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DYSPHAGIA ASSESSMENT AND TREATMENT PLANNING: A TEAM APPROACH
and early tube feeding may limit loss of
weight during chemoradiotherapy for
advanced head and neck cancer: A preliminary study. Clinical Otolaryngology,
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H., Gumbley, R., & Robb, M. (2008). The
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Van Gossum, M. (2019). Malnutrition in
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Zafereo, M. E., Weber, R. S., Lewin, J. S., &
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Zebralla, V., Wichmann, G., Pirlich, M.,
Hammermuller, C., Berger, T., Zimmermann, K., . . . Weigand, S. (2021). Dysphagia, voice problems, and pain in
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3985–3994.
Laryngopharyngeal Reflux
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James H. Clark, Catherine J. Rees Lintzenich,
and Peter C. Belafsky
DEFINITION AND
NOMENCLATURE OF
LARYNGOPHARYNGEAL REFLUX
Laryngopharyngeal reflux (LPR) is
the backflow of stomach contents into
the laryngopharynx (Koufman, Aviv,
et al., 2002). LPR has been implicated
in the pathophysiology of numerous
disorders of the upper aerodigestive
tract, including dysphonia, laryngeal
granulomas, and subglottic stenosis.
Although LPR is currently the term
endorsed by the American Academy of
Otolaryngology-Head and Neck Surgery, multiple terms are used, including
reflux laryngitis, posterior laryngitis,
laryngeal reflux, gastroesophagopharyngeal reflux, esophagopharyngeal
reflux, pharyngoesophageal reflux, gastroesophageal-laryngeal reflux, atypical
reflux, silent reflux, and supraesophageal reflux. Perhaps the most common
synonym for LPR is extraesophageal
reflux (Belafsky, 2003; Koufman, Belafsky, et al., 2002).
The idea that acidic gastric contents
can affect structures above the upper
esophageal sphincter (UES) was put
forth in 1968 (Cherry & Margulies, 1968;
Delahunty & Cherry, 1968; Koufman,
2002). At that time, LPR was postulated
to relate to contact ulcers and granulomas, and the mechanism was felt to
be mediated by vagal nerve stimulation from acidic contents contacting the
lower esophagus. Although this theory
has not entirely lost favor, actual drops
in the pH of the pharynx in patients with
LPR symptoms were demonstrated in
1987 and 1989 (Wiener et al., 1987, 1989).
These findings suggested that the physical presence of gastric contents in the
laryngopharynx was to blame in the disease process. Both theories of causality
likely play a role in LPR disease.
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DYSPHAGIA ASSESSMENT AND TREATMENT PLANNING: A TEAM APPROACH
EPIDEMIOLOGY OF
LARYNGOPHARYNGEAL REFLUX
The nonspecific presentation, combined
with the use of ad hoc diagnostic criteria and inconsistent reliance on objective measures, such as multichannel
intraluminal impedance-pH monitoring, presents a considerable challenge
when determining the true incidence
and prevalence of LPR (Lechien etal.,
2019). It has, however, been estimated
that up to 4% to 10% of patients with
otolaryngologic complaints have underlying LPR (Koufman, 1991; Toohill
et al., 1990). In a community cohort of
100 patients with no history of voice or
laryngeal complaints, 35% had symptoms of LPR, and 64% demonstrated
one or more physical findings of LPR
on laryngoscopic examination (Reulbach et al., 2001). This study suggested
that physical findings and symptoms
of LPR are frequently found in the general population and that some degree
of LPR may be normal. In a prospective cohort of 113 new patients with
laryngeal and voice disorders, 50%
were found to have abnormal results
on 24-hour dual pH probe testing
(Koufman et al., 2000). LPR was highest
in patients presenting with laryngeal
neoplasia (88%) and muscle tension
dysphonia (70%).
To a certain degree, reflux is ubiquitous in adults, and clinical disease
only occurs in the presence of excessive reflux or a breakdown of mucosal
defenses. In the lower esophagus, up to
50 reflux episodes at or below pH 4 in a
24-hour period are considered normal
(Demeester et al., 1976). In the pharynx, the normal or physiologic limit of
reflux is not as clear. Generally, up to
two episodes of reflux with a pH of less
than 4 may be seen in healthy controls
without LPR disease (Merati etal., 2005;
Vincent et al., 2000; Ylitalo et al., 2001;
Ylitalo & Ramel, 2002). However, animal studies have suggested that as few
as three pharyngeal reflux episodes per
week are sufficient to produce laryngeal damage in the face of a preexisting
mucosal injury (Koufman, 1991).
DIFFERENCE BETWEEN
LARYNGOPHARYNGEAL REFLUX
AND GASTROESOPHAGEAL
REFLUX DISEASE
While it is important to distinguish LPR
from classic gastroesophageal reflux
disease (GERD), they share common
physiological mechanisms (Lechien
et al., 2019). The American College of
Gastroenterology defines GERD as
the reflux of gastric contents into the
esophagus, resulting in symptoms or
complications such as heartburn or
regurgitation (Katz et al., 2022). GERD
is defined objectively by the presence
of characteristic mucosal injury seen at
endoscopy, such as esophagitis, or finding abnormal esophageal acid reflux on
a pH study.
Most patients with LPR deny heartburn (70%; Koufman, Aviv, et al., 2002),
and the incidence of esophagitis is
only about 25% in the LPR population (Koufman, 1991, 2002; Koufman
et al., 1996; Koufman, Belafsky, et al.,
2002; Wiener et al., 1989). Conversely,
between 30% and 40% of GERD patients
report laryngopharyngeal complaints,
including globus sensation, eructation
cough, and hoarseness (Dore et al.,
2007; Jaspersen et al., 2003).
GERD patients tend to have primarily
nighttime supine reflux, whereas LPR
patients tend to have daytime upright
reflux. Episodes of pathologic esopha-
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427
geal reflux may be prolonged, but LPR
episodes are typically brief. Patients
with GERD are more frequently obese,
whereas body mass index is not related
to LPR prevalence (Halum et al., 2005).
GERD is thought to be a result of lower
esophageal sphincter (LES) dysfunction
or esophageal dysmotility, but this does
not appear to be true for LPR. Esophageal acid clearance is better in LPR
patients than in classic GERD patients
(Postma et al., 2001), and LPR may be
related to UES dysfunction (Celik et al.,
2005; Gerhardt et al., 1978; Helm et al.,
1983; Koufman, 2002; Koufman, Belafsky, et al., 2002; Ormseth & Wong, 1999;
Ulualp et al., 1998).
In a healthy adult, the esophagus
is well equipped to handle intermittent exposure to acidic gastric contents
(Koufman, 1991). LES competence is
physically supported by the muscular
diaphragm, the acute angle of entry of
the esophagus into the stomach (i.e., the
cardiac angle), and the high abdominal
pressure imposed on the intra-abdominal segment of the esophagus. LES
pressure is also regulated by hormonal
mechanisms and in response to the
alkalization of gastric contents.
Primary peristalsis clears most of a
distal esophageal bolus, and secondary
peristalsis as a result of repetitive swallowing every 30 to 60 seconds allows
for improved clearance as well as buffering by saliva. Salivary bicarbonate
bathing of the esophagus helps neutralize refluxate within the esophageal
lumen, and increased acid in the distal
esophagus stimulates an increase in salivary production in normal individuals
(Koufman, 1991).
The esophageal lining displays
innate tissue resistance to physiologic
reflux events. The mucous lining of the
esophageal lumen prevents the pene-
tration of large molecules such as pepsin. The “unstirred water layer” below
is rich in bicarbonate and buffers the
environment adjacent to the esophageal mucosal cells. Furthermore, the
esophageal epithelium itself can block
both acid and pepsin with cell membranes and intracellular bridges. Local
blood flow is increased in the event of
esophageal injury to facilitate recovery
(Orlando, 1986).
In stark contrast, the larynx is
poorly protected from injury by gastric
refluxate, specifically acid and pepsin
(Axford et al., 2001; Johnston et al., 2003;
Koufman, 1991). The upper airway is
extremely sensitive to acid and activated pepsin. Pepsin has been shown
to be active above pH 4, suggesting that
a smaller drop in pH is more likely to
cause laryngeal injury than esophageal
injury (Johnston et al., 2004). As noted
above, very few episodes of pharyngeal
reflux (three per week) can damage the
larynx in the setting of a mucosal injury
(Koufman, 1991; Little et al., 1985). The
larynx is not protected by salivary
bicarbonate, endogenous tissue buffering, or peristalsis and has poor intrinsic tissue defenses. Carbonic anhydrase
isoenzyme III is an enzyme with buffering capacity that is increased in the
esophagus in response to acid; however, it is actually reduced in laryngeal
tissue damaged by acid and pepsin,
further decreasing laryngeal protection (Axford et al., 2001; Johnston et al.,
2003, 2004).
SYMPTOMS AND DIAGNOSIS OF
LARYNGOPHARYNGEAL REFLUX
The diagnosis of LPR is primarily based
on a constellation of clinical signs and
physical findings. In a 2002 survey sent
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DYSPHAGIA ASSESSMENT AND TREATMENT PLANNING: A TEAM APPROACH
to 415 members of the American Bronchoesophagological Association, the
respondents were in agreement about
certain LPR symptoms (Book et al.,
2002), including throat clearing (98%),
chronic cough (97%), globus (95%), dysphonia (95%), and postnasal drip (57%).
The reflux symptom index (RSI) has
been shown to be a reliable and valid
patient-administered questionnaire for
identifying patient symptoms (Belafsky et al., 2002b). One group, however,
reported 80.7% and 37.5% on the RSI
for sensitivity and specificity, respectively, in patients with hypopharyngeal
reflux documented by pH studies (Park
et al., 2006).
The most common complaint of
LPR patients appears to be dysphonia,
followed by chronic throat clearing,
cough, globus sensation, and dysphagia (Koufman, 1991; Woo et al., 1996).
The presentation of LPR can, however,
vary significantly according to the sex
and age of patients (Lechien et al.,
2019). LPR has been implicated in the
etiology of a multitude of otolaryngologic disorders and should be considered when managing conditions such
as subglottic stenosis, chronic sinusitis,
chronic otitis media, laryngeal granulomas, paroxysmal laryngospasm, Reinke’s edema, Zenker’s diverticulum,
and laryngeal carcinoma (Cohen et al.,
2002; DelGaudio, 2005; Koufman, 1991;
Lewin et al., 2003; Maronian et al., 2001;
Sasaki et al., 2003).
Physical Findings
Laryngeal examination with a flexible
or rigid laryngoscope is essential to the
diagnosis of LPR. Findings associated
with LPR include erythema, laryngeal
and vocal fold edema, subglottic edema/
pseudosulcus vocalis, ventricular obliteration, posterior commissure hypertrophy, laryngeal granulomas, lymphoid
hypertrophy, and excessive pharyngeal
mucus. Endoscopic findings can be succinctly described with the reflux findings score (RFS), which is an indicator
of overall laryngeal inflammation.
It is important to recognize that the
diagnosis is based on a constellation of
findings rather than any one finding.
For example, isolated posterior commissure hypertrophy does not correlate well with LPR, but it is felt to be an
important sign of LPR when associated
with other laryngeal findings listed in
the RFS. Laryngeal erythema has been
described in LPR (Hanson et al., 1998),
but this may be highly variable depending on the examiner’s video equipment.
Additionally, diffuse laryngeal erythema is thought to be a stronger indicator of LPR than erythema localized to
the arytenoids (Belafsky, 2003).
Endoscopic findings isolated to the
true vocal folds can range from mild
edema to Reinke’s edema, also known
as polypoid degeneration or polypoid
corditis (Figure 18–1; Belafsky, 2003).
Obliteration of the laryngeal ventricle
is the result of edema of the true and
false vocal folds (Figure 18–2). This may
be one of the first signs of improvement after the initiation of antireflux
therapy. Posterior commissure hypertrophy, or posterior laryngeal edema,
is graded from mild, producing a mustache-like appearance of the posterior
larynx, to severe, producing an actual
obstruction of the posterior airway by
the edematous mucosa (Figure 18–3).
Patients with LPR and posterior laryngeal edema appear to have a higher
incidence of laryngeal sensory deficits
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Figure 18–1. Reinke’s edema. Figure 18–2. Ventricular obliteration and
Reinke’s edema.
on functional endoscopic evaluation
of swallowing with sensory testing,
which improves with LPR treatment
(Aviv et al., 2000).
Pseudosulcus vocalis is also known
as infraglottic edema (Figure 18–4;
Koufman, 1995). This finding represents edema of the ventral surface of
the vocal folds and extends along the
entire length of the true vocal fold. This
detail differentiates pseudosulcus vocalis from sulcus vergeture, which stops at
the vocal process rather than extending
to the posterior larynx. The presence of
pseudosulcus is at least 70% sensitive
Figure 18–3. Posterior commissure hyper-
trophy.
and 77% specific for LPR (Belafsky et
al., 2002a; Hickson et al., 2001).
Vocal fold granulomas are typically
seen on the vocal processes and have
a high recurrence rate (Figure 18–5).
LPR has recently been identified as an
etiologic factor in the development of
granulomas. Lymphoid hyperplasia,
especially seen as hypertrophy of the
lingual tonsils (Mamede et al., 2000)
and cobblestoning of the posterior pharyngeal wall, can also be related to LPR,
although these findings are nonspecific.
Finally, LPR may be associated with
the sensation of increased mucus in the
throat, which can often be confused
with postnasal drip (Belafsky, 2003).
Figure 18–4. Pseudosulcus vocalis.
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DYSPHAGIA ASSESSMENT AND TREATMENT PLANNING: A TEAM APPROACH
the technique was found to be consistent across multiple studies. Up to
20% of normal subjects had brief reflux
events at the upper probe when it was
in the hypopharynx, and this number
increased when the probe was in the
UES (Merati et al., 2005).
The exact cutoff for the number of
reflux events in the pharynx is controversial (Richardson et al., 2004), but it is
clear that in the setting of mucosal airway injury, even one episode of LPR is
enough to exacerbate the injury (Little
et al., 1985). However, in an asymptom-
Figure 18–5. Vocal fold granuloma.
atic individual without voice or airway
concerns, one or two episodes of LPR
may be physiological rather than clini-
pH Monitoring
cally significant. The results of 24-hour
pH monitoring should be reviewed
Twenty-four-hour dual-probe pH testing is currently the gold standard for
diagnosing LPR. The upper pH probe
should be in the hypopharynx above
the UES, not in the proximal esophagus, and the lower probe is ideally 5 cm
above the LES, which is the standard
position used by gastroenterologists.
The hypopharyngeal probe should be
no more than 2 cm above the UES to
prevent drying of the probe and falsepositive readings. Esophageal manometry is very helpful in determining
proper probe placement, and a variety
of pH catheter lengths should be available. Placement of the upper probe
under endoscopic visualization does
not allow confirmation of the lower
probe position (Harrell et al., 2005;
Postma, Belafsky, et al., 2002).
Although up to 50 episodes of reflux
in the distal esophagus are normal,
when these reflux events reach the
pharynx, the diagnosis of LPR may
be made. In a recent meta-analysis of
24-hour dual-probe pH monitoring,
on an individual patient basis. Intake
of meals and beverages will give false
readings and must be considered in the
interpretation of pH studies. Finally,
both the number of LPR events and
acid exposure time should be considered. Although pH 4 or less is the
accepted cutoff for reflux events in the
esophagus, it has been suggested that
pH 5 or less may be clinically important
in the laryngopharynx, given the persistent activation of pepsin at this pH
(Postma, 2000).
Impedance testing overcomes some
of the pitfalls of pH testing described
above. Multichannel intraluminal
impedance testing describes anterograde or retrograde bolus or air movement in the esophagus, allowing the
clinician to more easily differentiate
between swallow and reflux events.
This also allows for testing reflux disease independently of the pH of the
refluxate. In addition, impedance testing is often combined with simultaneous pH studies.
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431
Other Diagnostic Studies
Cinefluoroscopy is used as an adjunct
by some clinicians to diagnose LPR.
Esophageal reflux can often be seen
with this testing technique, but LPR
can often be missed. Many clinicians
also believe that an evaluation of the
esophagus, by either the otolaryngologist or the gastroenterologist, is critical
in any patient diagnosed with LPR.
This recommendation is based on findings of esophageal pathology, in particular Barrett’s esophagus, in a significant proportion of patients with LPR
(Postma et al., 2005). LPR symptoms
may be more predictive of esophageal
adenocarcinoma than typical GERD
symptoms (Reavis et al., 2004), which
is a devastating disease that tends to
present at a late stage. Therefore, endoscopic evaluation of the esophagus
when LPR is present may facilitate earlier diagnosis in some patients.
TREATMENT OF
LARYNGOPHARYNGEAL REFLUX
Most patients with symptomatic LPR
require pharmacologic treatment with
H2-receptor antagonists or protonpump inhibitors (PPIs). The national
cost burden for the diagnosis and management of LPR is believed to be 5.6
times that of GERD, with a total estimated expenditure of over $50 billion
(Carroll, 2017; Francis et al., 2013), with
most of this expense resulting from
medical therapy costs. According to
the position statement on LPR by the
American Academy of OtolaryngologyHead and Neck Surgery, LPR treatment
should be more aggressive and of longer duration than GERD treatment
(Koufman, 2002). A common initial
therapy for suspected LPR remains
acid suppression with twice-daily PPI,
although this therapy has not been
well supported in placebo-controlled
trials (Carroll et al., 2017; Koufman,
Aviv, etal., 2002; Noordzij et al., 2001;
Park et al., 2005; Postma, Johnson, et al.,
2002; Steward et al., 2004). Twice-daily
dosing is important because none of
the PPIs suppress gastric acid for more
than 16 hours (Park et al., 2005; Peghini
et al., 1998).
There have been increasing concerns relating to the potential longterm effect of PPI treatment, but much
of this is based upon epidemiological
studies and may suffer from residual
confounding and, in some instances,
reverse causation (Fossmark et al.,
2019). This has, however, resulted in
the increased adoption of a treatment
approach in which a morning dose of a
PPI is combined with an evening dose
of H2-receptor antagonists (Carroll
et al., 2017). The authors investigated
the effectiveness of this approach and
reported that nearly two thirds of all
subjects improved on this regimen if
they were to ultimately respond to
empiric acid suppression (nearly 50%
of suspected LPR patients). However,
the cost analysis of such dual-agent
treatment proved to be unfavorable
compared to a twice-daily PPI regime.
The authors argue that the additional
cost might be offset by increased compliance, reduced risk, and patient satisfaction with the dual-agent regimen.
The manuscript ultimately suggests
that upfront objective measures such
as pH monitoring likely offer opportunities for significant cost savings
compared to empiric acid suppression.
Some investigators suggest using high-
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DYSPHAGIA ASSESSMENT AND TREATMENT PLANNING: A TEAM APPROACH
dose H2-receptor antagonists at night
in addition to twice-daily PPI therapy,
but the efficacy of this approach is
controversial (Tutuian & Castell, 2004;
Wang et al., 2009).
While prescribers need to recognize
the possibility of known (and most
likely unknown) side effects that might
arise as a consequence of long-term
gastric acid inhibition, it should be
remembered that many patients have
appropriate indications for long-term
PPI use that may outweigh this risk
(Fossmark et al., 2019). More important than avoiding initiating treatment
with a PPI is the need to identify PPI
users without real indication or benefit from treatment by ensuring patient
education, establishing parameters for
treatment duration, and discontinuing
treatment in nonresponders. Prescribers need to remember that more than
2 months of therapy may be necessary
for LPR symptom improvement, and
more than 6 months of therapy may be
required to see resolution of laryngeal
findings (Belafsky et al., 2001). Patients
should be carefully counseled about
the need for prolonged therapy and
the proper timing of medication doses.
For example, PPIs should be taken 30 to
45 minutes before a meal for maximum
efficacy. In addition, patients should
be reminded that PPI management
does not supersede the role of lifestyle
modification. LPR patients adhering
to dietary modifications in addition to
PPIs demonstrated improved outcomes
for LPR symptoms and vocal improvement compared to those managed
with PPIs alone (Lechien et al., 2018).
Patients with suspected LPR should
be counseled about the standard lifestyle changes recommended for GERD
patients (Table 18–1). Perhaps the most
important of these recommendations
are smoking cessation and alcohol
avoidance. In addition, chewing gum
has been shown to increase both pharyngeal and esophageal pH because of
an increase in salivary bicarbonate, salivary flow, and swallowing frequency.
Bicarbonate gum is an even more
effective adjunctive antireflux therapy
(Smoak & Koufman, 2001).
Over-the-counter antacids and liquid alginate certainly have a role in
mild GERD, but their effectiveness in
treating LPR is unclear. Liquid alginate,
especially the formulation available in
Europe and online, forms a physical
barrier to help prevent reflux (Mandel
et al., 2000).
Resistance to PPI therapy should
be considered in patients without improvement after 6 months of therapy,
Table 18 –1. Recommended Lifestyle
Modifications in LPR
Elevate head of bed 6 inches
Smoking cessation
Low-fat diet
Weight loss
Avoid lying down within 3 hours of
eating
Eat small frequent meals
Avoid refluxogenic foods:
Alcohol
Chocolate
Peppermint
High-fat foods
Tomato-based products
Spicy foods
Citrus
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and this can be documented by repeat
pH testing while on medication (Amin
et al., 2001). In refractory LPR, especially in life-threatening cases such as
subglottic stenosis, surgical therapy
may be an alternative to PPIs. Limited
data support endoscopic antireflux procedures in LPR at this point; however,
LPR symptoms often improve after
Nissen fundoplication or hiatal hernia
repair (Lindstrom et al., 2002; Westcott
et al., 2004; Wright & Rhodes, 2003).
CONCLUSION
LPR should be considered a contributing factor in most upper aerodigestive
tract disorders. It is important to note
that LPR is different from classic GERD
in that most patients do not experience
heartburn or have findings of esophagitis. Additionally, a constellation of patient symptoms and physical findings
is important in diagnosing LPR, and
24-hour dual-probe pH monitoring with
the upper probe in the hypopharynx is
the gold standard for LPR diagnosis.
Twice-daily PPI therapy for at least
6months is the mainstay of LPR therapy.
STUDY QUESTIONS
1. Which is most damaging to tissues:
pepsin, acid, or both combined?
2. Describe the mechanism of reflux.
3. What is the most typical sign of
laryngopharyngeal reflux?
4. What is more important in the diagnosis of reflux: a single sign or a
constellation of signs?
5. What would constitute a constellation of signs?
6. Is any reflux in the esophagus considered normal?
7. In the treatment of reflux, which
typically improve first: signs or
symptoms?
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Aviv, J. E., Liu, H., Parides, M., Kaplan, S.
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