Request an Appointment

“Dropping Acid” Blog

When Stupidity & Greed Collide

Standing in front of this corndog and fried food refluxitorium, Larry the Cable Guy tells us to take one Prilosec in the morning and be heartburn free all day long. He implies that if you take AstraZeneca’s purple pill, you can eat anything you want.

Nothing could be further than the truth. In fact, this strategy—cover up the heartburn but don’t control the disease—is probably why acid-reflux-caused esophageal cancer is the fastest growing cancer in the United States, up a whopping 850% since the 1970s.

Purple pills may stop some symptoms but have little or no effect on the progression of the disease. I should know; I am one of the world’s experts on reflux, and virtually every patient who comes to see me with complications of reflux is already on a purple pill, so in truth they don’t work very well.

Purple pills don’t control reflux! They just cover up its more serious manifestations.

The purple pills are a class of drugs called PPIs (proton pump inhibitors). They do not stop reflux, and they never should have been allowed (by the FDA) to be sold over the counter. Here’s why. After people take a PPI, they may feel better. But when they quit taking the PPI, they get rebound hyperacidity. That’s right, when you quit taking purple pills, you make more stomach acid than before. And so sales of purple pills escalate in a vicious cycle: You have heartburn and take purple pills—get some relief—then you stop purple pill—have rebound (worse acidity than before) —then you have to start taking the pills again. Wow! What a great strategy for the greedy drug companies that make the purple pills.

Much safer (and without the rebound hyperacidity) to take on an as-needed basis are the H2A class of drugs, including ranitidine (Zantac) and famotidine (Pepcid). PPIs should be taken under a doctor’s supervision, and when the patient is ready, tapering of the PPI should be done using H2As.

Fact is, the only really effective, long-term treatment of acid reflux is through a healthy diet and lifestyle. Overeating and overdrinking are key factors, and high-fat, high-acid foods are poison. I have written a lot about this topic in this blog and in my New York Times best-selling book, Dropping Acid: The Reflux Diet Cookbook & Cure.  Click here for more references on my reflux work

When stupidity and greed collide? Wake up America; what you eat may be eating you!

Silent Laryngopharyngeal Reflux (LPR): An Overview

Reflux is an expensive, high-prevalence disease1-4 and it affects approximately half of patients with laryngeal and voice disorders.5 It remains controversial because there are still no standard diagnostics or treatments.2-4 In addition, divisions between the medical specialties (otolaryngology, pulmonology, gastroenterology) each of which focuses on its own anatomic subdivision, have led to academic turf wars and fragmentation of research and the care of patients with diverse manifestations of reflux, particularly those with laryngopharyngeal reflux (LPR), the often “silent” (no heartburn or indigestion) backflow of gastric (stomach) contents into the laryngopharynx (throat and voice box).

Nevertheless, in addition to causing dysphonia (hoarseness), LPR affects large numbers of otolaryngologic patients with sinusitis, sore throat, globus (a lump-in-the-throat sensation), dysphagia (difficulty swallowing), chronic cough, and other reactive airways diseases such as asthma.2,6,7 Reflux remains a confusing topic even within otolaryngology (ENT), because most otolaryngology residency programs’ curricula often do not include specific training in the diagnosis and management of LPR. Among otolaryngologists, there isn’t even a clear consensus regarding the laryngeal findings.2,8

Having spent thirty-five years studying airway reflux in both laboratory and clinical settings, this chapter presents a paradigm of integrated aerodigestive medicine in which reflux play a unifying role. And therefore the structure of this chapter includes: nosology, epidemiology, etiology, pathophysiology, diagnosis, and treatment.

Nosology (Classification & Nomenclature) of Reflux

The term reflux is derived from two Latin roots, re-. back, and fluere, to flow. Therefore, reflux literally means backflow. The backflow in question here is the backflow of stomach contents into the esophagus and even into the airway, eg, laryngopharynx, trachea, lungs.

Patients and the lay media refer to this problem as “acid reflux,” but medical specialists have many different names and designations for diseases and disorders related to gastric reflux into the esophagus and airway; see Table 1. Specialists have coined different terms to express their different points of view. When describing reflux, gastroenterologists (GIs), for example, generally refer to GERD, gastroesophageal reflux disease, which describes their focus, the esophagus; however, when the airway is involved, GIs use terms like atypical reflux or supraesophageal reflux. Otolaryngologists generally use the term LPR.

I coined that term LPR in the 1980s specifically to call attention to the fact that the larynx and pharynx were the primary target organs when the refluxate extends above the esophagus. I also coined the term silent reflux because often patients with LPR do not have symptoms of heartburn or indigestion, symptoms that make reflux obvious.

It is worth noting that some people with “silent reflux” have no symptoms. This may occur when a person has nocturnal reflux; and such can be associated with seeming unrelated sinus and lung disease, eg, asthma, recurrent pneumonia, COPD.  Indeed, it is possible for LPR to be the underlying cause all of those problems.2-6

Table 1: Most Common Medical Terms for Reflux
Gastric reflux
Laryngopharyngeal reflux
Gastroesophageal reflux disease
Extraesophageal reflux disease
Supraesophageal reflux disease
Esophago-pharyngeal reflux
Gastropharyngeal reflux
Atypical reflux disease
Esophageal erosions
Barrett’s esophagus
Reflux esophagitis
Esophageal reflux
Airway reflux
Silent reflux

Why are there so many different terms? Besides otolaryngologists and gastroenterologists, many other specialists, including allergists, pulmonologists, pediatricians, internists, family practitioners, anesthesiologists, and critical care specialists regularly encounter diverse manifestations of reflux disease. Nevertheless, the two most popular terms for reflux across the different groups’ medical literature are GERD and LPR.

Since this reflux post was written for otolaryngologists and reflux patients as well, it makes sense dividing the aerodigestive tract into two basic components, the airway and the esophagus. These overarching anatomic designations are intuitive and appropriately broad. This chapter justifiably might have been termed airway reflux, as the latter term is more encompassing. The terms airway reflux and LPR may be used interchangeably as may the terms esophageal reflux and GERD.

Epidemiology (Prevalence)

The prevalence of reflux disease—both esophageal reflux (GERD) and airway reflux (LPR)—has increased dramatically in our lifetimes.1-4,9-15 Using a statistical model and an analysis of 17 studies, El-Serag1 showed that the average rate of increase of reflux disease since 1976 was 4% per year (P < .0001).

An even more ominous trend is the skyrocketing increase in the prevalence of esophageal cancer in the U.S.12-14 Based upon National Cancer Institute data, esophageal cancer is the fastest growing cancer in the country having increased 850% since 1975.12 During this same period, its mortality has increased seven-fold  despite increased esophageal surveillance.2-4,13,14 In addition, the prevalence of Barrett’s esophagus, the reflux-related precursor to esophageal cancer, is very high.12-14 Furthermore, Reavis, et al. reported that patients with hoarseness and chronic cough (airway symptoms) had Barrett’s esophagus just as frequently (8%) as GERD patients with heartburn.15 Today, routine esophageal screening is recommended for both airway and esophageal reflux patients.2-4,15,16

In the past, reflux was primarily a disease of overweight middle-aged people; however reflux is now common in thin, athletic, young people.3,4,17 This trend toward young patients with severe reflux has been observed by many experienced clinicians.

In 2010, the prevalence of airway and esophageal reflux (GERD and LPR) in the United States was estimated by interviewing a geographically random sample of 656 U.S. citizens.3 The data revealed that an astonishing 40% had reflux disease, 22% having classic esophageal reflux (GERD) and another 18% having airway reflux (LPR).3 There were no statistical differences seen between age, gender, and regions of the country. The most striking and unanticipated finding was that 37% of the 21-30 year-old age group had reflux.3,4
Historically, these trends have been primarily attributed to the obesity epidemic; however, it now appears that food additives (especially acid) in the American diet may be  in large measure responsible for the reflux epidemic.3,4

Etiology

There is considerable overlap between the causes of LPR and GERD, and this makes sense because the initial event for both is a transient LES (lower esophageal sphincter) relaxation that allows a bolus of refluxate to move from the stomach into the esophagus.5 The causes of gastroesophageal reflux (GER) are multifactorial and include many well-described factors2,5,6,8,17-19 (Table 2). Leaving congenital conditions and familial predisposition aside, over-eating, late-night eating, consumption of high-fat foods, fried foods, soft drinks (and other carbonated, caffeinated, and/or acidified beverages), smoking, and ethanol drinking all contribute GER.5

Chemicals like caffeine, ethanol, and theobromine (in chocolate), and medications like theophylline, are all refluxogenic and act by directly relaxing the LES.5 The same is true of fried and fatty foods, which cause the LES to relax, which lead to reflux. Reflux is also caused by anything that increases the intragastric pressure, such as overeating and carbonation, or anything that increases intra-abdominal pressure, such as obesity and exercise. Both increased intragastric and intra-abdominal pressure challenge the resistance of the LES.5

Table 2: Most Common Reported Causes and Risk Factors for Reflux
Ethanol (alcohol)
Chocolate (theobromine)
Tobacco/Smoking
Overeating/Obesity
Tight clothing / belts
Carbonated beverages (all soft drinks actually)
Lying down after eating / Late night eating (within 3 hours of bedtime)
Esophageal dysmotility (lazy esophagus)
High-fat and fried foods (eg, hamburger)
Xerostomia (dry mouth, especially after head & neck irradiation for cancer)
Hypotensive (low) lower esophageal sphincter pressure

One of the least understood, common factors is hiatal hernia (HH). As it turns out, one can have reflux without a HH, and one can have a HH without reflux. Today, we believe that HH decreases the LES pressure by approximately one-third, as the pinchcock effect of the diaphragm on the LES is lost. The size of the HH may, however, have some bearing on reflux, with large hernias being more likely to be associated with reflux.2,5

By comparison with the airway, the esophagus has four robust antireflux defenses.5,20,21 The first line of defense is the LES, and once it opens for any reason, gastric contents enter the esophagus, ie, GER.

The second defense is esophageal acid clearance, which actually is a sequence of events.5 The average person has up to fifty “physiologic” (normal) esophageal acid reflux events each day, occurring mostly after meals. Esophageal acid clearance is how normal pH is established after any reflux event.5

Once a bolus (“ball”) of gastric juice containing acid and pepsin (primary enzyme of stomach) enters the esophagus, a swallow must first clear the volume of the acid bolus, but even after volume clearance by the first swallow, the intraluminal pH remains low. It is only with a subsequent series of swallows, with the delivery of salivary bicarbonate that normal pH is restored. Normal esophageal acid clearance usually takes less than five minutes.5

Esophageal acid clearance requires saliva and salivary bicarbonate. Consequently, it is important for the otolaryngologist to know that xerostomia, particularly iatrogenic (doctor/treatment caused) xerostomia (dry mouth, not enough saliva), following head and neck cancer irradiation, is virtually always associated with reflux.  As a logical corollary, esophageal cancer is the most common metachronous (occurring later) cancer following head and neck cancer irradiation, giving further credence to the importance of esophageal acid clearance.

The third esophageal antireflux defense is esophageal epithelial resistance.2,5,20-24

The esophageal mucosa (lining) is more resistant to damage from acid and pepsin than any other aerodigestive structure, except the stomach. Remarkably, when inflamed, the esophageal mucosa secretes bicarbonate.5,20-22 All mammalian cells contain an important enzyme, carbonic anhydrase, which helps maintain intercellular acid-base balance by hydrolyzing CO2 to form bicarbonate. Carbonic anhydrase is usually found in the basal layer of the epithelium. That is the case in the normal esophagus; however, with esophagitis, the carbonic anhydrase diffuses through the superficial layers so that the esophagus actually secretes bicarbonate. This is an amazing defense, which is not shared by the laryngeal epithelium.5

The fourth defense is the UES (upper esophageal sphincter, also called the  cricopharyngeus), is actually not an esophageal antireflux defense, because it is the primary barrier to airway reflux (LPR).5

Pathophysiology of LPR

From both theoretical and practical perspectives, while LES failure is at fault in GERD; in LPR, the UES is faulty.  Under normal circumstances, UES pressure increases in response to esophageal acid exposure; but in patients with LPR, this protective reflexive function fails.5 Why the upper valve fails in LPR is uncertain; however, it is also clear that UES failure is reversible with effective antireflux treatment.2

Cell Biology of Airway Reflux

The biggest difference between the airway and the esophagus is simply that the airway epithelium (outer liming membrane) is profoundly fragile and easily damaged by gastric reflux compared to the esophageal epithelium (that is relatively robust). To understand these differences, the cell biology of LPR holds the key.2,20-27

First, it is important to recognize that the tissue damage is due to pepsin; it is peptic (not acid) injury.2-5,20-27 Second, it is tissue-bound pepsin that causes tissue injury. Johnston et al. reported that pepsin was found by Western blot determination in 95% of laryngeal biopsies in patients with documented LPR.27 Third, peptic injury is associated with depletion of key protective proteins including carbonic anhydrase, E-cadherin, and the stress proteins.20-24

Equally important in understanding the biology of LPR is consideration for the stability and spectrum of activity of human pepsin.24 Human pepsin retains some of its proteolytic activity well above pH 4.0 depending on the substrate. For example, pepsin can destroy collagen up to pH 6.5.24 Clinical LPR is associated with tissue-bound pepsin,27 and based upon both experimental and pH-monitoring data, it is that clear laryngeal epithelial damage occurs at pH 5; whereas, the threshold for esophageal epithelial damage is pH 4.21 Figure 1 shows the relationship between pH and the proteolytic activity of pepsin.  Note that 40% of peptic activity remains at pH 5.

Figure 1: The Human Pepsin 3b Activity Curve24


Initiation and Promotion of Reflux

From a clinical perspective, there is another way of looking at the pathophysiology of reflux. For most reflux patients, airway reflux has an “initiation phase” (actual reflux of acid and pepsin into the laryngopharynx with binding of pepsin to the epithelium) and a “promotion phase,” which is dependent on additional LPR and/or a source of dietary (HCl) acid. (The terms “initiation” and “promotion” are borrowed from the carcinogenesis literature and in this model pepsin is the initiator and “subsequent” dietary acid is the promoter.) In other words, pepsin is only found (and manufactured) in the stomach; initiation requires a true gastro-esophageal-pharyngeal reflux event or events. Once pepsin is tissue-bound, proteolytic activation is promoted by acid, usually from acidic foods and beverages.3,4 In other words, once pepsin is tissue-bound to laryngopharyngeal structures, hydrogen ions from any source can be the promoters.

The initiation-by-pepsin and promotion-by-dietary-acid model helps explain why for so many LPR patients pharmacologic acid-suppression is ineffective, that is, without dietary intervention medical treatment usually fails. At best, acid suppression from below is only half of the peptic-injury equation.3,4

It also explains why dietary bingers do poorly. Imagine a college student who is well-behaved most of the time, but on Saturday nights he goes out drinking, and on his way home stops for cheeseburgers, fries, and a soda. Tipsy and with a stomach full of acidic high-fat food, he falls asleep and refluxes all night. He awakes in the morning dysphonic with a sore throat and cough.

He has tissue-bound pepsin all over his laryngopharynx, and that is his initiation. First thing in the morning, he drinks orange juice pH<4, then during the day he drinks almost a half gallon of soft drinks (pH<3). Amazingly, in 2010, the average 12-29-year-old American drank 160 gallons of soft drinks; that’s almost a half-gallon per day.3 And that is acid promotion! Even if the student does not have another actual reflux event for a week, his airway reflux peptic damage is active, and tissue inflammation and injury can escalate over time dietary acid alone. The more acid he consumes, the more the tissues are affected including the UES and LES. In other words, after initiation has occurred, promotion can progress (or even escalate) inflammation and tissue damage leading to further impairment of anti-reflux defenses.

Based upon pH-monitoring data, most patients with airway reflux (LPR) are upright (daytime) refluxers; however when an LPR patient has supine (nocturnal) reflux, tissue damage tends to be more severe. When it comes to initiation, nighttime reflux is far more injurious than daytime reflux. For many LPR patients, regardless of dose of acid-suppressive medications, late-night eating must be curtailed before effective treatment can begin.

Reflux has the characteristics of a vicious cycle, a downward spiral. The more a person refluxes, the worse esophageal function is affected, which in turn leads to worsening reflux. This downward spiral may continue until symptomatic decompensation causes the patient to seek medical attention. Fortunately, it is also true that recovery is an upward spiral. The less a patient has acid and pepsin in the airway (or esophagus), the more likely recovery of the body’s natural antireflux defenses.

Diet: Where Epidemiology & Pathophysiology Meet

The dramatic increases in reflux over the past forty years cannot be explained by the obesity epidemic alone. The increases appear to be mostly related to other dietary and lifestyle-related factors. Coincident with the reflux epidemic, America’s diet has changed.In our lifetimes, there have been four unhealthy dietary trends:

(1) Increased saturated fat
(2) Increased high-fructose corn syrup
(3) Increased exposure to organic pollutants (e.g., DDT, PCBs, dioxins)
(4) Increased dietary acidity (and other food additives as well)

The last of these trends—increased dietary acid—may hold the key to understanding the growing reflux epidemic with its associated and dramatic increases in esophageal cancer.2-4 Dietary aid appears to be the missing link: In 1973, following an outbreak of food poisoning, the U.S. Congress mandated that the Food and Drug Administration (FDA) take responsibility for assuring the safety of processed food by establishing “Good Manufacturing Practices.”3,4 How was this accomplished? Through acidification of bottled and canned foods, which was intended to prevent bacterial growth and prolong shelf life.3,4 From the 1979 Title 21 Act:

“Foods should be so manufactured, processed, and packaged that a finished equilibrium pH value is achieved. If the finished equilibrium pH is 4.0 or below, then the measurement of acidity of the final product may be made by any suitable method.”3,4

Today, two generations later, the FDA has never wavered from this path and has never questioned the possibility that acidification of the food supply might have potential adverse health consequences. In other words, the FDA encourages food manufacturers to reduce the pH of their products to less than 4.0, the same pH level as stomach acid (Figure 3).  In the U.S., the arc of the reflux and the esophageal cancer epidemics closely follows soft drink consumption.2,32,33

At present, almost everything in a bottle or can is acidified to discourage bacterial growth and prolong shelf life. Bottled and canned foods and beverages are almost always pH <4,2-4,31-34 because ascorbic and/or citric acids are added. Sometimes the food label can be vaguer; it may just read “vitamin C enriched” or “vitamin C enhanced.”3,4 That is not really added to give you vitamins; it is done for purposes of acidification alone.

Knowing what we now know about the cell biology of reflux, the stability and activity of pepsin, and the contemporary American diet, it may be reasonable to postulate that acidification of America’s food supply is in large measure responsible for the reflux epidemic. Dietary acidity appears to be fundamental to the pathophysiology of airway reflux; and dietary acid appears to be the crucial factor in the prevalence (including neoplasia) and outcomes of reflux disease as it affects the laryngopharynx.3,4 See also the section on “Treatment.”

Diagnosis

The symptoms and manifestations of airway reflux go beyond those typically associated with esophageal reflux (Table 3), and there are red flags that make airway reflux highly likely. Waking in the middle of the night from a sound sleep coughing (and even gasping for air like a fish out of water, i.e., laryngospasm), chronic cough for more than two months (with a normal pulmonary evaluation), a sensation of a lump in the throat (globus) that is there all the time, except when the patient is actually eating, morning hoarseness, chronic-intermittent hoarseness and difficulty swallowing (dysphagia) all can be symptoms of LPR.

Table 3: Symptoms and Conditions Reportedly Related to Airway Reflux

Symptoms                         Conditions
Regurgitation                         Dental caries and erosions
Chest pain                              Esophageal spasm
Shortness of breath               Esophageal stricture
Choking episodes                   Esophageal cancer
Hoarseness                             Reflux laryngitis
Vocal fatigue                          Larynx (laryngeal) cancer
Voice breaks                           Endotracheal intubation injury
Chronic throat clearing          Contact ulcers and granulomas
Excessive throat mucus          Posterior glottis stenosis
Post-nasal drip                        Arytenoid fixation
Chronic cough                         Paroxysmal laryngospasm
Dysphagia                              Globus pharyngeus
Difficulty swallowing            Laryngeal cancer
Difficulty breathing               Vocal cord dysfunction
Choking episodes                   Paradoxical vocal fold movement
Lump-in-throat sensation       Vocal nodules and polyps
Food getting stuck                  Pachydermia laryngitis
Airway obstruction                 Recurrent leukoplakia
Wheezing                               Polypoid degeneration
Laryngomalacia
Laryngospasm
Vocal cord dysfunction
Sudden Infant Death Syndrome
Sinusitis and allergic symptoms
Sleep apnea
Asthma

What about asthma? Is it a symptom of reflux?  There is one question that every clinician should ask when a patient says they have asthma, particularly adult-onset asthma, “When you have breathing difficulties, do you have more trouble getting air in or out?”  If the patient says, “IN,” they do not have asthma. Their symptoms are due to reactive airway disease secondary to airway reflux.

At present, there is no one diagnostic reflux test for LPR that provides more accurate information than pharyngeal/UES/esophageal manometry combined with ambulatory 24-hour dual-probe (simultaneous pharyngeal and esophageal) pH monitoring.2 Impedance monitoring is, in the author’s experience, a second choice for diagnosing airway reflux though it is a good supplement to pH testing as it may identify injurious non-acid reflux. Under development are new diagnostic tests that are specific for airway reflux and utilize pepsin as a marker. The author currently uses a combination of diagnostics.

1. Clinical Parameters: The Reflux Symptom index28 (RSI) and The Reflux Finding Score29 (RFS)

When taken together the RSI and the RFS are the most reliable clinical diagnostics, and they are recommended for routine use by the otolaryngologist. The RSI (a nine-item, symptom severity scale) is completed by the patient, and it is a validated reflux outcomes instrument29 (Table 4). when a patient has a RSI of >15, s/he has a 90% chance of having pH-documented LPR.2

Table 4: The Reflux Symptom Index (RSI)


The RSI should be completed by every patient prior to being seen by the clinician, and the clinician should complete the RFS after each laryngoscopy, even if it is to note that the RFS was nil. The RFS is a system for grading the laryngeal findings of LPR (Table 5).

Theoretically, the RFS can be calculated on the fly during a visual laryngoscopy; however, grading the RFS after the examination is completed from an archived laryngeal image is preferred, and that image should show the larynx in abduction, not adduction. This grading system was developed using images obtained by transnasal flexible laryngoscopy (TFL), and TFL is the preferred examination. The RFS is a weighted nine-item scoring system devised by the author in 1986 and subsequently reported.8,29 The RFS is particularly useful in diagnosing LPR. In addition, when calculated at each visit, it is an excellent parameter to evaluate the effectiveness of therapy. Patients who are successfully treated will have a normal (less that 4) RFS. Below are descriptive parameters for each of the nine items:

Pseudosulcus vocalis refers to subglottic edema that gives the vocal fold the appearance of being three-dimensional, almost having the appearance of an open hotdog bun. The normal non-swollen, non-inflamed vocal fold appears to be a two-dimensional structure. Pseudosulcus is a finding usually associated with reflux and diffuse laryngeal edema. (Pseudosulcus can also sometimes be a “normal” finding when the vocal folds are atrophic, eg, presbylaryngis.) A finding of pseudosulcus gets two points in the RFS system.

Figure 2: LPR Findings (A. Before and B. After Treatment)

Ventricular obliteration. The ventricle is a grove-like structure or recess between the true and false vocal folds. When it is normal and open, the ventricular band is sharp and the depth of the ventricle glistens. If, however, both the true and false folds are swollen, the ventricle can be partly or completely obliterated. Partial ventricular obliteration scores two points, and complete ventricular obliteration scores four points in the RFS. The case, Figure 2-A, shows partial ventricular obliteration that resolves after treatment (Figure 2-B).


Erythema
, the third item, is graded two points for red arytenoids and four points for diffuse laryngeal erythema. In reality, erythema is grossly overcalled. The main finding of LPR is edema not erythema. The normal vascularity of the posterior larynx will vary a lot depending upon the brightness of the light source.

Vocal fold edema is graded as follows: “1 Mild” for slightly swollen vocal folds; “2 Moderate” if pseudosulcus is present; “3 Severe” if there is sessile or polypoid swelling that is occupying some of the intra-fold space; and “4 Polypoid” for Reinke’s edema.

Diffuse laryngeal edema is the most subjective finding of the RFS. It relates to the size of the glottal opening (chink) relative to the size of the entire larynx. Normally, the area of the glottal chink at near-full abduction occupies 50% of the total area. (Diffuse laryngeal edema is rarely graded more than one or two points.)

Posterior commissure hypertrophy is graded as follows: “1 Mild” when the moustache of the posterior commissure is still upwardly concave; “2 Moderate” when edge of the posterior commissure is straight; “3 Severe” when it is convex into the endolaryngeal lumen; and “4 Obstructing” when it is obstructing the airway.

Figure 3: Example of Tiger-Stripe Post-Cricoid Edema (Arrow)

 

A. (left): Before treatment for LPR; the reflux finding score is 11 (partial ventricular obliteration 2, vocal fold edema 2, diffuse laryngeal edema 1, posterior commissure hypertrophy 2, post-cricoid edema 2, endolaryngeal mucus 2). B. (right): After treatment; normal, the RFS is 0.

Tiger-stripe post-cricoid edema. Tiger-stripe post-cricoid edema is a highly reliable reflux finding (Figure 3). Under normal circumstances, the post-cricoid region is smooth. When swollen, it may give the appearance of having wet, edematous stripes. (Tiger-striping was not originally reported8,29 but added later.) Tiger-stripe edema is usually seen in patients who are supine (nocturnal) refluxers.

Figure 3: Severe LPR with Tiger-Stripe Post-Cricoid Edema (arrow)

The RFS is 17 (complete ventricular obliteration 4, vocal fold edema 4, diffuse laryngeal edema 3, posterior commissure hypertrophy 2, post-cricoid edema 2, endolaryngeal mucus 2). Endolaryngeal mucus. Thick, white, tenacious mucus on the vocal folds counts as two points in the RFS. Finally, arytenoid granuloma, granulation, and/or (contact) ulceration counts as two points as well.

2. Pepsin Immunoassay30: Spit Test Screening for Airway Reflux

The author has developed and is now using a “spit-in-a-cup test” that detects pepsin in airway secretions or saliva. The test is performed by putting a small sample of the patient’s saliva in buffer and then in a lateral flow device (similar to a pregnancy test). As a screening test for LPR, the sensitivity of the assay is 82% and its specificity is 100%. This useful screening test will become commercially available as soon as it receives FDA approval.

3. Ambulatory 24-hour pH-Monitoring with or without Impedance Testing

For the author, ambulatory, 24-hour, double-probe (simultaneous pharyngeal and esophageal) pH monitoring has been her gold-standard LPR diagnostic for twenty-five years. Impedance testing provides less information as there are no reliable pharyngeal data. Due to poor manufacturing quality control, in the author’s reflux-testing laboratory, antimony sensors have been replaced with more accurate ISFET technology. Finally, pharyngeal pH monitoring using an “aerosolized” sensor in the pharynx has proven to be highly inaccurate and not worthwhile as a clinical test.

Pharyngeal pH-Monitoring is especially useful if the data are examined in a number of ways: (1) Using pH >4.0 as a threshold, (2) using pH >5.0 as a threshold, (3) calculating mean pharyngeal pH, and (4) calculating the pharyngeal reflux injury score2 (RIS), which is a summation of the time at each pH level multiplied by the peptic activity coefficient; the RIS is comparable to the DeMeester score for overall pharyngeal reflux severity.2

pH-Monitoring following high-definition pharyngeal/UES/esophageal manometry will t only insure accurate pH-probe placement, but the data may also alter therapy, eg, a prokinetic medication may be added to the treatment regimen for patients with esophageal dysmotility.

5. Transnasal Esophagoscopy (TNE) with or without Biopsy9,16

Patients with both airway and esophageal reflux should be screened for esophageal disease as 8-10% will be found to have Barrett’s esophagus, a precursor to esophageal cancer.15 In addition, other pathology (eg, Candida esophagitis, erosive esophagitis, varices) is found in another 25% of LPR patients.9 The highest percentage of esophageal pathology (63%) is seen in LPR patients with a chief complaint of chronic cough [Koufman JA, unpublished data, 2013].

It is important to note that although esophageal endoscopy is necessary to rule out esophageal pathology, esophagoscopy is NOT the diagnostic test of choice for LPR. Indeed, it has been reported that up to 80% of LPR patients have normal esophagoscopy.9

6. Barium Swallow Esophagography

A generation ago, the barium swallow/esophagogram was routinely used to evaluate reflux. Unfortunately, this technology is relatively insensitive and non-specific, and the finding of a hiatal hernia alone has little clinical significance. Barium studies should be reserved for patients in whom structural esophageal abnormalities are suspected.5

7. Therapeutic Trial with Antireflux Medication

The world is changing and two of the most significant trends in the contemporary management of reflux-related disease are (1) that the medical treatment failure rates with PPIs (proton pump inhibitors) are increasing,3,4,19 and (2) that effective reflux management depends on dietary and lifestyle variables.2-4 Presumably this is because globalization and urbanization have brought about dramatic changes in where, when, and what people eat.

Fifty years ago, most people ate at home, and prepackaged foods and beverages were uncommon. Today, most big soft drink and fast-food companies are global brands, and by comparison people everywhere are being exposed to much higher levels of food additives (especially acids) than a generation ago. As the world’s diet has become Americanized, reflux has followed.

For many years, a therapeutic trial with PPIs (proton pump inhibitors) was considered a useful diagnostic test for LPR. Clearly, acid-suppressive medications alone no longer constitute an appropriate therapeutic trial and such is no longer considered to be reliable or cost-effective. It now appears that dietary and lifestyle issues are even more important than medication for the effective treatment of airway reflux.

Before leaving this section on the diagnosis of LPR, it is important to reemphasize the value of the laryngeal examination with determination of the RFS. In the author’s opinion, examination of the larynx, regardless of the severity of airway reflux symptoms, holds the key to understanding reflux within the entire aerodigestive system. This point cannot be overemphasized: sequential laryngeal examinations, using the RFS are the best way to evaluate the progress of treatment. The larynx is a window through which the clinician can view and assess the condition of the upper aerodigestive tract. It is the crossroads and it is responsive enough to accurately reflect the status of the entire system.

Treatment

Airway reflux (LPR) can be associated with minor symptoms (e.g., throat clearing) or with life-threatening disease (e.g. laryngeal stenosis, airway obstruction, and cancer). So it stands to reason that there cannot be any one-size-fits-all therapeutic regimen. Meanwhile, there are medical, lifestyle, dietary, and surgical treatment options.

Medical Treatment

There are several different approaches to medical treatment: antacids, acid suppressants, mucosal protection, and promotility agents.  These may be used alone or in combination depending on the patients reflux pattern and disease severity.

Antacids, once the cornerstone of antireflux treatment, are now just reserved for patients with mild and intermittent symptoms, or as adjunctive therapy to alleviate primarily heartburn in patients with recalcitrant disease. Today, proton pump inhibitors (PPIs) are the most commonly used antireflux drugs, followed by H2-antagonists. There are many different PPIs on the market today and they account for $15 billion in annual sales in the U.S. alone.

PPIs give the best acid suppression of any antireflux medication.  However, their use has become more controversial in recent years due to concerns about rebound hyperacidity following drug cessation, side effects, as well as short- and long-term complications. When they are used for airway reflux, they should be given in a twice-daily dose (before breakfast and before the evening meal). Patients with nocturnal reflux are also usually given an H2-antagonist at bedtime as the latter work better during sleep than PPIs.

In the past, clinicians recommended twice-daily PPIs (before breakfast and before the evening meal) with an H2-antagonist at bedtime for LPR patients. Today, there are concerned about the long-term safety and efficacy of PPIs, particularly the double-dose regimen.

Prokinetic agents (including reglan, erythomycin, and domperidone) can help improve esophageal function (peristalsis) and sphincter function. Their use should be reserved for patients who demonstrate poor esophageal motility and/or sphincter function.  Reglan and domperidone should be used with caution as they can cause significant and permanent side effects.  Reglan has numerous side effects including irreversible tardive dyskinesia and Domperidone is not FDA approved in the United States.

Many patients with airway reflux need long-term medical treatment, but many also can get off medications after the acute phase improves as long as they remain compliant with a reasonable maintenance antireflux diet.

Lifestyle and Dietary Treatment

Control of dietary and lifestyle factors are probably more important that antireflux medication; although, when patients present with severe reflux, particular those with reactive airways diseases such as chronic cough, laryngospasm, and asthma, the clinician must use acid-suppressive medications as well as diet/lifestyle modifications in combination.

Obesity and reflux go together especially when the patient overeats, consumes a lot of fried and fatty foods, chocolate, carbonated beverages, and eats late at night. Those are among the high-risk behaviors for reflux disease. Interestingly, smoking also causes reflux. However, it is important to recognize that many patients with LPR are thin, athletic, and generally eat healthy food. For that group, an overly acidic diet and lifestyle issues such as late night eating are commonest reflux risk factors.

One of the most difficult problems in treating reflux patients is how much variation there is from patient to patient. While fried food, ethanol, and soft drinks in excess are almost universally associated with reflux, many other marginal (eg, acidic fruits like papaya and strawberries) or idiosyncratic foods (eg, nuts, tomatoes, onions, garlic, peppers) or even “healthy” foods (eg, banana, pears, oatmeal) can trigger reflux in some people.

When a patient has severe LPR, it is well worth prescribing a two-week induction (“detox”) reflux diet in which nothing consumed that is pH <5; no eating within four hours of bed, and consumption of alkaline (pH >8) water.3,4, 31 While this seems severe, it really works to get patients better fast.3 Recommendations for dietary and lifestyle modifications are summarized in Table 6.

Table 6: Recommended Lifestyle and Dietary Modifications for Reflux

General Lifestyle Recommendations
If you use tobacco, quit. Smoking causes reflux
Don’t wear clothing that is too tight, especially trousers, corsets, bras, and belts
Avoid exercising right after eating (especially weightlifting, jogging, and yoga)
Do not lie down right after eating, and do not eat anything within three hours of bedtime
Elevate the head of your bed if you’re a nighttime refluxer; that is, if you have symptoms
of hoarseness, sore throat, and/or cough in the morning
An overweight patient should start a low-acid, pH-balanced diet

Worst For Reflux Foods and Beverages to Avoid
Onions (This is an “idiosyncratic” food that affects some people, not others)
Peppers / Hot Sauce (All peppers including bell and black pepper)
Citrus fruit/juice (These are naturally too acidic and more is added)
Fried Food (This is restaurant food and different from sautéed)
Fatty Meats (bacon, pork, lamb, some fatty steak cuts like rib eye)
Alcoholic beverages (More than one drink and you’ll probably reflux)
Chocolate (Sorry, this is one of the most common reflux trigger foods)
Almost all bottled/canned beverages (except water), all soft drinks are acidified
Really avoid all carbonated beverages (Coke, Pepsi, and all sodas including seltzer)
Anything that you eat before bed is a “worst for reflux” food

The Best-For-Reflux Food and Beverage List
Bananas (A rich, low-acid fruit, strangely a trigger food for 5% of people)
Melons (Best fruits for most refluxers: watermelon, cantaloupe, honeydew, etc.)
Aloe Vera (Great thickener and good for digestion, make sure no acid added)
Salads and Vegetables (A staple, excluding onions, tomatoes, garlic and peppers)
Rice and Whole Grains (Best is brown rice, Bulgur wheat, and healthy bread)
Oatmeal (One of the best breakfast foods that there is and great with banana)
Ginger (Spicy, zesty flavor but good for reflux–try ginger tea, candy, jam, etc.)
Poultry (Baked, grilled, but never fried; sorry, skinless preferred; high protein)
Tofu (Tofu, coagulated soy milk in many forms is a vegetarian staple protein)
Fish (All seafood— raw, grilled, baked, boiled, or boiled—is good for reflux)

Surgical Treatment

The primary effective surgical option for the treatment of reflux is a laparoscopic Nissen laparoscopic fundoplication. The term “fundoplication” refers to wrapping fundus (the dome of the stomach) around the esophagus and then plicating (sewing it) there to produce a tight angle where the esophagus enters the stomach.  This surgical procedure is by far the single most effective treatment for both esophageal and airway reflux. There is controversy surrounding which LPR patients are the best candidates for a fundoplication.  When chosen correctly it is an extremely effective procedure. Indeed, surgical treatment is often recommended for patients with lung disease related to reflux and for patients who cannot tolerate or fail medical treatment.

Conclusions

The diagnosis of LPR is difficult because there is no gold-standard diagnostic test; nevertheless, the reflux symptom index and the reflux finding score are invaluable and reliable clinical measures.

Airway reflux (LPR) has different pathophysiology than esophageal reflux (GERD) based upon the relative sensitivity of airway (compared to esophageal) epithelium to peptic injury. In addition, the sine qua non for laryngeal tissue injury is the presence of tissue-bound pepsin, because once pepsin is attached to epithelium, any source of hydrogen ions, including dietary acid, will maintain extended periods (days or weeks) of proteolytic activity.

Because of this distinctive mechanism, dietary and lifestyle modifications, particularly low-acid diet, is essential for treatment to be effective.

References

  1. El-Serag HB. Time trends of gastroesophageal reflux disease: A systematic review. Clin Gastroenterol Hepatol 2007;5:17-26.
  2. Koufman JA. Perspective on Laryngopharyngeal Reflux: From Silence to Omnipresence. Classics in Voice and Laryngology. Branski R, Sulica L, Eds. Pages 179-266, Plural Publishing, San Diego, 2009.
  3. Koufman JA. Low-Acid Diet for Recalcitrant Laryngopharyngeal Reflux: Therapeutic Benefits and Their Implications. Ann Otol Rhinol Laryngol 120:281-87, 2011.
  4. Koufman JA, Stern JC, Bauer MM. Dropping Acid: The Reflux Diet Cookbook & Cure. Reflux Cookbooks LLC (Midpoint Distributors), New York, NY, 2010.
  5. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease (GERD): A clinical investigation of 225 patients using ambulatory 24-hour pH monitoring and an experimental investigation of the role of acid and pepsin in the development of laryngeal injury. Laryngoscope 1991;101 (Suppl. 53):1-78.
  6. Koufman JA, Amin M, Panetti M.  Prevalence of reflux in 113 consecutive patients with laryngeal and voice disorders. Otolaryngol Head Neck Surg  123:385-388, 2000.
  7. Koufman JA, Block C. Differential diagnosis of paradoxical vocal fold movement. Amer J Speech and Hearing. 2008;17:327-34.
  8. Belafsky PC, Postma GN, Koufman KA.  Laryngopharyngeal reflux symptoms improve before changes in physical findings.  Laryngoscope 111: 979-981, 2001.
  9. Koufman JA, Belafsky PC, Daniel E, et al. Prevalence of esophagitis in patients with pH-documented laryngopharyngeal reflux.  Laryngoscope 2002;112:1606-9.
  10. El-Serag H, Becher A, Jones R. Systematic Review: Persistent Reflux Symptoms on Proton Pump Inhibitor Therapy in Primary Care and Community Studies. Alimentary Pharmacology and  Therapeutics. Blackwell Publishing, Ltd., Pages 1-18, 2010.
  11. Altman KW, Stephens RM, Lyttle CS, et al. Changing impact of gastroesophageal reflux in medical and otolaryngology practice. Laryngoscope 2005;115:1145-53.
  12. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst 2005;97:142-6.
  13. Lund O, Hasenkam JM, Aagaard MT, Kimose HH. Time-related changes in characteristics of prognostic significance in carcinomas of the oesophagus and cardia. Br J Surg 1989;76:1301.
  14. Conio M, Blanchi S, Lapertosa G, et al. Long-term endoscopic surveillance of patients with Barrett’s esophagus. Incidence of dysplasia and adenocarcinoma: A prospective study. Am J Gastroenterol 2003;98:1931-9.
  15. Reavis KM, Morris CD, Gopal DV, Hunter JG, Jobe BA. Laryngopharyngeal reflux symptoms better predict the presence of esophageal adenocarcinoma than typical gastroesophageal reflux symptoms. Ann Surg 2004;239:849-56.
  16. Amin MR, Postma GN, Setzen M, Koufman JA. Transnasal esophagoscopy: A position statement from the American Broncho-Esophagological Association. Otolaryngol Head Neck Surg 2008;138:411-3.
  17. Halum SL, Postma GN, Johnston C, Belafsky PC, Koufman JA. Patients with isolated laryngopharyngeal reflux are not obese. Laryngoscope 2005;115:1042-5.
  18. Postma GN, Tomek MS, Belafsky PC, Koufman JA.  Esophageal motor function in laryngopharyngeal reflux is superior to that of classic gastroesophageal reflux disease. Ann Otol Rhinol Laryngol 2001;110:1114-6.
  19. Amin MR, Postma GN, Johnson P, Digges N, Koufman JA.  Proton pump inhibitor resistance in the treatment of laryngopharyngeal reflux. Otolaryngol Head Neck Surg 2001;125:374-8.
  20. Axford SE, Sharp S, Ross PE, Pearson JP, Dettmar PW, Panetti M, Koufman JA.  Cell biology of laryngeal epithelial defenses in health and disease: Preliminary studies.  Ann Otol Rhinol Laryngol 2001;110:1099-1108.
  21. Johnston N, Bulmer D, Gill GA, Panetti M, Ross PE, Pearson JP, Pignatelli M, Axford A, Dettmar PW, Koufman JA.  Cell biology of laryngeal epithelial defenses in health and disease: Further studies. Ann Otol Rhinol Laryngol 2003;112:481-91.
  22. Gill GA, Johnston N, Buda A, Pignatelli M, Pearson J, Dettmar PW, Koufman J. Laryngeal epithelial defenses against laryngopharyngeal reflux (LPR): Investigations of pepsin, carbonic anhydrase III, pepsin, and the inflammatory response.  Ann Otol Rhinol Laryngol 2005;114:913-21.
  23. Johnston N, Dettmar PW, Lively MO, Koufman JA.  Effect of pepsin on laryngeal stress protein (Sep70, Sep53, and Hsp70) response: Role in laryngopharyngeal reflux disease.  Ann Otol Rhinol Laryngol 2006;115:47-58.
  24. Johnston N, Dettmar PW, Bishwokarma B, Lively MO, Koufman JA. Activity/stability of human pepsin: Implications for reflux attributed laryngeal disease. Laryngoscope 2007;117:1036-9.
  25. Lillemoe KD, Johnson LF, Harmon JW. Role of the components of the gastroduodenal contents in experimental acid esophagitis. Surgery 1982;92:276-84.
  26. Samuels TL, Johnston N. Pepsin as a marker of extraesophageal reflux. Ann Otol Rhinol Laryngol 2010;119:203-8.
  27. Johnston N, Knight J, Dettmar PW, Lively MO, Koufman J. Pepsin and carbonic anhydrase isoenzyme III as diagnostic markers for laryngopharyngeal reflux disease. Laryngoscope 2004;114:2129-34.
  28. Belafsky PC, Postma GN, Koufman JA.  Validity and reliability of the reflux symptom index (RSI). J Voice 2002;16:274-7.
  29. Belafsky PC, Postma GN, Koufman JA. The validity and reliability of the reflux finding score (RFS).  Laryngoscope 2001;111:1313-17.
  30. Knight J, Lively MO, Johnston N, Dettmar PW, Koufman JA. Sensitive pepsin immunoassay for detection of laryngopharyngeal reflux. Laryngoscope 2005;115:1473-8.
  31. Koufman JA, Johnston N. Potential Benefits of pH 8.8 Alkaline Drinking Water as an Adjunct in the Treatment of Reflux Disease. Ann Otol Rhinol Laryngol 121:431-34, 2012.

Prevalence of occult laryngeal pathology in a community-based cohort of adults over 40 years of age.

The adult voice is perceived to change with advancing age. This more senescent voice is thought to result from multiple structural and functional changes that occur within the larynx as a normal part of the aging process. Structural changes may include atrophy of the intrinsic laryngeal musculature and ossification and degeneration of the cartilaginous portions of the larynx. Functional changes often include increased dryness and stiffness of the vocal fold mucosa as a result of both decreased glandular secretion as well as reduced elastin production. Most elderly people adjust for these gradual degenerative changes by using compensatory hyperfunctional voicing techniques (supraglottic contraction) and/or by improving breath support. However, the risk for eventual voice and swallowing decompensation is high, and it has been estimated that approximately 12% of the elderly have some degree of vocal dysfunction.
Continue reading Prevalence of occult laryngeal pathology in a community-based cohort of adults over 40 years of age.

Glossary of Common Terms in Singing and Laryngology

A

A CAPPELLA. Singing without instrumental accompaniment.

ALTO. The lowest pitched female singing voice; CONTRALTO.

APHONIA. No voice; loss of voice.

ARIA. Song, especially an operatic solo.

ARPEGGIO. Notes of a chord sung (or played) in succession.

ART SONG. Song, usually composed to erudite poetry, generally intended for formal performance.

ARTICULATION. Pronunciation of vowels and consonants.

ASPIRATE. Breathy.

ATROPHY. Withering or wasting away of a tissue or organ, as may occur in paralysis or aging.

ATTACK. Beginning of the vocal tone; ONSET.

Continue reading Glossary of Common Terms in Singing and Laryngology

Who Gets Voice Disorders And Why?

A voice disorder may prevent a professional singer from performing or a business person from effectively managing his or her affairs, or it may prohibit simple, daily, verbal communication between elderly spouses. A person’s vocal quality may influence the type of work that person does, and conversely, the type of work a person does may influence the importance of avoiding voice difficulties and the degree of professional impairment that may result from a voice disorder. Voice disorders are ubiquitous, and many have severe social, psychological, professional, and economic consequences.

Continue reading Who Gets Voice Disorders And Why?

Vocal Decompensation: A Model of Voice Disorders

In laryngology as well, things are not always what they seem

VOCAL DECOMPENSATION

I have been practicing laryngology most of my life (www.voiceinstituteny.com), and throughout my career, I have had the luxury of uninhibited intellectual freedom. I have always sought to understand the pathophysiology of laryngeal function and dysfunction. I examined my first larynx in a patient with a mirror almost 40 years ago, and despite advances in the field of laryngology and the voice, I still strongly disagree with many aspects of the prevailing medical paradigm. And among colleagues, I have encountered tremendous resistance to both new ideas and to the principles of precision diagnostic. For example, for more than two decades, I have believed in précis diagnosis and to that end, I have helped develop several diagnostic methods. Continue reading Vocal Decompensation: A Model of Voice Disorders

Vocal Decompensation: Why and How Professional Singers and Actors Lose It

Even though voice problems in singers and actors seem to occur suddenly, in fact, they may start slowly over a prior period of months or years; and often in retrospect, there may have been protracted warning symptoms that were minimized or ignored. The “obvious” causes of voice problems may be bogus. Acute voice strain is infrequently the underlying cause of acute vocal collapse; although having a perennially vocally-demanding occupation is a key risk factor.

Continue reading Vocal Decompensation: Why and How Professional Singers and Actors Lose It