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Laryngopharyngeal reflux disease:Updated examination of mechanisms,pathophysiology,treatment,and association with gastroesophageal reflux disease

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World Journal of Gastroenterology 2024年第16期30卷 2209-2219页

作者： Na Cui Ting Dai Yang Liu Ya-Yu Wang Jia-Yu Lin Qing-Fan Zheng Dong-Dong Zhu Xue-Wei Zhu Department of Otorhinolaryngology Head and Neck Surgery China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Ultrasound China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina Department of Gastroenterology China-Japan Union Hospital of Jilin UniversityChangchun 130033Jilin ProvinceChina

Laryngopharyngeal reflux disease(LPRD)is an inflammatory condition in the laryngopharynx and upper aerodigestive tract mucosa caused by reflux of stomach contents beyond the esophagus.LPRD commonly presents with symptoms such as hoarseness,cough,sore throat,a feeling of throat obstruction,excessive throat mucus.This complex condition is thought to involve both reflux and reflex mechanisms,but a clear understanding of its molecular mechanisms is still lacking.Currently,there is no standardized diagnosis or treatment protocol.Therapeutic strategies for LPRD mainly include lifestyle modifications,proton pump inhibitors and endoscopic surgery.This paper seeks to provide a comprehensive overview of the existing literature regarding the mechanisms,pathophysiology and treatment of LPRD.We also provide an in-depth exploration of the association between LPRD and gastroesophageal reflux disease.

关键词： Laryngopharyngeal reflux gastroesophageal reflux Head neck surgery Laryngitis Otolaryngology

Immunoglobulin G-mediated food intolerance and metabolic syndrome influence the occurrence of reflux esophagitis in Helicobacter pylori-infected patients

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World Journal of Gastroenterology 2024年第8期30卷 855-862页

作者： Li-Hui Wang Bin-Bin Su Sheng-Shu Wang Guan-Chao Sun Kun-Ming Lv Yi Li Hui Shi Qian-Qian Chen College Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology Second Medical Center of Chinese PLA General HospitalBeijing 100853China Institute of Geriatrics The 2nd Medical CenterBeijing Key Laboratory of Aging and GeriatricsNational Clinical Research Center for Geriatrics DiseasesSecond Medical Center of Chinese PLA General HospitalBeijing 100853China Department of Gastroenterology First Medical Center of Chinese PLA General HospitalBeijing 100853China

BACKGROUND reflux esophagitis has an increasing prevalence and complex and diverse symptoms.Identifying its risk factors is crucial to understanding the etiology,prevention,and management of the disease.The occurrence of reflux esophagitis may be associated with food reactions,Helicobacter pylori(H.pylori)infection,and metabolic syndromes.AIM To investigate the risk factors for reflux esophagitis and analyze the effects of immunoglobulin(Ig)G-mediated food intolerance,H.pylori infection,and metabolic syndrome on reflux esophagitis.METHODS Outpatients attending the Second Medical Center of the PLA General Hospital between 2017 and 2021 were retrospectively enrolled.The patients’basic information,test results,gastroscopy results,H.pylori test results,and IgG-mediated food intolerance results were collected.Multivariate logistic regression analysis was used to analyze risk factors for reflux esophagitis.Statistical mediation analysis was used to evaluate the effects of IgG-mediated food intolerance and metabolic syndrome on H.pylori infection affecting reflux esophagitis.RESULTS A total of 7954 outpatients were included;the prevalence of reflux esophagitis,IgG-mediated food intolerance,H.pylori infection,and metabolic syndrome were 20.84%,61.77%,35.91%,and 60.15%,respectively.Multivariate analysis showed that the independent risk factors for reflux esophagitis included IgG-mediated food intolerance(OR=1.688,95%CI:1.497-1.903,Preflux esophagitis was H.pylori infection(OR=0.400,95%CI:0.351-0.456,Preflux esophagitis(P=0.0200).Metabolic syndrome had a partially negative mediating effect on H.pylori infection and reduced the occurrence of reflux esophagitis(P=0.0220).CONCLUSION Patients with IgG-mediated food intolerance and metabolic syndrome were at higher ris

关键词： gastroesophageal reflux Esophagitis Food intolerance Metabolic syndrome Helicobacter pylori Chemokines

gastroesophageal reflux disease in children: What’s new right now?

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World Journal of Gastrointestinal Endoscopy 2023年第3期15卷 84-102页

作者： Palittiya Sintusek Mohamed Mutalib Nikhil Thapar Thai Pediatric Gastroenterology Hepatology and Immunology Research Unit(TPGHAI)Division of GastroenterologyDepartment of PediatricsKing Chulalongkorn Memorial Hospital and Thai Red CrossFaculty of MedicineChulalongkorn UniversityBangkok 10330BangkokThailand Department of Paediatric Gastroenterology Pediatric and Gastroenterology ServicesEvelina London Children’s HospitalLondon SE17EHUnited Kingdom Department of Gastroenterology Hepatology and Liver TransplantQueensland Children’s HospitalBrisbaneQueensland 4101Australia School of Medicine University of QueenslandBrisbaneQueensland 4006Australia Woolworths Centre for Child Nutrition Research Queensland University of TechnologyBrisbaneQueensland 4101Australia

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.

关键词： gastroesophageal reflux gastroesophageal reflux disease Children Infant Impedance study Lower esophageal sphincter

Local inflammatory response to gastroesophageal reflux:Association of gene expression of inflammatory cytokines with esophageal multichannel intraluminal impedance-pH data

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World Journal of Clinical Cases 2022年第26期10卷 9254-9263页

作者： Sergey Morozov Tatyana Sentsova Department of Gastroenterology Hepatology and NutritionFederal Research Center of NutritionBiotechnology and Food SafetyMoscow 115446Russia Department of Hospital Pediatrics No.2 Russian National Research Medical University named after N.I.PirogovMoscow 117997Russia

BACKGROUND Gene expression of inflammatory cytokines may take part in the pathophysiology of different forms of gastroesophageal reflux disease(GERD).AIM To explore gene expression of inflammatory cytokines in esophageal mucosa in patients with erosive esophagitis(EE)and non-erosive forms of GERD(NERD)and its association with data of esophageal multichannel intraluminal impedancepH(MII-pH)measurements.METHODS This was a single-center prospective study.Esophageal mucosa samples were taken from the lower part of the esophagus during endoscopy.Expression of interleukin(IL)-1β,IL-10,IL-18,tumor necrosis factorα(TNFA),toll-like receptor 4(TLR4),GATA binding protein 3(GATA3),differentiation cluster 68(CD68)andβ-2 microglobulin genes in esophageal mucosa was assessed with ImmunoQuantex assays.MII-pH measurements were performed on all the participants.Diagnosis of GERD was confirmed by the results of the MII-pH data.Based on the endoscopy,patients were allocated to the groups of EE and NERD.The control group consisted of non-symptomatic subjects with normal endoscopy and MII-pH results.We used nonparametric statistics to compare the differences between the groups.Association of expression of the mentioned genes with the results of the MII-pH data was assessed with Spearman’s rank method.RESULTS Data from 60 patients with GERD and 10 subjects of the control group were available for the analysis.Higher expression of IL-18(5.89±0.4 vs 5.28±1.1,P=0.04)and GATA3(2.92±0.86 vs 2.23±0.96,P=0.03)was found in the EE group compared to NERD.Expression of IL-1β,IL-18,TNFA,and TLR4 was lower(Pgastroesophageal refluxes was found.CONCLUSION In patients with EE,local expression of IL-18 a

关键词： gastroesophageal reflux disease Gene expression Cytokines Erosive esophagitis Non-erosive gastroesophageal reflux disease Esophageal multichannel intraluminal impedance-pH gastroesophageal reflux

Pre-Lung transplant reflux testing demonstrates high prevalence of gastroesophageal reflux in cystic fibrosis and reduces chronic rejection risk

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World Journal of Transplantation 2023年第4期13卷 138-146页

作者： Wai-Kit Lo Ryan Flanagan Nirmal Sharma Hilary J Goldberg Walter W Chan Division of Gastroenterology Hepatology and EndoscopyBrigham and Women's HospitalHarvard Medical SchoolBostonMA Division of Pulmonary and Critical Care Medicine Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115United States

BACKGROUND gastroesophageal reflux(GER)has been associated with poor outcomes after lung transplantation for chronic lung disease,including increased risk of chronic rejection.GER is common in cystic fibrosis(CF),but factors influencing the likelihood of pre-transplant pH testing,and the impact of testing on clinical management and transplant outcomes in patients with CF are unknown.AIM To evaluate the role of pre-transplant reflux testing in the evaluation of lung transplant candidates with CF.METHODS This was a retrospective study from 2007-2019 at a tertiary medical center that included all patients with CF undergoing lung transplant.Patients with pretransplant anti-reflux surgery were excluded.Baseline characteristics(age at transplantation,gender,race,body mass index),self-reported GER symptoms prior to transplantation,and pre-transplant cardiopulmonary testing results,were recorded.reflux testing consisted of either 24-h pH-or combined multichannel intraluminal impedance and pH monitoring.Post-transplant care included a standard immunosuppressive regimen,and regular surveillance bronchoscopy and pulmonary spirometry in accordance with institutional practice as well as in symptomatic patients.The primary outcome of chronic lung allograft dysfunction(CLAD)was defined clinically and histologically per International Society of Heart and Lung Transplantation criteria.Statistical analysis was performed with Fisher’s exact test to assess differences between cohorts,and time-to-event Cox proportional hazards modeling.RESULTS After applying inclusion and exclusion criteria,a total of 60 patients were included in the study.Among all CF patients,41(68.3%)completed reflux monitoring as part of pre-lung transplant evaluation.Objective evidence of pathologic reflux,defined as acid exposure time>4%,was found in 24 subjects,representing 58%of the tested group.CF patients with pre-transplant reflux testing were older(35.8 vs 30.1 years,P=0.01)and more commonly reported typical esophageal reflux symptoms(53.7%vs 26.3%,P=0.06

关键词： Cystic fibrosis gastroesophageal reflux Lung transplantation pH monitoring

Prevalence of gastroesophageal reflux disease in children with extraesophageal manifestations using combined-video,multichannel intraluminal impedance-pH study

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World Journal of Clinical Pediatrics 2023年第3期12卷 151-161页

作者： Sutha Eiamkulbutr Termpong Dumrisilp Anapat Sanpavat Palittiya Sintusek Department of Pediatrics King Chulalongkorn Memorial HospitalBangkok 10330Thailand Department of Pediatrics Bhumibol Adulyadej HospitalBangkok 10220Thailand Department of Pathology Chulalongkorn UniversityBangkok 10330Thailand Thai Pediatric Gastroenterology Hepatology and Immunology Research UnitKing Chulalongkorn Memorial HospitalFaculty of MedicineChulalongkorn UniversityBangkok 10330Thailand

BACKGROUND gastroesophageal reflux disease(GERD)might be either a cause or comorbidity in children with extraesophageal problems especially as refractory respiratory symptoms,without any best methods or criterion for diagnosing it in children.AIM To evaluate the prevalence of extraesophageal GERD using conventional and combined-video,multichannel intraluminal impedance-pH(MII-pH),and to propose novel diagnostic parameters.METHODS The study was conducted among children suspected of extraesophageal GERD at King Chulalongkorn Memorial Hospital between 2019 and 2022.The children underwent conventional and/or combined-video MII-pH.The potential parameters were assessed and receiver operating characteristic was used for the significant parameters.RESULTS Of 51 patients(52.9%males),aged 2.24 years were recruited.The common problems were cough,recurrent pneumonia,and hypersecretion.Using MII-pH,35.3%of the children were diagnosed with GERD by reflux index(31.4%),total reflux events(3.9%),and symptom indices(9.8%)with higher symptom recorded in the GERD group(94 vs 171,P=0.033).In the video monitoring group(n=17),there were more symptoms recorded(120 vs 220,P=0.062)and more GERD(11.8%vs 29.4%,P=0.398)by symptom indices.Longest reflux time and mean nocturnal baseline impedance were significant parameters for diagnosis with receiver operating characteristic areas of 0.907(P=0.001)and 0.726(P=0.014).CONCLUSION The prevalence of extraesophageal GERD in children was not high as expected.The diagnostic yield of symptom indices increased using video monitoring.Long reflux time and mean nocturnal baseline impedance are novel parameters that should be integrated into the GERD diagnostic criteria in children.

关键词： Extraesophageal reflux pH-impedance Children gastroesophageal reflux Mean nocturnal baseline impedance

Relationship between symptom response and esophageal pH level on standard dose of esomeprazole treatment for gastroesophageal reflux disease

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Chinese Medical Journal 2010年第15期123卷 2012-2017页

作者： PENG Sui XIONG Li-shou XIAO Ying-lian WANG An-jiang LIN Jin-kun HU Pin-jin CHEN Min-hu Division of Gastroenterology & Hepatology the First Affiliated Hospital of Sun Yat-sen University Guangzhou Guangdong 510080 China

Background The relationship between symptom elimination and normalization of esophageal acid level of gastroesophageal reflux disease （GERD） on proton-pump inhibitor （PPI） therapy has been questioned. This study aimed to evaluate the relationship between symptom response and gastro-esophageal acidity control in Chinese patients with GERD on esomeprazole therapy, and to assess the role of 24-hour esophageal pH-metry after therapy in GERD patients.Methods GERD patients with typical reflux symptoms were enrolled and received esomeprazole 40 mg once daily for 4 weeks. Patients with positive baseline 24-hour esophageal pH-metry were divided into two groups depending on an additional dual-channel 24-hour pH-metry after treatment. The pH- group achieved normalization of esophageal pH level whereas the pH＋ group did not.Results Of the 80 patients studied, 76 had abnormal baseline esophageal pH levels. Of these, 90% （52/58） of symptom-free patients and 67% （12/18） of symptom-persistent patients achieved esophageal pH normalization after therapy （P=0.030）. The mean post-therapy gastric nocturnal percent time of pH 〈4.0 was significantly higher in pH＋group than that in pH- group （P 〈0.001） after therapy. The multivariate regression analysis identified hiatus hernia （P〈0.001） and persistent reflux symptom （P=0.004） were two independent factors predicting the low post-therapy esophageal pH level.Conclusions Symptom elimination is not always accompanied by esophageal pH normalization, and vice verse.Esophageal pH-metry is recommended for GERD patients with hiatus hernia or with persistent reflux symptoms after PPI therapy.

关键词： gastroesophageal reflux esomeprazole symptom response esophageal pH level

Insult of gastroesophageal reflux on airway： clinical significance of pharyngeal nozzle

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Frontiers of Medicine 2015年第1期9卷 117-122页

作者： Zhonggao Wang Zhiwei Hu Jimin Wu Feng Ji Hongtao Wang Yungang Lai Xiang Gao Yachan Ning Chengchao Zhang Zhitong Li Weitao Liang Jianjun Liu Center for GER the Second Artillery General Hospital of PLA Beijing 100088 China Xuanwu Hospital Capital Medical University Beijing 100053 China Center for GER the First Ajfiliated Hospital of Zhengzhou University Zhengzhou 450052 China Center for GER the Fourth Affiliated Hospital of Zhengzhou University Zhengzhou 450044 China

At the very time of global paying the highest attention to the worst insults of smoking as well as haze on the airway, everybody knows both are exogenous and noticeable. However, people mostly, including many medical personnel, do not know how badly the gastroesophageal reflux （GER） insults on our own airway. Symptoms of GER are commonly seen as heartburn and regurgitation, which can be mostly tolerated. However, when the up going gastric content reversely passes the esophagus and then the distal pharynx, where it appears a beak like stricture, serving as a nozzle, so as to produce numerous micro-particles and reach the oro-nasal cavity and also the airway causing allergic rhinitis and asthmatic attacks, even pulmonary parenchyma lesions. It will reduce life quality or even jeopardize life. The point that the endogenous insult appears in the respiratory system, but originates from the digestive tract is not well known and often undiagnosed and not correctly treated. The GER induced airway challenge is a treatable and preventive entity, as soon as a diagnosis is made, a good relief could be expected by means of life style adjustment, medicine, or fixation of the patulous cardia through radiofrequency or fundoplication. The author Dr. Zhonggao Wang had suffered it for long and symptoms disappeared for 8 years after anti-reflux surgery. Here is a presentation of Dr. Zhonggao Wang and his team＇s work and would call attention to the public so as to recognize this relatively unknown entity -- a treatable condition occurring from human itself, but not from outside surroundings as smoking or haze does.

关键词： gastroesophageal reflux airway pharyngeal nozzle micro-aspiration asthma

Animal study for airway inflammation triggered by gastroesophageal reflux

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Chinese Medical Journal 2009年第22期122卷 2775-2778页

作者： LAI Yun-gang WANG Zhong-gao JI Feng WU Ji-min CHEN Xiu LI Zhen DONG Shu-kui Department of Vascular Surgery Xuanwu Hospital Capital Medical University Beijing 100053 China Center for GERD the Second Artillery General Hospipital Beijing 100088 China

Background gastroesophageal reflux disease with extra-esophageal symptoms, especially those with respiratory distress was attracting more and more attention. The related mechanisms were still in controversy. The purpose of the work was to explore airway inflammation triggered by gastroesophageal reflux. Methods Sixteen Sprague-Dawley rats were used as study group and 9 as control. In the study group, a plastic extender with a trumpet-shaped distal end was inserted into the lower esophagus to dilate the cardia, the pylorus was ligated. One ml of 0.1 mol/L hydrochloric acid was injected into the stomach. While a simple laparotomy was performed for control animals. All animals from two groups were sacrificed 24 hours after operation. Then tracheotomy was carried and the bronchoalveolar lavage fluid was collected in all animals. Cells in the fluid were counted and levels of interleukin （IL）-5, -6, -8 in it were measured. Results Compared with control group, the study group presented a neutrophil pattern of airway inflammation and an elevated concentration of IL-5, -6, -8 with no significant difference regarding eosinophil count. Conclusion The gastroesophageal reflux-triggered airway inflammation is characterized by a neutrophilic airway inflammation which differed from that caused by asthma, and enhanced levels of IL-5, -6 and -8, which are similar to that caused by asthma.

关键词： gastroesophageal reflux inflammation interleukins