SS Gastropharyngeal and Gastroesophageal Reflux in Globus and Hoarseness Conrad F. Smit, MD: Justin A. M. J. van Leeuwen, MD; Lisbeth M. H. Mathus-Vliegen, MD, PRD: Pieter P. Devriese, MD, PhD; Astrid Semin, RN, MS: Joep Tan, MD, PhD; Paul F. Schouwenburg, MD, PhD Background: The role of gastropharyngeal reflux in pa- tients with globus pharyngeus and hoarseness remains unclear. Objectives To evaluate patients with complaints of glo- bus, hoarseness, or globus and hoarseness combined for the presence of gastropharyngeal and gastroesophageal reflux, Design: Prospective clinical cohort study of 3 groups of patients undergoing ambulatory 24-hour double- probe pH monitoring. In patients with pathologic gas- troesophageal reflux, an upper gastrointestinal endos- copy was also performed. Setting: Tertiary care, outpatient clinic Patlents: Twenty-seven patients with globus alone, 20 patients with hoarseness alone, and 25 patients with glo- bus and hoarseness combined, Results: Patients with well-defined pathologic reflux (le, gastroesophageal reflux with or without gastropharyn- geal reflux) were present mainly in the group of p: jents with globus combined with hoarseness: 18 (72%) 0f25 patients, compared with 7 (35%) of 20 patients with hoarseness alone and 8 (30%) of 27 with globus alone. Seven (10%) ofall 72 patients had prolonged acid expo- sure at the laryngopharyngeal junction in the presence of a normal gastroesophageal pH registration. Abnor- ‘mal findings in the esophagus were found al endoscopy in 17 (65%) of 26 patients with pathologic gastroesopha- geal reflux (with or without gastropharyngeal reflux) Conclusions: We found « high prevalence of pathologic reflux in patients with both globus and hoarseness. Based on these findings, we strongly advise upper gastrointesti- nal endoscopy for symptomatic otolaryngological pa- tients with pathologie gastroesophageal reflux. Arch Otolaryngol Head Neck Surg. 2000;126:827-850 LOBUS PHARYNGEUS isde- fined as the persisting sensation of a lump in the throat without dys- phagia or odynophagia up to of above the upper esophageal sphincter (UES) may cause laryngological complaints." This phenomenon is called gastropharyngeal reflux (GPR) oF laryngopharyngeal reflu. From the Departments of (Otorhinolaryngology—Head and [Neck Surgery (Drs Smt, van Leeuwen, Devise, Tan and Schowwenburg), Gastroenterology (Dr Mathus-Vlegen), and Epidemiology and Biostansties (Ms Semin), Academic Medical Genter, University of Amsterdam, Amsterdam, the [Netherlands: Dr Smits now ith the Department of Otolaryngolegy-Head and [Neck Surgery, University Hospital Vie Universite, Amsterdam, The act of just swallowing brings no re- lief, but drinking or eating does.’ Gastro- esophageal reflux (GER) is thought to play a role in various otolaryngological symp- toms such as globus pharyngeus and hoarseness, Reportsin the literature on the relation between GER and these symp- toms re contradictory.” For example, the presence of GER in patients with globus varies from 23% to 90%.257°!2 Part of this wide range may be caused by at it- cortect definition of globus and by differ- ences in the method of assessment for GER. Nowadays, one of the most reliable methods for detecting GER is 24-hour ambulatory pH monitoring ° However, i seems that not only reflux of gastric con- tents into the esophagus but also reflux (aepnu\TED) SCH OTOTARINCOL HERD NECK SUORCIVON JOLY OT (©2000 American Med Reports on the relation between GPR and otolaryngological symptoms are scarce. Therefore, we decided to evaluate the role of GPR and GER in patients with globus pharyngeus and/or hoarseness by ‘means of 24-hour pH monitoring et SS The study group with complaints of glo- bus pharyngeus alone consisted of 27 patients (9 men and 18 women; mean age, 48.8 years; range, 20-08 years) Twenty patients (10 men and 10 women; ‘mean age, 49.9 years; range, 22-81 years) had complaints of hoarseness alone for longer than 3 months, and 25 patients (3 men and 12 women; mean age, 46.3 Association, All rights reserved.PATIENTS AND METHODS PATIENTS From April 1, 1994 trough July 32, 1998, patents pre- senlng with complaints of globus hoarseness or both were invited wo participate inthe study. They underwent oto- Inryngologlcal examination and barium wallow videofao- roscopy of the upper arodigestve tract to exclude con- Comitan disease” Only patients with normal findings at routine otolaryngolopca examination (le, lexibleendos- Copy ofthe laryns) were included inthe study. Excision érleria consisted of abnormal benign lesions (eg, post ‘orlarynglts edema polyp, jst) and mas sons Subtle sbnormalities suggestive of reflux, including thickening of ihe posterior larynx and the presence of erythema or tmucus strands, were only rarely present, The patients Completed a more detailed questionnaire on esophageal tnd lalarygologa sympoms sich ss Beare, regurgitation, dysphagia, hoarseness, coughing and dil Calc with swallowing and on thelr smaking abs and Alcohol intake ase on their complains at presentation, linia is tory, and answers lo the questionnaire, we divided pa- tients into the fellowing 3 groups: globus only, howse- ness only. and globus and hoarseness combined. Hoarsenes tas sel-reported by the patients as a“rough voce or vo- Cal fague and was not objecified “The ethical committee ofthe Academic Medical Cen- tes, Amsterdam, the Netherlands, approved the study and tnformed consent was obtained (rm all patients METHODS, Double-probe pH monitoring was performed with 2 monocrystalline antimony pHi sensors positioned along a single catheter (diameter, 2.1 mm), withthe sensors 15 cm apart and a silver-silver chloride eutancous relerence electrode (Digitrapper Mark Ill; Medtronic Synectics, ‘Maastricht, the Netherlands). Both probes (pH sensors) were calibrated simultaneously in baler solutions of pH 7 snd pit 1 before monitoring. A flexible laryngoscope was Introduced transnasally until a good view of the hypo- [Pharm was cbiained. The proximal probe was placed in the UES during endoscopy to ensure thatthe proximal probe was surrounded by esophageal mucosa The distal probe was postioned 13cm distal tothe proximal probe, tell above the lower esophageal sphincter. “The patients were encouraged cat thelr regular meals without any restriction and to maintain their normal daly ‘nd nocturnal routines The patent reported thelr body ositions, meals and drinks ina di Posh teria of Richter ta” were used forthe distal probe o distinguish between physiologic and pathologic GER Thus, «pl below 4 less than 3.5% ofthe foal ne, Jes than 8.2% ofthe time inthe upright postion, and less than 34 ofthe ime in the supine postion was defined as having no pathologie reflux” or the proximal probe placed atthe entrance ofthe csophagus, recently established reference values for GPR twere used that are based on 20 healthy subjects (14 men znd 6 women; mean age, 32.5 years; range, 1937 yeas) ‘wth hardly any period of ples than # found atthe level bf the UES. Thus, a pH below # for more than 0.1% ofthe {otal time: more than 0.2% of the time In the upright po- Sion, and more than O¥ of the ume in the supine post tion, or the occurrence of more than 3 reflux epeodes of pl below 4 were considered to have pathologie relax." “To assess GPR, i ie necessary to perform dual-probe plt monitoring with the proximal probe placed tn the UES" [Api drop below 4, recorded by the proximal probe, iscon- sidered to be postive evidence for GPR only ii ts pre- Ceded by a pH drop a the distal probe of sila or larger smagoitude >" Patients in whom pathologic GER was detected were refered for upper gasioinestinal endoscopy. DATA ANALYSIS. We analyzed the proportions per group by means of de- scriptive statistics. Differences in overweight, heartburn, cough, belching, regurgitation, smoking, and alcohol and caflee use between the groups with and without patho- logic reflux were analyzed by x test of Fisher exact test a5 appropriate years; range, 2 ‘and hoarseness, 80 years) had complaints of both globus Patient characteristics are shown in Table 1. Pa- tients with and those without pathologic reflux were alike ‘on all variables except heartburn: patients with both pathologic GER and GPR tended to suffer more from heartburn (x'=5.22; P<.02) The percentage of me with pH below 4at the proxt- mal probe, indicating GPR, and at the distal probe, in- dicating GER, forthe patients with globus alone, hoarse- ness alone, and globus and hoarseness combined are shown in Fable 2. The number of patients with patho- logic GPR and GER, with pathologic GER only, and with pathologic GPR only, according to the reference values slready deseribed, is shown in Table 3. Patients with ‘well-defined pathologic reflux (ie, GER with or without GPR) were mainly from the group with globus com- bined with hoarseness: 18 (72%) of 25 patients, com- (aepnu\TED) SCH OTOTARINCOL HERD NECK SURCIVON JOLY OT (©2000 American Med jamanetwork.com/ on 09/19/2022 pared with 7 (35%) of 20 with hoarseness and 8 (30%) of 27 with globus. Seven (10%) of 72 patients with any laryngological symptoms (ic, globus and/or hoarseness) hhad prolonged acid exposure at the laryngopharyngeal junction with a normal gastroesophageal pH. Thirty-three patients with pathologic GER with or without GPR were referred for upper gastrointestinal en- doscopy. Four patients with hoarseness alone and 3 pa- Udents with globus and hoarseness combined refused en- doscopy. Of 26 patients who underwent endoscopy, 17 (65%) had abnormal indings in the esophagus Tale 4). A slight reflux esophagitis (grade 1) was detected in 6 of the 8 patients with globus alone and in 1 of the 3 pa- dents with hoarseness alone. Ten ofthe 15 patients with globus and hoarseness combined had abnormalities in the esophagus. Five ofthese patients had reflux esopha- gitis grade I, 2 had reflux esophagitis grade II,and 1 had reflux esophagitis grade Ill Barrett esophagus was de- Association, All rights reserved.‘Table 1. Characteristics of Patients Patologle Patologle Patholole Pathologie characterise _(n=82) (0=23) =n Meanage 70 22-8) 489,480) 475 27-65) 3.9 2L8T) (cng) Notmen- 13191812 dad Oversight = 18) 1248) 38) 2) Hearbun 12138) 17168) 416) Cough Si) 3) 14) (d) Baling wos Bi) 2025) 2) Requgiaion 3) As) o Smoing 50) (18) 2a Aeotoluse —4(12) 312) 228) Cotes 1344!) 13162) 3.) Date gen as under (ecentage) of patents uns aevice linda GR nates gastoparygel eh GER, astoesophagel ete ‘Table 2, Percentage of Time With pH Below & During 24 Hours for the Proximal and Distal Probes ‘raxnal Probe (aR) Total op(oor7) o0;029 02/0096) Inupigt positon 00(0027) 0.0(0032) 0200-08) Insipina positon 0.0(0001) 0.0(0000) 00(0020) Distal Probe (9ER) Total 26(00288) 2601214) 6.4(02422) Inupigt positon 23(00284) 36(01214) 75(03280) Insupina positon 01(00205) 0.0(00215) 24(00705) Datu are he as medan (ange). GPR inde gastopharyngea ref, GER, gashaesopageal fine ‘Table 3, Distribution of Patients Wit Pathologic GPR and GER, GER, or GPR* to Laryngol Moarseness Symptoms (w=25) (= 72) Paaope 7 4 1" 2 (GPR ana GER Patialope 1 3 4 . ‘GER eny Patialope 2 2 a 7 PR ony Data are gen as number of pats. GPR ideale gasophannge ‘eta GER, gato ph tected in one patie low the UES were detected in another. ‘All 6 patients with globus and reflux esophagitis had pathologic GER and pathologic GPR. The patient with hoarseness alone and reflux esophagitis had pathologie GER only. The 8 patients with globus and hoarseness com- bined and reflux esophagitis at endoscopy had patho- ©2000 American Medi Table 4. Results of Endoscopy n 7 Patents With Pathologie GGER and 19 Patients With Pathologic GPR and GER® Fnaogson| naose0ny Diagnosis Symptom Norma _Aonor (PRand GER Globus done (n= 7) 1 6 Hoaseressalone(a=1) 1 0 Ghobusandhowsanese| 3 e amtined n= 11) en Glbus aloe (n= 1), 1 o Hoaseress aloe (n 1 1 Globus and hersaness (n= 8) 2 2 her Total Ary aryngoogeal smnptoms 935) 17 (65) Mo.) (=25) Data are gen as number of patents unless omer inated GER Ingeatespisossophagea fu GPR gastophatymgel efi Table 5. Characteristics of 17 Patients With Any Laryngotogical Symptoms, ‘and Abnormalities at Endoscopy Grancleae nag ean age ang) y waar) No.of men-omen oe Diagnosis, No of patents Pathologic GER 2 Pathologic GPR and GER “ overweight 9183) Hearbum 10159) Cough 3108) Bachng Ba Regurgitation 116) smokang 59 ‘caholus 2112) Cote use 10150) =Larymgoogical symptoms were defied a bus aoe, hoarseness ‘one, or obs and oa 5 combed, Dal agen as nunter logic GER and GPR. The patient with Barrett esophagus hhad severe pathologic GER and GPR. The patient with islands of Barrett mucosa below the UES had borderline abnormal pH valuesat the UES and above the lower esoph- geal sphincter. The characteristics ofall patents with abnormal find ings at endoscopy are shown in Table 5. Most of these patients had pathologic GPR in addition to pathologic GER, Although they had proven abnormalities in the esopha- us, 7 patients (419%) did not complain about heartburn, a By the use of dual-probe pH monitoring, we found a high prevalence of pathologic GER in our patients with glo- bus combined with hoarseness. Of the patients with glo- bus only, we found pathologic GER (with or without GPR) {in 30%, which is in agreement with the findings of Wil- son et al! (23%), Curran et al! (38%), and Hill et al!* (30.5%). OF the patients with hoarseness only, we found Association, All rights reserved.pathologic GER (with oF without GPR) in approxi mately one third ofthe patients. Forty (50%) of 72 patients presenting wit laryngo- logical complains (ie, globus, hoarseness, or globus and hoarseness combined) had pathologic reflux, disclosed by 24-hour pH monitoring. At present, this technique isthe ‘rterion standard for the assessment of rela. The quan- fication of reflux with 24-hour pH monitoring, however, has its limitations because of day-to-day variability °2" Although patients were free to arty ut their normal dally activities, reflux-promoting factors caused, for example, by ‘certain activities oF foods were not always present during the 24-hour monitoring period. Therefore, tnenmitent re flux episodes related to an occasional fatty oF heavy meal may have been missed, resulting ina negative finding on a pH test in «symptomatic patient Patients with pathologie GER also underwent en- doscopy of the esophagus. It appeared that 65% of the patients with pathologie GER had abnormal findings, rnainly inthe form of reflux esophagitisand twice as Bar. About 30 yearsago, the suggestion was raised thal GER ‘ould be an important factor in the cause of globus *" Since the introduction of 24-hour pH monitoring, globus caused bby GER scems les likely. The association of hoarseness and rellx isnot a well investigated, and controversy remains asto the posible role of reflux herewith "=" We found, however, high prevalence of rellux in patients with glo- ‘bus and hoarseness combined [AL present, there are at least 2 possible mecha- nisms to explain the association betwen relli and la ryngeal disease. One mechanism postulates a vagally me dated reflex from an acid-sensitive distal esophagus, provoking laryngeal complaints and epithelial lesions." The second deseribes a direet acid injury of the ary and is supported by animal studies, showing that minute amounts of gastric fluids are capable of inducing dam- Age to laryngeal structures."2: Therefore, the detection ‘of GER and of GPR seems to be important in otolaeyn- ological disorders Physiologic reflux is present inthe esophagus, and its upper limit is considered to be 5.5% ofthe total time.” The miost important defense mechanisins agains the cor rosive action of acidic gastric juice are esophageal acid clearance, mucosal resistance, and salivary seere~ tion. It may be that such a defense dacs not exist at the pharyngolsryngeal transition and that, because of the acid sensitivity, a small amount of acid reflux may have devastating effects. This might signify that eaaly any acid refliscat the laryngopharyngeal transition has to be con- sidered pathologie, and that rellux events atthe lower ‘csophageal sphincier defined as being physiologic may reach the UES and provoke symptoms and/or damage, ‘which was shown in 7 of our patients with otolaryngo- logical symptoms. Unfortunately, our small sample size did not allow for regression analysis, so we were unable to detect significant predicting variables with respect to refluxor the kind of reflux (GPR, GER, or GPR and GER). In conclusion, lor patients with «history of globus and hoarseness combined, the attention ofthe otolstyn- kologist should be directed towaed the gastrointestinal Uuact- This is highlighted by our finding of GER in 40% (anepnu\ TED) SCH OTOTARINCOL HERD NECK SURG IVON JOLY OT (©2000 American Med of all patients and in 72% of patients with globus and hoarseness combined, and ou finding of esophageal ab- normalities in 65% of patients with pathologie GER with, or without GPR_A history of heartburn and belching was disappointingly low in frequency and of no major help {in detecting GER, Accepted for publication January 26, 2000. The authors acknowledge the financial support ofJans- sen-Cilag BV, Tilburg, the Netherlands Presented in part atthe 24th World Congress ofthe In- emnational Association of Logopedics & Phoniatrics, Amster~ ddan, the Netherlands, August 26, 1998, and at the European Laryngological Society, Rome, Maly, September 25, 1998. Reprints: Conrad F. Smit, MD, Department of Otorh- nolaryngology-Head and Neck Surgery, University Hospi- tal Vrije Universiteit, PO Box 7057, 1007 MB Amsterdam, the Netherlands (e-mail: cf smit@azvu.n). EES] 1. Mai WS, oboe KE, Mods, Maurer alg ape th le bu symptom Langa O18 1se-1040, Nalsamsan KG, Radel fenge nobus etrius, Br Rad 196 sat 98, ‘hay. Seg Clauss Sl, Came Mt, Pans atin of yp tom of asrecophagel rn Aon i Abia Laynge TO: 7OSN2 Je Daun Aan Gotu tres: amanfeatonot abr osoph- is? J Layngo/ a a7 160-054 Freon A, Arran GM. Erys-Robars E-Glbushstcs ard etc ophaptis J Laynao Oa rg: 1026-406. leon 8, White oo Hache Wat Gasosaphgel tx and post fang Aon Dt Aina Lange 185 Seo, Visor Ped Petal Panpgoesophage emiy in globus se Son Arch Gatryga Ae ec Surg 0601 1086100. Wns, Konan 18, Wu WE, Cope J8, Rr J, Cart 0, Chrenic hateness secondary gastosophael ei disease: acumen wth eho anor gH monitor, AJ asrocrol 108034 T5008, 8 kazPO. 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