| Disclaimer: The information contained within the Grand Rounds Archive is intended for use by doctors and other health care professionals. These documents were prepared by resident physicians for presentation and discussion at a conference held at Baylor College of Medicine in Houston, Texas. No guarantees are made with respect to accuracy or timeliness of this material. This material should not be used as a basis for treatment decisions, and is not a substitute for professional consultation and/or peer-reviewed medical literature. Laryngopharyngeal Reflux Disease Good morning. My talk today will be laryngopharyngeal reflux disease, LPRD. Quickly, today I will go over a case presentation, talk about the history of LPR, and the history in our specialty compared to GERD . I will talk about the clinical manifestations of LPR as well as diagnosis and treatment options and then go over a research project that I worked on and presented at Academy in New York this year. So, this is the case presentation. J.V. is a 39-year-old Latin American male with a six month history of chronic hoarseness and throat pain. He reports that his voice fatigues near the end of the day. He does work as a telemarketing associate. He really had no other complaints other than that; specifically, no heartburn, otalgia, dysphagia, odynophagia, or globus sensation. On flexible laryngoscopy, he was found to have normal vocal cord mobility. There were no suspicious mucosal lesions. There was extensive erythema of the posterior glottis and inner arytenoid space and the remainder of the exam was essentially normal. He was diagnosed with LPRD and started on Prevacid p.o. b.i.d. and reflux precautions. He responded very well to that and on two month and six month follow up had complete resolution of symptoms and has resumed, unfortunately for us probably, a normal work schedule as a telemarketer. He is currently being maintained on the Prevacid b.i.d. and doing well. If you look at the history of the reflux in LPR in our specialty, in 1618 Frebouches described the GE junction, gastroesophageal junction. In 1890, Chevlar Jackson invented the lighted esophageal scope. In 1935, Winkelstein first described peptic esophagitis and then in 1968 Cherry and Margelise described a relationship between contact ulcers and granulomas of the larynx with reflux. That is a very well referenced article. Then in the mid-1970s to the mid-1980s, not much really happened, kind of a quiet time. Then late 1989, Weinert documented double blind pH findings and was really able to show that there are separate episodes of reflux that go up to the laryngopharynx, which are distinct. In 1996, there was a consensus conference report with groupd of well-known laryngologists first presented in the Journal of Voice and then recently in 2002 our academy Committee on Speech, Voice, and Swallowing made a position statement on LPR and gave treatment recommendations. Reflux is derived from the Latin word meaning re and fluxus, which literally means backflow. Gastroesophageal reflux is defined as backflow of stomach contents into the esophagus. This may be physiologic and actually occurs in normal persons up to 50 times a day. Gastroesophageal reflux disease is GER that is excessive and this results in tissue damage, i.e. esophagitis and or clinical symptoms, i.e. heartburn. Then there is laryngopharyngeal reflux, which is backflow of the stomach contents into the laryngopharynx and this consists mainly of acid and activated pepsin. There are a lot of synonyms for LPR; reflux laryngitis, laryngeal reflux, gastropharyngeal reflux, pharyngosupraesophageal or extraesophageal reflux, atypical reflux. They are all really referring to LPR. It is an interesting topic to think about from a primary care perspective because the extension of the damaging effects of acid into the laryngeal area occurs in a region of the digestive tract, which sometimes can be hands off between two major subspecialties and that is the gastroenterologist who deal with GERD and that is typically below the esophagus and then there is LPR with the otolaryngologist, which is typically above the esophagus. So, who should they refer the patient to and when and why is it sometimes difficult. We need to get the message out that we do take care of LPR. When you compare the two, they really are two different entities. They have different pathophysiologic mechanisms of reflux, different symptoms, manifestations, and responses to treatment. It is very important to know it very early on that the majority of patients with LPR will not have esophagitis or the primary symptom of esophagitis, which is heartburn. In fact, patients with LPR have an incidence of heartburn less than 40% and the incidence of esophagitis is less than 25%. Again, looking at the two and comparing them, LPR patients are predominantly upright daytime refluxers and GERD patients are predominantly supine or nocturnal refluxers. There are prolonged periods of acid exposure in GERD, but not LPR. It is really a short exposure, but high damage phenomenon. Patients with GERD have dysmotility and prolonged esophageal acid clearance and this is typically not true in LPR patients. Again, the primary defect in GERD is lower esophageal dysfunction while the primary defect in LPR is upper esophageal sphincter dysfunction. Saying all that, it is important to point out that some patients do indeed have both LPR and GERD. The laryngopharyngeal epithelium is far more susceptible to reflux related tissue injury than the esophageal epithelium. Kaufman in 1991 experimentally showed that as few as three reflux episodes per week can result in significant laryngeal damage. It does take less acid and pepsin exposure to cause tissue damage to the laryngopharynx and it is stated that the larynx is likely 100 x more sensitive to peptic injury than the esophagus. Listed below that are the esophageal protection barriers, mainly by carbonate production, a mucosal barrier in the esophagus as well as peristalsis; all mechanisms that really are not present in the laryngopharynx. So, this is a table out of the physician’s statement from the academy and it again just highlights that GERD patients typically have heartburn, typically are supine refluxers, and typically have esophagitis while the opposite is almost true for LPR. They are hoarse and have dysphagia and globus, they do not have heartburn, they have laryngeal inflammation, and they do not have esophagitis. When you look at symptoms, it is usually a pretty long list. The symptoms that are important to note are either intermittent or chronic intermittent and that makes it a little tricky for diagnosis sometimes, but this is the approximate order of incidence and you can see that chronic dysphonia and vocal complaints are at the top of the list and then swallowing and globus sensation type complaints are in the middle of the list and then near the bottom of the list are pulmonary manifestations. If you go to Dr. Kaufman’s talk on LPR at Academy, he will basically start his talk saying reflux causes everything and these lists really highlight that. There are a lot of clinical manifestations that are blamed on and accounted for LPR, though they all have not really been studied that well, but as you can imagine, there are laryngeal manifestations, laryngopulmonary, and miscellaneous including SIDS, sinusitis, dental erosions, and OSA have all been suspects or at least coordinate with patients having both LPR and its symptoms. So, when you look at voice disorders, there is a lot in the literature about this. These are just some highlighted studies in the literature. Kaufman in 2000 reported on 113 patients with voice disorders and it was found that at least 50% of them had LPR by pH probe. Earlier, Hanson was studying PPI therapy for GERD, but also was able to show that 96% of a series of greater than 200 patients with chronic laryngitis responded well to anti-reflux treatment and similarly Shaw showed in 1996, a year later, that 85% of patients with symptoms of chronic laryngitis were cured with reflux therapy. When you look at pulmonary disease, LPR is often reported as a cofactor in chronic cough and Irwin in 1993 was able to show that 75% of a series of patients that he had with chronic cough had no reflux symptoms, though they did have documented LPR. As well, 73% of asthmatics improved their asthma or at least their pulmonary function tests after three months with omeprazole. Asthma can cause large pleural abdominal pressure gradients and it is easy to see how there would be an association then between the reflux and their pulmonary disease. Finally, theophylline and oral beta-2 antagonists decreased lower esophageal sphincter pressure, which may result in significant reflux. When you look at laryngeal carcinoma, Dr. Weiner in 1987, and this was a small series, but he reported that half of his patients with laryngeal carcinoma had reflux by pH probe and then in 1991 Dr. Kaufman presented 31 patients and found that 71% of early glottic carcinoma had reflux. Recently, Dr. Lewing out of Anderson reported a series of 24-hour pH probes in newly diagnosed laryngeal cancer patients and again found that of early T 1, T 2 patients greater than 85% of them did have LPR. This is a picture, I really have to thank Dr. Stasney for it, he gave it to me, but it really does highlight how dental erosions can be caused by acid disease. So, how do you diagnose LPR? Well, patient history and clinical symptoms are at the top of the list and then laryngeal examination either by video stroboscopy or flexible scope is needed. If you are unsure with number one and number two, then ambulatory 24-hour double pH probe monitoring is the gold standard. Esophageal manometry, esophagoscopy, and laryngeal sensory testing, have all been used in the past, but really the top three on the list will be your main diagnostic tools. So, this is a normal larynx. This is what you hope to see with your patients. They have a nice posterior commissure, nice proximal trachea, clean true vocal cords, and false folds in the anterior commissure. These are some of the findings that you are going to find on your patients. There are really six big ones that you can look for. First is pseudosulcus vocalis, which you can see here. The second is ventricular obliteration. You can see on this picture how there is a nice ventricle and then in this patient with LPR how it is obliterated. Also, erythema or hyperemia will be present or your garden variety vocal fold edema can also be caused. Finally, you can see posterior commisure hypertrophy or posterior glottic granuloma or granular lesion tissue formation. When looking at pH monitoring, ambulatory 24-hour double probe pH monitoring is really both highly sensitive and specific for the disease and it really is superior to any other diagnostic modality other than physical exam and patient history. It does reveal patterns of reflux so that subsequent treatment can be custom tailored to each individual patient’s treatment protocol. Dr. Postma and the Wakeforest group are really emphasizing the importance of the pharyngeal probe. It really needs to be a dual pH probe. They looked at 334 patients and found that greater than one-third of them had esophageal acid exposure; however, they were all LPR patients diagnosed as having that by the pharyngeal probe. So, these are two sphincters that you are most interested in in the GE junction. The esophageal probe is usually about 5 cm above that and the pharyngeal probe usually lies just above the laryngeal inlet. This is a picture showing what the pharyngeal probe may look like on flexible scope. This is some of the recording that you would get. Again, here you have the pharynx and the esophagus and here is LPR episode with both the esophagus and the pharynx showing significant acid exposure, but here there is only an isolated esophageal reflux and the pharynx looks well. So, how do you define pharyngeal reflux? Well, again, Postma and the Wakeforest group have published the most on this and they basically defined it as a decrease in the pH level of less than 4 and a decrease in the pharyngeal pH level immediately following distal esophageal acid exposure. There should be no decrease in the pH level during eating or swallowing and the decreases in the valley on your testing curve will usually be a rapid and a sharp decrease in the proximal sensor pH level rather than a gradual one. You can have some variability. It is again important to note that this is chronic intermittent disease, so you are not always going to get the results that you expect. Viasi studied 32 patients on two occasions twenty days apart using ambulatory pH monitoring and found significant day to day variability in acid exposure of the proximal esophagus; however, he did find good intraesophageal reproducibility with the probe testing and he felt that the study demonstrated good specificity, but poor sensitivity for LPR monitoring. Laryngeal sensory testing typically is not used as an isolated test for LPR and LPR patients appear to have laryngeal sensory deficits. Oveed studied 35 patients with LPR and dysphagia and did sensation testing basically with a pulse from a flexible laryngoscope and air pulse before and after treatment and found statistically significant improvement in sensory deficits. He found that laryngeal edema and sensory deficits often correlated and there was return of normal sensation once the symptoms did resolve. So, how do you approach treatment? It is kind of a broad topic and there are a lot of treatment options for us as otolaryngologists and it just important to know that treatment needs to be individualized for each individual patient based on their symptoms and how they are responding to treatment. You can really divide treatment into three phases. The first would be behavioral modification. You need to elevate the head of the bed 6-8 inches, maintain an ideal body weight, do not lie down three hours after eating, avoid tobacco, foods high in fat, spices, acid, alcohol and caffeine, and avoid drugs that promote reflux including calcium channel blockers, sedatives, or nitrates. You can also chew gum, which increases salivary bicarbonate production and may neutralize the acid. Your second phase is really pharmacotherapy. You have antacids. These are to treat acute symptoms. They neutralize acid already in the stomach and they are non-prescription. Then you have the H 2 blockers. These are typically taken two to three times a day. They block the histamine receptor in the stomach and reduce acid secretion. Some are now available non-prescription. Then finally, your gold standard is going to be your proton pump inhibitors. You need to start your patients on a therapeutic trial for at least six weeks. B.i.d. dosing may be necessary and they are currently only available by prescription only. The mechanism of action – they directly target the HK, ATPAs, which is on the parietal cell and this is a key enzyme in the final acid production pathway. They work best when they are taken 30 minutes before a meal. So, this is a parietal cell and this is where-this is a question by the way for the residents-this is the parietal cell and this is where the PPI works. It is the last step before producing acid into the stomach. Again, the gastroenterologist recently published some data showing the percent of patients with a ph greater than 4 for greater than 12 hours and the different therapies and really Nexium is the best for the longest period of time. The remainder were all 30-40% of the time. Your third phase when the first two really fail is surgical therapy and that generally consists of referring to either a general surgeon or a thoracic surgeon for a Nissen fundoplication. This procedure tightens the lower esophageal sphincter by wrapping the upper part of the stomach around the lower part of the esophagus. It can be an open or endoscopic approach. It is very safe to say that this is very controversial when, where, and how effective it is, but it is a modality that some people are using. In conclusion for LPR, it is a very common among pharyngeal disorders and airway disorders. It is a chronic intermittent disease. H&P and digital exam either by video stroboscopy or flexible scope are necessary to establish diagnosis. At the very least, all patients should be started on a trial of PPI for at least six weeks and then you need to try to wean therapy as patients tolerate it. Initially, you need to see the patients every two to six months as they need and then try to start weaning them as they can tolerate. LPR typically does require higher dosing of PPI than GERD and the 24-hour dual pH probe is always available to assess treatment response if the diagnosis is doubtful and then again, although controversial, surgical options are available for referral. So, this is a project that we presented this year at Academy in New York in September. I would like to again acknowledge my coauthors and thank them for their help. So, LPR has been show to inevitably impair global quality of life when you look at outcomes. This is especially true in areas of social functioning and this is very especially true in your patients who are going to use their voice for their employment and for the ways of means. Dysphonia is an important aspect of LPR that affects quality of life and dysphonia due to LPR has been objectively demonstrated and improves in treatment in the past. There are some new shorter outcome instruments that are available that you can put in your office that really are only ten questions-Dr. Rosen put this one out in 2004-that the patient can answer and you can see how they feel they are responding to treatment. Previous studies evaluating vocal quality of life as another aspect of treatment effectiveness have been done and are present in the literature on spasmodic dysphonia, benign vocal fold lesions, early glottic carcinoma, unilateral vocal cord paralysis, or singers and professional with vocal complaints; however, there is nothing in the literature really that describes a relationship between the vocal quality of life, reflux symptoms, and physical exam scores in LPR. So, we sought to determine if vocal quality of life on an outcomes measure improves with treatment of LPR. We also wanted to assess the correlation between physical exam improvement and improvement in VQL scores and to assess correlation between improvement in VQL and improvement in symptoms scores. We ran a retrospective case control study at a tertiary referral center over an 18 month period. All patients had a diagnosis of LPR. Our inclusion criteria-patients had to have two or more of the following symptoms as well as video stroboscopy findings positive for LPR. Exclusion criteria-patients receiving maximum medical management already for LPR, recent surgical manipulation of the larynx, or patients that discontinued treatment prior to a six week period. Treatment consisted of a twice dosing of the PPI and possibly the addition of an H 2 antagonist and this was again based on the symptoms and severity of the LPR as felt by the treating physicians in the study. Then we studied pre- and post-treatment reflux symptoms, vocal quality of life, and physical exam scores. For the reflux symptoms, we used the RSI. This is a validated instrument by Balifasci in 2002. It is a nine point instrument and has a worst possible score of 45. Then we used the VHI-10, which is a streamlined version of the original VHI-30 again Dr. Rosen validated this just recently in 2004, but it is a ten point instrument and the worst possible score is 40. Then we used the LRDI, which is a physical exam instrument that Dr. Guver and several Baylor faculty as well as Dr. Stasney presented in 2003, and it is really a grading instrument and grades edema of the superglottis, the glottis, and the subglottis, and there is a worst possible score of 18 on that. Our endpoint for all final visits was the last visit during the study in which patients were both either receiving treatment for LPRD or all three instruments were completed on their visit. All data was analyzed in the SPSS and analysis included univariable analysis as well as comparisons between groups using the Chi-Square test and Pearson correlation coefficient. We set our significant statistical significance as p less than 0.05 and the correlation coefficient greater than 0.35. When we looked at our demographics, we were able to enroll 71 patients. The majority of them were female, however. Their average age was 52-years old and their average number of weeks of treatment for the study was 18 weeks. When we looked at the patient’s upper aerodigestive tract history, about 40% of the patients had a prior history of GERD, had a past history of smoking, and were currently complaining of allergy symptoms. When we looked at the pre- and post-treatment scores on the instruments, we were able to show an at least 30% improvement on all three scores for pre- and post-treatment. This is really a bar graph showing the data in the last slide, but the RSI improved from 18 to 12.6 and this was statistically significant. The VHI-10 improved from 13.5 to 8.4 and was statistically significant, and the LDR did trend towards improvement, though it was not statistically significant. When we looked at correlations between the instruments for pre- and post-treatment, we found that both the RSI and the VHI correlated very highly pre- and post-treatment; however, the RSI and the VHI did not correlate well with the LRDI. So, we felt we found significant improvement in post LPR treatment voice outcomes as demonstrated by both the VHI-10 and the RSI-10 and again these two correlated. The LRDI physical examination score also improved with treatment, but this degree of improvement did not correlate with the other two instruments. The VHI-10 did, however, demonstrate improvement in the VQL after treatment and again the degree of improvement in the VHI did correlate with the RSI, but not the LRDI. We are not sure why exactly this happened other than physical exam findings really do delay and some have reported that these objective physical findings will not really improve until up to six months of treatment, which is likely the guilty party here, but we did feel that the degree to which a voice disorder from LPR impacts an individual may vary significantly and this depends on the severity of the voice disorder and how it affects the patient, the severity of the LPRD, and again the vocal needs of the patient.
Case Presentation On flexible laryngoscopy, he was found to have normal bilateral true vocal fold mobility. There were no suspicious mucosal lesions. There was extensive erythema of the posterior glottis and inter-arytenoid space. The remainder of his head and neck exam was normal. He was diagnosed with laryngopharyngeal reflux disease (LPRD) and started on Prevacid 30 mg PO BID and reflux precautions. On two-month and six-month follow-up, he had complete resolution of symptoms and has resumed a normal work schedule. He is maintained with Prevacid 30 mg PO BID. Bibliography: Beaver ME, Stasney CR, Weitzel E, Stewart MG, Donovan DT, Parke RB, Rodriguez M. Diagnosis of laryngopharyngeal reflux disease with digital imaging. Otolaryngol Head Neck Surg 2003;128:103-108. Belafsky PC, Postma GN, Koufman JA. Laryngopharyngeal reflux symptoms improve before changes in physical findings. Laryngoscope 2001;111:979-981. Belafsky PC, Postma GN, Koufman JA. Validity and reliability of the reflux symptom index (RSI). J Voice 2002;16:274-277. Benninger MS, Ahuja AS, Gardner G, Grywalski C. Assessing outcomes for dysphonic patients. J Voice 1998;12:540-550. Bilgen C, Ogut F, Kesimli-Dinc H, Kirazli T, Bor S. The comparison of an empiric proton pump inhibitor trial vs. 24-hour double-probe Ph monitoring in laryngopharyngeal reflux. J Laryngol Otol 2003;117:386-390. Branski RC, Bhattacharyya N, Shapiro J. The reliability of the assessment of endoscopic laryngeal findings associated with laryngopharyngeal reflux disease. Laryngoscope 2002;112:1019-1024. Carrau RL, Khidr A, Crawley JA, Hillson EM, Davis JK, Pashos CL. The impact of laryngopharyngeal reflux on patient-reported quality of life. Laryngoscope 2004;114:670-674. Deary IJ, Wilson JA, Carding PN, MacKenzie K. VoiSS: A patient-derived voice symptom scale. J Psychosom Res 2003;54:483-489. DelGaudio JM, Waring JP. Empiric esomeprazole in the treatment of laryngopharyngeal reflux. Laryngoscope 2003;113:598-601. Hogikyan ND , Sethuraman G. Validation of an instrument to measure voice-related quality of life (V-RQOL). J Voice 1999;13:557-569. Jacobson BH, Johnson A, Grywalsky C et al. The Voice Handicap Index (VHI): Development and validation. Am J Speech Lang Path 1997;6:66-70. Koufman JA. Laryngopharyngeal reflux 2002: A new paradigm of airway disease. Ear Nose Throat J 2002 (Suppl 2):1-26. Koufman JA, Aviv JE, Casiano RR, Shaw GY. Laryngopharyngeal reflux: Position statement of the Committee on Speech, Voice, and Swallowing Disorders of the American Academy of Otolaryngology-Head and Neck Surgery. Otolaryngol Head Neck Surg 2002;127 Koufman J, Sataloff RT, Toohill R. Laryngopharyngeal reflux: Consensus conference report. J Voice 1996;10:215-216. Lenderking WR, Hillson E, Crawley JA, Moore D, Berzon R, Pashos CL. The clinical characteristics and impact of laryngopharyngeal reflux disease on health-related quality of life. Value Health 2003;6:560-565. Murry T, Medrado R, Hogikyan ND, et al. The relationship between ratings of voice quality and quality of life measures. J Voice 2004;18:183-192. Pribuisiene R, Uloza V, Saferis V. Multidimensional voice analysis of reflux laryngitis patients. Eur Arch Otorhinolaryngol 2004 (in press). Rosen CA, Lee AS, Osborne J, Zullo T, Murry T. Development and validation of the Voice Handicap Index-10. Laryngoscope 2004;114:1549-1556. Shaw GY, Searl JP, Young JL, Miner PB. Subjective, laryngoscopic, and acoustic measurements of laryngeal reflux before and after treatment with omeprazole. J Voice 1996;10:410-418. Stewart MG, Coker NJ, Jenkins HA, Manolidis S, Bautista MH. Outcomes and quality of life in conductive hearing loss. Otolaryngol Head Neck Surg 2000;123:527-532. Stewart MG, Johnson RF. Chronic sinusitis: Symptoms versus CT scan findings. Curr Opin Otolaryngol Head Neck Surg 2004;12:27-29. Stewart MG, Neely JG, Hartman JM, Wallace MS, Forsen JW Jr. Junior tutorials in clinical research: Part V: Outcomes research. Laryngoscope 2002;112:248-254. Yorulmaz I, Ozlugedik S, Kucuk B. Gastroesophageal reflux disease: Symptoms versus pH monitoring results. Otolaryngol Head Neck Surg 2003;129:582-586. BCM Public | BCM Intranet | Privacy Notices | Contact BCM | BCM Site Map | ©2001-2005
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