnormally frequent reflux was seen in the distal esophagus in 12.4%, proximal esophagus in 25.7%, and in the pharynx in 82.9%. Patients with poor scintigraphic clearance had higher Demeester scores (p = 0.043), more proximal reflux episodes (p = 0.046), more distal acid reflux episodes (p = 0.023), and more prolonged bolus clearance times (p = 0.002). CONCLUSION Reflux scintigraphy has a high yield in LPR patients. Scintigraphic time-activity curves correlated with validated MII-pH results. A high rate of pulmonary microaspiration was found in LPR patients. This study demonstrated a high level of pharyngeal contamination by scintigraphy and MII-pH, which supports the use of digital reflux scintigraphy in diagnosing LPR.
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Affiliation(s)
- Jin-Soo Park
- Department of Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia. .,School of Medicine, University of Notre Dame, Sydney, NSW, Australia.
| | - Oleksandr Khoma
- Department of Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia.,School of Medicine, University of Notre Dame, Sydney, NSW, Australia
| | - Leticia Burton
- School of Medicine, University of Notre Dame, Sydney, NSW, Australia.,CNI Meadowbank, Sydney, NSW, Australia
| | - Hans Van der Wall
- School of Medicine, University of Notre Dame, Sydney, NSW, Australia.,CNI Meadowbank, Sydney, NSW, Australia
| | - Gregory Leighton Falk
- Department of Surgery, Concord Repatriation General Hospital, Sydney, NSW, Australia.,University of Sydney, Sydney, NSW, Australia
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Bao YY, Jiang Q, Li ZW, Yu E, Zhou SH, Yao HT, Fan J, Yong WW. Gastric H +/K +-ATPase Expression in Normal Laryngeal Tissue and Laryngeal Carcinoma. Onco Targets Ther 2020; 13:12919-12931. [PMID: 33363389 PMCID: PMC7751835 DOI: 10.2147/ott.s276233] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2020] [Accepted: 11/30/2020] [Indexed: 12/24/2022] Open
Abstract
Background Several studies have suggested that laryngopharyngeal reflux disease (LPRD) or gastroesophageal reflux disease (GERD) is an independent risk factor for laryngeal carcinoma. However, it remains unclear whether either condition affects the level of H+/K+-ATPase expression in laryngeal carcinoma. Materials and Methods Immunohistochemistry, real-time RT-PCR, and Western blotting were used to explore the distributions of proton pump (H+/K+-ATPase) α- and β-subunits in normal laryngeal tissue and laryngeal carcinoma. Results Messenger RNAs encoding both the α- and β-subunits were found in the normal epiglottic, ventricular fold, vocal fold, and arytenoid mucosae, as well as epiglottic cartilage. The distributions and expression levels of H+/K+-ATPase α-subunits in various laryngeal subregions did not significantly differ in IHC, RT-PCR, or Western blotting. However, Western blotting revealed a significant difference between the expression level of the β-subunit protein in the epiglottic cartilage and the levels in other sites. The expression levels of both subunits were significantly higher in carcinomatous than in paracarcinomatous tissue and normal laryngeal tissue. The mean follow-up duration was 66.2 months (range, 17–162 months). In all, 4 patients died during follow-up, 4 were lost to follow-up, and 22 were alive and free of disease at the end of follow-up. Two patients developed lung metastases and six developed disease recurrences (at 2, 8, 14, 16, 36, and 41 months). The 3- and 5-year overall survival (OS) rates were 93.0% and 77.0%, respectively. Univariate analyses showed that the 5-year OSs were significantly associated with the T, N, and clinical stages but not with age, alcohol use, pathological differentiation, or the expression levels of the α- or β-subunits (as revealed by IHC, RT-PCR, or Western blotting). However, in multivariate regression analyses, the 5-year OSs were not significantly associated with any clinicopathological factor or the expression levels of either subunit. Conclusion H+/K+-ATPase is expressed in the normal larynx, including in the epiglottic cartilage and the mucosae of the epiglottis, ventricular fold, and arytenoid vocal fold. The expression levels of the H+/K+-ATPase α- and β-subunits in laryngeal carcinomas were higher than in normal laryngeal tissues.
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Affiliation(s)
- Yang-Yang Bao
- Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China
| | - Qian Jiang
- Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China
| | - Zhen-Wei Li
- Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China.,Department of Otolaryngology, The First People's Hospital of Hangzhou City, Hangzhou, Zhejiang 310013, People's Republic of China
| | - Er Yu
- Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China
| | - Shui-Hong Zhou
- Department of Otolaryngology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China
| | - Hong-Tian Yao
- Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China
| | - Jun Fan
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China
| | - Wei-Wei Yong
- Department of Pathology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, People's Republic of China
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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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Barrett CM, Patel D, Vaezi MF. Laryngopharyngeal Reflux and Atypical Gastroesophageal Reflux Disease. Gastrointest Endosc Clin N Am 2020; 30:361-376. [PMID: 32146951 DOI: 10.1016/j.giec.2019.12.004] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Laryngopharyngeal reflux and atypical manifestations of gastroesophageal reflux disease have a high economic and social burden in the United States. There is increasing research supporting the reflex theory and hypersensitivity syndrome underlying this disease pathophysiology. Novel diagnostic biomarkers have gained more traction in the search for a more reliable diagnostic tool, but further research is needed. Current standard-of-care treatment relies on proton pump inhibitor therapy. Antireflux surgery is usually not recommended. Neuromodulators and treatments targeting specific neuronal receptors are discussed. A diagnostic algorithm is proposed for the evaluation of laryngeal symptoms suspected to be related to extraesophageal reflux disease.
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Affiliation(s)
- Caroline M Barrett
- Department of Internal Medicine, Vanderbilt University Medical Center, 719 Thompson Lane, Suite 20400, Nashville, TN 37204, USA
| | - Dhyanesh Patel
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 1301 Medical Center Drive, TVC # 1660, Nashville, TN 37232, USA.
| | - Michael F Vaezi
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, 1301 Medical Center Drive, TVC # 1660, Nashville, TN 37232, USA
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14
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Lechien JR, Bock JM, Carroll TL, Akst LM. Is empirical treatment a reasonable strategy for laryngopharyngeal reflux? A contemporary review. Clin Otolaryngol 2020; 45:450-458. [PMID: 32097534 DOI: 10.1111/coa.13518] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2019] [Revised: 12/25/2019] [Accepted: 01/15/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Diagnosis and treatment of presumed laryngopharyngeal reflux (LPR) remain controversial. Empiric medication trials remain widespread for suspected LPR despite emerging evidence against proton pump inhibitor (PPI) safety and for pepsin as a mediator of LPR symptoms. Ongoing concerns exist related to inaccurate diagnosis, the cost and morbidity of potentially unnecessary PPI prescriptions, and availability and interpretation of objective reflux testing. OBJECTIVES To review contemporary evidence that does and does not support empiric medication trials for presumed LPR. METHODS PubMed, Scopus and Cochrane Library were searched for literature about benefits, limitations and alternatives to empiric medication trial for LPR, in order to present both sides of this debate and identify best practices. RESULTS The majority of physicians perform prolonged empiric medication trial with PPIs for patients with suspected LPR. Because symptoms and signs of LPR are non-specific, empiric medication trials require exclusion of other conditions that can mimic LPR. Following a PPI empiric medication trial, over one-third of patients remain non-responders. The use of hypopharyngeal-oesophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH) has benefits and limitations in objective diagnosis of LPR. CONCLUSIONS Use of PPIs for single-agent empiric medication trial does not account for possible non-responders with non-acid or mixed LPR. If LPR diagnosis remains uncertain, alginates can be added to PPI trials. HEMII-pH testing upfront is ideal for patients with suspected LPR, but not always practical; it is indicated when PPI and alginate empiric medication trials have failed or when comorbidities confuse the diagnosis. A more comprehensive, combination therapy empiric medication trial regimen may be needed.
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Affiliation(s)
- Jerome R Lechien
- Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies (YO-IFOS), Paris, France.,Department of Human Anatomy and Experimental Oncology, Faculty of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons (UMons), Mons, Belgium.,Department of Otolaryngology-Head and Neck Surgery, CHU Saint-Pierre, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium.,Department of Otolaryngology-Head and Neck Surgery, Foch Hospital, UFR Simone Veil, University Versailles Saint-Quentin-en Yvelines (University Paris Saclay), Paris, France
| | - Jonathan M Bock
- Division of Laryngology and the Professional Voice Department of Otolaryngology, Communication Science Medical College of Wisconsin, Milwaukee, WI, USA
| | - Thomas L Carroll
- Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School, Boston, MA, USA.,Division of Otolaryngology, Department of Surgery, Brigham and Women's Hospital, Boston, MA, USA
| | - Lee M Akst
- Laryngopharyngeal Reflux Study Group of Young-Otolaryngologists of the International Federations of Oto-rhino-laryngological Societies (YO-IFOS), Paris, France.,Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins Hospital, Johns Hopkins School of Medicine, Baltimore, MD, USA
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15
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16
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Esophageal Impedance-pH Monitoring and Pharyngeal pH Monitoring in the Diagnosis of Extraesophageal Reflux in Children. Gastroenterol Res Pract 2019; 2019:6271910. [PMID: 30944563 PMCID: PMC6421743 DOI: 10.1155/2019/6271910] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 11/21/2018] [Indexed: 12/14/2022] Open
Abstract
Various clinical symptoms are attributed to extraesophageal reflux disease (EERD). Multichannel intraluminal impedance-pH monitoring (MII-pH) is considered to correlate symptoms with acid and nonacid gastroesophageal reflux (GER) events. Pharyngeal pH monitoring (Dx-pH) is considered to correlate the decrease in the pH level in the oropharynx with reported symptoms and to diagnose supraesophageal reflux. We aimed to assess the correlation between acid reflux episodes recorded by Dx-pH and GER detected via MII-pH in children with suspected EERD. The study enrolled 23 consecutive children (15 boys and 8 girls; median age 8.25 [range 3-16.5] years) with suspected EERD. MII-pH and Dx-pH were conducted concurrently in all patients. A total of 1228 reflux episodes were recorded by MII-pH. With the antimonic sensor placed inside the impedance probe, 1272 pH-only reflux episodes were recorded. Of these, 977 (76.81%) were associated with a retrograde bolus transit. Regarding GER, 630 full-column episodes extended to the most proximal pair of impedance sensors; 500 (83.33%) demonstrated an acidic character. The following acid reflux numbers were determined by the Dx-pH system: for pH < 4, n = 126; pH < 4.5, n = 136; pH < 5, n = 167; and pH < 5.5, n = 304, and for a decrease in pH > 10% relative to the baseline, n = 324. There was no significant correlation between the number of pharyngeal reflux episodes detected by Dx-pH and that of GERs identified by MII-pH. The proportion of oropharyngeal pH events that were temporally related to a GER episode increased with the extended pH criteria. The highest proportion was observed for a pH decrease of ≥10% from the baseline and did not exceed 5.2%. The application of the extended pH criteria in the Dx-pH system resulted in an increase in the number of diagnosed laryngopharyngeal refluxes; most were not temporally associated with GER episodes confirmed by MII-pH. Thus, the efficacy of the exclusive application of Dx-pH for supraesophageal gastric reflux diagnosis is uncertain.
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17
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Lechien JR, Akst LM, Hamdan AL, Schindler A, Karkos PD, Barillari MR, Calvo-Henriquez C, Crevier-Buchman L, Finck C, Eun YG, Saussez S, Vaezi MF. Evaluation and Management of Laryngopharyngeal Reflux Disease: State of the Art Review. Otolaryngol Head Neck Surg 2019; 160:762-782. [PMID: 30744489 DOI: 10.1177/0194599819827488] [Citation(s) in RCA: 239] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
OBJECTIVE To review the current literature about the epidemiology, clinical presentation, diagnosis, and treatment of laryngopharyngeal reflux (LPR). DATA SOURCES PubMed, Cochrane Library, and Scopus. METHODS A comprehensive review of the literature on LPR epidemiology, clinical presentation, diagnosis, and treatment was conducted. Using the PRISMA statement, 3 authors selected relevant publications to provide a critical analysis of the literature. CONCLUSIONS The important heterogeneity across studies in LPR diagnosis continues to make it difficult to summarize a single body of thought. Controversies persist concerning epidemiology, clinical presentation, diagnosis, and treatment. No recent epidemiologic study exists regarding prevalence and incidence with the use of objective diagnostic tools. There is no survey that evaluates the prevalence of symptoms and signs on a large number of patients with confirmed LPR. Regarding diagnosis, an increasing number of authors used multichannel intraluminal impedance-pH monitoring, although there is no consensus regarding standardization of the diagnostic criteria. The efficiency of proton pump inhibitor (PPI) therapy remains poorly demonstrated and misevaluated by incomplete clinical tools that do not take into consideration many symptoms and extralaryngeal findings. Despite the recent advances in knowledge about nonacid LPR, treatment protocols based on PPIs do not seem to have evolved. IMPLICATIONS FOR PRACTICE The development of multichannel intraluminal impedance-pH monitoring and pepsin and bile salt detection should be considered for the establishment of a multiparameter diagnostic approach. LPR treatment should evolve to a more personalized regimen, including diet, PPIs, alginate, and magaldrate according to individual patient characteristics. Multicenter international studies with a standardized protocol could improve scientific knowledge about LPR.
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Affiliation(s)
- Jerome R Lechien
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,2 Department of Anatomy and Experimental Oncology, Mons School of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium.,3 Laboratory of Phonetics, Faculty of Psychology, Research Institute for Language Sciences and Technology, University of Mons, Mons, Belgium.,4 Department of Otorhinolaryngology and Head and Neck Surgery, CHU Saint-Pierre, Faculty of Medicine, University Libre de Bruxelles, Brussels, Belgium
| | - Lee M Akst
- 5 Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Abdul Latif Hamdan
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,6 Department of Otorhinolaryngology and Head and Neck Surgery, American University of Beirut Medical Center, Beirut, Lebanon
| | - Antonio Schindler
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,7 Department of Biomedical and Clinical Sciences, Phoniatric Unit, L. Sacco Hospital, University of Milan, Milan, Italy
| | - Petros D Karkos
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,8 Department of Otorhinolaryngology and Head and Neck Surgery, Thessaloniki Medical School, Thessaloniki, Greece
| | - Maria Rosaria Barillari
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,9 Division of Phoniatrics and Audiology, Department of Mental and Physical Health and Preventive Medicine, University of Naples SUN, Naples, Italy
| | - Christian Calvo-Henriquez
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,10 Department of Otorhinolaryngology and Head and Neck Surgery, Hospital Complex of Santiago de Compostela, Santiago de Compostela, Spain
| | - Lise Crevier-Buchman
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,11 Department of Otorhinolaryngology and Head and Neck Surgery, Foch Hospital, Paris, France
| | - Camille Finck
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,2 Department of Anatomy and Experimental Oncology, Mons School of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium.,12 Department of Otorhinolaryngology and Head and Neck Surgery, CHU de Liège, Faculty of Medicine, University of Liège, Liège, Belgium
| | - Young-Gyu Eun
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,13 Department of Otorhinolaryngology and Head and Neck Surgery, School of Medicine, Kyung Hee University, Seoul, Korea
| | - Sven Saussez
- 1 Laryngopharyngeal Reflux Study Group of Young Otolaryngologists, International Federation of Oto-rhino-laryngological Societies, Paris, France.,2 Department of Anatomy and Experimental Oncology, Mons School of Medicine, UMONS Research Institute for Health Sciences and Technology, University of Mons, Mons, Belgium.,4 Department of Otorhinolaryngology and Head and Neck Surgery, CHU Saint-Pierre, Faculty of Medicine, University Libre de Bruxelles, Brussels, Belgium
| | - Michael F Vaezi
- 14 Division of Gastroenterology, Hepatology, Nutrition, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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Kim SY, Park B, Lim H, Kim M, Kong IG, Choi HG. Gastroesophageal reflux disease increases the risk of chronic rhinosinusitis: a nested case-control study using a national sample cohort. Int Forum Allergy Rhinol 2018; 9:357-362. [PMID: 30548214 DOI: 10.1002/alr.22259] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2018] [Revised: 11/06/2018] [Accepted: 11/13/2018] [Indexed: 12/21/2022]
Abstract
BACKGROUND The purpose of this study was to evaluate the relations between gastroesophageal reflux disease (GERD) and chronic rhinosinusitus (CRS) in a Korean population. METHODS Subjects from the Korean National Health Insurance Service-National Sample Cohort, all ≥20 years old, were assessed from 2002 to 2013. In total, 23,489 CRS participants were matched with 93,956 controls at a ratio of 1:4 with respect to age, group, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia. We analyzed previous history of GERD in the CRS and control groups. The CRS group included patients identified using International Classification of Diseases 10th edition (ICD-10) codes (J32) who had treated their CRS ≥2 times and had undergone head and neck computed tomography (CT). The GERD group included patients identified using the ICD-10 (K21) code who had treated their GERD ≥2 times and had taken a proton pump inhibitor (PPI) for ≥2 weeks. Crude and adjusted odds ratios (ORs) were analyzed using unconditional logistic regression analyses. The 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed according to age and sex. RESULTS The rate of GERD was higher in the CRS group (17.1% [4020 of 23,489]) than in the control group (9.1% [8522 of 93,956]; p < 0.001). The adjusted OR of GERD was 2.04 (95% CI, 1.96-2.13; p < 0.001) in the CRS group. The results of the subgroup analyses were consistent. CONCLUSION The ORs of GERD were increased in CRS participants. This relationship was consistent in all age and sex groups.
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Affiliation(s)
- So Young Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Korea
| | - Bumjung Park
- Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Anyang, Korea
| | - Hyun Lim
- Department of Internal Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Miyoung Kim
- Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea
| | - Il Gyu Kong
- Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Anyang, Korea
| | - Hyo Geun Choi
- Department of Otorhinolaryngology-Head and Neck Surgery, Hallym University College of Medicine, Anyang, Korea
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Tseng WH, Tseng PH, Wu JF, Hsu YC, Lee TY, Ni YH, Wang HP, Hsiao TY, Hsu WC. Double-blind, placebo-controlled study with alginate suspension for laryngopharyngeal reflux disease. Laryngoscope 2018; 128:2252-2260. [PMID: 29399800 DOI: 10.1002/lary.27111] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2017] [Revised: 12/08/2017] [Accepted: 12/26/2017] [Indexed: 12/21/2022]
Abstract
OBJECTIVE Treatment for laryngopharyngeal reflux disease (LPRD) is challenging because of delays in recognition and poor responsiveness to proton-pump inhibitor therapy. The aim of this study was to determine the efficacy and safety of liquid alginate suspension for treating LPRD. METHODS A double-blind, placebo-controlled, prospective study comparing 8 weeks of treatment with Alginos Oral Suspension (TTY Biopharm Co. Ltd., Taipei, Taiwan) (sodium alginate 1,000 mg three times daily) with a placebo was conducted on patients who fulfilled the criteria of at least one symptom consistent with LPRD, a total reflux symptom index (RSI) score of > 10, and a total reflux finding score (RFS) of > 5. Those with erosive gastroesophageal reflux disease, as evidenced through screened transnasal upper gastrointestinal endoscopy, were excluded. Efficacy was assessed by RSI, RFS, and ambulatory multichannel intraluminal impedance and pH (MII-pH) monitoring. RESULTS A total of 80 patients aged 22 to 72 years were enrolled. Compared with baseline, both Alginos (TTY Biopharm Co. Ltd.) and the placebo significantly reduced the total RSI (P < 0.001) and the total number of reflux episodes shown by MII-pH monitoring (P < 0.05) after 8 weeks of treatment. However, liquid alginate suspension was unable to show superiority over the placebo. The incidence of various adverse events from Alginos (TTY Biopharm Co. Ltd.) was relatively low (7.7%) and mild. CONCLUSION This study showed that liquid alginate suspension was well tolerated by LPRD patients. It effectively improved symptoms and reflux numbers but was unable to show superiority over placebo. As observed in previous studies, a great placebo effect was present. The importance of lifestyle modification could not be overlooked. LEVEL OF EVIDENCE 2. Laryngoscope, 128:2252-2260, 2018.
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Affiliation(s)
- Wen-Hsuan Tseng
- Department of Otolaryngology, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Ping-Huei Tseng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Feng Wu
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Ya-Chin Hsu
- Department of Otolaryngology, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan
| | - Ting-Yi Lee
- Department of Otolaryngology, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan
| | - Yen-Hsuan Ni
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Hsiu-Po Wang
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tzu-Yu Hsiao
- Department of Otolaryngology, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan
| | - Wei-Chung Hsu
- Department of Otolaryngology, College of Medicine, National Taiwan University and National Taiwan University Hospital, Taipei, Taiwan
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20
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Chae S, Richter JE. Wireless 24, 48, and 96 Hour or Impedance or Oropharyngeal Prolonged pH Monitoring: Which Test, When, and Why for GERD? Curr Gastroenterol Rep 2018; 20:52. [PMID: 30259210 DOI: 10.1007/s11894-018-0659-0] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
PURPOSE OF REVIEW pH monitoring technologies are routinely utilized in practice to further evaluate symptoms of gastro-esophageal reflux disease and laryngopharyngeal reflux (LPR). This is a review of the recent literature of the available pH monitoring technology and creates an algorithm in the diagnostic work up of a patient with GERD or LPR. RECENT FINDINGS The catheter-free wireless pH monitor traditionally collects data for 48 h. Recent studies have found that extending to 96 h can be helpful in patients with conflicting results on the first 2 days of the study. In addition, 96 h can allow for testing both on and off of PPI therapy. The oropharyngeal monitoring device is a newer technology that is designed to aid in the diagnoses of LPR. There are limitations with this technology as there is no universal abnormal cutoff and some studies have suggested a poor correlation between multichannel intraluminal impedance-pH (MII-pH) and the oropharyngeal monitoring device. MII-pH has recently developed two additional parameters, the measurement of three 10-min nighttime periods and the post-reflux swallow-induced peristaltic wave (PSPW) index, both of which may increase accuracy of testing. Each of these technologies can provide unique data regarding acid reflux exposure in the esophagus and oropharynx. The wireless pH monitor performed off of PPI therapy can help to establish or exclude the diagnosis of GERD. For those patients with refractory symptoms on PPI, MII-pH study can be performed while on therapy and provides data regarding the response to treatment. Oropharyngeal pH monitoring is being utilized in some practices to aid in diagnosis of LPR, but the scientific validity is controversial.
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Affiliation(s)
- Soojong Chae
- The Joy McCann Culverhouse Center for Esophageal Diseases, Division of Digestive Diseases and Nutrition, University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd., MDC 72, Tampa, FL, 3361, USA
| | - Joel E Richter
- The Joy McCann Culverhouse Center for Esophageal Diseases, Division of Digestive Diseases and Nutrition, University of South Florida, Morsani College of Medicine, 12901 Bruce B. Downs Blvd., MDC 72, Tampa, FL, 3361, USA.
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21
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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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22
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Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout AJPM, Vaezi M, Sifrim D, Fox MR, Vela MF, Tutuian R, Tack J, Bredenoord AJ, Pandolfino J, Roman S. Modern diagnosis of GERD: the Lyon Consensus. Gut 2018; 67:1351-1362. [PMID: 29437910 PMCID: PMC6031267 DOI: 10.1136/gutjnl-2017-314722] [Citation(s) in RCA: 920] [Impact Index Per Article: 131.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2017] [Revised: 01/11/2018] [Accepted: 01/14/2018] [Indexed: 12/12/2022]
Abstract
Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD in isolation, but are of value in determining need for further investigation. Conclusive evidence for reflux on oesophageal testing include advanced grade erosive oesophagitis (LA grades C and D), long-segment Barrett's mucosa or peptic strictures on endoscopy or distal oesophageal acid exposure time (AET) >6% on ambulatory pH or pH-impedance monitoring. A normal endoscopy does not exclude GERD, but provides supportive evidence refuting GERD in conjunction with distal AET <4% and <40 reflux episodes on pH-impedance monitoring off proton pump inhibitors. Reflux-symptom association on ambulatory reflux monitoring provides supportive evidence for reflux triggered symptoms, and may predict a better treatment outcome when present. When endoscopy and pH or pH-impedance monitoring are inconclusive, adjunctive evidence from biopsy findings (histopathology scores, dilated intercellular spaces), motor evaluation (hypotensive lower oesophageal sphincter, hiatus hernia and oesophageal body hypomotility on high-resolution manometry) and novel impedance metrics (baseline impedance, postreflux swallow-induced peristaltic wave index) can add confidence for a GERD diagnosis; however, diagnosis cannot be based on these findings alone. An assessment of anatomy, motor function, reflux burden and symptomatic phenotype will therefore help direct management. Future GERD management strategies should focus on defining individual patient phenotypes based on the level of refluxate exposure, mechanism of reflux, efficacy of clearance, underlying anatomy of the oesophagogastric junction and psychometrics defining symptomatic presentations.
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Affiliation(s)
- C Prakash Gyawali
- Division of Gastroenterology, Washington University School of Medicine, St Louis, Missouri, USA
| | - Peter J Kahrilas
- Division of Gastroenterology, Department of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Edoardo Savarino
- Division of Gastroenterology, Department of Surgical, Oncological and Gastroenterological Sciences, University of Padua, Padua, Italy
| | - Frank Zerbib
- Department of Gastroenterology, Bordeaux University Hospital, Université de Bordeaux, Bordeaux, France
| | - Francois Mion
- Digestive Physiology, Hopital E Herriot, Hospices Civils de Lyon, Université de Lyon, Lyon, France,Digestive Physiology, Université de Lyon, Lyon I University, Lyon, France,Université de Lyon, Inserm U1032, Lyon, France
| | - André J P M Smout
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Michael Vaezi
- Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Daniel Sifrim
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Mark R Fox
- Gastroenterology, St. Claraspital, Kleinriehenstrasse 30, Basel, Switzerland,Zürich Neurogastroenterology and Motility Research Group, Clinic for Gastroenterology and Hepatology, University Hospital of Zürich, Zürich, Switzerland
| | - Marcelo F Vela
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Radu Tutuian
- Division of Gastroenterology, University Clinics for Visceral Surgery and Medicine, Bern University Hospital, Bern, Switzerland
| | - Jan Tack
- Department of Gastroenterology, Catholic University of Leuven, Leuven, Belgium
| | - Albert J Bredenoord
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - John Pandolfino
- Division of Gastroenterology, Department of Medicine, Northwestern University, Chicago, Illinois, USA
| | - Sabine Roman
- Digestive Physiology, Hopital E Herriot, Hospices Civils de Lyon, Université de Lyon, Lyon, France,Digestive Physiology, Université de Lyon, Lyon I University, Lyon, France,Université de Lyon, Inserm U1032, Lyon, France
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23
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Rosen R, Vandenplas Y, Singendonk M, Cabana M, DiLorenzo C, Gottrand F, Gupta S, Langendam M, Staiano A, Thapar N, Tipnis N, Tabbers M. Pediatric Gastroesophageal Reflux Clinical Practice Guidelines: Joint Recommendations of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition. J Pediatr Gastroenterol Nutr 2018; 66:516-554. [PMID: 29470322 PMCID: PMC5958910 DOI: 10.1097/mpg.0000000000001889] [Citation(s) in RCA: 522] [Impact Index Per Article: 74.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
This document serves as an update of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition (NASPGHAN) and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) 2009 clinical guidelines for the diagnosis and management of gastroesophageal reflux disease (GERD) in infants and children and is intended to be applied in daily practice and as a basis for clinical trials. Eight clinical questions addressing diagnostic, therapeutic and prognostic topics were formulated. A systematic literature search was performed from October 1, 2008 (if the question was addressed by 2009 guidelines) or from inception to June 1, 2015 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Clinical Trials. The approach of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) was applied to define and prioritize outcomes. For therapeutic questions, the quality of evidence was also assessed using GRADE. Grading the quality of evidence for other questions was performed according to the Quality Assessment of Studies of Diagnostic Accuracy (QUADAS) and Quality in Prognostic Studies (QUIPS) tools. During a 3-day consensus meeting, all recommendations were discussed and finalized. In cases where no randomized controlled trials (RCT; therapeutic questions) or diagnostic accuracy studies were available to support the recommendations, expert opinion was used. The group members voted on each recommendation, using the nominal voting technique. With this approach, recommendations regarding evaluation and management of infants and children with GERD to standardize and improve quality of care were formulated. Additionally, 2 algorithms were developed, 1 for infants <12 months of age and the other for older infants and children.
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Affiliation(s)
- Rachel Rosen
- Center for Motility and Functional Gastrointestinal Disorders, Division of Gastroenterology, Children's Hospital Boston, Boston, MA
| | - Yvan Vandenplas
- KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium
| | | | - Michael Cabana
- Division of General Pediatrics, University of California, San Francisco, CA
| | - Carlo DiLorenzo
- Division of Pediatric Gastroenterology, Nationwide Children's Hospital, The Ohio State University, Columbus, OH
| | - Frederic Gottrand
- CHU Lille, Division of Pediatric Gastroenterology, Hepatology and Nutrition, Lille, France
| | - Sandeep Gupta
- Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of Illinois, Peoria, IL
| | - Miranda Langendam
- Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center/University of Amsterdam, Amsterdam, The Netherlands
| | - Annamaria Staiano
- Department of Translational Medical Science, Section of Pediatrics, University of Naples ‘‘Federico II,’’ Naples, Italy
| | - Nikhil Thapar
- Great Ormond Street Hospital for Children, London, UK
| | - Neelesh Tipnis
- Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS
| | - Merit Tabbers
- Emma Children's Hospital/AMC, Amsterdam, The Netherlands
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Abstract
Gastroesophageal reflux disease encompasses a wide spectrum of disorders related to the reflux of gastric contents into the esophagus. Extraesophageal reflux (EER) may be suspected in patients with unexplained chronic cough, pharyngolaryngeal symptoms, and asthma. For physicians, suspected EER is challenging as there is currently no tool that can reliably make a definitive diagnosis. Endoscopic signs are not specific, pharyngeal and proximal reflux monitoring are not reliable, and if distal pH or pH-impedance monitoring can identify patients with abnormal reflux, they cannot predict the response to therapy. Controlled randomized trials have failed to reliably demonstrate any benefit of high-dose proton-pump inhibitors over placebo in patients with laryngeal symptoms, chronic cough, and asthma. Overall, the role of gastroesophageal reflux has been largely overestimated in patients with suspected EER. Especially when proton-pump inhibitors failed to improve symptoms, other diagnosis should be considered, such as functional laryngeal disorders which are probably much more prevalent in these patients than pathologic gastroesophageal reflux.
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Oropharyngeal pH Testing Does Not Predict Response to Proton Pump Inhibitor Therapy in Patients with Laryngeal Symptoms. Am J Gastroenterol 2016; 111:1517-1524. [PMID: 27091320 PMCID: PMC5071144 DOI: 10.1038/ajg.2016.145] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/01/2016] [Accepted: 03/01/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Predicting response to proton pump inhibitor (PPI) therapy in patients with laryngeal symptoms is challenging. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. In this study, we aimed to investigate the prognostic potential of oropharyngeal pH monitoring to predict responsiveness to PPI therapy in patients with laryngeal symptoms. METHODS We conducted a physician-blinded prospective cohort study at a single academic institution between January 2013 and October 2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-h oropharyngeal pH monitoring, followed by an 8- to 12-week trial of omeprazole 40 mg daily. Prior to and following PPI therapy, patients completed various symptom questionnaires. The primary outcome was the association between PPI response and oropharyngeal pH metrics. PPI response was separated into three subgroups based on the post-treatment RSI score and % RSI response: non-response=RSI ≥13; partial response=post-treatment RSI <13 and change in RSI <50%; and complete response=post-treatment RSI <13 and change in RSI ≥50%. The primary analysis utilized a multinomial logistic regression controlling for the pre-treatment RSI score. A secondary analysis assessed the relationship between the change in RSI (post-pre) and oropharyngeal pH metrics via ordinary least square regression. RESULTS Thirty-four patients completed the study and were included in final analysis. Symptom response to PPI therapy was as follows: 50% no response, 15% partial response, and 35% complete response. Non-responders had a higher pre-treatment RSI (P<0.01). There were no significant differences in oropharyngeal acid exposure (below pH of 4.0, 5.0, 5.5, 6.0, and RYAN scores) between responder types. The secondary analysis noted a trend between lower PPI response and a greater total percent time below pH of 5.0 (P=0.03), upright percent time below pH of 5.0 (P=0.07), and RYAN supine (corrected; P=0.03), as well as an association between PPI response and greater decreases in the Anxiety Sensitivity Inventory (P<0.01), Brief Symptom Inventory-18 (P<0.01), and Negative Affect Scale (P<0.01). CONCLUSIONS Oropharyngeal pH testing did not predict laryngeal symptom response to PPI therapy. Contrary to hypothesis, our study signaled that the degree of oropharyngeal acid exposure is inversely related to PPI response. In addition, reduction in negative affect and psychological distress parallels PPI response.
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Patel DA, Harb AH, Vaezi MF. Oropharyngeal Reflux Monitoring and Atypical Gastroesophageal Reflux Disease. Curr Gastroenterol Rep 2016; 18:12. [PMID: 26908280 DOI: 10.1007/s11894-016-0486-0] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The prevalence of gastroesophageal reflux disease (GERD) has been increasing since the 1990 s, with up to 27.8 % of people in North America affected by this disorder. The healthcare burden of patients who primarily have extra-esophageal manifestations of GERD (atypical GERD) is estimated to be 5 times that of patients with primarily heartburn and regurgitation due to lack of a gold standard diagnostic test, poor responsiveness to PPI therapy, and delay in recognition. Empiric twice daily PPI therapy for 1-2 months is currently considered the best diagnostic test, but due to poor responsiveness to PPIs in patients with atypical GERD in multiple randomized controlled trials, newer modes of diagnostic procedures such as oropharyngeal pH monitoring have gained significantly more traction. The utility of oropharyngeal pH monitoring systems such as Restech Dx-pH is currently limited due to lack of consensus on normal and abnormal cutoff values. Recent studies suggest its utility as a prognostic tool and its ability to predict responsiveness to medical and surgical therapy. However, routine use of oropharyngeal pH monitoring is still not widespread due to the lack of well-controlled prospective studies.
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Affiliation(s)
- Dhyanesh A Patel
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Ali H Harb
- Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Michael F Vaezi
- Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA.
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27
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Abstract
Gastro-oesophageal reflux is associated with a wide range of respiratory disorders, including asthma, isolated chronic cough, idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease and cystic fibrosis. Reflux can be substantial and reach the proximal margins of the oesophagus in some individuals with specific pulmonary diseases, suggesting that this association is more than a coincidence. Proximal oesophageal reflux in particular has led to concern that microaspiration might have an important, possibly even causal, role in respiratory disease. Interestingly, reflux is not always accompanied by typical reflux symptoms, such as heartburn and/or regurgitation, leading many clinicians to empirically treat for possible gastro-oesophageal reflux. Indeed, costs associated with use of acid suppressants in pulmonary disease far outweigh those in typical GERD, despite little evidence of therapeutic benefit in clinical trials. This Review comprehensively examines the possible mechanisms that might link pulmonary disease and oesophageal reflux, highlighting the gaps in current knowledge and limitations of previous research, and helping to shed light on the frequent failure of antireflux treatments in pulmonary disease.
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28
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de Bortoli N, Martinucci I, Bertani L, Russo S, Franchi R, Furnari M, Tolone S, Bodini G, Bolognesi V, Bellini M, Savarino V, Marchi S, Savarino EV. Esophageal testing: What we have so far. World J Gastrointest Pathophysiol 2016; 7:72-85. [PMID: 26909230 PMCID: PMC4753191 DOI: 10.4291/wjgp.v7.i1.72] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2015] [Revised: 12/02/2015] [Accepted: 01/04/2016] [Indexed: 02/06/2023] Open
Abstract
Gastroesophageal reflux disease (GERD) is a common disorder of the gastrointestinal tract. In the last few decades, new technologies have evolved and have been applied to the functional study of the esophagus, allowing for the improvement of our knowledge of the pathophysiology of GERD. High-resolution manometry (HRM) permits greater understanding of the function of the esophagogastric junction and the risks associated with hiatal hernia. Moreover, HRM has been found to be more reproducible and sensitive than conventional water-perfused manometry to detect the presence of transient lower esophageal sphincter relaxation. Esophageal 24-h pH-metry with or without combined impedance is usually performed in patients with negative endoscopy and reflux symptoms who have a poor response to anti-reflux medical therapy to assess esophageal acid exposure and symptom-reflux correlations. In particular, esophageal 24-h impedance and pH monitoring can detect acid and non-acid reflux events. EndoFLIP is a recent technique poorly applied in clinical practice, although it provides a large amount of information about the esophagogastric junction. In the coming years, laryngopharyngeal symptoms could be evaluated with up and coming non-invasive or minimally invasive techniques, such as pepsin detection in saliva or pharyngeal pH-metry. Future studies are required of these techniques to evaluate their diagnostic accuracy and usefulness, although the available data are promising.
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29
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Wilhelm D, Jell A, Feussner H, Schmid RM, Bajbouj M, Becker V. Pharyngeal pH monitoring in gastrectomy patients - what do we really measure? United European Gastroenterol J 2015; 4:541-5. [PMID: 27536364 DOI: 10.1177/2050640615617637] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/28/2015] [Accepted: 10/24/2015] [Indexed: 12/19/2022] Open
Abstract
AIM Diagnosis of laryngopharyngeal reflux (LPR) has dramatically increased over the last years. For diagnosis of gastroesophageal reflux, a newly designed pharyngeal probe (Dx-pH) was recently introduced. It is also recommended to guide therapy decision in antireflux surgery. However, diagnostic results are questionable. Therefore, we establish a reliable reference group with asymptomatic patients after total gastrectomy and, thus, complete extinction of gastric acid production. METHODS Pharyngeal pH monitoring was performed in 10 consecutive patients with history of total gastrectomy. All patients were off proton pump inhibitor (PPI) therapy and followed a non-acid diet during the complete measurement period. RESULTS All procedures were performed without any complication. Six of the 10 asymptomatic gastrectomy patients (60%) had pathological results derived from the validated reference values (Ryan score) in pharyngeal pH monitoring. CONCLUSION Pathological pH values assessed by the Dx-pH device, usually interpreted as pathological aerosolized acidic gastroesophageal and/or laryngopharyngeal reflux, are obviously dissociated from gastric acid production. Further studies are required to determine diagnostic value of the new system. Therefore, the pharyngeal pH monitoring system seems currently not to be useful to guide any diagnostic or therapeutic decisions, in particular if surgical therapy is considered.
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Affiliation(s)
- Dirk Wilhelm
- Chirurgische Klinik, Klinikum rechts der Isar, Technische Universität München, Germany
| | - Alissa Jell
- Chirurgische Klinik, Klinikum rechts der Isar, Technische Universität München, Germany
| | - Hubertus Feussner
- Chirurgische Klinik, Klinikum rechts der Isar, Technische Universität München, Germany
| | - Roland M Schmid
- Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Germany
| | - Monther Bajbouj
- Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Germany
| | - Valentin Becker
- Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Germany
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30
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Becker V, Drabner R, Graf S, Schlag C, Nennstiel S, Buchberger AM, Schmid RM, Saur D, Bajbouj M. New aspects in the pathomechanism and diagnosis of the laryngopharyngeal reflux-clinical impact of laryngeal proton pumps and pharyngeal pH metry in extraesophageal gastroesophageal reflux disease. World J Gastroenterol 2015; 21:982-987. [PMID: 25624734 PMCID: PMC4299353 DOI: 10.3748/wjg.v21.i3.982] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 08/22/2014] [Accepted: 10/15/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the laryngeal H+K+-ATPase and pharyngeal pH in patients with laryngopharyngeal reflux (LPR)-symptoms as well as to assess the symptom scores during PPI therapy.
METHODS: Endoscopy was performed to exclude neoplasia and to collect biopsies from the posterior cricoid area (immunohistochemistry and PCR analysis). Immunohistochemical staining was performed with monoclonal mouse antibodies against human H+K+-ATPase. Quantitative real-time RT-PCR for each of the H+K+-ATPase subunits was performed. The pH values were assessed in the aerosolized environment of the oropharynx (DxpH Catheter) and compared to a subsequently applied combined pH/MII measurement.
RESULTS: Twenty patients with LPR symptoms were included. In only one patient, the laryngeal H+K+-ATPase was verified by immunohistochemical staining. In another patient, real-time RT-PCR for each H+K+-ATPase subunit was positive. Fourteen out of twenty patients had pathological results in DxpH, and 6/20 patients had pathological results in pH/MII. Four patients had pathological results in both functional tests. Nine out of twenty patients responded to PPIs.
CONCLUSION: The laryngeal H+K+-ATPase can only be sporadically detected in patients with LPR symptoms and is unlikely to cause the LPR symptoms. Alternative hypotheses for the pathomechanism are needed. The role of pharyngeal pH-metry remains unclear and its use can only be recommended for patients in a research study setting.
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31
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Mazzoleni G, Vailati C, Lisma DG, Testoni PA, Passaretti S. Correlation between oropharyngeal pH-monitoring and esophageal pH-impedance monitoring in patients with suspected GERD-related extra-esophageal symptoms. Neurogastroenterol Motil 2014; 26:1557-64. [PMID: 25208949 DOI: 10.1111/nmo.12422] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 08/06/2014] [Indexed: 12/11/2022]
Abstract
BACKGROUND 24-hour esophageal pH-impedance (pH-MII) is not totally reliable for laryngopharyngeal reflux (LPR). Oropharyngeal (OP) pH-monitoring with the Dx-pH probe may detect LPR better. The correlation between these two techniques is not thoroughly established. Aim of this study is to examine the correlation between OP pH-metry and esophageal pH-MII monitoring. METHODS Thirty-six consecutive patients with suspected gastroesophageal reflux disease-related extra-esophageal symptoms were evaluated using 24-h OP-pH and concomitant esophageal pH-MII monitoring. OP events were defined as: drop in pH below thresholds of 5.5, 5.0, 4.5, 4.0 or drop in pH of at least 10% from a running baseline. Temporal relationship between OP and esophageal reflux events and outcomes of the two tests were evaluated. KEY RESULTS 2394 refluxes were detected by pH-MII; of these only 120 were detected also by OP Dx-probe. On the other hand, the proportion of OP-pH events which were temporally related to an episode of distal reflux ranged from 0% to 17%, depending on the proximal pH criteria used. In 8/36 patients both tests were pathological, while in 10/36 they were both normal; 14/36 patients had pathological OP reflux, but a normal pH-MII test; 4/36 patients had pathological pH-MII, but a normal OP reflux. CONCLUSIONS & INFERENCES The correlation between OP pH-metry and pH-MII was weak. At present, the absence of a reliable gold standard for the diagnosis of LPR and the uncertain etiology of the pharyngeal pH alterations make it difficult to decide which is the most reliable technique for the diagnosis of true LPR.
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Affiliation(s)
- G Mazzoleni
- Division of Gastroenterology and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, San Raffaele Scientific Institute, Milan, Italy
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32
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Abstract
PURPOSE OF REVIEW The purpose of this review is to highlight recent work and provide recommendations on the approach for diagnosis and management of chronic cough in a gastroenterology clinic. RECENT FINDINGS Chronic cough is a burdensome symptom affecting a large number of patients and contributes significant cost to the healthcare system. Recent work has shown that select patients may benefit from acid-suppressive therapy and even surgery when there is true pathologic evidence of reflux disease with cough. However, judicious use and proper interpretation of diagnostic testing for gastroesophageal reflux in the setting of cough is important to avoid unnecessary or inappropriate therapy. SUMMARY Chronic cough remains a vexing problem for many physicians, including gastroenterologists. It is important that physicians approach refractory cough in a multidisciplinary manner. Future research is needed to better understand the likely central hypersensitivity response mediating reflux-related cough and potential alternative approaches to therapy.
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33
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Abstract
PURPOSE OF REVIEW Cough lasting more than 8 weeks is a common presenting complaint to the otolaryngologist. Historically, chronic cough has been attributed to post-nasal drip, laryngopharyngeal reflux and cough-variant asthma. This study reviews chronic cough from the viewpoint of an otolaryngologist. RECENT FINDINGS More recent studies suggest the influence of laryngeal neuropathy and its interplay with laryngopharyngeal reflux. There is limited evidence for post-nasal drip or cough-variant asthma causing chronic cough. SUMMARY In this study, we review the evidence for cause of chronic cough, as well as up to date techniques for the otolaryngologist, including transnasal esophagoscopy, to assess the patient in clinic allowing accurate diagnosis. Treatment options for the otolaryngologist are discussed and the role of multidisciplinary input emphasized.
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34
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Desjardin M, Roman S, des Varannes SB, Gourcerol G, Coffin B, Ropert A, Mion F, Zerbib F. Pharyngeal pH alone is not reliable for the detection of pharyngeal reflux events: A study with oesophageal and pharyngeal pH-impedance monitoring. United European Gastroenterol J 2014; 1:438-44. [PMID: 24917995 DOI: 10.1177/2050640613513016] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2013] [Accepted: 10/16/2013] [Indexed: 01/26/2023] Open
Abstract
BACKGROUND Pharyngeal pH probes and pH-impedance catheters have been developed for the diagnosis of laryngo-pharyngeal reflux. OBJECTIVE To determine the reliability of pharyngeal pH alone for the detection of pharyngeal reflux events. METHODS 24-h pH-impedance recordings performed in 45 healthy subjects with a bifurcated probe for detection of pharyngeal and oesophageal reflux events were reviewed. Pharyngeal pH drops to below 4 and 5 were analysed for the simultaneous occurrence of pharyngeal reflux, gastro-oesophageal reflux, and swallows, according to impedance patterns. RESULTS Only 7.0% of pharyngeal pH drops to below 5 identified with impedance corresponded to pharyngeal reflux, while 92.6% were related to swallows and 10.2 and 13.3% were associated with proximal and distal gastro-oesophageal reflux events, respectively. Of pharyngeal pH drops to below 4, 13.2% were related to pharyngeal reflux, 87.5% were related to swallows, and 18.1 and 21.5% were associated with proximal and distal gastro-oesophageal reflux events, respectively. CONCLUSIONS This study demonstrates that pharyngeal pH alone is not reliable for the detection of pharyngeal reflux and that adding distal oesophageal pH analysis is not helpful. The only reliable analysis should take into account impedance patterns demonstrating the presence of pharyngeal reflux event preceded by a distal and proximal reflux event within the oesophagus.
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Affiliation(s)
- Marie Desjardin
- CHU Bordeaux, Bordeaux, France ; Bordeaux Segalen University, Bordeaux, France
| | - Sabine Roman
- Hospices Civils de Lyon, Lyon, France ; Claude Bernard Lyon 1 University, Lyon, France
| | | | | | - Benoit Coffin
- Assistance Publique-Hôpitaux de Paris, Colombes, France ; INSERM U987, Boulogne Billancourt, France
| | | | - François Mion
- Hospices Civils de Lyon, Lyon, France ; Claude Bernard Lyon 1 University, Lyon, France
| | - Frank Zerbib
- CHU Bordeaux, Bordeaux, France ; Bordeaux Segalen University, Bordeaux, France
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35
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Abstract
This article reviews the evaluation and management of patients with suspected extraesophageal manifestations of gastroesophageal reflux disease, such as asthma, chronic cough, and laryngitis, which are commonly encountered in gastroenterology practices. Otolaryngologists and gastroenterologists commonly disagree upon the underlying cause for complaints in patients with one of the suspected extraesophageal reflux syndromes. The accuracy of diagnostic tests (laryngoscopy, endoscopy, and pH- or pH-impedance monitoring) for patients with suspected extraesophageal manifestations of gastroesophageal reflux disease is suboptimal. An empiric trial of proton pump inhibitors in patients without alarm features can help some patients, but the response to therapy is variable.
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Affiliation(s)
- Ryan D Madanick
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, CB# 7080, Chapel Hill, NC 27599, USA.
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36
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Kahrilas PJ, Smith JA, Dicpinigaitis PV. A causal relationship between cough and gastroesophageal reflux disease (GERD) has been established: a pro/con debate. Lung 2013; 192:39-46. [PMID: 24221340 DOI: 10.1007/s00408-013-9528-7] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2013] [Accepted: 10/21/2013] [Indexed: 01/10/2023]
Abstract
Along with upper airway cough syndrome (formerly, postnasal drip syndrome) and eosinophilic airway inflammation (asthma, nonasthmatic eosinophilic bronchitis), gastroesophageal reflux disease (GERD) is generally considered among the most common etiologies of chronic cough. Indeed, cough management guidelines published by numerous respiratory societies worldwide recommend evaluation and treatment of GERD as an integral component of the diagnostic/therapeutic algorithm for the management of chronic cough. However, a significant number of patients with chronic cough presumed due to GERD do not report improvement despite aggressive acid-suppressive therapy. Some of these refractory cases may be due to the recently appreciated entity of nonacid or weakly acidic reflux. Further contributing to the controversy are recent studies that demonstrate that patients with chronic cough do not have excessive reflux events relative to healthy volunteers. Although a temporal relationship between cough and reflux events has been suggested by studies utilizing impedance-pH monitoring of reflux events and objective cough recording, consensus is lacking in terms of whether this temporal relationship proves a causal link between reflux and cough. The fourth American Cough Conference (New York, June 2013) provided an ideal forum for the debate of this issue between two internationally recognized experts in the field of reflux and chronic cough.
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Affiliation(s)
- Peter J Kahrilas
- Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
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37
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Jobe BA, Richter JE, Hoppo T, Peters JH, Bell R, Dengler WC, DeVault K, Fass R, Gyawali CP, Kahrilas PJ, Lacy BE, Pandolfino JE, Patti MG, Swanstrom LL, Kurian AA, Vela MF, Vaezi M, DeMeester TR. Preoperative diagnostic workup before antireflux surgery: an evidence and experience-based consensus of the Esophageal Diagnostic Advisory Panel. J Am Coll Surg 2013; 217:586-97. [PMID: 23973101 DOI: 10.1016/j.jamcollsurg.2013.05.023] [Citation(s) in RCA: 129] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2013] [Revised: 05/01/2013] [Accepted: 05/28/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND Gastroesophageal reflux disease (GERD) is a very prevalent disorder. Medical therapy improves symptoms in some but not all patients. Antireflux surgery is an excellent option for patients with persistent symptoms such as regurgitation, as well as for those with complete symptomatic resolution on acid-suppressive therapy. However, proper patient selection is critical to achieve excellent outcomes. STUDY DESIGN A panel of experts was assembled to review data and personal experience with regard to appropriate preoperative evaluation for antireflux surgery and to construct an evidence and experience-based consensus that has practical application. RESULTS The presence of reflux symptoms alone is not sufficient to support a diagnosis of GERD before antireflux surgery. Esophageal objective testing is required to physiologically and anatomically evaluate the presence and severity of GERD in all patients being considered for surgical intervention. It is critical to document the presence of abnormal distal esophageal acid exposure, especially when antireflux surgery is considered, and reflux-related symptoms should be severe enough to outweigh the potential side effects of fundoplication. Each testing modality has a specific role in the diagnosis and workup of GERD, and no single test alone can provide the entire clinical picture. Results of testing are combined to document the presence and extent of the disease and assist in planning the operative approach. CONCLUSIONS Currently, upper endoscopy, barium esophagram, pH testing, and manometry are required for preoperative workup for antireflux surgery. Additional studies with long-term follow-up are required to evaluate the diagnostic and therapeutic benefit of new technologies, such as oropharyngeal pH testing, multichannel intraluminal impedance, and hypopharyngeal multichannel intraluminal impedance, in the context of patient selection for antireflux surgery.
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Affiliation(s)
- Blair A Jobe
- Department of Surgery, The Western Pennsylvania Hospital, West Penn Allegheny Health System, Pittsburgh, PA.
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Smith JA, Houghton LA. The oesophagus and cough: laryngo-pharyngeal reflux, microaspiration and vagal reflexes. COUGH 2013; 9:12. [PMID: 23590893 PMCID: PMC3640905 DOI: 10.1186/1745-9974-9-12] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Accepted: 03/17/2013] [Indexed: 12/25/2022]
Abstract
Gastro-oesophageal reflux disease is generally considered to be one of the commonest causes of chronic cough, however randomised controlled trials of proton pump inhibitors have often failed to support this notion. This article reviews the most recent studies investigating the mechanisms thought to link reflux and cough, namely laryngo-pharyngeal reflux, micro-aspiration and neuronal cross-organ sensitisation. How recent evidence might shed light on the failure of acid suppressing therapies and suggest new approaches to treating reflux related cough are also discussed.
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Affiliation(s)
- Jaclyn A Smith
- Respiratory and Allergy Centre, The University of Manchester, University Hospital of South Manchester, Manchester, UK.
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