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D. de Raucourt, P.-Y. Salaun, J.-C. Ferrié, Sébastien Vergez, F. Dubrulle, Dominique Chevalier, E. de Monès, Michel Lapeyre, Sylvain Morinière, B. Barry, Stéphane Temam, Philippe Schultz, F. Lagarde, C. Bertolus, S. Tronche, Service d'ORL, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Department of Maxillofacial Surgery, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Department of Nuclear Medicine, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Service de Radiologie (LILLE - Radio), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Radiologie (POITIERS - Radio), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Institut Gustave Roussy (IGR), Service d'ORL et de Chirurgie Cervico-Faciale (LILLE - ORL et CCF), Department of Head and Neck Surgery, Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service d'ORL et de Chirurgie Cervico-Faciale (ORLEANS - ORL et CCF), Centre Hospitalier Régional d'Orléans (CHRO), Service d'ORL et de Chirurgie Cervico-Faciale (STRASBOURG - ORL et CCF), CHU Strasbourg, Service de Radiothérapie (CLERMONT FERRAND - Radiothérapie), CHU Clermont-Ferrand, Service d'ORL et de Chirurgie Cervico-Faciale (PARIS - BICHAT - ORL et CCF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), SFORL (SFORL), SFORL, Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'ORL et de Chirurgie Cervico-Faciale (TOURS - ORL et CCF), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Chirurgie Maxillo-Faciale ( PARIS - PSL - Chir Maxillo-Faciale ), Assistance publique - Hôpitaux de Paris (AP-HP), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Service de Radiologie ( LILLE - Radio ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de Radiologie ( POITIERS - Radio ), CHU de Poitiers, Département de cancérologie cervico-faciale [Gustave Roussy] ( CCF ), Institut Gustave Roussy ( IGR ), Service d'ORL et de Chirurgie Cervico-Faciale ( LILLE - ORL et CCF ), University Hospital Rangueil-Larrey, Service d'ORL et de Chirurgie Cervico-Faciale ( ORLEANS - ORL et CCF ), Centre Hospitalier Régional d'Orléans ( CHR ), Service d'ORL et de Chirurgie Cervico-Faciale ( STRASBOURG - ORL et CCF ), Service de Radiothérapie ( CLERMONT FERRAND - Radiothérapie ), Service d'ORL et de Chirurgie Cervico-Faciale ( PARIS - BICHAT - ORL et CCF ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], SFORL ( SFORL ), Service d'ORL et de Chirurgie Cervico-Faciale ( CAEN - ORL et CCF ), CHU Caen, Service d'ORL et de Chirurgie Cervico-Faciale ( TOURS - ORL et CCF ), and CHRU Tours

Francois Bobin, Jerome R. Lechien, Mihaela Horoi, Alexandra Rodriguez, Camille Finck, Marie Paule Thill, Sven Saussez, Vinciane Muls, Didier Dequanter, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), SFORL (SFORL), SFORL, ELSAN-Polyclinique de Poitiers, International Business Machines Corporation, IBM BE076201837630, Patients with LPR symptoms and signs were enrolled from three European hospitals (University Hospital Center Saint-Pierre, Cesar De Paepe Hospital, Brussels, Belgium, Elsan Private Hospital of Poitiers, Poitiers, France) from January 2018 to June 2019. The LPR diagnostic was based on the occurrence of one or more acid or nonacid hypopharyngeal reflux episodes at the HEMII-pH.8 Elderly patients (?60 years old) and those with gastrointestinal (GI) symptoms benefited from GI endoscopy for excluding esophagitis. Patients with the following conditions were excluded: smoker, alcohol dependence, pregnancy, neurological or psychiatric illness, upper respiratory tract infection within the last month, current use of antireflux treatment, previous history of neck surgery or trauma, benign vocal fold lesions, malignancy, history of ear, nose, and throat radiotherapy, and active seasonal allergies or asthma. The local ethics committee approved the study protocol (CHU Saint-Pierre, Universit? Libre de Bruxelles (ULB), No. BE076201837630). Patients were invited to participate, and informed consent was obtained. Patients with LPR symptoms and signs were enrolled from three European hospitals (University Hospital Center Saint-Pierre, Cesar De Paepe Hospital, Brussels, Belgium, Elsan Private Hospital of Poitiers, Poitiers, France) from January 2018 to June 2019. The LPR diagnostic was based on the occurrence of one or more acid or nonacid hypopharyngeal reflux episodes at the HEMII-pH.8 Elderly patients (?60 years old) and those with gastrointestinal (GI) symptoms benefited from GI endoscopy for excluding esophagitis. Patients with the following conditions were excluded: smoker, alcohol dependence, pregnancy, neurological or psychiatric illness, upper respiratory tract infection within the last month, current use of antireflux treatment, previous history of neck surgery or trauma, benign vocal fold lesions, malignancy, history of ear, nose, and throat radiotherapy, and active seasonal allergies or asthma. The characteristics of the HEMII-pH device, placement, and analyses have been described in previous publications.9,10 In summary, eight impedance segments and two pH electrodes composed the HEMII-pH (Versaflex Z, Digitrapper pH-Z Testing System, Medtronic, Minneapolis, MN). The impedance segments were placed along the esophagus zones (Z1 to Z6, centered at 19, 17, 11, 9, 7, and 5 cm above the lower esophagus sphincter (LES)). Two additional impedance segments were placed 1 and 2 cm above the upper esophagus sphincter (UES) in the hypopharynx. The pH electrodes were placed 2 cm above LES and 1?2 cm below the UES, respectively. A proximal/hypopharyngeal reflux event consisted of an episode reaching two impedance sensors in the hypopharynx. An acid reflux episode consisted of an episode with pH ? 4.0. A nonacid reflux episode consisted of an episode with pH > 4.0. The device was placed in the morning (8:00 a.m.), and was removed the next morning (8:00 a.m.). The patients collected three saliva samples, respectively, in the morning (fasting), and 1 to 2 hours after lunch and dinner, during 24-hour HEMII-pH testing. Patients carefully detailed foods and beverages consumed during the meals before the saliva sample collection. The saliva sample was collected into a 30-mL universal sample collection tube containing citric acid for preserving the action of any pepsin present. The saliva samples were stored in a refrigerator after the collection. The measurement of saliva pepsin level was performed through the Peptest device (RD Biomed, Hull, United Kingdom) by a trained lab technician. The steps of pepsin measurement were performed in a standardized procedure, which has been previously described.9 The saliva pepsin concentration was measured using the Cube Reader (RD Biomed, Hull, United Kingdom), which detects pepsin down to 16 ng/mL. If the results did not reach 16 ng/mL, the test was considered negative. The therapeutic algorithm was based on recent recommendations of the LPR Study Group of Young Otolaryngologists of the International Federation of Oto-Rhino-Laryngological Societies.1 Based on the HEMII-pH characteristics of LPR (daytime, nighttime, acid, nonacid, or mixed LPR), patients received a personalized therapeutic scheme associating diet, behavioral changes, and use of proton pump inhibitors (PPIs) (pantoprazole) ? alginate (Gaviscon Advance, Reckitt Benckiser, Slough, United Kingdom) ? magaldrate (Riopan, Takeda, Zaventem, Belgium) for 3 months. Medication intake was evaluated posttreatment through a visual analog scale ranging from 0 (?I did not take the medication?) to 10 (?I never forgot the medication?). Patients who did not take medication were excluded. Symptoms and findings were assessed from pre- to posttreatment with the Reflux Symptom Score (RSS)10 and Reflux Sign Assessment (RSA).11 The RSS is a 22-item, validated patient-reported outcome questionnaire assessing frequency, severity, and the impact of LPR symptoms on quality of life (Fig. 1).10 The RSA is a validated finding score rating both laryngeal and extralaryngeal signs associated with reflux (Fig. 2).11 The RSA was rated by three blinded laryngologists (j.r.l., f.b., c.f.) regarding the pre- to posttreatment status (videolaryngostroboscopy recordings and oral cavity photos). At the first consultation, patients were invited to report their diet habits through two standardized diet grids describing both foods and beverages usually consumed in Western Europe (Tables I and II).12 Western European foods and beverages were classified in five categories from ?very low refluxogenic food/beverage? (category 1) to ?very high refluxogenic food/beverage? (category 5). This classification of foods and beverages was based on the calculation of a score assessing the refluxogenic potential of foods and beverages (Refluxogenic Diet Score [REDS]). The REDS considers pH, fat, protein, sugar composition, and other specific factors.12 From the patient anamnesis, the authors calculated the Global Refluxonic Score (GRES), which consists of the addition of REDS of foods and beverages that have been consumed by patients over the past 2 weeks. The refluxogenic potential of foods and beverages that have been consumed during the 24-hour HEMII-pH testing (and before the saliva sample collections) was evaluated through the Refluxogenic Score of a Dish (RESDI), which consists of the weighted sum of the REDS of foods and beverages consumed during a meal.12 The RESDI may be calculated as absolute (sum of all RESDIs of the testing period) or mean (mean of all RESDIs of the testing period). At the end of the consultation, patients received a personalized diet grid identifying the foods and beverages to avoid (i.e., a diet therapeutic scheme). In practice, based on this table, laryngopharyngeal reflux patients selected the foods and beverages that they consumed once or more over the past 2 weeks, and the physician may add the categories corresponding of the consumed foods or beverages to get a score, called the Global Reflux Score. Several foods may be upgraded or downgraded according to characteristics. Raw vegetables are less digestible and may be associated with low gastric emptying time, in case of raw consumption, the food has to be upgraded 1 category. Except for green salad, the addition of vinegar or vinaigrette upgrades the category. In cases of the addition of spicy (for example, spicy ketchup), these foods have to be upgraded. For sugar, only the pH and the glycemic index have been considered regarding the lack of fat. Because spicy has no lipid and no pH, the authors based the classification of this food on the literature. If the patients only eat industrial foods (ready-made food), the foods may be upgraded regarding the acidifying potential of industrial conservative. REDS = Refluxogenic Diet Score. In practice, based on this table, laryngopharyngeal reflux patients selected the foods and beverages that they consume once or more over the past 2 weeks and the physician may add the categories corresponding of the consumed foods or beverages to get a score, called the Global Reflux Score. The classification of beverages depends on pH. For hot chocolate, the category is upgraded for additional sugar. GI high sugar-related osmolarity. The alcohol degree (>3% = upgrade). Sparkling (upgrade). Presence or lack of caffeine or theine (upgrade or downgrade). + beverage exhibits a GI>40. Cat. = category at baseline, GI = glycemic index, UCat. = upgraded category. Statistical analyses were performed using the Statistical Package for the Social Sciences for Windows (SPSS version 22.0, and IBM, Armonk, NY). The relationship between GRES, RESDI of meals preceding the saliva pepsin collection, HEMII-pH findings, pre- and posttreatment RSS, and RSA was analyzed through multiple linear regression. Pre- to posttreatment changes in RSS, RSA, and GRES were evaluated using the Wilcoxon signed rank test. A level of significance of P <.05 was used.

Lise Crevier-Buchman, Erwan de Mones, Marta P. Circiu, Jerome R. Lechien, Lea Distinguin, Stéphane Hans, Younes Chekkoury Idrissi, Daniel Brasnu, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Bordeaux (UB), Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), SFORL (SFORL), and SFORL

Duino Meucci, Carlos M. Chiesa-Estomba, Shazia Peer, Christian Calvo-Henriquez, Maria Rosaria Barillari, Jerome R. Lechien, Sven Saussez, Antonio Schindler, Fairouz Ben Abdelouahed, Marilena Trozzi, Lechien, J. R., CALVO-HENRIQUEZ, C., Chiesa-Estomba, C. M., Barillari, M. R., Trozzi, M., Meucci, D., Peer, S., Ben Abdelouahed, F., Schindler, A., Saussez, S., Université de Mons (UMons), Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Saint-Pierre, Université libre de Bruxelles, Bruxelles, SFORL (SFORL), SFORL, and University of Mons [Belgium] (UMONS)

Pierre Leich, Nicolas Fakhry, Chiara Falanga, Jerome R. Lechien, Christel Souchay, Stéphane Hans, Cosimo de Filippis, Tareck Ayad, Carlos M. Chiesa-Estomba, Fabrice Journe, Philippe Lavigne, Camelia Rossi, Myriam Edjlali, Fahd El Afia, Robert Carlier, Sven Saussez, Frédérique Coppée, Mohamad Khalife, Christian Calvo-Henriquez, Andrea Lovato, Maria Rosaria Barillari, Laurence Ris, Alexandra Rodriguez, Giovanni Cammaroto, Daniele R De Siati, Serge Blecic, Didier Dequanter, Julien Hsieh, Younes Chekkoury-Idrissi, Mihaela Horoi, Irene Lopez Delgado, Lea Distinguin, Serge D Le Bon, SFORL (SFORL), SFORL, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Aix Marseille Université (AMU), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Lechien, J. R., Chiesa-Estomba, C. M., De Siati, D. R., Horoi, M., Le Bon, S. D., Rodriguez, A., Dequanter, D., Blecic, S., El Afia, F., Distinguin, L., Chekkoury-Idrissi, Y., Hans, S., Delgado, I. L., Calvo-Henriquez, C., Lavigne, P., Falanga, C., Barillari, M. R., Cammaroto, G., Khalife, M., Leich, P., Souchay, C., Rossi, C., Journe, F., Hsieh, J., Edjlali, M., Carlier, R., Ris, L., Lovato, A., De Filippis, C., Coppee, F., Fakhry, N., Ayad, T., and Saussez, S.

Jerome R. Lechien, Maria Rosaria Barillari, Ahmed Bahgat, Francesco Freni, Francesco Galletti, Claudio Vicini, Giuseppe Meccariello, Giannicola Iannella, Cosimo Galletti, Christian Calvo-Henriquez, Carlos M. Chiesa-Estomba, Giovanni Cammaroto, Luigi Marco Stringa, Henry Zhang, Bruno Galletti, SFORL (SFORL), SFORL, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Cammaroto, G., Stringa, L. M., Iannella, G., Meccariello, G., Zhang, H., Bahgat, A. Y., Calvo-Henriquez, C., Chiesa-Estomba, C., Lechien, J. R., Barillari, M. R., Galletti, B., Galletti, F., Freni, F., Galletti, C., and Vicini, C.

S. Tronche, Stéphane Temam, J.-C. Ferrié, D. de Raucourt, Michel Lapeyre, C.-A. Righini, E. de Monès, Pierre-Yves Salaun, Sylvain Morinière, F. Lagarde, Sébastien Vergez, F. Dubrulle, B. Barry, Dominique Chevalier, Cécile Badoual, Chloé Bertolus, Philippe Schultz, Department of Head and Neck Surgery, Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service d'ORL et de Chirurgie Cervico-Faciale (TOURS - ORL et CCF), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Service de Radiologie (LILLE - Radio), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Department of Nuclear Medicine, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Department of Maxillofacial Surgery, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de cancérologie cervico-faciale [Gustave Roussy] (CCF), Institut Gustave Roussy (IGR), Service d'ORL et de Chirurgie Cervico-Faciale (LILLE - ORL et CCF), Service d'ORL et de Chirurgie Cervico-Faciale (ORLEANS - ORL et CCF), Centre Hospitalier Régional d'Orléans (CHRO), Service d'ORL et de Chirurgie Cervico-Faciale (STRASBOURG - ORL et CCF), CHU Strasbourg, Service de Radiothérapie (CLERMONT FERRAND - Radiothérapie), CHU Clermont-Ferrand, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Grenoble, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service d'ORL et de Chirurgie Cervico-Faciale (PARIS - BICHAT - ORL et CCF), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), SFORL (SFORL), SFORL, Service d'Oto-Rhino-Laryngologie (O.R.L.) et de Chirurgie Cervico-Faciale [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), University Hospital Rangueil-Larrey, Service d'ORL et de Chirurgie Cervico-Faciale ( TOURS - ORL et CCF ), CHRU Tours, Service de Radiologie ( LILLE - Radio ), Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Groupe d'Etude de la Thrombose de Bretagne Occidentale ( GETBO ), Université de Brest ( UBO ), Service de Chirurgie Maxillo-Faciale ( PARIS - PSL - Chir Maxillo-Faciale ), Assistance publique - Hôpitaux de Paris (AP-HP), Département de cancérologie cervico-faciale [Gustave Roussy] ( CCF ), Institut Gustave Roussy ( IGR ), Service d'ORL et de Chirurgie Cervico-Faciale ( LILLE - ORL et CCF ), Service d'ORL et de Chirurgie Cervico-Faciale ( ORLEANS - ORL et CCF ), Centre Hospitalier Régional d'Orléans ( CHR ), Service d'ORL et de Chirurgie Cervico-Faciale ( STRASBOURG - ORL et CCF ), Service de Radiothérapie ( CLERMONT FERRAND - Radiothérapie ), Institut d'oncologie/développement Albert Bonniot de Grenoble ( INSERM U823 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Joseph Fourier - Grenoble 1 ( UJF ) -CHU Grenoble, Service d'ORL et de Chirurgie Cervico-Faciale ( PARIS - BICHAT - ORL et CCF ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], SFORL ( SFORL ), Service d'ORL et de Chirurgie Cervico-Faciale ( CAEN - ORL et CCF ), CHU Caen, Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF)