Acta Oto-Laryngologica. 2014; 134: 831–837

ORIGINAL ARTICLE

Endoscopic evidence of reflux disease in the larynx

MAREK KRAWCZYK1, WOJCIECH SCIERSKI2, IRENEUSZ RYSZKIEL3,GRZEGORZ NAMYSŁOWSKI2, STANISŁAW GRZEGORZEK1 & MACIEJ MISIOŁEK2

1Department of Internal Diseases with a Gastroenterological Profile, Municipal Hospital, Tychy, 2ENT Department inZabrze, Medical University of Silesia, Katowice and and 3‘NOVAMED’ Private Clinic, _Zory, Poland

AbstractConclusion: The severity of laryngeal mucosal lesions in patients with gastroesophageal reflux disease (GERD) is significantlygreater than in controls. A higher degree of laryngeal mucosal injury is documented in patients in whom GERD is associatedwith more advanced esophageal lesions. Objectives: (1) To confirm the presence of inflammatory lesions in the laryngopharynxof patients with GERD. (2) To analyze the relationship between the severity of laryngopharyngeal and esophageal lesions on thebasis of the reflux finding score (RFS) and the Los Angeles (LA) scale of esophageal mucosal injury. Methods: The studyincluded 92 subjects, among them 46 patients with GERD and 46 individuals without endoscopic evidence of esophageallesions, qualified for routine endoscopy due to other indications. The endoscopic images of the inferior pharynx, larynx, andesophagus were analyzed during the video-endoscopic examination of the upper gastrointestinal tract. The laryngeal imageswere assessed according to RFS criteria and the numeric value of RFS was calculated. The degree of esophageal mucosal injurywas described according to the LA scale. Results: Both global RFS score and the scores of all RFS parameters except thepresence of granulomatous tissue were significantly higher in patients with GERD than in the controls. Patients in whomGERD was associated with more severe esophageal lesions (group B according to the LA scale) had significantly higher globalRFS score and scores of all analyzed parameters of laryngeal injury except subglottic edema than individuals in whom thedegree of esophageal involvement was classified as group A.

Keywords: Gastroesophageal reflux, endoscopy, laryngopharyngeal reflux, RFS, Los Angeles scale

Introduction

Gastroesophageal reflux disease (GERD) is a frequentgastrointestinal disorder. According to the 2006Montreal consensus, GERD is defined as a refluxof gastric contents into the esophagus, and is classifiedas esophageal and extra-esophageal types. The first ofthese types comprises non-erosive reflux disease(NERD) and the form associated with the injury ofesophageal mucosa (reflux esophagitis, Barrett’sesophagus, stricture associated with ulcerative esoph-agitis, and esophageal adenocarcinoma) [1,2].The extra-esophageal syndromes were divided into

two groups. The first group includes conditions andsymptoms that are probably associated with GERD:

laryngopharyngeal reflux (LPR) disease, dentalerosion, chronic cough, bronchial asthma. Thesecond group comprises conditions in the case ofwhich the causative relationship with GERD wasnot evidently proved, such as sinusitis, pharyngitis,otitis media, and sleep disorders [2–4].The term laryngopharyngeal reflux (LPR) refers to

the reflux of gastric contents to the upper airways andresultant injury to pharyngeal and laryngeal mucosa.The reflux contents can be liquid, gaseous or of mixedcharacter. A mild reflux occurs physiologically andhas no significant consequences as the time duringwhich the esophageal mucosa is exposed to gastriccontents is short. However, the reflux is consideredpathological when the number of reflux episodes

Correspondence: Wojciech Scierski, ENT Department in Zabrze, Medical University of Silesia, Katowice, Poland. Tel: +48 32 2717420. Fax: +48 32 2717420.E-mail: wojscier@mp.pl

(Received 17 November 2013; accepted 24 January 2014)

ISSN 0001-6489 print/ISSN 1651-2251 online � 2014 Informa HealthcareDOI: 10.3109/00016489.2014.890738

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(decrease in esophageal pH below 4) increases, andthe duration of contact between esophageal mucosaand gastric contents is longer than 3.45% of a sleepperiod (remaining in a horizontal position) and 8.42%of a day-time period (remaining in a vertical position)[5–7].Two mechanisms were proposed to be responsible

for the injury and irritation of the larynx. The first ofthem is a direct exposure of the laryngeal mucosa toacidic gastric contents and pepsin. The second mech-anism is associated with the vagal reflex of cough andpharynx pain caused by esophageal irritation with thereflux contents. Probably, these two mechanismsoverlap each other [8].Inmost cases, the diagnosis of reflux disease is based

on detailed history taking, physical examination, andgastrofiberoscopy with the examination of esophagealmucosa and mobility. Furthermore, 24 h pH-metrycan be used to detect acidic reflux as well as to assessits duration and related changes in esophageal pH.The gaseous reflux can be detected with a modern andmore efficient tool, i.e. esophageal impedance. Thediagnosis of LPR is based on the endoscopic exami-nation of the pharynx and larynx (video-endoscopy).Mucosal hyperemia at the level of the posterior com-missures is the most commonly detected abnormality,which is responsible for the majority of patient-reported symptoms (pharyngeal globe, laryngeal dis-comfort, hoarseness). The degree of reflux-relatedinjury to laryngeal and inferior pharyngeal mucosa isgraded with the reflux finding score (RFS). LPR canbe suspected if the values of RFS exceed 7. Moreover,the reflux symptom index (RSI) proposed byBelafsky et al. [9] is very useful in the assessment ofthe most common LPR-related symptoms.Noticeably, the GERD-specific gastric symptoms

are frequently missing in LPR patients. In most casesheartburn and regurgitation are not observed duringthe day. The most frequent symptoms include hoarse-ness, throat clearing, exudate in posterior pharynx,difficulty swallowing, cough after eating or changinginto a horizontal position, dyspnea, pharyngeal dis-comfort or globe, heartburn, and chest pain. None ofthese symptoms is specific to LPR, and they arefrequently observed in other infectious, allergic orneoplastic conditions. Consequently, strong diagnos-tic vigilance and accuracy are required if any of themis reported [10].The aim of this study was to confirm the presence of

inflammatory lesions in the laryngopharynx ofpatients with GERD. Moreover, we analyzed therelationship between the severity of laryngopharyn-geal inflammatory lesions and the extent of esoph-ageal lesions on the basis of the RFS and the LosAngeles (LA) scale of esophageal mucosal injury.

Material and methods

Patients

The study included 92 patients, diagnosed andtreated at the Department of Internal Diseases ofthe Municipal Hospital in Tychy between 2010 and2012. All the patients were referred to our clinic forenhanced diagnostics and gastroscopy. The protocolof the study was approved by the Local BioethicalCommittee of the Silesian Medical University inKatowice, Poland (decision no. KNW/0022/KB1/113/11), and was in accordance with the HelsinkiDeclaration of 1975, as revised in 1983. All thepatients gave their written informed consent toparticipate in the study.Gastroscopy was performed in all the patients and

the endoscopic images of the esophagus and larynxwere analyzed. On the basis of these findings, thesubjects were divided into the GERD group and thecontrols. The group of GERD patients included24 men between 19 and 63 years of age (mean45.5 years) and 22 women aged between 33 and88 years (mean 56.4 years). The most frequent com-plaints included heartburn, regurgitation, periodicalhoarseness, grunting, and foreign body sensation inthe throat. The control group comprised patientswithout endoscopic evidence of esophageal lesions,qualified for routine endoscopy due to other indica-tions. This group included 16 men between 30 and82 years of age (mean 55.9 years) and 30 women agedbetween 26 and 90 years (mean 63.2 years).

Methods

The endoscopic images of the inferior pharynx, larynxand esophagus were analyzed during the video-endoscopic examination of the upper gastrointestinaltract. The endoscopic examination was conductedwith GIF Q 145i video-endoscope (Olympus,Hamburg, Germany), and the images were storedin Endo Archive software (BL Soft, Siedlec, Poland).The laryngeal images were assessed according to

the RFS criteria and the numeric value of RFS wascalculated. The minimum and maximum values ofglobal RFS were equal to 7 and 26, respectively(Table I). The severity of macroscopic esophageallesions was assessed according to the LA scale andclassified into one of the following groups: (A) one (ormore) mucosal break no longer than 5 mm that doesnot extend between the tops of two mucosal folds; (B)one (or more) mucosal break more than 5 mm thatdoes not extend between the tops of two mucosalfolds; (C) one (or more) mucosal break that is con-tinuous between the tops of two or more mucosal

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folds but that involves less than 75% of the esophagealcircumference; and (D) one (or more) mucosal breakthat is continuous between the tops of two or moremucosal folds and involves at least 75% of the esoph-ageal circumference.

Statistical analysis

The results are presented as arithmetic means andtheir standard deviations (SDs) in the case of quan-titative variables or numbers and percentages in thecase of qualitative parameters. The normality of thedistribution of the studied variables was verified withthe Shapiro-Wilk test. The significance of intergroupdifferences in the quantitative parameters was testedwith the Mann–Whitney U test and the distributionsof discrete variables were compared with the Yates’chi-squared test. The Spearman’s coefficients of rankcorrelations were calculated to analyze relationshipsbetween pairs of quantitative variables. All the calcu-lations were carried out with Statistica 10 (StatSoft)package, and the level of statistical significance was setat p £ 0.05.

Results

None of the controls showed any esophageal pathol-ogies on endoscopic examination. Twenty patientswith GERD showed type A of esophageal mucosalinjury according to the LA classification; type B wasdocumented in another 20 individuals and type C orD in 6 patients (Figures 1,2,3,4).The RFS scores of all parameters except the pres-

ence of granulomatous tissue were significantly higherin patients with GERD, similar to the global value oflaryngeal RFS, which showed statistically significantdifferences between the groups (Table II).

Figure 5 summarizes differences in the distributionof individuals with various RFS scores in both studiedgroups. A significantly greater fraction of patients withlow RFS scores was documented in the control group.The values of RFS in the two groups of patients

with GERD differing in terms of the severity ofesophageal lesions (LA group A vs B) are presentedin Table III. Due to low numbers, patients with moresevere esophageal lesions (groups C and D) werenot included in this analysis. Patients with moresevere esophageal lesions (group B) had significantlyhigher scores of all analyzed parameters of laryngealinjury except subglottic edema. Also, the global valueof RFS in group B was significantly higher than ingroup A.

Table I. Components of the reflux finding score and their pointvalues.

Finding Score

Subglottic edema 2, present; 0, absent

Ventricular obliteration 2, partial; 4, complete

Erythema/hyperemia 2, arytenoids only; 4, diffuse

Vocal cord edema 1, mild; 2, moderate;3, severe; 4, polypoid

Diffuse laryngeal edema 1, mild; 2, moderate;3, severe; 4, obstructing

Posterior comissure hypertrophy 1, mild; 2, moderate;3, severe; 4, obstructing

Granuloma/granulation 2, present; 0, absent

Thick endolaryngeal mucus 2, present; 0, absent

Figure 1. Larynx in patient with gastroesophageal reflux disease(GERD) and type C of mucosal injury according to the Los Angeles(LA) classification.

Figure 2. Esophagus in patient with gastroesophageal reflux disease(GERD) and type C of mucosal injury according to the Los Angeles(LA) classification.

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The differences in the distribution of individualswith various RFS scores in subsets of patients whoseesophageal lesions corresponded to groups A and B ofthe LA scale are presented in Figure 6. The fraction ofpatients with low RFS scores was significantly higherin group A than in group B.

Discussion

Patients with reflux disease are an inhomogeneousgroup in terms of diagnostic findings and reportedsymptoms [1,8]. Consequently, some authors con-sider LPR as a separate condition [11,12]. Previousstudies of patients showing the signs of GERD

included individuals with both GERD and NERD.The patients were enrolled on the basis of pH-metry,survey, and diagnostic imaging of the larynx[10,11,13]. In contrast, the present study was limitedto the exclusive examination of laryngeal images frompatients with ulcerative esophagitis. The controlgroup comprised randomly selected diagnosticimages from patients who were free from esophagealulceration and were referred due to other gastrologicalproblems.Despite the Montreal consensus, many authors

discuss whether LPR and GERD represent thesame pathological entity. Both Barry and Vaezi [11]and Postma and Amin [12] addressed this issue in thecontext of response to proton pump inhibitor therapyin patients with the signs of LPR, and different symp-tomatology of laryngeal and esophageal reflux.Noticeably, not all individuals with laryngologicalsymptoms who participated in these two studieshad pH-metric evidence of laryngeal reflux. Accord-ing to Postma and Amin [12], patients with LPRusually experience reflux in a vertical position, andthose with GERD show a classic form of refluxassociated with a horizontal position, which predis-poses them to delayed esophageal emptying. Accord-ing to Ahuja et al. [14], a dysfunction of the loweresophageal sphincter (LES) and impaired esophagealmotility are observed in patients with GERD, whereasLPR is characterized by an impaired function of theupper esophageal sphincter (UES) and normal esoph-ageal motility. Similar doubts were reported by Kro-gulska and Wasowska-Królikowska [13] who notedthat while hoarseness is reported by 100% of patientswith LPR, only 6% of them complain of heartburn. Incontrast, the heartburn is reported by as many as 89%

Figure 3. Larynx in patient with gastroesophageal reflux disease(GERD) and type D of mucosal injury according to the Los Angeles(LA) classification.

Figure 4. Esophagus in patient with gastroesophageal reflux disease(GERD) and type D of mucosal injury according to the Los Angeles(LA) classification.

Table II. Mean (± SD) scores of the laryngeal components of thereflux finding score (RFS) and global laryngeal RFS in patients withgastroesophageal reflux disease (GERD) and in the controls.

FindingControls(n = 46)

GERD(n = 46) p value

Subglottic edema 0.78 ± 0.99 1.65 ± 0.77 < 0.0001

Ventricular obliteration 2.09 ± 0.41 2.96 ± 1.01 < 0.0001

Erythema/hyperemia 2.26 ± 0.68 3.43 ± 0.91 < 0.0001

Vocal cord edema 1.24 ± 0.48 1.87 ± 0.75 < 0.0001

Diffuse laryngeal edema 1.33 ± 0.56 2.04 ± 0.73 < 0.0001

Posterior comissurehypertrophy

1.37 ± 0.57 2.07 ± 0.68 < 0.0001

Granuloma/granulation 0.00 0.00 –

Thick endolaryngealmucus

0.57 ± 0.91 1.22 ± 0.99 0.002

Total 9.63 ± 1.99 15.24 ± 3.40 < 0.0001

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patients with GERD, and none of them complain ofhoarseness [13].The results of our study point to an evident asso-

ciation between the presence of gastroesophagealreflux and the injury of laryngeal mucosa. The RFSfor all parameters analyzed in patients with GERDwas significantly higher than in individuals withoutgastroesophageal reflux. This confirms that the refluxof gastric contents (both fluid and gaseous) can leadto laryngeal mucosal injury and causes a variety ofsymptoms. Analyzing the degree of esophageal muco-sal injury in patients with GERD, we observed that itsgreater severity (type B according to the LA scale) isassociated with more severe defect of the laryngealmucosa (higher RFS for all analyzed parameters).Relationships between GERD and LPR were

studied by many authors. Ylitalo et al. [15] examined

a group of 56 patients with epigastric pain and acontrol group of 26 subjects with posterior laryngitisand 19 individuals without laryngological and gastro-enterological symptoms. All the participants under-went 24 h pH-metry with two probes, one placedabove the LES and the other 1 cm above the UES.None of the participants showed any manometricevidence of significant impairment of esophagealmotility. The result of pH-metry was positive andconfirmed the presence of GERD in 70% of thepatients with gastric symptoms. However, the pHmonitoring produced positive findings in 58% ofthe subjects with posterior laryngitis and in 16% ofindividuals without the signs of LPR or GERD aswell. Nevertheless, the results of this study point tothe coexistence of esophageal and laryngeal reflux inmost of its participants. However, both the

GERD: 0GERD: 1

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Figure 5. Distribution of individuals with various reflux finding scores (RFS) in both studied groups.

Table III. Mean scores of the laryngeal components of the reflux finding score (RFS) and global laryngeal RFS in patients withgastroesophageal reflux disease (GERD) whose esophageal inflammatory lesions corresponded to group A or B of the Los Angeles (LA)classification.

Finding LA group A (n = 20) LA group B (n = 46) p value

Subglottic edema 1.60 ± 0.82 1.60 ± 0.82 1.000

Ventricular obliteration 2.30 ± 0.73 3.50 ± 0.89 < 0.0001

Erythema/hyperemia 2.80 ± 1.01 4.00 < 0.0001

Vocal cord edema 1.45 ± 0.51 2.10 ± 0.79 0.008

Diffuse laryngeal edema 1.60 ± 0.68 2.50 ± 0.51 < 0.0001

Posterior comissure hypertrophy 1.70 ± 0.57 2.30 ± 0.66 0.005

Granuloma/granulation 0.00 0.00 –

Thick endolaryngeal mucus 0.70 ± 0.98 1.80 ± 0.62 < 0.0001

Total 12.15 ± 2.21 17.80 ± 1.85 < 0.0001

Reflux disease in the larynx 835

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symptomatic group and the control groups includedpatients in whom the etiology of reported problemscould not be explained on the basis of pH-metricfindings [15].In another study, Pribuisiene et al. [16] confirmed

the presence of reflux disease on the basis ofendoscopic and histopathologic examination of theesophagus in 80.6% of patients showing the signs ofLPR. The prevalence of both typical and atypicalsigns of LPR was significantly higher than in thecontrols [16].Our observations suggest that the severity of

esophageal mucosal lesions is tightly associated withlaryngeal imaging findings in GERD patients. Theseverity of laryngeal lesions increased proportionallyto the degree of esophageal injury. This suggests thatit is esophageal reflux that is responsible for the injuryof the larynx, and GERD and LPR should be con-sidered as a common etiological entity. The spectrumof pathologies that can result from reflux diseasemakes the latter an interdisciplinary problem, requir-ing the involvement of many various specialists in thediagnostic and therapeutic process. However, theconsequences of gastroesophageal reflux diseaseand mechanisms responsible for related injury ofvarious organs and tissues are still not completelyunderstood. Continuous increase in the number ofpatients affected with reflux disease and problems inits treatment represent arguments for designing ran-domized controlled trials on the optimal methods ofevaluation and treatment of this condition [17].Our study was an attempt to explain one specific

aspect of reflux disease and perhaps contributed

somehow to our understanding of mechanismsinvolved in the development of reflux disease anddifferences between GERD and LPR.

Conclusions

(1) The severity of laryngeal mucosal lesions inpatients with GERD was significantly greater thanin the controls. (2) A higher degree of laryngealmucosal injury is documented in patients in whomGERD is associated with more advanced esophageallesions.

Declaration of interest: The authors report noconflicts of interest. The authors alone are responsiblefor the content and writing of the paper.

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LA class: ALA class: B

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Figure 6. Distribution of individuals with various reflux finding scores (RFS) in two subsets of patients with gastroesophageal reflux disease(GERD) (group A and B of esophageal lesions).

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