Evaluating the Role of Hoarseness in Diagnosing LPR: A Study of VHI and RSI Scores

Evaluating the Role of Hoarseness in Diagnosing LPR: A Study of VHI and RSI Scores | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Evaluating the Role of Hoarseness in Diagnosing LPR: A Study of VHI and RSI Scores Ebru KARAKAYA GOJAYEV, Zahide Çiler Büyükatalay, Resul Arjin OKSUZ, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7150868/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 11 You are reading this latest preprint version Abstract Background The Reflux Symptom Index (RSI) is commonly used to assess laryngopharyngeal reflux (LPR). However, hoarseness—a symptom included in the RSI—may be elevated due to non-reflux-related voice disorders, potentially leading to diagnostic inaccuracy. To evaluate the influence of hoarseness, measured by the Voice Handicap Index (VHI), on RSI scores, independent of gastroesophageal reflux disease (GERD), and to assess whether this affects the clinical diagnosis of LPR. Methods This retrospective study included 239 patients with voice disorders. RSI and VHI scores were recorded. Univariate linear regression and multivariate generalized linear modeling were performed to assess the relationship between VHI, GERD, and RSI scores. Results Univariate analysis showed that each 1-unit increase in VHI score corresponded to a 0.348-unit increase in RSI score (B: 0.348, SE: 0.056, p<0.001). Multivariate analysis demonstrated that VHI independently predicted RSI scores regardless of GERD status (p<0.001). Notably, 41.5% of patients without GERD had RSI scores ≥13. Conclusion Hoarseness-related voice handicap significantly elevates RSI scores independent of reflux. Clinicians should interpret elevated RSI values with caution in patients with voice disorders to avoid misdiagnosis and overtreatment of LPR. Gastroesophageal Reflux Disease Hoarseness Laryngopharyngeal reflux Voice Disorder Figures Figure 1 Figure 2 Figure 3 Background Laryngopharyngeal reflux (LPR) is a clinical condition in which gastric contents reflux into the upper aerodigestive tract, causing a variety of laryngeal and pharyngeal symptoms 1 . It has been reported that LPR affects up to 50% of individuals with voice complaints in the United States 2 , and it is implicated in the pathogenesis of several laryngeal disorders, including vocal fold nodules, granulomas, chronic laryngitis, and subglottic stenosis 3 , 4 . The gold standard for diagnosing LPR is 24-hour multichannel intraluminal impedance pH monitoring, which allows for objective detection of pharyngeal reflux episodes. However, its high cost, limited availability, and low patient tolerance have restricted its use in routine clinical practice 1 . To overcome these limitations, clinicians have increasingly relied on subjective assessment tools, such as the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS), both developed by Belafsky et al. 5 , 6 . The RSI is a nine-item self-administered questionnaire designed to evaluate the severity of LPR-related symptoms, with scores ≥ 13 considered indicative of LPR 5 . Notably, the first item in the RSI—“Hoarseness or a problem with your voice”—targets a symptom that is not unique to LPR and is commonly observed in numerous other laryngeal pathologies. Hoarseness can result from structural lesions (e.g., nodules, polyps), inflammatory or infectious processes, neurologic conditions, or functional voice disorders 7 . Thus, patients with non-reflux-related voice disorders may score high on the RSI solely due to hoarseness, even in the absence of true reflux pathology. This raises concern about the specificity of the RSI in accurately diagnosing LPR among patients with primary voice disorders. Despite its widespread use, few studies have critically examined the potential confounding effect of hoarseness on RSI scoring. Although gastroesophageal reflux disease (GERD) and LPR are conceptually distinct entities—differing in pathophysiology, symptomatology, and diagnostic criteria—their clinical manifestations often overlap 8 . Moreover, current patient-reported outcome tools such as the RSI do not differentiate between these conditions. Given this diagnostic ambiguity, we defined reflux status based on clinical GERD diagnosis established by the gastroenterology department using 24-hour pH manometry. This classification was used to stratify patients into reflux-positive and reflux-negative groups for the purpose of statistical analysis. In this context, we hypothesised that hoarseness—regardless of underlying reflux status—may artificially inflate RSI scores, potentially leading to overdiagnosis of LPR. Therefore, the aim of this study was to evaluate the relationship between hoarseness (measured by the Voice Handicap Index [VHI]) and the RSI score, and to determine whether the RSI score remains significantly elevated in patients with voice disorders even in the absence of GERD. Methods Study Design and Participants This retrospective study included 239 patients who presented to the otolaryngology outpatient clinic with complaints of hoarseness and were diagnosed with various voice disorders. The study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ankara University Human Research Ethics Committee (Approval No. I8-539-20; 28 September 2020). The requirement for written informed consent was waived due to the retrospective design. Demographic characteristics, RSI scores, and VHI scores were collected from patient records. GERD was diagnosed by the gastroenterology department based on 24-hour pH manometry results. To evaluate the presence of LPR, RSI scoring was used. According to the original study by Belafsky et al., scores ≥ 13 are considered indicative of LPR 5 . Additionally, the Turkish validity study by Akbulut et al. supports a similar diagnostic threshold 9 . Statistical Analysis All statistical analyses were performed using SPSS version 27.0 (IBM Corp., Armonk, NY, USA). Continuous variables were presented as mean ± standard deviation (SD) or median (range), and categorical variables as counts and percentages. The Shapiro–Wilk test was used to assess the normality of data distribution. Comparisons between groups were conducted using the independent samples t-test or Mann–Whitney U test for continuous variables, and the chi-square test or Fisher’s exact test for categorical variables. Spearman’s correlation coefficient was used to evaluate the association between RSI and VHI scores. Univariate linear regression was used to assess the effect of VHI on RSI scores. A multivariate generalized linear model was then employed to determine whether VHI independently predicted RSI scores, adjusting for GERD status. A p-value < 0.05 was considered statistically significant. Results The study included 239 patients with a mean age of 43.4 ± 12.6 years. Of the total cohort, 54.0% were female, 54.8% had a history of smoking, and 49.4% reported vocal abuse or misuse. Comorbidities other than GERD were present in 25.1% of patients, with hypertension being the most common. The distribution of voice disorders was as follows: vocal fold polyps (30.5%), sulcus vocalis (21.8%), Reinke’s edema (20.9%), vocal fold nodules (10.5%), intracordal cysts (7.5%), muscle tension dysphonia (3.8%), chronic laryngitis (1.7%), mutational falsetto (1.7%), spasmodic dysphonia (1.3%), and vocal tremor (0.4%). A confirmed diagnosis of GERD based on 24-hour pH monitoring was present in 104 patients (43.5%). No statistically significant differences were observed between GERD-positive and GERD-negative patients in terms of age, gender, smoking status, vocal abuse history, comorbidities, or distribution of voice disorders (Table 1 ). Table 1 Comparison of baseline characteristics of patients with and without GERD. Characteristics Total, n = 239 GERD p value Present, n = 104 Absent, n = 135 Age, mean ± SD, years 43.4 ± 12.6 43.1 ± 12.7 43.6 ± 12.5 0.788 Female sex, n (%) 129 (54.0) 58 (55.8) 71 (52.6) 0.625 Smoking, n (%) 131 (54.8) 59 (56.7) 72 (53.3) 0.601 Vocal abuse/misuse, n (%) 118 (49.4) 53 (51.0) 65 (48.1) 0.666 Comorbidities, n (%) Hypertension Hypothyroidism Diabetes mellitus Asthma Others 60 (25.1) 22 (9.2) 17 (7.1) 11 (4.6) 5 (2.1) 23 (9.6) 21 (20.2) 9 (8.7) 5 (4.8) 5 (4.8) 0 (0.0) 7 (6.7) 39 (28.9) 13 (9.6) 12 (8.9) 6 (4.4) 5 (3.7) 16 (11.9) 0.124 0.796 0.224 0.894 0.070 0.183 Voice disorder, n (%) Vocal fold polyps Sulcus vocalis Reinke's edema Vocal fold nodules Intracordal cysts MTD Chronic laryngitis Mutational falsetto Spasmodic dysphonia Vocal tremor 73 (30.5) 52 (21.8) 50 (20.9) 25 (10.5) 18 (7.5) 9 (3.8) 4 (1.7) 4 (1.7) 3 (1.3) 1 (0.4) 35 (33.7) 21 (20.2) 22 (21.2) 10 (9.6) 8 (7.7) 3 (2.9) 1 (1.0) 2 (1.9) 1 (1.0) 1 (1.0) 38 (28.1) 31 (23.0) 28 (20.7) 15 (11.1) 10 (7.4) 6 (4.4) 3 (2.2) 2 (1.5) 2 (1.5) 0 (0.0) 0.948 VHI, median (min-max) 23 (0–44) 25 (0–43) 21 (0–44) 0.003 RSI, median (min-max) 15 (0–49) 22 (1–49) 10 (0–40) < 0.001 * Bold text indicates statistical significance at p < 0.05 level. Abbreviations ; GERD: gastroesophageal reflux disease, MTD: muscle tension dysphonia, RSI: reflux symptom index, SD: standard deviation, VHI: voice handicap index. The median VHI score for the entire population was 23 (range: 0–44), and the median RSI score was 15 (range: 0–49). Patients with GERD had significantly higher VHI and RSI scores compared to those without GERD (p = 0.003 and p < 0.001, respectively). In total, 141 patients (59%) had RSI scores ≥ 13. Among patients without GERD, 56 individuals (41.5%) also exceeded this threshold, suggesting a high rate of potentially false-positive RSI results in the absence of reflux (Fig. 2 ). When examined by voice disorder subtype, the proportion of patients with RSI scores ≥ 13 varied: 57.5% for vocal fold polyps, 61.5% for sulcus vocalis, 68.0% for Reinke’s edema, 44.0% for vocal fold nodules, 50.0% for intracordal cysts, 66.7% for muscle tension dysphonia, 100.0% for chronic laryngitis, 50.0% for mutational falsetto, 0.0% for spasmodic dysphonia, and 100.0% for vocal tremor (Fig. 1 ). Spearman’s correlation analysis revealed a moderate positive correlation between VHI and RSI scores (r = 0.399, p < 0.001; Fig. 3 ). In univariate linear regression, each 1-unit increase in VHI score resulted in a 0.348-unit increase in RSI score (B = 0.348, SE = 0.056, p < 0.001). Multivariate generalized linear modeling confirmed that the VHI score remained an independent predictor of RSI score after adjusting for GERD status (Table 2 ). Table 2 Multivariate generalized linear model assessing the effects of GERD and VHI on reflux symptom index. Parameters B SE Wald chi-square p value GERD 8.563 1.336 41.11 < 0.001 VHI 0.283 0.053 28.45 < 0.001 * Bold text indicates statistical significance at p < 0.05 level. Abbreviations ; B: beta coefficient, GERD: gastroesophageal reflux disease, SE: standard error, VHI: voice handicap index. Discussion LPR is recognised as the most common extraesophageal manifestation of GERD 3 . Its typical symptoms include postnasal drip, dysphagia, hoarseness, chronic cough, and frequent throat clearing, many of which overlap with other benign laryngeal conditions 3 , 6 , 10 – 12 . In clinical practice, the Reflux Symptom Index (RSI), introduced by Belafsky et al., is widely used for the assessment of LPR symptoms due to its simplicity and non-invasive nature 5 . However, emerging literature has raised concerns regarding the diagnostic limitations of the RSI, particularly when used in isolation 13 – 16 . Several studies have shown that both the RSI and the Reflux Finding Score (RFS) exhibit limited sensitivity and specificity for confirming LPR, especially when not supported by objective diagnostic tools such as 24-hour impedance pH monitoring 13 – 17 . In particular, Nacci et al. highlighted the risk of false positives associated with relying solely on RSI scores, and advocated for refinement of the RSI to improve its diagnostic accuracy 17 . One key factor contributing to the potential overestimation of reflux symptoms on the RSI is hoarseness—a symptom included as the first item in the scale. Hoarseness is a non-specific complaint that may arise from a wide range of aetiologies, including vocal fold lesions, inflammatory disorders, neurogenic conditions, and functional dysphonia 7 , 18 – 21 . While LPR may indeed contribute to hoarseness, it is rarely the sole cause in patients with established voice disorders. The present study addresses this gap by demonstrating a significant association between VHI and RSI scores, independent of reflux status. Our univariate and multivariate analyses confirmed that hoarseness-related voice handicap can independently elevate RSI scores, even in the absence of GERD. This was further evidenced by the finding that 41.5% of patients without GERD exhibited RSI scores ≥ 13—the conventional cut-off for suspected LPR. These results suggest that the RSI may overestimate reflux symptoms in patients whose hoarseness originates from non-reflux-related causes, potentially leading to misdiagnosis and unnecessary treatment. Clinicians should be cautious when interpreting elevated RSI scores in patients with known voice disorders, and consider complementary assessment tools such as the VHI or laryngeal examination findings before initiating empirical antireflux therapy. Moreover, these findings raise important questions regarding the design of the RSI itself. Given that hoarseness is a frequent but non-specific symptom, future iterations of the RSI may benefit from item reweighting or stratified interpretation when applied to populations with pre-existing voice disorders. Conclusion This study demonstrated that hoarseness—quantified by the Voice Handicap Index (VHI)—is an independent contributor to elevated Reflux Symptom Index (RSI) scores, regardless of gastroesophageal reflux status. A substantial proportion of patients with voice disorders but without confirmed GERD exhibited RSI scores above the diagnostic threshold, indicating that RSI may overestimate reflux symptoms in this population. These findings suggest that the presence of hoarseness from non-reflux-related etiologies can lead to false-positive RSI results, potentially resulting in misdiagnosis and overtreatment of laryngopharyngeal reflux (LPR). Clinicians should interpret RSI scores with caution in patients presenting with primary voice disorders and consider adjunctive tools such as the VHI or objective pH monitoring when making treatment decisions. Future research should focus on refining the RSI by adjusting symptom weighting or developing modified scoring systems that better account for overlapping laryngeal pathologies. Declarations Human Ethics and Consent to Participate declarations: The study was approved by the Ankara University Human Research Ethics Committee (Approval No. I8-539-20; 28 September 2020), and the requirement for written informed consent was waived due to the retrospective nature of the study. Funding: The authors received no financial support for the research, authorship, or publication of this article. Author Contribution E: Collecting the data of the study, conceiving and designing the study, obtaining ethics approval, writing the manuscript. C: Conceiving and designing the study. A: Collecting the data of the study. S: Collecting the data of the study. G: Conceiving the study. Acknowledgement We would like to express my deepest gratitude to all those who have supported and contributed to this study. We thank all the patients for their participation. Data Availability The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author ( Z.C.B.) upon reasonable request. References Koufman JA, Aviv JE, Casiano RR, Shaw GY (2002) Laryngopharyngeal reflux: position statement of the committee on speech, voice, and swallowing disorders of the American Academy of Otolaryngology-Head and Neck Surgery. Otolaryngology—Head Neck Surg 127:32–35 Hopkins C, Yousaf U, Pedersen M (2006) Acid reflux treatment for hoarseness. Cochrane Database Syst Reviews Koufman JA (1991) The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 101:1–78 Ford CN (2005) Evaluation and management of laryngopharyngeal reflux. JAMA 294:1534–1540 Belafsky PC, Postma GN, Koufman JA (2002) Validity and reliability of the reflux symptom index (RSI). J Voice 16:274–277 Belafsky PC, Postma GN, Koufman JA (2001) The validity and reliability of the reflux finding score (RFS). Laryngoscope 111:1313–1317 Stinnett S, Chmielewska M, Akst LM (2018) Update on management of hoarseness. Med Clin 102:1027–1040 Karkos P, Leong S, Benton J, Sastry A, Assimakopoulos D, Issing W (2009) Reflux and sleeping disorders: a systematic review. J Laryngology Otology 123:372–374 Akbulut S, Aydinli FE, Kuşçu O et al (2020) Reliability and validity of the Turkish reflux symptom index. J Voice 34:965 e923-965. e928 Wong R, Hanson DG, Waring PJ, Shaw G (2000) ENT manifestations of gastroesophageal reflux. Am J Gastroenterol 95:S15–22 Little FB, Kohut RI, Koufman JA, Marshall RB (1985) Effect of gastric acid on the pathogenesis of subglottic stenosis. Annals Otology Rhinology Laryngology 94:516–519 Koufman J (2000) Laryngopharyngeal reflux is different from classical gastroesophageal reflux disease: current concepts and a new paradigm of airway disease. Chevalier Jackson Lecture. Transactions of the American Broncho-Esophagological Association. Hoon Park K, Myung Choi S, UK Kwon S, Won Yoon S, Kim UK (2006) Diagnosis of laryngopharyngeal reflux among globus patients. Otolaryngology—Head Neck Surg 134:81–85 de la Iglesia FV, de la González SF (2007) Cámara Gómez M. Laryngopharyngeal reflux: correlation between symptoms and signs by means of clinical assessment questionnaires and fibroendoscopy. Is this sufficient for diagnosis? Acta Otorrinolaringologica (English Edition) 58:421–425 Kelchner LN, Horne J, Lee L et al (2007) Reliability of speech-language pathologist and otolaryngologist ratings of laryngeal signs of reflux in an asymptomatic population using the reflux finding score. J Voice 21:92–100 Watson N, Kwame I, Oakeshott P, Reid F, Rubin J (2013) Comparing the diagnosis of laryngopharyngeal reflux between the reflux symptom index, clinical consultation and reflux finding score in a group of patients presenting to an ENT clinic with an interest in voice disorders: a pilot study in thirty-five patients. Clin Otolaryngol ;38 Nacci A, Bastiani L, Barillari MR et al (2020) Assessment and diagnostic accuracy evaluation of the reflux symptom index (RSI) scale: psychometric properties using optimal scaling techniques. Annals Otology Rhinology Laryngology 129:1020–1029 Reiter R, Hoffmann TK, Pickhard A, Brosch S (2015) Hoarseness—causes and treatments. Deutsches Ärzteblatt international 112:329 Coca–Pelaz A, Rodrigo JP, Takes RP et al (2013) Relationship between reflux and laryngeal cancer. Head Neck 35:1814–1818 Lechien JR, Bobin F, Muls V et al (2021) Changes of laryngeal and extralaryngeal symptoms and findings in laryngopharyngeal reflux patients. Laryngoscope 131:1332–1342 Stinnett S, Chmielewska M, Akst LM (2018) Update on management of hoarseness. Med Clin N Am 102:1027–1040 Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7150868","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":504859701,"identity":"4f276a55-c3e8-4c56-8764-34452691e8ad","order_by":0,"name":"Ebru KARAKAYA GOJAYEV","email":"","orcid":"","institution":"Sincan Education and Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ebru","middleName":"KARAKAYA","lastName":"GOJAYEV","suffix":""},{"id":504859702,"identity":"5ef360a8-b63f-4984-8d99-a734962f9c04","order_by":1,"name":"Zahide Çiler 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2","display":"","copyAsset":false,"role":"figure","size":32646,"visible":true,"origin":"","legend":"\u003cp\u003eDistribution of patients with and without gastroesophageal reflux disease according to RSI scores (p\u0026lt;0.001).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7150868/v1/cd0397eae816ce0d1b6ce6d4.png"},{"id":90001846,"identity":"82f4eb98-9352-4702-b71b-c24ab322e874","added_by":"auto","created_at":"2025-08-27 08:58:13","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":47917,"visible":true,"origin":"","legend":"\u003cp\u003eSpearman correlation analysis between VHI and RSI scores.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7150868/v1/67c7ad57e90eafe37c312d9b.png"},{"id":90004186,"identity":"7aabcf7c-a352-42dc-bcd3-241f486f11c3","added_by":"auto","created_at":"2025-08-27 09:22:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":639300,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7150868/v1/a3be5d9b-70b4-40b4-98d9-1155b09dbb71.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Evaluating the Role of Hoarseness in Diagnosing LPR: A Study of VHI and RSI Scores","fulltext":[{"header":"Background","content":"\u003cp\u003eLaryngopharyngeal reflux (LPR) is a clinical condition in which gastric contents reflux into the upper aerodigestive tract, causing a variety of laryngeal and pharyngeal symptoms \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. It has been reported that LPR affects up to 50% of individuals with voice complaints in the United States \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e, and it is implicated in the pathogenesis of several laryngeal disorders, including vocal fold nodules, granulomas, chronic laryngitis, and subglottic stenosis \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe gold standard for diagnosing LPR is 24-hour multichannel intraluminal impedance pH monitoring, which allows for objective detection of pharyngeal reflux episodes. However, its high cost, limited availability, and low patient tolerance have restricted its use in routine clinical practice \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. To overcome these limitations, clinicians have increasingly relied on subjective assessment tools, such as the Reflux Symptom Index (RSI) and Reflux Finding Score (RFS), both developed by Belafsky et al. \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e. The RSI is a nine-item self-administered questionnaire designed to evaluate the severity of LPR-related symptoms, with scores ≥ 13 considered indicative of LPR \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eNotably, the first item in the RSI—“Hoarseness or a problem with your voice”—targets a symptom that is not unique to LPR and is commonly observed in numerous other laryngeal pathologies. Hoarseness can result from structural lesions (e.g., nodules, polyps), inflammatory or infectious processes, neurologic conditions, or functional voice disorders \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. Thus, patients with non-reflux-related voice disorders may score high on the RSI solely due to hoarseness, even in the absence of true reflux pathology.\u003c/p\u003e\u003cp\u003eThis raises concern about the specificity of the RSI in accurately diagnosing LPR among patients with primary voice disorders. Despite its widespread use, few studies have critically examined the potential confounding effect of hoarseness on RSI scoring.\u003c/p\u003e\u003cp\u003eAlthough gastroesophageal reflux disease (GERD) and LPR are conceptually distinct entities—differing in pathophysiology, symptomatology, and diagnostic criteria—their clinical manifestations often overlap \u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Moreover, current patient-reported outcome tools such as the RSI do not differentiate between these conditions. Given this diagnostic ambiguity, we defined reflux status based on clinical GERD diagnosis established by the gastroenterology department using 24-hour pH manometry. This classification was used to stratify patients into reflux-positive and reflux-negative groups for the purpose of statistical analysis.\u003c/p\u003e\u003cp\u003eIn this context, we hypothesised that hoarseness—regardless of underlying reflux status—may artificially inflate RSI scores, potentially leading to overdiagnosis of LPR. Therefore, the aim of this study was to evaluate the relationship between hoarseness (measured by the Voice Handicap Index [VHI]) and the RSI score, and to determine whether the RSI score remains significantly elevated in patients with voice disorders even in the absence of GERD.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cb\u003eStudy Design and Participants\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis retrospective study included 239 patients who presented to the otolaryngology outpatient clinic with complaints of hoarseness and were diagnosed with various voice disorders. The study was conducted in accordance with the principles of the Declaration of Helsinki and approved by the Ankara University Human Research Ethics Committee (Approval No. I8-539-20; 28 September 2020). The requirement for written informed consent was waived due to the retrospective design.\u003c/p\u003e\u003cp\u003eDemographic characteristics, RSI scores, and VHI scores were collected from patient records. GERD was diagnosed by the gastroenterology department based on 24-hour pH manometry results.\u003c/p\u003e\u003cp\u003eTo evaluate the presence of LPR, RSI scoring was used. According to the original study by Belafsky et al., scores ≥ 13 are considered indicative of LPR \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Additionally, the Turkish validity study by Akbulut et al. supports a similar diagnostic threshold \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eAll statistical analyses were performed using SPSS version 27.0 (IBM Corp., Armonk, NY, USA). Continuous variables were presented as mean ± standard deviation (SD) or median (range), and categorical variables as counts and percentages. The Shapiro–Wilk test was used to assess the normality of data distribution.\u003c/p\u003e\u003cp\u003eComparisons between groups were conducted using the independent samples t-test or Mann–Whitney U test for continuous variables, and the chi-square test or Fisher’s exact test for categorical variables. Spearman’s correlation coefficient was used to evaluate the association between RSI and VHI scores. Univariate linear regression was used to assess the effect of VHI on RSI scores. A multivariate generalized linear model was then employed to determine whether VHI independently predicted RSI scores, adjusting for GERD status. A p-value \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe study included 239 patients with a mean age of 43.4\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6 years. Of the total cohort, 54.0% were female, 54.8% had a history of smoking, and 49.4% reported vocal abuse or misuse. Comorbidities other than GERD were present in 25.1% of patients, with hypertension being the most common. The distribution of voice disorders was as follows: vocal fold polyps (30.5%), sulcus vocalis (21.8%), Reinke\u0026rsquo;s edema (20.9%), vocal fold nodules (10.5%), intracordal cysts (7.5%), muscle tension dysphonia (3.8%), chronic laryngitis (1.7%), mutational falsetto (1.7%), spasmodic dysphonia (1.3%), and vocal tremor (0.4%).\u003c/p\u003e\n\u003cp\u003eA confirmed diagnosis of GERD based on 24-hour pH monitoring was present in 104 patients (43.5%). No statistically significant differences were observed between GERD-positive and GERD-negative patients in terms of age, gender, smoking status, vocal abuse history, comorbidities, or distribution of voice disorders (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eComparison of baseline characteristics of patients with and without GERD.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eCharacteristics\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eTotal, n\u0026thinsp;=\u0026thinsp;239\u003c/p\u003e\n\u003c/th\u003e\n\u003cth colspan=\"2\" align=\"left\"\u003e\n\u003cp\u003eGERD\u003c/p\u003e\n\u003c/th\u003e\n\u003cth rowspan=\"2\" align=\"left\"\u003e\n\u003cp\u003ep value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ePresent, n\u0026thinsp;=\u0026thinsp;104\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eAbsent, n\u0026thinsp;=\u0026thinsp;135\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eAge, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, years\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43.4\u0026thinsp;\u0026plusmn;\u0026thinsp;12.6\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43.1\u0026thinsp;\u0026plusmn;\u0026thinsp;12.7\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e43.6\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.788\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eFemale sex, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e129 (54.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e58 (55.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e71 (52.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.625\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eSmoking, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e131 (54.8)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e59 (56.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e72 (53.3)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.601\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVocal abuse/misuse, n (%)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e118 (49.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e53 (51.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e65 (48.1)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.666\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eComorbidities, n (%)\u003c/p\u003e\n\u003cp\u003eHypertension\u003c/p\u003e\n\u003cp\u003eHypothyroidism\u003c/p\u003e\n\u003cp\u003eDiabetes mellitus\u003c/p\u003e\n\u003cp\u003eAsthma\u003c/p\u003e\n\u003cp\u003eOthers\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e60 (25.1)\u003c/p\u003e\n\u003cp\u003e22 (9.2)\u003c/p\u003e\n\u003cp\u003e17 (7.1)\u003c/p\u003e\n\u003cp\u003e11 (4.6)\u003c/p\u003e\n\u003cp\u003e5 (2.1)\u003c/p\u003e\n\u003cp\u003e23 (9.6)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (20.2)\u003c/p\u003e\n\u003cp\u003e9 (8.7)\u003c/p\u003e\n\u003cp\u003e5 (4.8)\u003c/p\u003e\n\u003cp\u003e5 (4.8)\u003c/p\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003cp\u003e7 (6.7)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e39 (28.9)\u003c/p\u003e\n\u003cp\u003e13 (9.6)\u003c/p\u003e\n\u003cp\u003e12 (8.9)\u003c/p\u003e\n\u003cp\u003e6 (4.4)\u003c/p\u003e\n\u003cp\u003e5 (3.7)\u003c/p\u003e\n\u003cp\u003e16 (11.9)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.124\u003c/p\u003e\n\u003cp\u003e0.796\u003c/p\u003e\n\u003cp\u003e0.224\u003c/p\u003e\n\u003cp\u003e0.894\u003c/p\u003e\n\u003cp\u003e0.070\u003c/p\u003e\n\u003cp\u003e0.183\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVoice disorder, n (%)\u003c/p\u003e\n\u003cp\u003eVocal fold polyps\u003c/p\u003e\n\u003cp\u003eSulcus vocalis\u003c/p\u003e\n\u003cp\u003eReinke's edema\u003c/p\u003e\n\u003cp\u003eVocal fold nodules\u003c/p\u003e\n\u003cp\u003eIntracordal cysts\u003c/p\u003e\n\u003cp\u003eMTD\u003c/p\u003e\n\u003cp\u003eChronic laryngitis\u003c/p\u003e\n\u003cp\u003eMutational falsetto\u003c/p\u003e\n\u003cp\u003eSpasmodic dysphonia\u003c/p\u003e\n\u003cp\u003eVocal tremor\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e73 (30.5)\u003c/p\u003e\n\u003cp\u003e52 (21.8)\u003c/p\u003e\n\u003cp\u003e50 (20.9)\u003c/p\u003e\n\u003cp\u003e25 (10.5)\u003c/p\u003e\n\u003cp\u003e18 (7.5)\u003c/p\u003e\n\u003cp\u003e9 (3.8)\u003c/p\u003e\n\u003cp\u003e4 (1.7)\u003c/p\u003e\n\u003cp\u003e4 (1.7)\u003c/p\u003e\n\u003cp\u003e3 (1.3)\u003c/p\u003e\n\u003cp\u003e1 (0.4)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e35 (33.7)\u003c/p\u003e\n\u003cp\u003e21 (20.2)\u003c/p\u003e\n\u003cp\u003e22 (21.2)\u003c/p\u003e\n\u003cp\u003e10 (9.6)\u003c/p\u003e\n\u003cp\u003e8 (7.7)\u003c/p\u003e\n\u003cp\u003e3 (2.9)\u003c/p\u003e\n\u003cp\u003e1 (1.0)\u003c/p\u003e\n\u003cp\u003e2 (1.9)\u003c/p\u003e\n\u003cp\u003e1 (1.0)\u003c/p\u003e\n\u003cp\u003e1 (1.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e38 (28.1)\u003c/p\u003e\n\u003cp\u003e31 (23.0)\u003c/p\u003e\n\u003cp\u003e28 (20.7)\u003c/p\u003e\n\u003cp\u003e15 (11.1)\u003c/p\u003e\n\u003cp\u003e10 (7.4)\u003c/p\u003e\n\u003cp\u003e6 (4.4)\u003c/p\u003e\n\u003cp\u003e3 (2.2)\u003c/p\u003e\n\u003cp\u003e2 (1.5)\u003c/p\u003e\n\u003cp\u003e2 (1.5)\u003c/p\u003e\n\u003cp\u003e0 (0.0)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e0.948\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVHI, median (min-max)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e23 (0\u0026ndash;44)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e25 (0\u0026ndash;43)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e21 (0\u0026ndash;44)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e0.003\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eRSI, median (min-max)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e15 (0\u0026ndash;49)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e22 (1\u0026ndash;49)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003e10 (0\u0026ndash;40)\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e* Bold text indicates statistical significance at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 level.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e\u003cem\u003eAbbreviations\u003c/em\u003e; GERD: gastroesophageal reflux disease, MTD: muscle tension dysphonia, RSI: reflux symptom index, SD: standard deviation, VHI: voice handicap index.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eThe median VHI score for the entire population was 23 (range: 0\u0026ndash;44), and the median RSI score was 15 (range: 0\u0026ndash;49). Patients with GERD had significantly higher VHI and RSI scores compared to those without GERD (p\u0026thinsp;=\u0026thinsp;0.003 and p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, respectively). In total, 141 patients (59%) had RSI scores\u0026thinsp;\u0026ge;\u0026thinsp;13. Among patients without GERD, 56 individuals (41.5%) also exceeded this threshold, suggesting a high rate of potentially false-positive RSI results in the absence of reflux (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eWhen examined by voice disorder subtype, the proportion of patients with RSI scores\u0026thinsp;\u0026ge;\u0026thinsp;13 varied: 57.5% for vocal fold polyps, 61.5% for sulcus vocalis, 68.0% for Reinke\u0026rsquo;s edema, 44.0% for vocal fold nodules, 50.0% for intracordal cysts, 66.7% for muscle tension dysphonia, 100.0% for chronic laryngitis, 50.0% for mutational falsetto, 0.0% for spasmodic dysphonia, and 100.0% for vocal tremor (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cp\u003eSpearman\u0026rsquo;s correlation analysis revealed a moderate positive correlation between VHI and RSI scores (r\u0026thinsp;=\u0026thinsp;0.399, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001; Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e). In univariate linear regression, each 1-unit increase in VHI score resulted in a 0.348-unit increase in RSI score (B\u0026thinsp;=\u0026thinsp;0.348, SE\u0026thinsp;=\u0026thinsp;0.056, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Multivariate generalized linear modeling confirmed that the VHI score remained an independent predictor of RSI score after adjusting for GERD status (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n\u003cdiv class=\"colspec\" align=\"left\"\u003e\u0026nbsp;\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\u003ccaption\u003e\n\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n\u003cdiv class=\"CaptionContent\"\u003e\n\u003cp\u003eMultivariate generalized linear model assessing the effects of GERD and VHI on reflux symptom index.\u003c/p\u003e\n\u003c/div\u003e\n\u003c/caption\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eParameters\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eB\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eSE\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003eWald chi-square\u003c/p\u003e\n\u003c/th\u003e\n\u003cth align=\"left\"\u003e\n\u003cp\u003ep value\u003c/p\u003e\n\u003c/th\u003e\n\u003c/tr\u003e\n\u003c/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eGERD\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e8.563\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e1.336\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e41.11\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd align=\"left\"\u003e\n\u003cp\u003eVHI\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.283\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e0.053\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e28.45\u003c/p\u003e\n\u003c/td\u003e\n\u003ctd align=\"char\" char=\".\"\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026lt;\u0026thinsp;0.001\u003c/strong\u003e\u003c/p\u003e\n\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tbody\u003e\n\u003ctfoot\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e* Bold text indicates statistical significance at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 level.\u003c/td\u003e\n\u003c/tr\u003e\n\u003ctr\u003e\n\u003ctd colspan=\"5\"\u003e\u003cem\u003eAbbreviations\u003c/em\u003e; B: beta coefficient, GERD: gastroesophageal reflux disease, SE: standard error, VHI: voice handicap index.\u003c/td\u003e\n\u003c/tr\u003e\n\u003c/tfoot\u003e\n\u003c/table\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eLPR is recognised as the most common extraesophageal manifestation of GERD \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Its typical symptoms include postnasal drip, dysphagia, hoarseness, chronic cough, and frequent throat clearing, many of which overlap with other benign laryngeal conditions \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn clinical practice, the Reflux Symptom Index (RSI), introduced by Belafsky et al., is widely used for the assessment of LPR symptoms due to its simplicity and non-invasive nature \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. However, emerging literature has raised concerns regarding the diagnostic limitations of the RSI, particularly when used in isolation \u003csup\u003e\u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eSeveral studies have shown that both the RSI and the Reflux Finding Score (RFS) exhibit limited sensitivity and specificity for confirming LPR, especially when not supported by objective diagnostic tools such as 24-hour impedance pH monitoring \u003csup\u003e\u003cspan additionalcitationids=\"CR14 CR15 CR16\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. In particular, Nacci et al. highlighted the risk of false positives associated with relying solely on RSI scores, and advocated for refinement of the RSI to improve its diagnostic accuracy \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOne key factor contributing to the potential overestimation of reflux symptoms on the RSI is hoarseness\u0026mdash;a symptom included as the first item in the scale. Hoarseness is a non-specific complaint that may arise from a wide range of aetiologies, including vocal fold lesions, inflammatory disorders, neurogenic conditions, and functional dysphonia \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e. While LPR may indeed contribute to hoarseness, it is rarely the sole cause in patients with established voice disorders.\u003c/p\u003e\u003cp\u003eThe present study addresses this gap by demonstrating a significant association between VHI and RSI scores, independent of reflux status. Our univariate and multivariate analyses confirmed that hoarseness-related voice handicap can independently elevate RSI scores, even in the absence of GERD. This was further evidenced by the finding that 41.5% of patients without GERD exhibited RSI scores\u0026thinsp;\u0026ge;\u0026thinsp;13\u0026mdash;the conventional cut-off for suspected LPR.\u003c/p\u003e\u003cp\u003eThese results suggest that the RSI may overestimate reflux symptoms in patients whose hoarseness originates from non-reflux-related causes, potentially leading to misdiagnosis and unnecessary treatment. Clinicians should be cautious when interpreting elevated RSI scores in patients with known voice disorders, and consider complementary assessment tools such as the VHI or laryngeal examination findings before initiating empirical antireflux therapy.\u003c/p\u003e\u003cp\u003eMoreover, these findings raise important questions regarding the design of the RSI itself. Given that hoarseness is a frequent but non-specific symptom, future iterations of the RSI may benefit from item reweighting or stratified interpretation when applied to populations with pre-existing voice disorders.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study demonstrated that hoarseness\u0026mdash;quantified by the Voice Handicap Index (VHI)\u0026mdash;is an independent contributor to elevated Reflux Symptom Index (RSI) scores, regardless of gastroesophageal reflux status. A substantial proportion of patients with voice disorders but without confirmed GERD exhibited RSI scores above the diagnostic threshold, indicating that RSI may overestimate reflux symptoms in this population.\u003c/p\u003e\u003cp\u003eThese findings suggest that the presence of hoarseness from non-reflux-related etiologies can lead to false-positive RSI results, potentially resulting in misdiagnosis and overtreatment of laryngopharyngeal reflux (LPR). Clinicians should interpret RSI scores with caution in patients presenting with primary voice disorders and consider adjunctive tools such as the VHI or objective pH monitoring when making treatment decisions.\u003c/p\u003e\u003cp\u003eFuture research should focus on refining the RSI by adjusting symptom weighting or developing modified scoring systems that better account for overlapping laryngeal pathologies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eHuman Ethics and Consent to Participate declarations:\u003c/h2\u003e\u003cp\u003e The study was approved by the Ankara University Human Research Ethics Committee (Approval No. I8-539-20; 28 September 2020), and the requirement for written informed consent was waived due to the retrospective nature of the study.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eThe authors received no financial support for the research, authorship, or publication of this article.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eE: Collecting the data of the study, conceiving and designing the study, obtaining ethics approval, writing the manuscript. C: Conceiving and designing the study. A: Collecting the data of the study. S: Collecting the data of the study. G: Conceiving the study.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to express my deepest gratitude to all those who have supported and contributed to this study. We thank all the patients for their participation.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from the corresponding author ( Z.C.B.) upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKoufman JA, Aviv JE, Casiano RR, Shaw GY (2002) Laryngopharyngeal reflux: position statement of the committee on speech, voice, and swallowing disorders of the American Academy of Otolaryngology-Head and Neck Surgery. Otolaryngology\u0026mdash;Head Neck Surg 127:32\u0026ndash;35\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHopkins C, Yousaf U, Pedersen M (2006) Acid reflux treatment for hoarseness. Cochrane Database Syst Reviews\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoufman JA (1991) The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): a clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 101:1\u0026ndash;78\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFord CN (2005) Evaluation and management of laryngopharyngeal reflux. JAMA 294:1534\u0026ndash;1540\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBelafsky PC, Postma GN, Koufman JA (2002) Validity and reliability of the reflux symptom index (RSI). J Voice 16:274\u0026ndash;277\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBelafsky PC, Postma GN, Koufman JA (2001) The validity and reliability of the reflux finding score (RFS). Laryngoscope 111:1313\u0026ndash;1317\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStinnett S, Chmielewska M, Akst LM (2018) Update on management of hoarseness. Med Clin 102:1027\u0026ndash;1040\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKarkos P, Leong S, Benton J, Sastry A, Assimakopoulos D, Issing W (2009) Reflux and sleeping disorders: a systematic review. J Laryngology Otology 123:372\u0026ndash;374\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAkbulut S, Aydinli FE, Kuş\u0026ccedil;u O et al (2020) Reliability and validity of the Turkish reflux symptom index. J Voice 34:965 e923-965. e928\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWong R, Hanson DG, Waring PJ, Shaw G (2000) ENT manifestations of gastroesophageal reflux. Am J Gastroenterol 95:S15\u0026ndash;22\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLittle FB, Kohut RI, Koufman JA, Marshall RB (1985) Effect of gastric acid on the pathogenesis of subglottic stenosis. Annals Otology Rhinology Laryngology 94:516\u0026ndash;519\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoufman J (2000) Laryngopharyngeal reflux is different from classical gastroesophageal reflux disease: current concepts and a new paradigm of airway disease. Chevalier Jackson Lecture. \u003cem\u003eTransactions of the American Broncho-Esophagological Association.\u003c/em\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHoon Park K, Myung Choi S, UK Kwon S, Won Yoon S, Kim UK (2006) Diagnosis of laryngopharyngeal reflux among globus patients. Otolaryngology\u0026mdash;Head Neck Surg 134:81\u0026ndash;85\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede la Iglesia FV, de la Gonz\u0026aacute;lez SF (2007) C\u0026aacute;mara G\u0026oacute;mez M. Laryngopharyngeal reflux: correlation between symptoms and signs by means of clinical assessment questionnaires and fibroendoscopy. Is this sufficient for diagnosis? Acta Otorrinolaringologica (English Edition) 58:421\u0026ndash;425\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKelchner LN, Horne J, Lee L et al (2007) Reliability of speech-language pathologist and otolaryngologist ratings of laryngeal signs of reflux in an asymptomatic population using the reflux finding score. J Voice 21:92\u0026ndash;100\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWatson N, Kwame I, Oakeshott P, Reid F, Rubin J (2013) Comparing the diagnosis of laryngopharyngeal reflux between the reflux symptom index, clinical consultation and reflux finding score in a group of patients presenting to an ENT clinic with an interest in voice disorders: a pilot study in thirty-five patients. Clin Otolaryngol ;38\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNacci A, Bastiani L, Barillari MR et al (2020) Assessment and diagnostic accuracy evaluation of the reflux symptom index (RSI) scale: psychometric properties using optimal scaling techniques. Annals Otology Rhinology Laryngology 129:1020\u0026ndash;1029\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eReiter R, Hoffmann TK, Pickhard A, Brosch S (2015) Hoarseness\u0026mdash;causes and treatments. Deutsches \u0026Auml;rzteblatt international 112:329\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCoca\u0026ndash;Pelaz A, Rodrigo JP, Takes RP et al (2013) Relationship between reflux and laryngeal cancer. Head Neck 35:1814\u0026ndash;1818\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLechien JR, Bobin F, Muls V et al (2021) Changes of laryngeal and extralaryngeal symptoms and findings in laryngopharyngeal reflux patients. Laryngoscope 131:1332\u0026ndash;1342\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStinnett S, Chmielewska M, Akst LM (2018) Update on management of hoarseness. Med Clin N Am 102:1027\u0026ndash;1040\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-otolaryngology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Otolaryngology](https://ejo.springeropen.com/)","snPcode":"43163","submissionUrl":"https://submission.springernature.com/new-submission/43163/3","title":"The Egyptian Journal of Otolaryngology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Gastroesophageal Reflux Disease, Hoarseness, Laryngopharyngeal reflux, Voice Disorder","lastPublishedDoi":"10.21203/rs.3.rs-7150868/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7150868/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003cbr\u003e\n\u003c/strong\u003eThe Reflux Symptom Index (RSI) is commonly used to assess laryngopharyngeal reflux (LPR). However, hoarseness—a symptom included in the RSI—may be elevated due to non-reflux-related voice disorders, potentially leading to diagnostic inaccuracy. \u003cstrong\u003e\u003cbr\u003e\n\u003c/strong\u003eTo evaluate the influence of hoarseness, measured by the Voice Handicap Index (VHI), on RSI scores, independent of gastroesophageal reflux disease (GERD), and to assess whether this affects the clinical diagnosis of LPR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003cbr\u003e\n\u003c/strong\u003eThis retrospective study included 239 patients with voice disorders. RSI and VHI scores were recorded. Univariate linear regression and multivariate generalized linear modeling were performed to assess the relationship between VHI, GERD, and RSI scores.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003cbr\u003e\n\u003c/strong\u003eUnivariate analysis showed that each 1-unit increase in VHI score corresponded to a 0.348-unit increase in RSI score (B: 0.348, SE: 0.056, p\u0026lt;0.001). Multivariate analysis demonstrated that VHI independently predicted RSI scores regardless of GERD status (p\u0026lt;0.001). Notably, 41.5% of patients without GERD had RSI scores ≥13.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003cbr\u003e\n\u003c/strong\u003eHoarseness-related voice handicap significantly elevates RSI scores independent of reflux. Clinicians should interpret elevated RSI values with caution in patients with voice disorders to avoid misdiagnosis and overtreatment of LPR.\u003c/p\u003e","manuscriptTitle":"Evaluating the Role of Hoarseness in Diagnosing LPR: A Study of VHI and RSI Scores","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-27 08:58:08","doi":"10.21203/rs.3.rs-7150868/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-09-05T21:03:49+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-04T14:03:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-03T23:21:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"143649629144510865521612616032298495923","date":"2025-08-24T16:36:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-22T03:53:06+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313223212379489730187852477226047298367","date":"2025-08-21T13:19:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"117251183418383401576969608484347296151","date":"2025-08-19T03:41:30+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-18T22:37:28+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-07-24T12:19:29+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-07-24T12:19:21+00:00","index":"","fulltext":""},{"type":"submitted","content":"The Egyptian Journal of Otolaryngology","date":"2025-07-17T16:03:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"the-egyptian-journal-of-otolaryngology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [The Egyptian Journal of Otolaryngology](https://ejo.springeropen.com/)","snPcode":"43163","submissionUrl":"https://submission.springernature.com/new-submission/43163/3","title":"The Egyptian Journal of Otolaryngology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Open","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8bd6d950-0db4-40d3-b000-061c491f3d38","owner":[],"postedDate":"August 27th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-10-17T11:23:48+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-27 08:58:08","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7150868","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7150868","identity":"rs-7150868","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}