Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association

doi:10.1053/S1542-3565(03)00177-0

Clinical Gastroenterology and Hepatology

Volume 1, Issue 5, September 2003, Pages 333-344

https://doi.org/10.1053/S1542-3565(03)00177-0 Get rights and content

Abstract

Gastroesophageal reflux disease (GERD) has been associated increasingly with ear, nose, and throat (ENT) signs and symptoms. However, the cause and effect relationship between these two clinical entities are far from established. Many patients diagnosed initially with GERD as the cause of laryngeal signs do not symptomatically or laryngoscopically respond to aggressive acid suppression and do not have abnormal esophageal acid exposure by pH monitoring. This has resulted in frustration on the part of both gastroenterologists and ENT physicians and confusion on the part of patients. In this article we discuss the reasons for this controversy and highlight the recent data attempting to clarify this complex area.

Section snippets

Pathophysiology

The specific agent(s) responsible for producing ENT symptoms and laryngeal pathology currently are unknown and the subject of many debates.1, 8 Potential candidates include the gastric contents, acid and pepsin, and duodenal contents, both bile acids and the pancreatic enzyme trypsin. It is difficult to isolate the injurious potential of each of the earlier-listed agents because the gastric milieu refluxing into the esophagus is commonly a mixture of gastric and duodenal contents. Furthermore,

Laryngoscopy

The laryngeal structures are located immediately above the upper esophageal sphincter, which at rest is in a contracted state, protecting this sensitive area. Normal laryngeal tissue is often smooth and glistening in nature (Figure 2). However, the laryngeal examination in patients suspected of having GERD-related symptoms may show subtle or dramatic changes (Figure 3). Contact ulcers in the larynx were the first laryngeal signs associated with GERD.8 However, since then other routinely

Therapy

The skepticism about the accuracy of pH monitoring and laryngoscopy has led some physicians to suggest empiric therapy for suspected cases of GERD-related laryngeal abnormalities. However, the dilemma in treating these patients is their unpredictable response to acid-suppressive therapy. The paradox of GERD therapy is that patients with erosive esophagitis who have severe GERD are also the group who respond best and most predictably to acid-suppressive regimens. In contrast, those with

Conclusions

Although GERD is associated with laryngeal signs and symptoms, the frequency of this association is not well established. Given the fact that the laryngoscopic examination is the driving test in identifying patients whose laryngeal symptoms may be related to GERD, improving the specificity of this test is an important task requiring large multidiscipline studies. Until we have identified these specific laryngeal signs, both gastroenterologists and ENT physicians will be forced to use empiric

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214 high school choir singers, ages 14 through 18, responded to a voice health questionnaire, which included questions about phonotraumatic behaviors and other lifestyle measures regarding voice care, perceived knowledge of the voice, and potential correlational factors such as past singing experience, having a friend or family member when is a professional voice user or possesses an in-depth knowledge of the voice, use of the Internet to sing better or improve understanding of the voice, and other factors. These data were analyzed using descriptive statistics and multivariable linear regressions.
Results showed poor voice hygiene. Phonotraumatic behaviors were frequent and the mean daily water intake was only 5.24 cups. However, 94.4% of the respondents warmed up their voices before rehearsals or performances. The mean total knowledge score, from 0 to 6, was only 2.09. In addition, feeling that one took care of his/her voice well, and use of Internet to sing better or advance knowledge of the voice, were correlated with improved knowledge or measures of voice health.
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The Reflux Symptom Score (RSS) is a patient-related outcomes measure (PROM) that was developed to diagnose Laryngopharyngeal reflux (LPR), by assessing the severity and frequency of specific symptoms and their respective impact on quality of life (QoL).
To develop the Arabic version of RSS-12 (Ar-RSS-12), and to assess its validity and reliability.
The RSS-12 was translated from French into Arabic using the forward–backward translation method, and the translated version underwent transcultural validation. A case–control study was conducted at the otolaryngology clinics of a referral hospital, during the period November to December 2022. It included 61 patients with LPR-related symptoms and a Reflux Symptom Index (RSI) score >13, and 61 control without LPR-related symptoms and negative RSI scores ≤13. The internal consistency, internal and external validity, and Test–Retest reliability of Ar-RSS-12 were analyzed.
Patients had significantly higher scores than controls in all 12 items and total Ar-RSS and QoL impact scores, with high Z score values. Item scores showed variable correlation levels with total Ar-RSS score, with ear-nose-throat items showing the strongest correlation (Spearman’s rho 0.592–0.866). The QoL scores were more strongly correlated to the symptoms’ severity than frequency. The internal consistency was high, with Cronbach’s alpha = 0.878. Regarding external validity, correlations with RSI score showed high Spearman’s rho values for total Ar-RSS (0.905) and QoL total score (0.903). No statistically significant difference was observed between Test and Retest results in any of the 12 items’ score or the total score and QoL, indicating the reproducibility of the test.
The Ar-RSS is a valid and reproducible tool for the screening, assessment, and monitoring of LPR in Arabic speaking patients. The inclusion of symptoms severity and frequency, as well as their individual effects on patient’s QoL, support the superior clinical applications of RSS compared to other existing PROMs.
Anatomical and physiological characteristics in patients with Laryngopharyngeal Reflux Symptoms: A case-control study utilizing high-resolution impedance manometry
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This study aimed to explore the anatomical and physiological characteristics of patients with laryngopharyngeal reflux (LPR) symptoms, such as hoarseness, throat clearing, throat pain, globus, and chronic cough, with the novel high-resolution impedance manometry (HRIM).
Consecutive patients exhibited at least one LPR symptom for ≥4 weeks after 2-month proton-pump inhibitor treatment were enrolled during November 2014 and March 2018 from single tertiary medical center. All patients completed validated symptom questionnaires, esophagogastroduodenoscopy, and HRIM. Healthy volunteers were also recruited for comparison of esophageal parameters on HRIM.
Eighty-nine LPR patients and 63 healthy volunteers were analyzed. Compared with healthy volunteers, LPR patients had significantly shorter upper and lower esophageal sphincters (UES and LES), a shorter intraabdominal esophagus (all P < 0.01), higher 4-s integrated relaxation pressures (IRP-4s) (P = 0.011) of the LES. After adjusted for age, sex, body weight, body height and alcohol consumption, multiple regression analysis showed that age, LES IRP-4s and the UES length were independent risk factors for LPR symptoms (OR 1.056, 95% CI 1.019–1.094; OR 1.107, 95% CI 1.004–1.222; OR 0.432, 95% CI 0.254–0.736, respectively). In subgroup analysis, patients with moderate LPR symptoms had lower IRP-4s (6.64 ± 4.55 vs. 8.69 ± 5.10, P = 0.049) and more failed peristalsis (27.33 ± 29.26 vs. 11.36 ± 21.20, P = 0.004) than those with mild LPR symptoms.
Our study suggests that esophageal structural factors and LES IRP-4s may contribute to the occurrence of LPR symptoms. Patients with moderate LPR symptoms were more likely to present with failed peristalsis.
Predictive Value of Laryngeal Mucosa Pepsin in Therapeutic Response of Laryngopharyngeal Reflux
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To investigate the predictive capability of pepsin level in the laryngeal mucosa to the therapeutic effect of proton-pump inhibitors in patients with suspected laryngopharyngeal reflux (LPR), so as to verify whether it can be referred to as a biomarker of LPR.
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Sixty patients with clinical empiric LPR were enrolled, with an reflux symptom index (RSI) ≥ 13 and an reflux finding score (RFS) > 7 as screening criteria. Biopsy specimens from the interarytenoid mucosa were obtained under topical anesthesia for pepsin immunohistochemical staining. Two parameters were observed in these patients with different pepsin levels after the administration of esomeprazole for 12 weeks: the RSI and the RFS.
Among the 60 cases, 35 cases were negative or weakly positive for pepsin (Pepsin(-) group), and 25 cases were moderately positive or strongly positive for pepsin (Pepsin(+) group). After therapy, the RSI significantly decreased from 17.00 (15.00, 19.00) to 6.00 (5.00, 11.00) in the Pepsin(+) group (Z = -4.38, P < 0.01), but no difference was found in the RFS (T = 1.48, P > 0.05). No significant difference was observed in the RSI (T = 2.01, P > 0.05) or the RFS (T = 2.01, P > 0.05) in the Pepsin(-) group either before or after therapy. An improvement in the RSI ≥ 50% was taken as the standard of effective therapy. The effective rate in the Pepsin(+) group was 72.0% (18/25), while it was 14.3% (5/35) in the Pepsin(-) group. There was a significant difference in the effective rate between the two groups (χ² = 20.55, P < 0.01).
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ReviewLaryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association

Abstract

Section snippets

Pathophysiology

Laryngoscopy

Therapy

Conclusions

Gastroenterol Clin North Am

Am J Med

Am J Otolaryngol

Gastroenterology

Am J Gastroenterol

J Gastrointest Surg

Otolaryngol Head Neck Surg

J Voice

Gastroenterology

Otolaryngol Head Neck Surg

Gastroenterology

J Gastrointest Surg

Otolaryngol Head Neck Surg

Otolaryngol Head Neck Surg

Gastroenterology

Am J Med

Am J Gastroenterol

Am J Gastroenterol

Gastroenterology

Gastroenterology

Am J Gastroenterol

Am J Gastroenterol

Surgery

Chest

The otolaryngologic manifestation of gastroesophageal reflux disease

Laryngoscope

Reflux laryngitis and its sequela

J Voice

Otolaryngologic manifestation of gastroesophageal reflux

Am J Gastroenterol

Gastroesophageal reflux and laryngeal symptoms

Aliment Pharmacol Ther

Laryngeal refluxconsensus conference

J Voice

Experimentally produced vocal cord granulomas

Laryngoscope

Symptomatic gastroesophageal refluxincidence and precipitating factors

Am J Dig Dis

Evaluation of gastroesophageal reflux as a cause of idiopathic hoarseness

Dig Dis Sci

Cougha comprehensive review

Arch Intern Med

Chronic persistent cough in the adultthe spectrum and frequency of causes and successful outcome of specific therapy

Am Rev Respir Dis

Anatomic diagnostic protocol in evaluating chronic cough with specific reference to gastroesophageal reflux disease

Am J Med

Review
Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association