Impedance/pH-metry Findings in Patients with Laryngopharyngeal Reflux by Clinical Score ABSTRACT

Transcription

1 THAI J 28 GASTROENTEROL Original Clinical Score Article Impedance/pH-metry Findings in Patients with Laryngopharyngeal Reflux by Clinical Score Prapruetkit J Leelakusolvong S Maneerattanaporn M ABSTRACT Background & Aim: Although micro-aspiration of gastric contents particularly acid reflux may be responsible for laryngopharyngeal reflux (LPR), half of the patients fail to respond to antisecretory therapy. The aims of this prospective study were to elucidate correlation between clinical score; reflux symptom index (RSI) and reflux finding score (RFS) and impedance/ph metry finding in LPR patients Methods: Sixty-three consecutive patients with signs and symptoms of chronic laryngitis and with clinical score (reflux symptom index (RSI) 13, or reflux finding score (RFS) 7) were enrolled. After 2-week cessation of acid-suppression medication, participants underwent monitoring of gastroesophageal reflux episodes using multichannel intraluminal impedance (MII) 24-hour ph testing. Results: There were 63 patients (44 females and 19 males), aged 48.6 ± 11.4 years (range years). The mean reflux symptom index (RSI) scores was ± 6.0, and the mean reflux finding score (RFS) was 8.69 ± 3.6. Sixteen of 63 patients (25.4%) had pathological acid reflux. Based on the MII-pH results, 6.3% of patients had acid reflux while 15.9% had weakly acid reflux. Most patients had pure abnormal gas reflux (39.7%), 15.9% had abnormal mixed reflux, 20.6% had abnormal mixed and gas reflux and 23.8% had no reflux. Comparing RSI and RFS score with any types of refluxate, there were no differences in both RSI and RFS score between any types of refluxate, (p = and p = 0.658), respectively. The most common presenting symptom in acid reflux and weakly acid reflux patients was globus sensation (60%, 85% respectively). In gas reflux, however, heartburn was rare (15%). Conclusion: The results from this study suggest that retrograde flow of gastric contents may be a cause of chronic laryngitic symptoms in LPR patients. RSI and RFS clinical scores were not helpful to discriminate the different types of reflux. The symptoms of heartburn and regurgitation were more with acid or weakly acid reflux than gas reflux. MII-pH monitoring could be helpful in further refinement of LPR treatment. Key words : Laryngopharyngeal reflux, reflux symptom index (RSI), reflux finding score (RFS), multichannel intraluminal impedance [Thai J Gastroenterol ; 15(1):28-34.] Division of Gastroenterology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand. Address for Correspondence: Somchai Leelakusolvong, M.D., Division of Gastroenterology, Faculty of Medicine, Siriraj Hospital, Bangkok, Thailand.

2 Prapruetkit J, et al. THAI J GASTROENTEROL Vol. 15 No. 1 Jan. - Apr. 29 INTRODUCTION Laryngopharyngeal reflux (LPR) is the most common laryngeal manifestation of GERD, estimated at 4-10% of patients presenting to an otolaryngology practice (1-3). Patients have symptoms or findings related to GERD, hoarseness, vocal fatigue, chronic throat clearing, excessive throat mucus, chronic cough, dysphagia, and globus sensation. However, there is conflicting evidence concerning the cause and effect relationship between LPR and GERD. LPR differs in many ways from GERD in that it is predominantly upright reflux, less associated with regurgitation and heartburn symptoms, less esophagitis when comparing with GERD (10% vs. 40%), and low response rate to antireflux therapy (4,5). The proposed hypotheses speculate that laryngeal and esophageal mucosa may have different defensive mechanisms and laryngeal mucosa is susceptible to both acid and pepsin (activated at ph >5) or other types of refluxate. Although micro-aspiration of gastric contents particularly acid reflux may be responsible for LPR, up to 50% of patients do not respond to aggressive acid suppression therapy (6). Moreover, recent meta-analysis showed that PPI therapy is no more effective than placebo in producing symptom relief in patients suspected of LPR (7). It is not clear whether acid reflux pattern and esophageal mucosal sensitivity are involved in the development of LPR. The gold standard method for diagnosis of LPR is 24-hour ph monitoring, a procedure with low sensitivity for detection of acid reflux (50% sensitivity) and inability to detect other type of refluxate. This procedure is thus not practical for clinical use. Reflux symptom index (RSI) and reflux finding score (RFS) were clinical scoring systems that were first proposed by Belafsky et al (11-12), utilizing the 9-items symptoms and 8-items of abnormal laryngoscopic finding for diagnosing LPR. Previous studies showed that abnormal acid reflux measured by 24-hour ph monitoring was associated with RSI 13 of 45 points, with 75.6% sensitivity and 18.8% specificity. And RFS 7 of 26 points was also associated with abnormal acid reflux, with 87.8% sensitivity and 37.5% specificity. Combined used of RSI and RFS provided ever higher sensitivity and specificity for abnormal acid reflux (11-12). Nowadays, with ambulatory multichannel intraluminal impedance (MII) and 24- hour ph-monitoring test, the recognition of reflux events could be better achieved. It allows the demonstration of strong acid, weak acid, non-acid as well as the type of acid reflux (e.g. gas, liquid or mixed liquid/gas) (8). The previous study showed that mostly LPR patients had gas reflux (46.8%), acid and weakly acid reflux, respectively We designed this prospective study to elucidate evidence of reflux content in LPR patients by using the multichannel intraluminal impedance (MII) and 24 hour ph-monitoring test. Our primary aim was to demonstrate the correlation of the reflux content and RSI, RFS clinical score and the second aim was to demonstrate the patterns and types of gastric reflux. MATERIALS AND METHODS Subjects The study was conducted at Siriraj Hospital, Faculty of Medicine, Mahidol University, Bangkok, Thailand from September 2012 to February LPR patients aged 18-80, with RSI 13 or RFS 7, diagnosed by otolaryngologist were eligible for this study. Others causes of otolaryngologic symptoms were excluded. Patients were excluded if there were contraindication to sedation, endoscopy, esophageal manometry or impedance/ph probe insertion, or if there was severe comorbidity (e.g. severe valvular heart disease, recent acute coronary event, sepsis, pregnancy, bleeding, bleeding tendency), or if no consent for interventions. Patients with recent peptic ulcer bleeding and those for when PPI could not be discontinued were also excluded. Interventions and protocol Enrolled patients were asked to stop taking any acid-suppression medication for two weeks. Medical history, demographic data, and duration and severity of GERD and LPR symptoms, duration of PPI and antacid therapy were recorded (Figure 1). Esophageal manometry and ambulatory impedance 24-hour ph-monitoring test Patients were asked to discontinue prokinetic drugs for at least 3 days before testing. Combined MIIpH testing after at least 6-hour fasting was preformed as an out-patient procedure. The combined MII-pH probe was placed with reference to the manometrically located proximal border of the lower esophageal

3 30 THAI J GASTROENTEROL Clinical Score Table 1. Reflux symptom index (RSI), Belafsky et al (11). Within the last MONTH, how did the following problems affect you? 0 = no problem 5 = severe problem 1. Hoarseness or a problem with your voice Clearing your throat Excess throat mucus or postnasal drip Difficulty swallowing food, liquids, or pills Coughing after you ate or after lying down Breathing difficulties or choking episodes Troublesome or annoying cough Sensations of something sticking in your throat or a lump in your throat Heartburn, chest pain, indigestion, or stomach acid coming up Total Table 2. Reflux finding score (RFS), Belafsky et al (12). Finding Subglottic edema Ventricular obliteration Erythema/hyperemia Vocal cord edema Diffuse laryngeal edema Posterior commissure hypertrophy Granuloma/granulation Thick endolaryngeal mucus/other Total Score 2 = present 0 = absent 2 = partial 4 = complete 2 = arytenoids only 4 = diffuse 1 = mild 2 = moderate 3 = severe 4 = polypoid 1 = mild 2 = moderate 3 = severe 4 = obstructing 1 = mild 2 = moderate 3 = severe 4 = obstructing 2 = present 0 = absent 2 = present 0 = absent sphincter (LES). On completion of the manometry, a 2.1 mm MII-pH catheter was passed transnasally, and the esophageal ph sensor was positioned 5 cm above the LES. The configuration of the catheter allowed monitoring changes in intraluminal impedance at 3, 5, 7, 9, 15, and 17 cm above the LES. In addition, ph was monitored at 5 cm above the LES. Patients then underwent 24-hour MII-pH monitoring, and diaries were provided for patients to record symptoms during the study period. Data from the impedance channels and ph electrodes were sampled at a frequency of 50 Hz and stored on a portable data recorder (intraluminal impedance and 24 hour-ph monitoring (Ohmega) impedance/ ph electrode, 6 impedance and 1 ph channel, Medical Measurement Systems, USA). At the end of the 24-hour recording period, data were transferred and analyzed using dedicated software (Virtual instructor Program Analysis; Medical Measurement Systems, USA). Tracings were reviewed and timing of meals, changes in body position, and the time of symptoms recorded were compared with the information written in the diaries. Meal periods were marked and excluded from the analysis. Twenty-four-hour ph data collected included the followings; (1) the total percentage of time ph <4, (2) the DeMeester score, (3) the percentage of proximal extent in upright and supine positions, (4) the number of reflux episodes, (5) acid reflux (decrease of ph to <4 for at least 5 seconds) and (6) weakly acid reflux (decrease in ph of at least 1 log unit for at least 5 seconds without a decrease in ph to <4). Impedance data collected included the followings: (1) liquid reflux events, defined as a retrograde decrease of impedance of at least 50%, beginning at the lower esophageal sphincter and involving at least 2 other proximal channels; (2) gas reflux events (defined as a simultaneous rapid increase in impedance (5,000-10,000 Ohm) noted in at least 2 distal impedance channels); (3) mixed reflux events, defined as gas reflux coming

4 Prapruetkit J, et al. THAI J GASTROENTEROL Vol. 15 No. 1 Jan. - Apr. 31 immediately before or immediately after liquid reflux; and (4) nonacid reflux events, defined as an impedance reflux event with less than 1 log unit of ph change during the episode (9). The study was approved by the Siriraj Ethics Committee. All patients were informed in detail about all steps of the study and written consent was provided by all patients before the study. 63 LPR patients diagnosed from ENT unit RSI 13 or RFS 7 Discontinue proton pump inhibitors for 2 weeks NPO 6 hours Statistical Analysis Data were analyzed using the SPSS 13.0 Basic software package of statistical programs. The patterns and types of gastric reflux were based on an observational data. One way ANOVA was used to compare RSI and RFS with refluxate type between groups and within groups. Statistical significance was established at p <0.05. Esophageal manometry Combined impedance-24 hour ph catheter insertion Catheter removal 24 hours Figure 1. Interventions and protocal. Data collection Table 3. Demographic data and characteristics of patients. Characteristics Total (n = 63) Age (years): mean (SD) Sex (female): number (%) Body mass index (kg/m 2 ) : mean (SD) Duration of symptom (month): range (median) Previous use of PPI: number (%) Reflux symptom index (RSI) : mean (SD) Hoarseness of voice Clearing throat Postnasal drip Difficulty swallowing Coughing after lying down Breathing difficulty Chronic cough Globus sensations Heartburn, regurgitation Reflux finding score (RFS) : mean (SD) Subglottic edema Ventricular obliteration Erythema Vocal cord edema Diffuse laryngeal edema Posterior commissure hypertrophy Granuloma/granulation Thick endolaryngeal mucus 48.6 (11.4) 44 (69.8) 22.5 (2.6) 3-84 (30) 54 (85.7%) 18.6 (6.0) 1.92 (1.7) 2.54 (1.6) 2.34 (1.6) 1.39 (1.7) 1.46 (1.5) 1.46 (1.5) 1.43 (1.7) 3.48 (1.8) 2.64 (1.7) 8.96 (3.6) 0.59 (0.9) 1.48 (1.1) 2.67 (1.1) 1.26 (0.8) 1.19 (0.8) 1.37 (0.8) 0.11 (0.4) 0.96 (1.0)

5 32 THAI J GASTROENTEROL Clinical Score RESULTS The 63 enrolled patients, 44 women and 19 men, ages 48.6 ± 11.4 years (range years) and mean body mass index 22.5 kg/m 2, were diagnosed as LPR by otolaryngologist for average duration of 30 months (range 3-84 months). Other potential causes of relevant signs and symptoms were excluded. Fifty-four patients were previously treated with proton pump inhibitors twice daily, while 9 patients never had any treatment before. The mean reflux symptom index (RSI) score was ± 6.0. The mean reflux finding score (RFS) was 8.96 ± 3.6. Clinical characteristics including age, body mass index, laryngeal and gastroesophageal symptoms, the RSI and RFS scores, and duration of anti-secretory therapy were shown in Table 3. Esophageal manometry was performed in all patients. Twenty of 63 patients (31.7%) had low baseline LES pressure, 6 patients (9.5%) had hypertensive LES while 36 (57.1%) had normal esophageal tracing. Sixteen of 63 patients (25.4%) had pathological acid reflux (positive monitoring test ph < 4). The average total reflux number was ± time (Table 4). Based on the MII-pH results, 22.2% of patients had acid and weakly acid reflux, while pure nonacid reflux was found in 1.6% of patients. Most patients had pure abnormal gas reflux (31.7%), and 23.8% had other mixed type reflux. No reflux was detected in 11 of 63 patients (17.5%) in our study. Data was shown in Table 4. The mean RSI in the acid and the weakly acid reflux groups was 19.35, (20.6 in pure gas reflux, Table 4. Acid exposure and type of refluxate. Total (N = 63) Pathological acid reflux (%) 16 (25.4%) Total reflux number ± % Proximal extent at upright position ± % Proximal extent at supine position 1.8 ± 5.27 Acid and weakly acid reflux (%) 14 (22.2%) Pure gas reflux (%) 20 (31.7%) Other mixed type reflux (%) 15 (23.8%) Non acid reflux (%) 1 (1.6%) No reflux (%) 11 (17.5%) Table 5. Comparison between RSI, RFS and type of refluxate. RSI Mean (SD) RFS Mean (SD) Acid and weakly acid reflux (5.1) 9.0 (1.4) Pure gas reflux 20.6 (5.5) 8.75 (3.4) Other mixed type reflux (6.2) 8.55 (4.9) No reflux (7.1) 10.2 (2.5) *No difference in both RSI and RFS scores between any type of refluxates in other mixed type reflux, and in non-reflux group). The mean RFS in acid and weakly acid reflux group was 9.0, 8.75 in pure gas reflux in other mixed type reflux and 10.2 in non-reflux group. The data was showed in Table 5. When comparing RSI and RFS scores with any types of refluxate, using one-way ANOVA method to Table 6. Subgroup analysis: comparison of acid, weakly acid and gas reflux and presenting symptoms & signs. Acid Weakly acid Gas Presenting symptoms n=16 n=7 n=20 Globus sensation 9 (60%) 6 (85%) 14 (66%) Heartburn 9 (60%) 5 (71%) 3 (15%) Excess mucous 3 (20%) - 8 (38%) Clearing throat - 4 (57%) 7 (33%) Laryngoscopic finding n=1 n=6 n=8 Ventricular obliteration 1 100%) 5 (83%) 7 (90%) Erythema 1 (100%) 6 (100%) 5 (60%) Vocal cord edema 1 (100%) - - Posterior commissure hypertrophy - 4 (66%) 4 (50%)

6 Prapruetkit J, et al. THAI J GASTROENTEROL Vol. 15 No. 1 Jan. - Apr. 33 compare more than one group, no difference in both RSI and RFS scores between any type of refluxates was noted ( p= and p= respectively). There was no correlation between the two clinical scores and any types of reflux using MII-pH metry (Table 5). Subgroup analysis in acid, weakly acid and gas reflux groups showed that the most common presenting symptom in acid reflux patients was globus sensation (60%) and heartburn (60%). Similarly, in the weakly acid reflux group, globus sensation (85%) and heartburn (71%) were the most common symptoms, followed by clearing throat. Gas reflux patients, also presented with globus sensation, clearing throat and excess mucus, but they rarely heartburn (15%). The data are shown in Table 6 and Figure 2. Symptoms % Globus sensation Heartburn Excess mucous Clearing throat 0 Acid Weakly acid Gas Reflux Figure 2. Subgroup analysis: comparison of acid, weakly acid and gas reflux and presenting symptoms. DISCUSSION Although the pathogenesis of LPR is not yet well established, two mechanisms have been proposed. LPR is considered mediated by a reaction originating from an acid sensitive esophagus. The other is related a consequence of direct acid injury by the acid gastric content. Only 50% of the LPR patients responded to the PPI therapy and require large dosages for a long period of time, making the treatment controversial. This led us to believe that there may be some other factors causing the difference, for example, greater sensitivity of the laryngeal mucosa to acid reflux destruction as in GERD, or gastric content as non-acid reflux is involved. Now a day, combined multichannel intraluminal impedance (MII) and 24 hour-ph monitoring test is more effective in detecting any irregularity of reflux than the traditional ph monitoring test, and is thus widely employed in NERD studies. However, available data and studies relating LPR to abnormal acid exposure are rather limited. Our study is apparently the largest on MII/pH metry finding in LPR patients. We found that 25.4% of patients had pathological acid reflux, 22.2% had acid and weakly acid reflux, and 1.6 % had pure nonacid. Most patients (31.7%) had pure abnormal gas refluxates, and 23.8% had other mixed type reflux. Non-reflux was detected in 17.5% of patients in our study. This indicated that there was evidence of retrograde gastric content, which could possibly be acid, weakly acid, non-acid, gas, liquid, or mixed type, in our study group. Comparing RSI and RFS score with any types of reflux, there was no difference in both RSI and RFS scores between any types of reflux (p= and p= respectively). Both clinical scores could not distinguish between any types of abnormal gastric reflux

7 34 THAI J GASTROENTEROL Clinical Score significantly, even in non-reflux patients. The most common presenting symptom in acid reflux patients and weekly acid patients was globus sensation (60%, 85% respectively), followed by heartburn and clearing throat. In gas reflux, (66%) of patients also had globus sensation, but only (15%) had heartburn. This suggested that the symptoms of heartburn and regurgitation were associated with acid or weakly acid reflux rather than gas reflux. In conclusion, our study suggests that retrograde flow of gastric contents may be a cause of chronic laryngitic symptoms in LPR patients. RSI and RFS clinical scores were not helpful to discriminate any type of reflux. MII-pH monitoring may be helpful in further refinement of LPR treatment. REFERENCES 1. Holtmann G. Reflux disease: the disorder of the third millennium. Eur J GastroenterolHepatol 2001; 13(suppl 1): S5-S Leelakusolvong S. Prevalence of gastroesophageal reflux disease in Thailand. WCOG Bangkok, Thailand 2002 (Abstract) 3. Koufman JA, Wiener GH, Wallace CW, et al. Reflux laryngitis and its sequela: the diagnostic role of ambulatory24-hour monitoring. J Voice 1988;2: Toohill RJ, Mushtag E, Lehman RH. Otolaryngologic mani- festations of gastroesophageal reflux. Proceedings of XIV World Congress of Otolaryngology, Head, Neck Surgery; p ENT 2002;81(9) suppl 2, Charles NF. Evaluation and management of laryngopharyngeal reflux. JAMA 2005;294: Koufman J, Sataloff RT, Toohill R. Laryngopharyngeal reflux: consensus conference report. J Voice 1996;10: Vaezi MF, Hicks DM, Richter JE, et al. Laryngeal signs and symptoms and gastroesophageal reflux disease (GERD): a critical assessment of cause and effect association. Clin Gastroenterol Hepatol 2003;1: Christina R, Peter B. Management of laryngopharyngeal reflux with proton pump inhibitors. Ther Clin Risk Management 2008;4: W oo P, Noordzij P. Association of esophageal reflux and symptom: comparison of larygoscopy and 24-hour ph manometry. Otolaryngol Head Neck Surg 1996;115: Belafsky PC, Postma GN, Koufman JA. Validityand reliability of the reflux symptom index (RSI). J Voice 2002;16: Belafsky PC, et al. Validity and reliability of reflux finding score (RFS). Laryngoscope 2001;111: Park KH, et al. Diagnosis of laryngopharyngeal reflux among globus patients. Otolaryngol Head Neck Surg 2006;134: Expert review. Multichannel intraluminal impedance and ph monitoring in GERD. Gastroenterol and Hepatol 2008;5: Sansak I, Leelakosulvong S, et al. Esophageal reflux episodes and endoscopic finding in laryngopharyngeal reflux patients with persistent symptoms despite acid suppression therapy. Thai J Gastroenterol 2010;11: