Validity of Reflux Symptom Index in the Diagnosis of Laryngopharyngeal Reflux Disease

Introduction

Laryngopharyngeal reflux (LPR) is a disease, in which the diagnosis and treatment are controversial. Numerous studies show that up to 10% of patients presenting to ENT outpatient clinic and up to 55% of patients presenting with hoarseness of voice may suffer from LPR.^[1] LPR disease (LPRD) is a disease caused by the retrograde flow of gastric contents to the laryngopharynx where it comes into contact with the tissues of the upper aerodigestive tract. LPR is considered a subset of gastroesophageal reflux disease (GERD), but the disease has its own identity, because the main region involved is the laryngopharynx.^[2] The precise mechanism of LPR has yet to be elucidated. The evolution of humans into upright, bipedal organisms has led to a unique predisposition to gastroesophageal reflux and consequent aspiration. Recent advances in the knowledge of the pathophysiology of GERD, including both the composition of the refluxate and the mechanisms of damage to the respiratory epithelium give us a better idea of the development of clinical manifestations of gastroesophageal reflux in the upper and lower respiratory tracts.^[3]

Patients with LPR may complain of a broad spectrum of symptoms, including dry cough, the need for constantly clearing their throat, foreign-body sensation, and voice changes.^[4] A detailed history should be taken with emphasis on occupational history and personal habits and addictions such as tobacco use, smoking, and alcoholism. During the clinical examination of the patient, the examiner should observe the patient for the quality of the voice, frequent throat clearing, cough or stridor, muscle tension in extra-laryngeal musculature, and general body habitus. The larynx has to be evaluated with indirect laryngoscopy along with rigid and/or flexible laryngoscopy.^[3],[5],[6]

Rigid endoscopy requires an extended neck and protruded tongue for the examination of larynx. Furthermore, the larynx during phonation can be assessed only saying sustained vowels. Flexible laryngoscopy does not require an extended neck or protruded tongue, and the larynx in phonation can be assessed during normal speech.^[7],[8] Laryngeal sensory testing can be used to assess the degree of damage to the laryngeal epithelium and to assess the response to the treatment of LPR.^[5] LPR has implications in several clinical disorders, which include chronic laryngitis, chronic dysphonia, laryngotracheal stenosis, head-and-neck carcinoma, cough, asthma, otitis media, dental caries and erosion, laryngeal papilloma, vocal fold granulomas and ulcers, laryngospasm, recurrent croup, paradoxical vocal fold movement disorder, and laryngomalacia.^[9],[10]

In this regard, the reflux symptom index (RSI) has a promising role in the clinical diagnosis of LPRD. The validity of this tool has been tested and proved in the US setting, but in spite of the fact that the Indian population is more prone for the development of GERD and hence LPRD, studies validating the usefulness of this tool are lacking in the Indian setting. The need for the validation of such a questionnaire is stressed by the fact that most of the clinics and hospitals in the Indian setting, especially in the rural areas do not have access to flexible fiber-optic laryngoscopy or even rigid telescopic laryngoscopy to confirm the findings of this disease. Most of the time even the specialized clinicians may have to diagnose the disease by indirect laryngoscopy which is an unreliable technique. The validation of RSI will allow the clinician to make a clinical diagnosis and start an empirical treatment which will save a lot of resources and limit the improper treatments given.^[7] The main objectives of this study were to assess the validity of the RSI in patients exhibiting symptoms of LPRD or GERD. In addition, the study aimed to determine the proportion of patients with GERD symptoms who also had LPRD. By investigating these aspects, the researchers aimed to gain a better understanding of the prevalence and diagnostic accuracy of RSI in relation to these two reflux-related conditions.

Materials and Methods

After getting IEC clearance (SMCSIMCH/EC (PHARM) 27/2014), this study was a hospital-based, cross-sectional study that utilized a consecutive sampling method. The study was conducted at the Department of ENT, Dr. Somervell Memorial CSI Medical College in Karakonam, Trivandrum, India, from November 2014 to October 2015. The study included all patients above the age of 12 years who presented to the ENT outpatient department (OPD) with symptoms of LPRD or GERD. Patients who refused to give consent for the study, those who had undergone medical treatment the past 6 weeks or surgical treatment for similar complaints, patients with malignancy of the hypopharynx and esophagus, patients with neurological causes of dysphonia and dysphagia, patients with a history of throat trauma or prior intubation, patients with allergies or chronic upper respiratory tract infections, and pregnant patients were excluded from the study. The variables examined in this study included age, sex, RSI, and Reflux Finding Score (RFS).

The sample size was calculated using the following formula: n = 4pq/d², where p represents the available prevalence rate in the target population (obtained from comparable studies), q is equal to 100 − p, and d represents the relative precision (20% of the previous prevalence). In this study, p was assumed to be 50 based on the various literature reviews, q was 50, and d was 10. Therefore, the sample size was determined to be 100. Consecutive participants attending the ENT OPD, who met the inclusion and exclusion criteria, were included in the study after obtaining their informed consent. Approval from the Institutional Scientific and Ethical Committee was obtained before the commencement of the study. Written informed consent was obtained from all the participants of the study. Privacy and confidentiality of the details collected from the patients are being maintained.

Data were collected from 105 patients in this study who presented with symptoms suggestive of GERD or LPRD. The patients underwent a questionnaire based on a pro forma, a detailed general and ENT examination, and flexible fiber-optic laryngoscopy to collect the data for the study. The grading of symptoms was done using the RSI, and further diagnosis was made using flexible fiber-optic laryngoscopy based on the RFS.

The data were recorded using Microsoft Excel software and analyzed using the Statistical Package for the Social Sciences (SPSS) software version 25.0, (IBM, Chicago, Illinois, USA). The validity of the RSI for the diagnosis of LPRD was assessed by determining the sensitivity, specificity, positive predictive value, and diagnostic accuracy.

Results

The majority of the patients (49.3%) were in the age group of 31–50 years, followed by 29% of patients under 30 years of age and 21.7% of patients above 50 years of age. Among the patients diagnosed with LPRD, the majority of patients (65.2%) were females. Among the patients diagnosed with LPRD, only 15 patients (21.7%) had diabetes mellitus. Among the 69 patients diagnosed with LPRD, only 7 patients (10.1%) had bronchial asthma. Around 4 patients (5.8%) had a history of thyroid disease. Around 32 patients (46.4%) were found to take spicy diet regularly. Among the 69 patients positive for LPRD, 6 patients (8.7%) had a history of smoking/tobacco usage addiction. Sinus infection was found in 11 of the 69 LPRD-diagnosed patients (15.9%). Recurrent throat infection was associated in 13 of the 69 (18.8%) patients diagnosed to have LPRD [Table 1].

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Table 1

Association of study variables with laryngopharyngeal reflux disease (n=105)

The association between LPRG diagnosed by RSI (>12) and those diagnosed with LPRD by RFS (>7) gives us the sensitivity of 97.1%, specificity 66.7%, positive predictive value 84.8%, and the negative predictive 92.3% [Table 2]. Hence, the diagnostic accuracy of RSI was calculated and found to be 86.7%. Among the 105 patients studied, it was found that only 46 of the 69 LPRD-positive patients (66.7%) showed symptoms suggestive of GERD.

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Table 2

Diagnostic accuracy of laryngopharyngeal reflux disease with reflux finding score and gastroesophageal reflux disease (n=105)

Discussion

LPR is a disease, in which the diagnosis and treatment are controversial. The term “LPRD” was coined to describe a subset of GERD patients who had extra esophageal manifestations of gastric reflux and presented with an additional array of laryngeal and pharyngeal symptoms. These patients may or may not have typical symptoms of GERD. There is a lot of debate regarding which all symptoms should be used to diagnose LPRD. Patients with LPRD can present with a variety of symptoms and these symptoms overlap with those of other diseases. This stresses the need for a proper symptom grading tool that can make a preliminary diagnosis of LPRD so that wrong diagnosis and treatment can be kept to the lowest. In this regard, the RSI has a promising role as an effective clinical tool for the initial diagnosis of LPRD.

In our study done of 105 patients who presented with at least one symptom of LPRD or GERD, it was found that the RSI had a high sensitivity of 97.1%, an acceptable specificity of 66.7%, and hence a high diagnostic accuracy of 86.7%, making it an ideal tool for screening for LPRD. The RSI has been validated for the diagnosis and follow-up of patients with LPRD by the prospective study done by Belafsky et al. in 2002. This study was done on 25 patients using RSI and a 30-point voice handicap index (VHI) for the diagnosis and posttreatment follow-up of LPRD patients. It was found in this study that the improvement in RSI scores significantly correlated with the improvement in the VHI and the quality of life of the patients.^[7] The findings of another study done by Li et al. in 2015 on 105 patients who underwent RSI assessment by questionnaire, RFS assessment by fiber-optic laryngoscopy and pH monitoring showed a sensitivity of 61.76%, specificity of 75%, and the positive and negative predictive values of 80.8% and 53.6%. The difference in observations may be due to the fact that the methodology used in their study is different and also because the population under the study is different from our population.^[11]

The correlation between RSI and RFS was well established in our study (r = 0.711) with a P < 0.001, which is statistically highly significant. These findings of our study agree well with the findings of the study done by Mesallam et al. in 2007, which was a retrospective chart review done on forty patients comparing RSI found out by questionnaire and RFS found by videostroboscopy which also showed a high correlation between RSI as a clinical tool and RFS as a confirmatory test with a P < 0.0001.^[12] Another objective of our study was to find out the occurrence of GERD symptoms in the patients diagnosed with LPRD. It was found that only 46 of the total 69 LPRD-diagnosed patients (66.7%) showed symptoms suggestive of GERD. This finding agrees with that of the study done by Wiener et al. in 1989 on 33 patients with chronic hoarseness and laryngeal lesions suggestive of acid irritation, using 24-h ambulatory pH monitoring which showed that only 50% of reflux patients, proven by pH monitoring and laryngoscopic findings, develop symptoms of GERD.^[13] This observation supports the notion that esophageal mucosa may be more resistant to the gastric refluxate than the pharyngeal or laryngeal mucosa; hence, LPRD patients need not show GERD manifestations.

The age of the patients in our study was found to range from 13 to 68 years. When the patients were grouped into three groups based on age (Group 1 → up to 30 years, Group 2 → 30–50 years, and Group 3 → above 50 years), although the majority of patients (49.3%) belonged to the 30–50-year age group, this distribution was not found to be statistically significant, with P = 0.979. This is in agreement with the results of the study done by Karakaya et al. in 2005 on 44 patients using RSI questionnaire and RFS by videostroboscopy, which showed no significant preponderance to any age group.^[14] In our study, among patients diagnosed with LPRD, the majority of patients (65%) were female. However, this association was not statistically significant with P = 0.102. In a prospective cohort study done by Moloy and Charter on 85 patients assessing the demographics of LPRD, a higher prevalence of LPRD (64%) was found among females as opposed to 34% in males which correlates well with the findings of our study.^[15] Although the incidence of diabetes mellitus among patients diagnosed with LPRD in our study was found to be 21.7% (15 out of 69 patients), the association was not statistically significant (P = 0.955). This finding is supported by the study done by Hamdan et al., which was a cross-sectional study done on 100 patients to assess the relation between LPRD symptoms and type 2 diabetes mellitus. With respect to the duration of diabetes and glycemic control, they could not establish any significant association between LPRD and diabetes mellitus.^[16]

The relationship between regular intake of spicy diet and the presence of LPRD was found to be highly statistically significant from the findings of our study. Out of 69 LPRD-positive patients, 32 had a positive history of regular intake of spicy foods. This association had highly significant with P < 0.001, making it a definite etiologic factor in the development of LPRD. This finding indirectly supports the findings of the study done by Jamie A Koufman on twenty proton-pump inhibitor (PPI)-resistant LPRD patients who followed a low-acid diet (of pH <5) for 2 weeks. Using pre- and post-diet RSI and RFS, it was found that there is a significant improvement in RSI and RFS (with P = 0.020 and < 0.001, respectively).^[17] There was a weak association between smoking/tobacco addiction and LPRD in our study. Out of the 69 patients diagnosed with LPRD, 6 of them (8.7%) had a positive history of smoking/tobacco usage addiction. These findings are in confirmation with the findings of the study published by Ford in 2005 which was an extensive systematic literature review based on PubMed and Ovid databases and described positive association between LPRD and smoking/tobacco addiction. The same study reported a significant presence of sinus infections along with LPRD.^[6] Our study also investigated such a relationship, but the P value being 0.13, a statistically significant association could not be established between sinus infection and LPRD. The relationship between recurrent episodes of pharyngitis and LPRD was assessed in our study. Out of the 69 LPRD-diagnosed patients, 13 had recurrent throat infection (18.8%). This association was found to be very significant with P = 0.005. This observation agrees with that of the study done by Yazici et al. in 2010, in which fifty patients with symptoms of pharyngitis were observed prospectively and showed a high association between recurrent pharyngitis and LPRD.^[18]

The results highlight that LPRD commonly affects individuals in the age range of 31–50 years, with a higher prevalence among females. The findings reveal associations between LPRD and other conditions such as thyroid disease, sinus infection, and recurrent throat infection. Clinicians should be aware of these potential coexisting conditions and evaluate patients with LPRD for their presence. This knowledge can guide comprehensive patient care and potentially lead to improved outcomes. The study evaluates the diagnostic accuracy of the RSI and RFS for identifying LPRD. The calculated sensitivity, specificity, and predictive values can aid clinicians in choosing appropriate diagnostic tools and interpreting the test results effectively. The study reports that only 66.7% of LPRD-positive patients showed symptoms suggestive of GERD. This suggests that clinicians should be cautious about solely relying on GERD symptoms for diagnosing LPRD, as a significant number of patients may not exhibit typical GERD symptoms. Overall, these findings contribute valuable insights into the clinical characteristics, associated conditions, and diagnostic approaches for LPRD. Incorporating this knowledge into clinical practice can improve the accuracy of diagnosis, guide appropriate management strategies, and enhance patient outcomes.

Conducting longitudinal studies can provide valuable information on the progression and outcomes of LPRD over time. Further investigation into the risk factors associated with LPRD can help identify potential causative factors and develop preventive strategies. Comparative studies comparing different diagnostic modalities for LPRD can be conducted to evaluate their sensitivity, specificity, and overall diagnostic accuracy. Conducting interventional studies to evaluate the efficacy of different treatment approaches for LPRD is crucial. This can include assessing the effectiveness of lifestyle modifications, dietary interventions, medication regimens, and surgical interventions in managing LPRD symptoms, improving patient outcomes, and preventing complications.

Conclusion

LPRD is predominantly a lifestyle-related disease. It affects the quality of life of the patients drastically as well as increases the risk of the patient to develop esophageal adenocarcinoma. This study assessed the validity of the RSI in patients exhibiting symptoms of LPRD or GERD. The fast-food lifestyle and the irregular and unhealthy spicy high-acid dietary habits have led to a rapid increase in the prevalence of gastroesophageal reflux and hence the LPR in the general population, especially India. While the treatment of this disease with PPIs for longer duration has been widely accepted and followed by clinicians, there is a lack of consensus pertaining to the symptomatology and hence a diagnostic tool. This deficiency was rectified to a great extent by the introduction of the RSI and its validation in 2002. Making the diagnosis of LPRD using a confirmatory test such as flexible fiber-optic laryngoscopy or 24-h ambulatory dual probe pH monitoring is a costly affair, and in a country like India, it comes close to impossible, especially in the rural areas. The validation of RSI, in the Indian setting, will allow this tool to be used widely for the early diagnosis and prompt management of LPRD, hence decreasing the case load of the disease in the Indian community and thereby improving the quality of life.