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Eiamkulbutr S, Dumrisilp T, Sanpavat A, Sintusek P. Prevalence of gastroesophageal reflux disease in children with extraesophageal manifestations using combined-video, multichannel intraluminal impedance-pH study. World J Clin Pediatr 2023; 12:151-161. [PMID: 37342455 PMCID: PMC10278077 DOI: 10.5409/wjcp.v12.i3.151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/13/2023] [Accepted: 05/06/2023] [Indexed: 06/08/2023] Open
Abstract
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.
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Affiliation(s)
- Sutha Eiamkulbutr
- Department of Pediatrics, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand
| | - Termpong Dumrisilp
- Department of Pediatrics, Bhumibol Adulyadej Hospital, Bangkok 10220, Thailand
| | - Anapat Sanpavat
- Department of Pathology, Chulalongkorn University, Bangkok 10330, Thailand
| | - Palittiya Sintusek
- Thai Pediatric Gastroenterology, Hepatology and Immunology Research Unit, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Goldhaber NH, Kohn JN, Ogan WS, Sitapati A, Longhurst CA, Wang A, Lee S, Hong S, Horton LE. Deep Dive into the Long Haul: Analysis of Symptom Clusters and Risk Factors for Post-Acute Sequelae of COVID-19 to Inform Clinical Care. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:16841. [PMID: 36554723 PMCID: PMC9778884 DOI: 10.3390/ijerph192416841] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Revised: 12/07/2022] [Accepted: 12/13/2022] [Indexed: 05/13/2023]
Abstract
Long COVID is a chronic condition characterized by symptoms such as fatigue, dyspnea, and cognitive impairment that persist or relapse months after an acute infection with the SARS-CoV-2 virus. Many distinct symptoms have been attributed to Long COVID; however, little is known about the potential clustering of these symptoms and risk factors that may predispose patients to certain clusters. In this study, an electronic survey was sent to patients in the UC San Diego Health (UCSDH) system who tested positive for COVID-19, querying if patients were experiencing symptoms consistent with Long COVID. Based on survey results, along with patient demographics reported in the electronic health record (EHR), linear and logistic regression models were used to examine putative risk factors, and exploratory factor analysis was performed to determine symptom clusters. Among 999 survey respondents, increased odds of Long COVID (n = 421; 42%) and greater Long COVID symptom burden were associated with female sex (OR = 1.73, 99% CI: 1.16-2.58; β = 0.48, 0.22-0.75), COVID-19 hospitalization (OR = 4.51, 2.50-8.43; β = 0.48, 0.17-0.78), and poorer pre-COVID self-rated health (OR = 0.75, 0.57-0.97; β = -0.19, -0.32--0.07). Over one-fifth of Long COVID patients screened positive for depression and/or anxiety, the latter of which was associated with younger age (OR = 0.96, 0.94-0.99). Factor analysis of 16 self-reported symptoms suggested five symptom clusters-gastrointestinal (GI), musculoskeletal (MSK), neurocognitive (NC), airway (AW), and cardiopulmonary (CP), with older age (β = 0.21, 0.11-0.30) and mixed race (β = 0.27, 0.04-0.51) being associated with greater MSK symptom burden. Greater NC symptom burden was associated with increased odds of depression (OR = 5.86, 2.71-13.8) and anxiety (OR = 2.83, 1.36-6.14). These results can inform clinicians in identifying patients at increased risk for Long COVID-related medical issues, particularly neurocognitive symptoms and symptom clusters, as well as informing health systems to manage operational expectations on a population-health level.
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Affiliation(s)
- Nicole H. Goldhaber
- Department of Surgery, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
- Division of Biomedical Informatics, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Jordan N. Kohn
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - William Scott Ogan
- Division of Biomedical Informatics, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Amy Sitapati
- Division of Biomedical Informatics, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Christopher A. Longhurst
- Division of Biomedical Informatics, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
- Department of Pediatrics, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Angela Wang
- Division of Pulmonology, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Susan Lee
- Division of Rheumatology, Allergy, and Immunology, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
| | - Suzi Hong
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
- Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA 92093, USA
| | - Lucy E. Horton
- Division of Infectious Diseases and Global Public Health, Department of Medicine, School of Medicine, University of California San Diego, La Jolla, CA 92093, USA
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3
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Ahmad SR, Iyer VN. The Evolving Clinical Practice of Chronic Cough. Mayo Clin Proc 2022; 97:1164-1175. [PMID: 35483988 DOI: 10.1016/j.mayocp.2022.02.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/02/2021] [Revised: 12/13/2021] [Accepted: 02/09/2022] [Indexed: 11/24/2022]
Abstract
Chronic cough, defined as a cough lasting for greater than 8 weeks, accounts for a substantial number of primary care and specialist consultations in the United States. Although cough can arise from a myriad number of serious respiratory diseases, attention has traditionally focused on diagnosing and treating gastroesophageal reflux, upper airway cough syndrome, and eosinophilic airway inflammation (asthma and nonasthmatic eosinophilic bronchitis) in patients with normal chest imaging. The newly described paradigm and entity of cough hypersensitivity syndrome (CHS) becomes useful when the etiology of cough remains elusive or when the cough remains refractory despite appropriate therapy for underlying causes. We present an update on the evolving understanding of refractory chronic cough and/or unexplained chronic cough as manifestations of laryngeal hypersensitivity and CHS. This includes a focus on understanding the pathophysiology underlying current and novel therapeutics for CHS, while also ensuring that common causes of chronic cough continue to be evaluated and treated in a systematic multidisciplinary manner.
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Affiliation(s)
- Sumera R Ahmad
- Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN, USA.
| | - Vivek N Iyer
- Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, MN, USA
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Swallowing disorders after treatment for head and neck cancer. Radiol Oncol 2019; 53:225-230. [PMID: 31194691 PMCID: PMC6572490 DOI: 10.2478/raon-2019-0028] [Citation(s) in RCA: 67] [Impact Index Per Article: 11.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Accepted: 04/23/2019] [Indexed: 12/14/2022] Open
Abstract
Background Dysphagia is a common consequence of treatment for head and neck cancer (HNC). The purpose of the study was to evaluate the prevalence of dysphagia in a group of patients treated for HNC in Slovenia, and to identify factors contributing to the development of dysphagia. Patients and methods One-hundred-nine consecutive patients treated for HNC at two tertiary centers were recruited during their follow-up visits. They fulfilled EORTC QLQ-H&N35 and “Swallowing Disorders after Head and Neck Cancer Treatment questionnaire” questionnaires. Patients with dysphagia were compared to those without it. Results Problems with swallowing were identified in 41.3% of the patients. Dysphagia affected their social life (in 75.6%), especially eating in public (in 80%). Dysphagia was found the most often in the patients with oral cavity and/or oropharyngeal cancer (in 57.6%) and in those treated less than 2 years ago (p = 0.014). In univariate analysis, a significant relationship was observed between dysphagia prevalence and some of the consequences of anti-cancer treatment (impaired mouth opening, sticky saliva, loss of smell, impaired taste, oral and throat pain, persistent cough, and hoarseness), radiotherapy (p = 0.003), and symptoms of gastroesophageal reflux (p = 0.027). After multiple regression modelling only persistent cough remained. Conclusions In order to improve swallowing abilities and, consequently, quality of life of the patients with HNC a systematic rehabilitation of swallowing should be organized. A special emphasis should be given to gastroesophageal reflux treatment before, during and after therapy for HNC
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Cesario S, Scida S, Miraglia C, Barchi A, Nouvenne A, Leandro G, Meschi T, De' Angelis GL, Di Mario F. Diagnosis of GERD in typical and atypical manifestations. ACTA BIO-MEDICA : ATENEI PARMENSIS 2018; 89:33-39. [PMID: 30561415 PMCID: PMC6502210 DOI: 10.23750/abm.v89i8-s.7963] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Indexed: 12/23/2022]
Abstract
The manifestations of gastroesophageal reflux disease (GERD) have been recently classified into either esophageal or extra-esophageal syndromes. Clinical history, questionnaire data and response to antisecretory therapy are insufficient to make a conclusive diagnosis of GERD. Endoscopy had a low sensitivity. Recently, the availability of multichannel intraluminal impedance and pH-monitoring (MII-pH) has modified the diagnostic approach towards atypical manifestations of GERD. There is a rising consensus that this technique should be considered as the gold standard for GERD diagnosis. Gastrin 17 (G-17) has been proposed as a non-invasive marker of GERD, due to the negative feedback between acid and the hormone. G17 levels seem able to identify patients with acid and non-acid reflux.
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Affiliation(s)
- Silvia Cesario
- Department of Medicine and Surgery, University of Parma, Parma, Italy.
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Ioan I, Poussel M, Coutier L, Plevkova J, Poliacek I, Bolser DC, Davenport PW, Derelle J, Hanacek J, Tatar M, Marchal F, Schweitzer C, Fontana G, Varechova S. What is chronic cough in children? Front Physiol 2014; 5:322. [PMID: 25221517 PMCID: PMC4148026 DOI: 10.3389/fphys.2014.00322] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2014] [Accepted: 08/05/2014] [Indexed: 01/28/2023] Open
Abstract
The cough reflex is modulated throughout growth and development. Cough—but not expiration reflex—appears to be absent at birth, but increases with maturation. Thus, acute cough is the most frequent respiratory symptom during the first few years of life. Later on, the pubertal development seems to play a significant role in changing of the cough threshold during childhood and adolescence resulting in sex-related differences in cough reflex sensitivity in adulthood. Asthma is the major cause of chronic cough in children. Prolonged acute cough is usually related to the long-lasting effects of a previous viral airway infection or to the particular entity called protracted bacterial bronchitis. Cough pointers and type may orient toward specific etiologies, such as barking cough in croup or tracheomalacia, paroxystic whooping cough in Pertussis. Cough is productive in protracted bacterial bronchitis, sinusitis or bronchiectasis. Cough is usually associated with wheeze or dyspnea on exertion in asthma; however, it may be the sole symptom in cough variant asthma. Thus, pediatric cough has particularities differentiating it from adult cough, so the approach and management should be developmentally specific.
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Affiliation(s)
- Iulia Ioan
- Service D'explorations Fonctionnelles Pédiatriques, Hôpital D'enfants Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France
| | - Mathias Poussel
- Service Des Examens de la Fonction Respiratoire et de L'aptitude à L'exercice Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France ; EA 3450 DevAH - Laboratoire de Physiologie, Faculté de Médecine, Université Lorraine Vandoeuvre, France
| | - Laurianne Coutier
- EA 3450 DevAH - Laboratoire de Physiologie, Faculté de Médecine, Université Lorraine Vandoeuvre, France
| | - Jana Plevkova
- Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University Martin, Slovakia
| | - Ivan Poliacek
- Institute of Medical Biophysics, Jessenius Faculty of Medicine, Comenius University Martin, Slovakia
| | - Donald C Bolser
- Department of Physiological Sciences, University of Florida Gainesville, FL, USA
| | - Paul W Davenport
- Department of Physiological Sciences, University of Florida Gainesville, FL, USA
| | - Jocelyne Derelle
- Service de Médecine Infantile et de Génétique Clinique, Hôpital D'enfants Vandœuvre-lès-Nancy, France
| | - Jan Hanacek
- Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University Martin, Slovakia
| | - Milos Tatar
- Department of Pathophysiology, Jessenius Faculty of Medicine, Comenius University Martin, Slovakia
| | - François Marchal
- Service D'explorations Fonctionnelles Pédiatriques, Hôpital D'enfants Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France ; EA 3450 DevAH - Laboratoire de Physiologie, Faculté de Médecine, Université Lorraine Vandoeuvre, France
| | - Cyril Schweitzer
- Service D'explorations Fonctionnelles Pédiatriques, Hôpital D'enfants Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France ; EA 3450 DevAH - Laboratoire de Physiologie, Faculté de Médecine, Université Lorraine Vandoeuvre, France ; Service de Médecine Infantile et de Génétique Clinique, Hôpital D'enfants Vandœuvre-lès-Nancy, France
| | - Giovanni Fontana
- Department of Internal Medicine, University of Florence Florence, Italy
| | - Silvia Varechova
- Service D'explorations Fonctionnelles Pédiatriques, Hôpital D'enfants Centre Hospitalier Universitaire de Nancy, Vandoeuvre les Nancy, France ; EA 3450 DevAH - Laboratoire de Physiologie, Faculté de Médecine, Université Lorraine Vandoeuvre, France
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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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Nilius B, Szallasi A. Transient receptor potential channels as drug targets: from the science of basic research to the art of medicine. Pharmacol Rev 2014; 66:676-814. [PMID: 24951385 DOI: 10.1124/pr.113.008268] [Citation(s) in RCA: 377] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2025] Open
Abstract
The large Trp gene family encodes transient receptor potential (TRP) proteins that form novel cation-selective ion channels. In mammals, 28 Trp channel genes have been identified. TRP proteins exhibit diverse permeation and gating properties and are involved in a plethora of physiologic functions with a strong impact on cellular sensing and signaling pathways. Indeed, mutations in human genes encoding TRP channels, the so-called "TRP channelopathies," are responsible for a number of hereditary diseases that affect the musculoskeletal, cardiovascular, genitourinary, and nervous systems. This review gives an overview of the functional properties of mammalian TRP channels, describes their roles in acquired and hereditary diseases, and discusses their potential as drug targets for therapeutic intervention.
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Affiliation(s)
- Bernd Nilius
- KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research, Campus Gasthuisberg, Leuven, Belgium (B.N.); and Department of Pathology, Monmouth Medical Center, Long Branch, New Jersey (A.S.)
| | - Arpad Szallasi
- KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Ion Channel Research, Campus Gasthuisberg, Leuven, Belgium (B.N.); and Department of Pathology, Monmouth Medical Center, Long Branch, New Jersey (A.S.)
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Harding SM, Allen JE, Blumin JH, Warner EA, Pellegrini CA, Chan WW. Respiratory manifestations of gastroesophageal reflux disease. Ann N Y Acad Sci 2013; 1300:43-52. [PMID: 24117633 DOI: 10.1111/nyas.12231] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gastroesophageal reflux disease (GERD) is highly associated with a range of respiratory symptoms, arising from a variety of etiologies. The following commentaries on respiratory manifestations of GERD address evidence for a role of a vagally mediated bronchoconstriction reflex in the development of asthma; the direct effects of airway obstruction on lower esophageal sphincter (LES) pressure and reflux episodes; the mechanisms by which reflux may play roles in chronic cough and airway stenosis; the limited efficacy of laparoscopic antireflux surgery (LARS) in improving GERD-related respiratory symptoms; the search for a marker for microaspiration and reflux-induced airway disease; and the potential of proton pump inhibitor (PPI) treatment for patients presenting with asthma and GERD.
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Affiliation(s)
- Susan M Harding
- Department of Medicine/Pulmonary Allergy & Critical Care, University of Alabama at Birmingham, Birmingham, Alabama
| | - Jacqui E Allen
- Department of Otolaryngology, Northshore Hospital, Auckland, New Zealand
| | - Joel H Blumin
- Division of Laryngology & Professional Voice, Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin
| | | | | | - Walter W Chan
- Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Homen's Hospital, Harvard Medical School, Cambridge, Massachusetts
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Mandal P, Morice AH, Chalmers JD, Hill AT. Symptoms of airway reflux predict exacerbations and quality of life in bronchiectasis. Respir Med 2013; 107:1008-13. [PMID: 23683772 DOI: 10.1016/j.rmed.2013.04.006] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2012] [Revised: 03/30/2013] [Accepted: 04/05/2013] [Indexed: 12/11/2022]
Abstract
AIM We have explored the association of the upper airway symptoms related to cough with exacerbation frequency, sputum microbiology and inflammatory markers in patients with non cystic fibrosis bronchiectasis. METHODS Patients with bronchiectasis completed the Hull Airway Reflux Questionnaire (HARQ). A score of >13 was taken to indicate the presence of reflux. Patients were followed-up with longitudinal spirometry, sputum culture and Leicester cough questionnaire (LCQ). Myeloperoxidase (MPO), free neutrophil elastase (NE) activity, Interleukin (IL)-8 and Tumour Necrosis Factor (TNF)-α was measured from spontaneous sputum samples. RESULTS 163 completed the study. 59.5% were female. Mean age was 65.7 years. 73.6% reported airway reflux using HARQ. Patients with airway reflux had more severe cough symptoms as assessed by the LCQ [15.2 (3.5) vs. 19.4 (1.9)], p < 0.001. Sputum levels of MPO, NE, IL-8 and TNF-α were all significantly higher in the reflux positive group (p < 0.05 for all comparisons). In a multivariable logistic regression, airway reflux was independently associated with cough severity (-3.27, standard error 0.81, p = 0.0002). Airway reflux, age, FEV1 % predicted and colonization with Pseudomonas aeruginosa were independently associated with an increased risk of ≥3 bronchiectasis exacerbations in one year. CONCLUSION The symptoms of airway reflux independently predict severity and exacerbation frequency in non cystic fibrosis bronchiectasis.
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Affiliation(s)
- P Mandal
- Centre for Inflammation Research, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
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Abstract
It is increasingly accepted that the effects of gastro-oesophageal reflux are not limited to the gastrointestinal tract. The adjacent respiratory structures are also at risk from material ejected from the proximal oesophagus as a result of the failure of anatomical and physiological barriers. There is evidence of the influence of reflux on several respiratory and otorhinological conditions and although in many cases the precise mechanism has yet to be elucidated, the association alone opens potential novel avenues of therapy to clinicians struggling to treat patients with apparently intractable respiratory complaints. This review provides a description of the airway reflux syndrome, its effects on the lung and current and future therapeutic options.
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Affiliation(s)
- Ian D Molyneux
- Cardiovascular and Respiratory Studies, Hull York Medical School, University of Hull, Castle Hill Hospital, Cottingham, UK
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Wang YT, Yazaki E, Sifrim D. High-resolution Manometry: Esophageal Disorders Not Addressed by the "Chicago Classification". J Neurogastroenterol Motil 2012; 18:365-72. [PMID: 23105996 PMCID: PMC3479249 DOI: 10.5056/jnm.2012.18.4.365] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2012] [Revised: 09/22/2012] [Accepted: 09/28/2012] [Indexed: 12/16/2022] Open
Abstract
The development of the high-resolution esophageal manometry (HRM) and the Chicago classification have improved the diagnosis and management of esophageal motility disorders. However, some conditions have yet to be addressed by this classification. This review describes findings in HRM which are not included in the current Chicago classification based on the experience in our center. This includes the analysis of the upper esophageal sphincter, proximal esophagus, longitudinal muscle contraction, disorders related to gastroesophageal reflux disease and respiratory symptoms. The utility of provocative tests and the use of HRM in the evaluation of rumination syndrome and post-surgical patients will also be discussed. We believe that characterization of the manometric findings in these areas will eventually lead to incorporation of new criteria into the existing classification.
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Affiliation(s)
- Yu Tien Wang
- Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom
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de Bortoli N, Nacci A, Savarino E, Martinucci I, Bellini M, Fattori B, Ceccarelli L, Costa F, Mumolo MG, Ricchiuti A, Savarino V, Berrettini S, Marchi S. How many cases of laryngopharyngeal reflux suspected by laryngoscopy are gastroesophageal reflux disease-related? World J Gastroenterol 2012; 18:4363-70. [PMID: 22969200 PMCID: PMC3436052 DOI: 10.3748/wjg.v18.i32.4363] [Citation(s) in RCA: 121] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Revised: 08/15/2012] [Accepted: 08/18/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the prevalence of gastroesophageal reflux disease (GERD) in patients with a laryngoscopic diagnosis of laryngopharyngeal reflux (LPR).
METHODS: Between May 2011 and October 2011, 41 consecutive patients with laryngopharyngeal symptoms (LPS) and laryngoscopic diagnosis of LPR were empirically treated with proton pump inhibitors (PPIs) for at least 8 wk, and the therapeutic outcome was assessed through validated questionnaires (GERD impact scale, GIS; visual analogue scale, VAS). LPR diagnosis was performed by ear, nose and throat specialists using the reflux finding score (RFS) and reflux symptom index (RSI). After a 16-d wash-out from PPIs, all patients underwent an upper endoscopy, stationary esophageal manometry, 24-h multichannel intraluminal impedance and pH (MII-pH) esophageal monitoring. A positive correlation between LPR diagnosis and GERD was supposed based on the presence of esophagitis (ERD), pathological acid exposure time (AET) in the absence of esophageal erosions (NERD), and a positive correlation between symptoms and refluxes (hypersensitive esophagus, HE).
RESULTS: The male/female ratio was 0.52 (14/27), the mean age ± SD was 51.5 ± 12.7 years, and the mean body mass index was 25.7 ± 3.4 kg/m2. All subjects reported one or more LPS. Twenty-five out of 41 patients also had typical GERD symptoms (heartburn and/or regurgitation). The most frequent laryngoscopic findings were posterior laryngeal hyperemia (38/41), linear indentation in the medial edge of the vocal fold (31/41), vocal fold nodules (6/41) and diffuse infraglottic oedema (25/41). The GIS analysis showed that 10/41 patients reported symptom relief with PPI therapy (P < 0.05); conversely, 23/41 did not report any clinical improvement. At the same time, the VAS analysis showed a significant reduction in typical GERD symptoms after PPI therapy (P < 0.001). A significant reduction in LPS symptoms. On the other hand, such result was not recorded for LPS. Esophagitis was detected in 2/41 patients, and ineffective esophageal motility was found in 3/41 patients. The MII-pH analysis showed an abnormal AET in 5/41 patients (2 ERD and 3 NERD); 11/41 patients had a normal AET and a positive association between symptoms and refluxes (HE), and 25/41 patients had a normal AET and a negative association between symptoms and refluxes (no GERD patients). It is noteworthy that HE patients had a positive association with typical GERD-related symptoms. Gas refluxes were found more frequently in patients with globus (29.7 ± 3.6) and hoarseness (21.5 ± 7.4) than in patients with heartburn or regurgitation (7.8 ± 6.2). Gas refluxes were positively associated with extra-esophageal symptoms (P < 0.05). Overall, no differences were found among the three groups of patients in terms of the frequency of laryngeal signs. The proximal reflux was abnormal in patients with ERD/NERD only. The differences observed by means of MII-pH analysis among the three subgroups of patients (ERD/NERD, HE, no GERD) were not demonstrated with the RSI and RFS. Moreover, only the number of gas refluxes was found to have a significant association with the RFS (P = 0.028 and P = 0.026, nominal and numerical correlation, respectively).
CONCLUSION: MII-pH analysis confirmed GERD diagnosis in less than 40% of patients with previous diagnosis of LPR, most likely because of the low specificity of the laryngoscopic findings.
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Tolone S, Del Genio G, Docimo G, Brusciano L, del Genio A, Docimo L. Objective outcomes of extra-esophageal symptoms following laparoscopic total fundoplication by means of combined multichannel intraluminal impedance pH-metry before and after surgery. Updates Surg 2012; 64:265-71. [PMID: 22875788 DOI: 10.1007/s13304-012-0171-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2011] [Accepted: 07/26/2012] [Indexed: 12/13/2022]
Abstract
Identifying and treating patients with extra-esophageal symptoms is a challenge. When the patient is unable to control his symptoms with pharmacological therapy alone, anti-reflux surgery may be indicated. This study aims to evaluate the outcomes of total fundoplication in the resolution of extra-esophageal manifestations and verify changes in 24-h MII-pH monitoring before and after surgery. From October 2005 to October 2010, patients who reported respiratory symptoms, possibly related to GERD, have been sent to our Institute. All patients were practiced ambulatory 24-h MII-pH before and after surgery. Thirty-five patients selected for the antireflux surgery have undergone all the same surgical procedures. Data were collected prospectively at 6 and 12 months after laparoscopic fundoplication. After laparoscopic fundoplication, the total percentage of exposure time with esophageal pH < 4, and both in upright and supine position was very low. A statistically significant difference (p < 0.05) was found in the number of detected refluxes at MII and detected refluxes at MII 15-cm segment in pre and post-operative period. Symptom relief was obtained in all patients. Laparoscopic fundoplication is a safe and effective procedure to protect from refractory GERD and extra-esophageal symptoms, when evaluated with a thorough pre-operative selection.
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Affiliation(s)
- Salvatore Tolone
- Division of General and Obesity Surgery, Department of Surgery, Second University of Naples, Via Pansini, 5, 80131, Naples, Italy.
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Brown SR, Gyawali CP, Melman L, Jenkins ED, Bader J, Frisella MM, Brunt LM, Eagon JC, Matthews BD. Clinical outcomes of atypical extra-esophageal reflux symptoms following laparoscopic antireflux surgery. Surg Endosc 2011; 25:3852-8. [PMID: 21717265 DOI: 10.1007/s00464-011-1806-y] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2010] [Accepted: 02/21/2011] [Indexed: 01/27/2023]
Abstract
INTRODUCTION While it is well established that antireflux surgery is effective in relieving typical gastroesophageal reflux disease (GERD) symptoms such as heartburn and regurgitation, it is currently unclear whether atypical symptoms (cough, hoarseness, wheeze) foreshadow a less satisfactory outcome following laparoscopic antireflux surgery (LARS). The purpose of this study is to critically analyze the clinical outcomes of atypical symptoms in patients undergoing LARS. METHODS Patients scheduled for LARS for GERD were prospectively enrolled over a 7-year period; all subjects underwent preoperative high-resolution manometry (HRM) and had evidence of GERD on ambulatory pH study. Cough, wheeze, and hoarseness were considered atypical symptoms. During preoperative and postoperative examinations, patients completed detailed foregut symptomatology questionnaires, using both 5-point Likert and 10-point visual analog scales (VAS) to document typical as well as atypical symptoms. Atypical symptom burden was calculated as a sum of VAS for the three atypical symptoms, termed the atypical score (ATS). HRM patterns were grouped into normal, spastic, and hypomotile. Statistical significance (p < 0.05) was determined using paired t-test, and analysis of variance with post hoc least significant difference (LSD). RESULTS One hundred thirteen patients (age 49 ± 1.26 years, range 20-84 years, M:F 47:66) with mean follow-up of 28 ± 2.31 months (range 1-92 months) fulfilled inclusion criteria, having mean modified DeMeester score of 45.5 ± 2.78. Heartburn was noted in 84.1%, while atypical symptoms of some degree were reported by 92.0% (104 patients). Heartburn improved from a preoperative score of 7.1 ± 0.54 to 0.9 ± 0.24 after LARS, and ATS improved from 8.9 ± 0.71 to 2.2 ± 0.42. Significant improvements were noted for all atypical symptoms analyzed (p < 0.0001 for each). Improvement in atypical symptoms was least in the presence of hypomotility features on HRM (21.7% improvement), compared with normal motility (72.4%) and spastic features (83.9%). Preoperative atypical score (p < 0.0001) and esophageal hypomotility (p = 0.04) demonstrated a linear relationship with postoperative atypical score. CONCLUSIONS In an unselected cohort of patients undergoing LARS, atypical GERD symptoms improved as significantly as typical symptoms. Symptom improvement was significantly lower in the presence of esophageal hypomotility and with higher symptomatic state. Therefore, patients with severe atypical symptoms or hypomotile esophagus may not achieve the same clinical satisfaction from LARS.
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Affiliation(s)
- Shaun R Brown
- Section of Minimally Invasive Surgery, Department of Surgery, Washington University School of Medicine, 660 South Euclid Avenue, Campus Box 8109, St. Louis, MO 63110, USA
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Dicpinigaitis PV. Cough: an unmet clinical need. Br J Pharmacol 2011; 163:116-24. [PMID: 21198555 PMCID: PMC3085873 DOI: 10.1111/j.1476-5381.2010.01198.x] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2010] [Revised: 11/20/2010] [Accepted: 11/23/2010] [Indexed: 12/13/2022] Open
Abstract
Cough is among the most common complaints for which patients worldwide seek medical attention. Thus, the evaluation and treatment of cough result in tremendous financial expenditure and consumption of health care resources. Yet, despite the clinical significance of cough, research efforts aimed at improving diagnostic capabilities and developing more effective therapeutic agents have been, to date, disappointing in their limited scope and outcomes. Acute cough due to the common cold represents the most common type of cough. Currently, available medications for the symptomatic management of acute cough are inadequate due to lack of proven efficacy and/or their association with undesirable or intolerable side effects at anti-tussive doses. Subacute cough, often representing a prolonged post-viral response, is typically refractory to standard anti-tussive therapy. Few clinical trials have evaluated therapeutic options for subacute cough. Diagnostic challenges facing the clinician in the management of chronic cough include the determination of whether symptoms of upper airway cough syndrome (formerly, postnasal drip syndrome) or gastro-oesophageal reflux disease are indeed the underlying cause of cough. Chronic, refractory unexplained (formerly, idiopathic) cough must be distinguished from cough that has not been fully evaluated and treated according to current guideline recommendations. Eagerly awaited are new safe and effective anti-tussive agents for use when cough suppression is desired, regardless of underlying aetiology of cough, as well as practical, validated ambulatory cough counters to aid clinical assessment and future research in the field of cough.
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Affiliation(s)
- Peter V Dicpinigaitis
- Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10461, USA.
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Pacheco-Galván A, Hart SP, Morice AH. Relationship between gastro-oesophageal reflux and airway diseases: the airway reflux paradigm. Arch Bronconeumol 2011; 47:195-203. [PMID: 21459504 DOI: 10.1016/j.arbres.2011.02.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2011] [Revised: 02/02/2011] [Accepted: 02/04/2011] [Indexed: 12/21/2022]
Abstract
Our understanding of the relationship between gastro-oesophageal reflux and respiratory disease has recently undergone important changes. The previous paradigm of airway reflux as synonymous with the classic gastro-oesophageal reflux disease (GORD) causing heartburn has been overturned. Numerous epidemiological studies have shown a highly significant association of the acid, liquid, and gaseous reflux of GORD with conditions such as laryngeal diseases, chronic rhinosinusitis, treatment resistant asthma, COPD and even idiopathic pulmonary fibrosis. However, it has become clear from studies on cough hypersensitivity syndrome that much reflux of importance in the airways has been missed, since it is either non- or weakly acid and gaseous in composition. The evidence for such a relationship relies on the clinical history pointing to symptom associations with known precipitants of reflux. The tools for the diagnosis of extra-oesophageal reflux, in contrast to the oesophageal reflux of GORD, lack sensitivity and reproducibility. Unfortunately, methodology for detecting such reflux is only just becoming available and much additional work is required to properly delineate its role.
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Affiliation(s)
- Adalberto Pacheco-Galván
- Servicio de Neumología, Unidad de Asma y Tos de Difícil Manejo, Hospital Ramón y Cajal, Madrid, Spain.
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Relationship Between Gastro-Oesophageal Reflux and Airway Diseases: The Airway Reflux Paradigm. ACTA ACUST UNITED AC 2011. [DOI: 10.1016/s1579-2129(11)70046-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Damsch S, Eichenbaum G, Tonelli A, Lammens L, Van den Bulck K, Feyen B, Vandenberghe J, Megens A, Knight E, Kelley M. Gavage-related reflux in rats: identification, pathogenesis, and toxicological implications (review). Toxicol Pathol 2010; 39:348-60. [PMID: 21422261 DOI: 10.1177/0192623310388431] [Citation(s) in RCA: 70] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
After oral gavage dosing of rats, reflux may occur, resulting in serious respiratory effects and mortality. Published information on gavage-related reflux is limited, as it has not yet been a focus of research. Nevertheless, it represents a recurrent challenge in daily toxicology practice of oral gavage dosing. The absence of clear guidance and criteria for the identification and management of reflux-induced effects can limit the ability to properly interpret toxicity study results. The review presented herein includes an overview of experimental data from gavage studies in rats, in which reflux was observed, and provides a comprehensive analysis of the literature on reflux in general and the different potential pathways contributing to gavage-related reflux in rats. The article aims to increase the awareness and understanding of the pathogenesis of gavage-related reflux and provides guidance on identification of potential risk factors, as well as interpretation of histological changes and their toxicological relevance. Furthermore, differentiation of reflux-induced effects from direct compound-related toxicity and from gavage errors is addressed in particular, and the importance of nasal histology is discussed.
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Affiliation(s)
- Siegrid Damsch
- Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium.
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Damsch S, Eichenbaum G, Looszova A, Lammens L, Feyen B, Van den Bulck K, Knight E, Kelley M, Tonelli A. Unexpected nasal changes in rats related to reflux after gavage dosing. Toxicol Pathol 2010; 39:337-47. [PMID: 21422260 DOI: 10.1177/0192623310388430] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
In a three-week oral gavage toxicity study in rats, a high incidence of respiratory symptoms and high mortality was noted in compound-dosed rats only. Because of audible respiration, an effect in the upper respiratory tract was suspected and the nasal cavity was included for examination. Histology revealed extensive necrosis and purulent inflammation within the nasal passages, indicative of direct irritation. Since posterior nasal regions were most affected, with food material present within the inflammatory exudates, reflux and retrograde aspiration of irritant material (possibly stomach contents with test formulation) into the nasal cavity were suspected. Lowering the dose volume and fasting the rats prior to gavage dosing substantially reduced the respiratory effects and mortality. The current article focuses on the histological changes in the nasal cavity indicative of gavage-related reflux and provides guidance on differentiation between technical gavage error and gavage-related reflux.
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Affiliation(s)
- Siegrid Damsch
- Johnson & Johnson Pharmaceutical Research and Development, Beerse, Belgium.
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DiMango E, Holbrook JT, Simpson E, Reibman J, Richter J, Narula S, Prusakowski N, Mastronarde JG, Wise RA. Effects of asymptomatic proximal and distal gastroesophageal reflux on asthma severity. Am J Respir Crit Care Med 2009; 180:809-16. [PMID: 19661245 DOI: 10.1164/rccm.200904-0625oc] [Citation(s) in RCA: 40] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
RATIONALE Silent gastroesophageal reflux (GER) is common in patients with asthma, but it is unclear whether GER is associated with worse asthma symptoms or reduced lung function. OBJECTIVES To determine in patients with poorly controlled asthma, whether proximal or distal esophageal reflux is associated with asthma severity, symptoms, physiology, or functional status. METHODS Baseline asthma characteristics were measured in patients with asthma enrolled in a multicenter trial assessing the effectiveness of esomeprazole on asthma control. All participants underwent 24-hour esophageal pH probe monitoring. Lung function, methacholine responsiveness, asthma symptoms, and quality-of-life scores were compared in subjects with and without GER. MEASUREMENTS AND MAIN RESULTS Of 304 participants with probe recordings, 53% had reflux. Of 242 participants with recordings of proximal pH, 38% had proximal reflux. There was no difference in need for short-acting bronchodilators, nocturnal awakenings, dose of inhaled corticosteroid, use of long-acting beta-agonists, lung function, or methacholine reactivity between individuals with and without proximal or distal GER. Participants with GER reported more use of oral corticosteroids and had worse asthma quality of life and subjects with proximal GER had significantly worse asthma quality of life and health-related quality of life compared with participants without GER. CONCLUSIONS Asymptomatic GER is not associated with distinguishing asthma symptoms or lower lung function in individuals with suboptimal asthma control who are using inhaled corticosteroids. Patients with proximal reflux report significantly worse asthma and health-related quality of life despite lack of physiologic impairment or increase in asthma symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT00069823).
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Affiliation(s)
- Emily DiMango
- Columbia University, College of Physicians and Surgeons, New York, New York, USA.
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