allaboutlpr

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A Major LPR Review

(NOTE: Dear followers, after 139 posts over almost 4 years I am ending this series of what I hope has been some help to you. Because of health issues, not related to LPR I am going to turn my energies to other pursuits. I will keep this blog open so that you and others can glean the information that I have gathered and summarized for you. I wish you all good health and good fortune.)

The authors of this important review, based at the University of Mons, Belgium, have reviewed the records of 6457 patients who had been treated for LPR over the last 29 years. These records have been extracted from 76 research papers selected from 1355 publications on LPR on the basis of strict criteria to assure accuracy and relevance. (These authors refer to LPR as LPRD, meaning “laryngopharyngeal reflux disease.”

The typical treatment for LPR has been proton pump inhibitors (PPIs). The regime has consisted of once or twice daily PPIs for a period of 4 to 24 weeks. These included omeprazole (Prilosec), esomeprazole (Nexium), rabeprazole (Aciphex Pro), lansoprazole (Prevacid Pro) and pantoprazole (Protonix IV). However, these treatments overall have had an “uncertain success rate.” “More than 40% of patients have less or no symptom relief with an empirical therapeutic trial based on PPIs”

A number of studies utilized treatments which included additional medications - alginate, prokinetics, and H2R antagonists. MII-pH studies ( multichannel intraluminal impedance) studies (see earlier posts) have revealed 3 LPR subtypes - acid, nonacid and mixed. Future treatment studies will have to consider which type is present. “Three recent studies found that the majority of patients have in fact nonacid or mixed LPRD.”

Based on current evidence, the authors did not recommend the use of H2R for LPRD. These H2 “blockers” such as Tagamet Pro and Zantax Pro decrease stomach acid production, but have a “short duration of action.”

Prokinetics strengthen the lower esophaageal sphincter and cause the stomach contents to empty faster into the small intestine. However, “the addition of prokinetics to PPIs” has shown “mixed evidence.” 

I have discussed alginates in earlier posts. These, such as Gaviscon and magaldrate form a raft that can float over stomach contents, thus blocking reflux. The authors state “Our recent results also support that the addition of alginate or magaldrate to PPIs seems to significantly improve symptoms in patients with mixed and nonacid LPRD.”

This report concludes with advising “diet and behavioral changes” and Importantly, underlines the relevance of diet and behavioral changes as “the first therapeutic step of the LPRD treatment.” As well, they suggest “the concomitant use of twice daily PPIs and twice or thrice daily alginate of magaldrate could provide a persistent protective against...mucosal irritation.”

Lechien JR, Mouawad F, Barillari MR et al. Treatment of laryngopharyngeal reflux disease: A systematic review. World J Clin Cases. 2019 Oct. 6; 7(19): 2995-3011

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Maybe it’s Your Nerves

Our autonomic nervous system acts unconsciously while regulating important functions including heart rate and digestion. The vagus nerve that we have mentioned in earlier posts is part of this system. Chinese researchers have been studying the question of how the autonomic system might be involved in LPRD. (note - here they use the term LPRD to indicate laryngopharyngeal reflux disease.)

Fifty-three people with LPRD and 55 healthy people ( the controls) were examined using a specific test for autonomic function - the short-term heart rate variability analysis.

All of the LPRD subjects had been treated with a PPI, esomeprazole, along with mosapride, and had followed the usual lifestyle modifications.

The researchers found “...vagal nerve function[s] were significantly lower in the case group than in the control group.” This pointed to “autonomic nerve dysfunction” in the subjects with LPRD. Because “The gastrointestinal system is regulated by the autonomic system...the dysfunctionality...can cause abnormal regulation of gastric peristalsis and UES and LES functions, making laryngopharyngeal reflux a risk factor for LPRD.” I have often mentioned in previous posts, as well is my book, that the gateway to the throat for gastric reflux is the UES, the upper esophageal sphincter. 

They add, “This study also showed that autonomic nerve dysfunction is correlated with LPRD, and an effective treatment for it needs to be explored.” After citing studies that found patients with anxiety and depression “have marked autonomic nerve dysfunction, which significantly improved after anxiety and depression were treated,” they indicated their aim to “determine if improvement in anxiety and depression before treating LPRD can increase the cure rate of LPRD.”

Wang AM, Wang G, Huang N, et al. Association between laryngopharyngeal reflux disease and autonomic nerve dysfunction. European Archives of Oto-Rhino-Laryngology 2019; 276:2283-2287

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More PPIs

PPIs, those proton pump inhibitors that I have written about often on this blog and in my book, have been the subject of considerable research over the years. There have been many studies since the early 1980s on PPIs, using a wide variety of approaches. (PPIs include such forms as Prilosec, Prevacid, Aciphex, Protonix.)

The authors of this recent report examined all those studies, and I want to pass on their conclusions to you. They reflect the controversy over PPI use that has continued for a long time.

Here are some of their principal conclusions:

“Based on the existing data, the use of PPI therapy for the treatment of LPR remains questionable.”

“Six [major] analyses concluded that PPI therapy is not superior to placebo [fake PPI] and three concluded that PPI therapy significantly improved LPR symptoms although they did not identify any difference in the post-treatment laryngoscopic findings [ viewing the vocal cords and larynx].”

“In the meantime, the use of PPI therapy for the treatment of LPR will continue even though existing evidence is poor and weak...”

It is the decision of your health care provider along with yourself about whether to  take PPIs for LPR and for what duration. Always keep in mind the “lifestyle changes” that may play an important role in treatment.

Nikolaos S, Drosou E, Bougea A, and Al Abdulwahed R. Proton Pump Inhibitors for the Treatment of Laryngopharyngeal Reflux. A Systematic Review. Journal of Voice, 2019 May 13.

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“Well doc, I am taking some CBD oil. You think that’s it?”

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“There’s something strange about this doctor’s waiting room...”

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A NEW MEDICATION

Let me begin by telling you that this new medication does not appear to be available in the U.S. This blog is based on a publication by researchers at the Center of Regenerative Medicine in Genoa, Italy.

This medication is Marial, which they state “is effective in the treatment of gastroesophageal reflux disease and also of laryngopharyngeal reflux.” It is aimed at the body’s inflammatory response to reflux which they regard as a “potential protective event and not only harmful.” They refer specifically to mechanisms involved in tissue repair, which allows “ new therapeutic approaches.”

The scientists describe a new compound, named E-Gastryal that “has been proved to effectively relieve the discomfort caused by gastric reflux, preventing and alleviating the injury to mucous membranes. In fact, this compound is able to actively regenerate the damaged tissue...”

Combining E-Gastryal with magnesium alginate - a popular ingredient for relieving heartburn- results in Marial. It has been introduced into the market in Italy, and is made by Aurora, Milan, Italy. This is reminiscent of Gaviscon, the most concentrated form being available in Europe but not in the U.S.

Aragona SE, Mereghetti G, Ciprandi G. Gastric Reflux: The Therapeutic Role of Marial. Journal of Biological Regulators and Homeostatic Agents 2018, 32(4): 969-972.

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Just try to relax...

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Sleep Position?

An earlier blog indicated that there is a consensus that sleeping on the left side may reduce nighttime reflux. I came across an article that shows that this may be a more subtle point. Two researchers have published a study in which they maintain “...in the majority of cases” when they examined a person complaining of LPR symptoms and their laryngoscope exam showed more inflammation on one side of the vocal chords, “...our prediction of which side the patient slept on the previous night has been correct.”

I bring this up so that you realize that sleeping on either side may not always prevent LPR triggering reflux while sleeping. Management of LPR sometimes requires trial and error.

Urban MJ, Sataloff RT. Asymmetric Laryngopharyngeal Reflux Findings Following Sleep in the Lateral Recumbent Position. Ear, Nose & Throat Journal, 2019 April 9.

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You Now Have Skin in the Game

LPR affects various sites in the larynx and the hypopharynx. The latter is the part of the throat that is beside and behind the larynx. It is the entrance to the esophagus. Because of this, it would be advantageous to have a research system that could distinguish among the  effects of reflux exposure on the tissues in different sites. This system could also interpret the therapeutic effectiveness of various treatments at the cellular level. The article summarized below describes the work of researchers in China who successfully isolated tissues from vulnerable areas and grew them in the lab.

The tissue layer that lines the throat and larynx is the mucosa. The outer surface of cells is the epithelium. The investigators sampled various sites within the laryngopharynx, taking specimens of the mucosa. The tissue was treated with enymes, then passed through a strainer and suspended in a growth medium.

The cells grew and divided, and the cultures attained a density of 94.9% epithelial cells. These cells could be transferred to fresh medium and they continued to grow.

This above description comes under the category of cell culture. Successful culturing (growth) of cells, (whether animal or plant), requires finding the proper nutrients and temperature to stimulate growth. This can be a long and complicated process. If successful, as in this case, this allows researchers to analyze down to the cellular level the effects of refluxed materials on specific areas of the throat. They can also measure the effects of potential pharmceuticals on those stressed cells. This kind of research allows investigations that would be difficult or impossible with living human subjects.

Optimized Generation of Primary Human Epithelial Cells from Larynx and Hypopharynx: A Site-Specific Epithelial Model for Reflux Research. Cell Transplantation. 2019 March 27

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You Are What You (don’t) Eat

The following is a summary of a recent article written by medical researchers in Belgium. They wanted to add to the relatively limited research on the effects of diet in controlling LPR. I devoted a chapter in my book to this subject, and there are earlier posts on this subject in this blog. 

Spoiler alert- almost everything most of you love to eat and drink is forbidden! However, as you read this account, remember that individuals vary as to their sensitivity to specific foods. In other words, certain foods and liquids may effect some people more than others. The old adage, “moderation in all things” perhaps should be modified in this situation to “moderation in some things, and absolutely no in others.” 

According to the authors, “...the long-term control of LPR symptoms and signs still remains difficult with 25% to 50% of patients [having a] chronic course.” They looked at 65 patients with a diagnosis of LPR. All were treated with the PPI pantoprazole (Protonix) and were given recommendations for lifestyle modifications and a diet. The latter is summarized below. The major modifications were ( from a very long list) - smaller meals, no steroids, lose weight, no tight clothing, head of bed elevation.

The diet recommendations were to avoid the following: fatty meats and fish, poultry, chocolate, ice cream, whole milk, hard cheese, peanuts, white bread, French fries, nuts, onions, chili, tomatoes, alcohol, sparkling beverages, sodas, coffee, tea, citrus, butter, sauces, sugar.

The 26 individuals in Group 1 (16 females) followed the diet recommendations for three months. Group 2 ( 39 individuals, 18 females) did not. The diet followers experienced “significant” improvement in post-nasal drip, throat clearing, heartburn, globus (lump in throat) sensation, and coughing. Their larynx exams showed improvement as well. (Even the non-dieters had some relief from symptoms, presumably because of behavioral modifications.) Both groups also had some improvements in voice symptoms, although the dieters had more relief.

In summary, the authors conclude “...treatment with PPI therapy, alkaline, protein, low-acid and low-fat diet is significantly more effective than PPI therapy alone on laryngopharyngeal symptoms and voice quality.”

NOTE: If you have been following this blog or read my LPR book, you know that the effects of various foods are often related to their influence on the rings of muscles (sphincters) that mark the passage from the pharynx to the esophagus and the passage from the esophagus to the stomach. Also, refluxed pepsin from the stomach that enters the tissues in the pharynx, larynx and beyond  may be activated by more acidic substances, which trigger inflammation. As well, fatty foods delay the residence time of food in the stomach, leading to the possibility of more reflux episodes.

As often happens in research reports, the authors here admit the limitations of their study. In this case the fact that there was a “low number of patients...[and] ...it would have been interesting to have a control group of LPR patients treated with diet without PPIs.”

 LeChien JR, Huet K, Khalife M, et al. Alkaline, protein, low-fat and low-acid diet in laryngopharyngeal reflux disease: Our experience on 65 patients. Clinical Otolaryngology 2018, 11 Dec.

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Dear Blog readers:

I hope you don't mind if I mention here that I have written a novel - my first work of fiction of seven books - and I hope you might be interested in taking a look at it. Of course, I highly recommend it. Below is my summary. You can see it at http://amzn.to/2j3WZRV. Thank you!

Sean Francis Xavier Murphy, a retired Irish American detective, is urged back into service to solve a brutal murder on a New Hampshire Catholic college campus. The school, under the direction of Benedictine monks, reflects the panoply of issues dividing the Catholic people – including abortion, birth control, pedophilia, and homosexuality. Sean finds himself, to his surprise and chagrin, searching for his lost faith as he also looks to solve the crime.

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Another LPR Summary

The following is along the same lines as my last post, with a few new points. The authors of this 2018 update in LPR symptoms, diagnosis and therapy trace the steady increase in scientific publications about LPR. In 2000 there were 10, by 2010 there were over 60, and in 2017 there were 85.

However, there still remains no universal agreement on all aspects of diagnosis and treatment, topics which have been raised in previous posts. The authors, located in France, Belgium and Greece offer their systematic approach to detect and manage this troublesome disorder.

I have written before about two clinical tools used in diagnosis, the Reflux Symptoms Index (RSI) and the Reflux Finding Score (RFS). Scores on these indices of symptoms and the appearance of the larynx are often used in diagnosis and research. Currently, the LPR study group of the Young Otolaryngologists of the International Federation of OtoRhino-Laryngological Societies (YO-IFOS) has developed the Reflux Symptom Score (RSS). It will be used as a new tool to evaluate symptoms of LPR, GERD, and pulmonary-related disease.

Meanwhile, it appears that the typical approach uses an RSI score of greater than 13, and an RFS score of greater than 7 to warrant the use of a 3-month trial of proton pump inhibitors (PPIs), perhaps followed by an additional 3 months if called for.

The authors stress the importance of applying diet and lifestyle changes as a supplement to PPIs, or even on their own without PPIs. They also strongly suggest "the first-line LPR treatment combines diet, PPIs, sodium alginate ([if]acid or mixed reflux), magaldrate anhydrous ([if ] biliary reflux), in association with [a]gastroprokinetic." (note- the latter is not generally available in the U.S.) They recommend the magaldrate be taken after meals and the alginate before bedtime. Earlier posts have covered the topic of the alginate Gaviscon. Note that magaldrate has been withdrawn for approval in the U.S. I mention this because these are good examples of how medical treatment may differ between the U.S. and other countries.

They emphasize that there should not be long-term prescription of PPIs. Also, they report that after 3-6 months of treatment, 66% of patients can be weaned, "although 25-50% patients will have [a] chronic course of the disease."

Lechien JR, Saussez S, Karkos PD. Laryngopharyngeal reflux disease: clinical presentation, diagnosis, and therapeutic challenges in 2018. Curr Opin otolaryngol Head Neck Surg 2018 Voluime 26.

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LPR Summary

(Note: The article summarized below is a welcome and important addition to the medical literature concerning LPR. It is a clear presentation of the current status of research and recommendations regarding the diagnosis and treatment of this disease condition.)

I will summarize by listing the main points in the article below...

·    LPR (laryngopharyngeal reflux, airway reflux, extraesophageal reflux, etc.) accounts for 10% of all ear, nose and throat clinic patients. However, this number may be overestimated due to the difficulty in achieving a definitive diagnosis.

·    The disease is typically characterized by hoarseness (71%), cough (51%), "lump" in throat (47%), and throat clearing (42%).

·    Two mechanisms have been offered to explain these symptoms. One cause might be direct exposure of the larynx to acid and pepsin refluxed from the stomach. The other is the idea that acid exposure of the lower esophagus might trigger symptoms due to a reflux mediated through the vagus nerve.

·    In either case, these explanations have led to the use of acid-suppressive agents to eliminate the injuries caused by reflux.

·    There are problems with the various methods to diagnose LPR. For example, laryngoscopy has "poor sensitivity and reliability." "There is a disconnect between LPR symptoms and laryngoscopic findings." "Pharyngeal pH monitoring is not used routinely in clinical practice with its poor sensitivity..." "The role of intraluminal impedance monitoring...is currently uncertain..."

·    A new method, measuring "mucosal impedance"(MI), or conductivity of the esophageal epithelium, shows promise. "Studies using MI for diagnosis and for predicting treatment response...are underway."

·    Currently, the treatment for suspected LPR is twice daily PPIs. The authors recommend a two-month trial.

·    Those who "experience improvement in symptoms with PPI therapy should be weaned to the lowest effective dose."

·    Those who do not respond to the PPI trial, and "have negative reflux testing [pH studies] off [acid-suppressive] therapy" probably do not have reflux causing their symptoms. They should be evaluated for alternative causes by "allergy, neurology, and pulmonary specialists."

·    If pH testing does not reveal a reflux problem, and no other disorders surrounding laryngeal symptoms are found, the authors propose a diagnosis of "functional laryngeal disorder."

·    The authors recommend treating this disorder with "neuromodulating agents." The most common agent used in this scenario has been gabapentin. Another agent is amitriptyline. Both, as usual, may be accompanied by side effects which require discussion with the patient before using.

Patel DA, Blanco M, Vaezi MF. Laryngopharyngeal Reflux and Functional Laryngeal Disorder. Gastroenterol Hepatol (NY) 2018 Sept. 14(9) 512-520

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Eye Reflux

Researchers in Italy have reported on what seems, at first, to be a rather unusual manifestation of LPR. They studied 290 people with ocular surface disease (OSD) and determined how many of those had LPR symptoms.

They point out that the possible connection between extraesophageal reflux and eye problems may lie in the fact that studies have shown that pepsin, a major irritant of LPR, may be present in tears. The authors propose that  “Pepsin can move to lacrimal film passing through the nasal cavity, the inferior meatus, and the nasolacrimal duct.” In the current study , the subjects were given two tests, the Ocular Surface Disease Index (OSDI) and the Reflux Symptom Index (RSI). The former is a 12-item questionnaire asking about eye symptoms, and the latter assesses symptoms in people with reflux disease.

Of the 290 subjects, 101 tested positive for possible LPR. The authors state, “...ocular symptoms, vision related functioning, and environmental triggers were significantly more frequently reported by RSI positive patients...pain, poor vision, and problems when using a computer or watching TV were almost 5-fold more frequent in RSI positive patients...[they also] showed an almost 7-fold more frequent gritty feeling or problems when reading or having problems in low humidity [and] more frequent problems if windy conditions or in air conditioned spaces were reported 10- to 20-fold more frequently.”

The authors conclude “...a suspected LPR may be common in patients with OSD and an OSDI score >42 may be predictive for positive RSI.”

Mazzacane D, Damiani V, Silvestri M, et al. Eye Reflux: an ocular extraesophageal manifestation of gastric reflux. Int J Opthalmol 2018, 11(9): 1503-1507

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New Book

Two UK professors, internationally recognized experts in the relationship between reflux and respiratory disease, are the editors of a new book, Reflux Aspiration and Lung Disease. This is a collection of papers by numerous researchers whose work has contributed to the emerging picture of the relationship between gastroesophageal reflux and pathological changes in the respiratory tract. The aim of the book is to “educate and inform professionals of these latest developments and give practical advice to their application in the clinical setting.”

The publication of this book is a welcome addition to the developing awareness of “airway reflux” and its numerous possible effects, including cough, difficulty in swallowing, and constriction of the bronchi. It also emphasizes the latest approaches to diagnosis of the complex interaction of mainly non-acid gaseous reflux with the sensitive tissues in the airway.

Those of you who have read my book, All About LPR: The Silent Reflux Story, and have followed this blog, will appreciate the fact that this new publication expands the awareness of this disorder and its many permutations. Its price and highly technical language does not recommend it to the general public, but I wanted you to be aware of this welcome addition to the medical literature.

Morice, Alyn H.,Dettmar, Peter W.(Eds.) Reflux Aspiration and Lung Disease. Springer Publishing Company 2018.

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Gaviscon Advance Report

Treating LPR often involves administering protein pump inhibitors (PPIs). These act to block the production of stomach acid, and  have been discussed often in this blog. Treatment also often includes the use of antacids and alginates. The former are familiar products such as Mylanta and TUMS. They neutralize stomach acid which has refluxed. The alginates form a layer, or “raft” in the stomach to block reflux from occurring. They may also have antacid effects.

Several UK scientists report that using the alginate Gaviscon Advance alone “is effective in treating symptoms of LPR, while co-prescription with a high-dose PPI offers no additional benefit.”

Note that this product, made by Reckitt Benckiser, Slough, UK, is not sold in the U.S. However, there are vendors on Amazon.com that are a source for this product. The difference between this product and the Gaviscon sold in the U.S. is the higher concentration of alginate in the UK product. It is the alginate - a product derived from seaweed - that is effective in forming the “raft,” a mechanical barrier in the stomach limiting reflux.

The authors of this study suggest that health care professionals should be “mindful” of these results “when treating this common condition.” They are careful to suggest that further studies should be done to solidify these conclusions.

Wilkie MD, Fraser HM, Raja H. Gaviscon Advance alone versus co-prescription of Gaviscon Advance and proton pump inhibitors in the treatment of laryngopharyngeal reflux. European Archives of Oto-Rhino=Laryngology 30 July 2018. (Epub)

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Reflux Symptom Index-Spanish

The Reflux Symptom Index (RSI) is a widely used questionnaire. It is employed in the diagnosis of LPR and in LPR research. Despite the fact that millions experience symptoms of this condition, apparently it is only now that the RSI has been translated into Spanish.

A recent report states that this Spanish version of the RSI (Sp-RSI) is a “valid, inexpensive, and reliable tool for assessing laryngopharyngeal reflux symptoms and may be used for screening among the Spanish-speaking medical community.”

Calvo-Henriquez C, Ruano-Ravina A, Vaamonde P, et al.Translation and Validation of the Reflux Symptom Index to Spanish. J. Voice 2018. July 31.Epub.