PJMS- Volume 2 Number 1: January-June 2012
Review Article Laryngo-pharyngeal reflux- A review Abstract: Laryngo-pharyngeal reflux or atypical gastro-esophageal reflux disease (GERD) syndrome commonly known as extra-esophageal reflux is a controversial subject. The available literature remains non-conclusive regarding the patho-physiology, investigations and management of patients presenting with symptoms of extra-esophageal disease. It remains unknown whether symptoms are caused by direct exposure to refluxate or are via a referred sensation or cough reflex or both. Mucosal changes are not specific to laryngo-pharyngeal reflux although laryngeal pseudo-sulcus has a positive predictive value of 67- 90 % for laryngo-pharyngeal reflux. The symptoms of laryngo- pharyngeal reflux include hoarseness of voice, throat clearing, dysphagia, increased phlegm and globus sensation; patients may also have asthma like symptoms. Physical findings which may be secondary to associated smoking, alcohol, allergic, asthma, viral illness and vocal abuse, include laryngeal edema, erythema, leukoplakia, granulation or even malignancy. The aims of the treatment include decreasing reflux, improving esophageal clearance and protecting esophageal and laryngo-pharyngeal mucosa. Lifestyle modification like weight loss, avoiding sweets,
tomatoes, onions, alcohol and caffeine and finishing dinner 3 hours before going to bed may help. Antacids, H2
receptor antagonists, proton pump inhibitors, prokinetic drugs and anti-reflux surgery like fundoplication and
injection of biopolymers in lower esophageal sphincter are used.
Key words : Laryngopharygeal reflux, laryngeal pseudosulcus, H2 receptor antagonists, prokinetic drugs. Laryngo-pharyngeal reflux
research work shows the possibility of cellular mechanisms,
Laryngo-pharyngeal reflux (LPR), also extra-
whereby reflux might affect the upper airway. Acidified pepsin
esophageal reflux disease (EERD) refers to retrograde flow of
damages inter cellular spaces and pepsin is taken by human
gastric contents to the upper aero-digestive tract, which
laryngeal ephithelial cells by receptor mediated endocytosis
causes a variety of symptoms, such as cough, hoarseness, and
Pathogenesis
Although heartburn is a primary symptom among
people with gastro-esophageal reflux disease (GERD),
Laryngo-pharyngeal reflux differs from gastro-
heartburn is present in fewer than 50% of the patients with
esophageal reflux disease (GERD) in that it is often not
LPR. Other terms used to describe this condition include
associated with heartburn and regurgitation symptoms. The
atypical reflux, and supra-esophageal reflux (2).
larynx is vulnerable to gastric reflux, so patients often present with laryngo-pharyngeal symptoms in the absence of
Gastro-esophageal reflux disease (GERD) was
heartburn and regurgitation (6). There are 4 physiological
recognized as a clinical entity in the mid-1930s and now is the
barriers protecting the upper aero-digestive tract from reflux
most prevalent upper gastrointestinal (GI) disorder in clinical
injury: the lower esophageal sphincter, esophageal motor
practice. Acid-related laryngeal ulcerations and granulomas
function with acid clearance, esophageal mucosal tissue
were first reported by Chery in 1968 (3). Subsequent studies
resistance, and the upper esophageal sphincter. The delicate
suggested that acid reflux might be a contributory factor in
ciliated respiratory epithelium of the posterior larynx that
other laryngeal and respiratory conditions. In 1979, Pellegrini
normally functions to clear mucus from the tracheo-bronchial
and DeMeester (4) were the first to document the link
tree is altered when these barriers fail, and the resultant ciliary
between these airway symptoms and reflux of gastric
dysfunction causes mucus stasis (7). The subsequent
contents. They also proved that treatment of reflux disease
accumulation of mucus produces postnasal drip sensation and
results in elimination of these airway symptoms.
provokes throat clearing. Direct refluxate irritation can cause
coughing and choking (laryngospasm) because sensitivity in
Laryngo-pharyngeal reflux or a typical GERD
laryngeal sensory endings is up-regulated by local
syndrome or commonly known as extra esophageal reflux is a
inflammation (8). This combination of factors can lead to vocal
controversial subject. The available literature remains
fold edema, contact ulcers, and granulomas that cause other
controversial regarding the pathophysiology, investigations
LPR-associated symptoms: hoarseness, globus pharyngeus,
and management of patients presenting with symptoms of
extra-esophageal disease. The terms acid laryngitis was coined 40 years ago as most of the extra-esophageal reflux
Recent investigations suggest that vulnerable
manifestations affect the laryngopharynx (1). The recent
laryngeal tissues are protected from reflux damage by the pH-
PJMS- Volume 2 Number 1: January-June 2012
Review Article
regulating effect of carbonic anhydrase in the mucosa of the
Diagnosis of Laryngopharyngeal Reflux
posterior larynx (10). Carbonic anhydrase catalyzes hydration of carbon dioxide to produce bicarbonate; this protects tissues
History- It is important for physicians to appreciate
from acid refluxate. In the esophagus, there is active
the potential significance of hoarseness and the relative non-
production of bicarbonate in the extracellular space that
specificity of laryngitis. Laryngitis is a nonspecific designation
functions to neutralize refluxed gastric acid. There is no active
of laryngeal inflammation. Often, it is mild and resolves
pumping of bicarbonate in laryngeal epithelium and carbonic
spontaneously. When persistent, laryngitis must be further
anhydrase isoenzyme III, expressed at high levels in normal
defined based on probable etiologic factors: viral or bacterial
laryngeal epithelium, was absent in 64% (47/75) of biopsy
infection, allergy, vocal trauma, postnasal discharge or LPR.
specimens from laryngeal tissues of LPR patients (11).
Persistent or progressive hoarseness lasting beyond 2 to 3 weeks requires examination of the laryngopharynx to rule out
Measurement of exposure to refluxate- It remains
cancer and other serious conditions. This is generally
unknown whether symptoms are caused by direct exposure to
considered good practice; however, laryngeal examination is
refluxate or are via referred sensation or cough reflex or both.
particularly important in suspected LPR because of the
Upto 50% controls have measurable pH drop to < pH 4, 2cm
apparent known association of LPR and upper aerodigestive
above the upper esophageal sphincter. Techniques of
measuring refluxate exit are varied and yet not standardized across specialties (10).
Laryngopharyngeal reflux should be suspected when
clinical history and initial findings are suggestive. Failure to
Mucosal Changes- Mucosal changes are not specific
appreciate LPR as different from GERD has been a major
to laryngo-pharyngeal reflux although laryngeal pseudo-
source of skepticism about the diagnosis in the past. Koufman
sulcus has a positive predictive value of 67 -90% for laryngo-
was the first to clearly distinguish LPR from GERD, noting that
pharyngeal reflux. Exposure of laryngeal mucosa to biliary
in a combined reported series of 899 patients, throat clearing
secretions for many years post gastrectomy appears to be
was a complaint of 87% of LPR patients vs 3% of those with
carcinogenic. The role of Helicobacter pylori is not clear.
GERD, while only 20% of LPR patients complained of heartburn
Treating reflux may reduce the risk of recurrence of laryngeal
vs 83% in the GERD group(6). An international survey of
cancer, but there is no prospective evidence (12).
American Broncho-esophagological Association members revealed that the most common LPR symptoms were throat
Clinical Features
clearing (98%), persistent cough (97%), globus pharyngeus (95%), and hoarseness (95%) (11).
The symptoms of laryngo-pharyngeal reflux includes
hoarseness of voice, throat clearing, dysphagia, increased
Since there is no pathognomonic LPR finding,
phlegm and globus sensation. Many patients may have asthma
Belafsky et al (13) developed an 8-item clinical severity scale
like symptoms. Laryngo-pharyngeal reflux may be suspected if
for judging laryngoscopic findings, the Reflux Finding Score,
the onset of asthma comes in adults without any family history
which appears to be useful for assessment and follow-up of
and heart burn precedes onset of asthma.
LPR patients. They rated 8 LPR-associated findings on a variably weighted scale from 0 to 4: subglottic edema,
Physical finding which may be secondary to
ventricular obliteration, erythema/hyperemia, vocal fold
associated smoking, alcohol, allergic asthma, viral illness and
edema, diffuse laryngeal edema, posterior commissure
vocal abuse, include laryngeal edema, erythema, leukoplakia,
hypertrophy, granuloma, and thick endolaryngeal edema. The
granulation or even malignancy. Laryngoscopic findings such
results could range from 0 (normal) to 26 (worst possible
as erythema, edema, laryngeal granulomas, and inter-
score). Based on their analysis, one can be 95% certain that a
arytenoid hypertrophy have been used to establish the
patient with a Reflux Finding Score of 7 or more will have LPR
diagnosis, but these findings are very nonspecific, and have
been described in the majority of asymptomatic subjects undergoing laryngoscopy (9,11).
Management
Response to acid suppression therapy has been
Patient Education and Lifestyle Changes-
suggested as a diagnostic tool to confirm diagnosis of LPR, but
Patients with LPR should be educated as to the nature of the
studies have shown that the response to empirical trials of
problem and counseled on helpful behavioral and dietary
such therapy (as with proton-pump inhibitors) in these
changes (15). Important behavioral changes include weight
patients is often disappointing. Several studies have
loss, smoking cessation, and alcohol avoidance. Ideal dietary
emphasized the importance of measuring proximal
changes would restrict chocolate, fats, citrus fruits,
esophageal, or, ideally, pharyngeal acid exposure in patients
carbonated beverages, spicy tomato-based products, red
with clinical symptoms of LPR, to document reflux as the cause
wines, caffeine, and late-night meals. Such behavioral changes
appear to be an independently significant variable in
PJMS- Volume 2 Number 1: January-June 2012
Review Article
determining response to medical therapy. Education should
laparoscopic Nissen fundoplication surgery (21). In Nissen's
include the optimal schedule for taking PPI medications
fundoplication, fundus of stomach is wrapped around LES.
(omeprazole, esomeprazole, rabeprazole, lansoprazole, and
Fundoplication appears superior to medical management in
pantoprazole), which work best when taken 30 to 60 minutes
Recent developments Medical Management- There are 4 categories of
drugs used in treating LPR: PPIs, H2-receptor antagonists,
A l t h o u g h t h e r e i s i n t e r e s t i n r e c e n t
prokinetic agents, and mucosal cytoprotectants. Proton pump
nonfundoplication endoscopic techniques like Bard
inhibitors are considered the mainstay of medical treatment,
EndoCinch System for endoluminal plication, System for
although there is some controversy regarding their efficacy. A
radiofrequency-induced thermal injury and Enteryx liquid
3-month empirical trial is a cost-effective approach for initial
polymer injection, to improve lower esophageal sphincteric
assessment and management. Responders can be weaned,
function, there are no controlled studies and there is no long-
while non-responders should undergo studies to confirm LPR
term follow-up evidence to support their use. References
Other drugs have been used to treat LPR. Ranitidine
has proved to be a more potent inhibitor of gastric secretion
Delahunty J E. Acid laryngitis. J. Laryngol. 1972; Otol. 86: 335-
than cimetidine and is the H2-receptor antagonist of choice,
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Chheda N N, Seybt M W, Schade R R et al. Normal values for
LPR (18). Prokinetic agents that accelerate esophageal
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clearance and increase lower esophageal sphincter pressure
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Johnston N. Review article: Uptake of pepsin at pH 7- in non-
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D R . J O S E F S T E I N E R K R E B S S T I F T U N G D R . J O S E F S T E I N E R K R E B S F O R S C H U N G S P R E I S 2 0 0 7 D R . J O S E F S T E I N E R K R E B S S T I F T U N G Der Dr. Josef Steiner Krebsforschungspreis 2007 Herr Agami ist holländisch/israelischer Doppelbürger und arbeitet als ausserordentlicher Professor an der Abteilung für Tumorbiolo
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