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THE AMERICAN JOURNAL OF GASTROENTEROLOGY

1999 by Am. Coll. of Gastroenterology


Published by Elsevier Science Inc.

Vol. 94, No. 10, 1999


ISSN 0002-9270/99/$20.00
PII S0002-9270(99)00477-3

CLINICAL REVIEWS

Reflux Laryngitis: Pathophysiology,


Diagnosis, and Management
Eric J. Ormseth, MAJ., M.C., and Roy K. H. Wong, COL., M.C.
Gastroenterology Service, Walter Reed Army Medical Center, Washington, D.C., and Uniformed Services
University of the Health Sciences, Bethesda, Maryland

ABSTRACT
Gastroesophageal reflux disease is felt to be associated with
a variety of laryngeal conditions and symptoms of which
reflux laryngitis is perhaps the most common. The most
likely mechanism for laryngeal injury and symptoms is
secondary to direct acid and pepsin contact, although studies
concerning the cause and effect between gastroesophageal
reflux disease and laryngeal disorders are conflicting. Likewise, the most effective method to diagnose such patients is
unclear. Empiric treatment of patients with reflux laryngitis
has been shown to be effective though none of the studies
are controlled. (Am J Gastroenterol 1999;94:28122817.
1999 by Am. Coll. of Gastroenterology)

INTRODUCTION
Dr. L. A. Coffin, in 1903, was one of the first to associate
gastroesophageal reflux (GER) with laryngeal disorders. He
speculated that the eructation of gases from the stomach
and hyperacidity were responsible for the symptoms in
many of his patients with postnasal catarrh, and stated that
this problem was overlooked because many patients had no
gastrointestinal symptoms. Years later, in 1968, Cherry and
Margulies (1) reported three patients with contact ulcers of
the larynx and gastroesophageal reflux disease (GERD)
diagnosed by acid barium studies. Treatment with antacids,
dietary modification, and elevation of the head of the bed
resulted in resolution of the contact ulcers. Ohman et al. (2),
in 1978, used 24-h pH monitoring to document GERD in 43
men with either a history of or current laryngeal contact
ulcers, and noted that 51% of their patients had abnormal
GER.
It is estimated that 4 10% of patients presenting to an
otolaryngology practice will have symptoms and/or findings
related to GERD (3, 4). The most common symptoms associated with reflux laryngitis are hoarseness, vocal fatigue,
chronic throat clearing, excessive throat mucus, chronic
cough, dysphagia, and globus sensation. Though not the
focus of this article, several other laryngeal conditions (see
Table 1) have also been associated with GERD and some of
Disclaimer: The opinions and assertions expressed in this report contained herein
are the private ones of the authors and are not to be construed as official policy or
reflecting the views of the Department of Defense.

which are associated with significant morbidity. Several


studies have identified GERD as a potential risk factor for
the development of laryngeal carcinoma though a definitive
relationship remains to be proven (5, 6). The term esophagopharyngeal reflux (EPR) is used to describe esophageal
acid reflux into the laryngeal and pharyngeal areas. This
article reviews the literature concerning the pathophysiology, diagnosis, and management of patients with reflux
laryngitis.

PATHOPHYSIOLOGY
There are two schools of thought concerning how gastric
acid causes laryngeal pathology. The first implicates a direct
acid-peptic injury to the larynx and surrounding tissues via
EPR (710). Data to support this hypothesis come from
animal studies (7, 8, 11, 12). The second hypothesis suggests that acid in the distal esophagus stimulates vagally
mediated reflexes resulting in chronic throat clearing and
coughing which eventually lead to laryngeal lesions and
symptoms (1316). Perhaps a combination of these mechanisms could be present in the same patient. Lastly, it may
be that EPR only results in laryngeal injury and symptoms
when acting in concert with other risk factors for laryngitis,
such as voice overuse and chronic throat clearing behavior.
The notion that significant laryngeal injury occurs with
only minute amounts of acid is based on the canine and
rabbit model where acid and pepsin are applied directly to
the laryngeal mucosa (4, 7). Because the laryngeal apparatus
is not continually coated by saliva, the gastric refluxate
cannot be neutralized, diluted, or mechanically washed off
of the mucosa, resulting in a greater propensity for injury
(17). Also, because laryngeal mucosa is not normally exposed to acid and pepsin, the intrinsic cellular mechanism to
protect against chemical injury may not be present, although
this has not been well studied. Kambic and Radsel (12)
biopsied the larynx of 44 patients with posterior laryngitis
and noted that the laryngeal epithelium was often thickened
due to hyperplasia of the prickle cell layer, and in some the
epithelium was keratinized. In patients with laryngeal ulcers, there were abundant lymphocytes and plasma cells
infiltrating the epithelium. These changes are similar to
esophageal biopsies of reflux esophagitis patients.

AJG October, 1999

Table 1. Laryngeal Conditions Associated With GERD


Reflux laryngitis
Subglottic stenosis
Carcinoma of the larynx
Contact ulcers and granulomas
Endotracheal intubation injury
Paroxysmal laryngospasm
Arytenoid fixation
Globus pharyngeus
Vocal nodules
Laryngomalacia
Pachydermia laryngis
Recurrent leukoplakia

To implicate acid-induced laryngeal damage, the gastric


contents must reflux proximally from the distal and proximal esophagus and through the upper esophageal sphincter
(UES) into the laryngeal area. Some authors have attempted
to identify whether patients with reflux laryngitis experience
more acid reflux in the proximal esophagus than controls
with only typical GERD symptoms. Jacob et al. (18) found
that a subset of patients who experience laryngeal symptoms
had significantly more proximal esophageal acid exposure
compared to a control group of GERD patients. Shaker et al.
(17) noted that, although proximal esophageal acid exposure
time was not increased in patients with reflux laryngitis, a
significantly higher percentage of distal reflux episodes
reached the proximal esophagus compared to both normal
controls and those with typical GERD symptoms. Wo et al.
(19), on the other hand, found that there were no significant
differences in the amount of proximal reflux in a large group
of patients with atypical reflux symptoms, including hoarseness, compared to a group with typical reflux symptoms.
Likewise, Waring et al. (20) found that proximal esophageal
reflux had no predictive value in identifying patients with
atypical reflux symptoms, including hoarseness, or in those
who responded to therapy. It seems, therefore, that although
patients with reflux laryngitis as well as those with typical
GER symptoms experience proximal esophageal acid reflux, the distribution of these reflux episodes may be different. The significance of these findings with respect to reflux
laryngitis, however, remains unknown. To gain a better
understanding of the pathophysiology of reflux laryngitis,
we may have to look elsewhere than the proximal esophagus, such as the hypopharynx.
Given that reflux laryngitis probably results from direct
exposure of the hypopharynx and larynx to acid and pepsin,
some have studied pharyngeal acid reflux or EPR. EPR has
been well documented to occur in those with suspected
reflux laryngitis (17, 21, 22); however, EPR also occurs in
normal healthy controls with a prevalence of 16 21% (17,
22). All of the studies that have looked at pharyngeal acid
exposure have noted EPR to occur much more frequently in
those with reflux laryngitis than in controls, though the
question of how much and how often EPR occurs in normal
healthy controls remains unanswered. It may be that in some
patients with posterior laryngitis, only infrequent and small

Reflux Laryngitis

2813

amounts of EPR are required to cause damage whereas in


others, frequent and copious amounts of pharyngeal acid
reflux may occur and not be associated with laryngeal injury
or symptoms.
Some have postulated that a defective UES is present in
reflux laryngitis patients and have looked manometrically at
the UES to determine if it differs from normal controls.
Though one study (23) noted elevated UES pressures in
reflux laryngitis patients, others have found normal resting
UES pressures (17, 24). In one of the studies that found
normal resting UES pressures, researchers noted that it takes
significantly larger volumes of refluxate to trigger UES
contraction, and hence prevent EPR, in reflux laryngitis
patients compared to controls, suggesting an abnormality in
the afferent sensory limb of the pharyngo-UES contractile
reflex (24). EPR has been noted to occur in three circumstances: 1) during spontaneous drops in UES pressure; 2)
during postprandial belching; and 3) during appropriate
decrements of UES pressure associated with swallowing
when gastric contents pooled in the proximal esophagus
overflow into the posterior pharynx especially during nocturnal supine state (25).
Some investigators have speculated that esophageal dysmotility plays a role in reflux laryngitis patients noting
abnormal acid clearance times and an increase in the prevalence of nonspecific motility (26). However, Ulualp et al.
(27) found that at least secondary peristalsis is preserved in
those with posterior laryngitis versus healthy controls. Furthermore, others found no significant difference in esophageal clearance times in patients with laryngitis compared to
a control group of GERD patients (28).

DIAGNOSIS
Patients with reflux laryngitis most commonly present with
hoarseness, globus sensation, frequent throat clearing, halitosis, frequent sore throats, chronic cough, and prolonged
vocal warm-up. Hoarseness is noted in 92% of patients (29,
30), but the differential diagnosis of hoarseness is broad.
Koufman (30) speculates that GERD plays a contributing
role in approximately 55% of patients seen with the complaint of hoarseness, though this prevalence has not been
verified in any studies. Patients with refractory chronic or
intermittent symptoms are often referred to an otolaryngologist.
Because the differential diagnosis of the symptoms of
reflux laryngitis is broad, a careful history is imperative.
Risk factors associated with these symptoms include frequent voice use, concurrent tobacco use, history of upper
respiratory tract infections with coughing, chronic idiopathic cough, allergic type symptoms, pets, recent air conditioner, postnasal drip, and new environmental conditions
that contain synthetic materials. A reflux history is important to obtain, but patients may deny associated heartburn as
has been mentioned.
Early in the evaluation of patients with laryngitis and

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Ormseth and Wong

Table 2. Laryngeal Findings Associated With GERD


Reflux laryngitis
Vocal cord nodules
Reinkes edema
Contact ulcers and granulomas
Laryngeal stenosis
Paroxysmal laryngospasm

associated symptoms, most patients will undergo laryngoscopic examination. There are several different instruments
used by laryngologists to evaluate the hypopharynx and
larynx, ranging from indirect mirror laryngoscopy to the
more sophisticated videostroboscopy, which is able to identify subtle mucosal abnormalities enhancing the ability to
evaluate laryngeal pathology and function. Indirect laryngoscopy may be used as a screening tool, but videostroboscopy is considered to be the best technique to study the
larynx. Unfortunately, videostroboscopy is expensive, and
the technology is limited to modern voice laboratories.
The term reflux laryngitis refers to a constellation
which includes classic posterior laryngitis with red arytenoids and piled-up interarytenoid mucosa but is not seen in
the majority of patients with reflux laryngitis (31). Rather,
laryngeal edema is the most common finding, which can
easily be missed because both indirect mirror and fiberoptic
laryngoscopy may not identify this lesion. In a group of 46
patients with the diagnosis of reflux laryngitis based on
symptoms of hoarseness and/or an abnormal laryngeal examination, the most common laryngeal findings were:
edema, 89%; erythema, 87%; granuloma/granulation, 19%;
and ulceration, 2% (30). Abnormalities, such as erythema
and edema, are more often seen on the posterior aspect of
the larynx, which may relate to its proximity to the esophagus and hence may be most exposed to acid-peptic refluxate. Table 2 lists some of the laryngeal findings associated
with GERD.

THE ROLE OF THE GASTROENTEROLOGIST IN


PATIENTS WITH SUSPECTED REFLUX LARYNGITIS
Most of the patients seen by a gastroenterologist with the
diagnosis of suspected reflux laryngitis will have been evaluated by an otolaryngologist and referred for either upper
endoscopy or pH monitoring to document the presence of
abnormal GER. Patients with reflux laryngitis may well
deny any associated heartburn symptoms of GER, and several authors have documented a low prevalence of heartburn
(6 43%) in those with reflux laryngitis (2, 26, 30). The
explanation of this finding is unclear, although some (26)
have noted a decreased esophageal mucosal sensitivity to
acid in patients with reflux laryngitis based on their finding
of a high incidence of acid reflux on pH monitoring combined with a low incidence of positive Bernstein acid tests
(5%), which is in fact lower than the rate of positive Bernstein tests for patients with typical GERD symptoms (range
32100%, mean 78%) (32).

AJG Vol. 94, No. 10, 1999

In addition, patients with reflux laryngitis have a low


prevalence of endoscopic esophagitis. Wiener et al. (33)
noted that although 61.5% of laryngitis patients with chronic
hoarseness had abnormal pH values, only 28% had evidence
of endoscopic esophagitis. Kamel et al. (34) noted that only
19% of a group of 16 patients with posterior laryngitis
refractory to H2RA treatment had endoscopic esophagitis.
The prevalence of esophagitis in those with typical GERD
symptoms ranges from 48% to 79% (35, 36). Because
patients with the diagnosis of reflux laryngitis have a low
prevalence of endoscopic esophagitis, the decision to perform upper endoscopy should be based on whether there are
other indications to do the procedure, such as Barretts
screening in patients with a long duration of heartburn
symptoms.
Documentation of abnormal GER by pH monitoring may
be appropriate in some patients. The reported prevalence of
abnormal GER by 24-h pH monitoring in patients with
suspected acid laryngitis ranges from 17.5% to 70% (17,
18, 21, 30, 37). This variability probably relates to patient
heterogeneity and methodology concerning whether the pH
probe is placed in the hypopharynx, distal, or proximal
esophagus.
Pharyngeal pH monitoring has been used to study patients
with suspected EPR to identify the culprit at the scene of the
crime. Interestingly, some patients with normal 24-h pH
studies have been shown to have EPR. Koufman (38) found
that 23% (28 of 122) of reflux laryngitis patients with a
normal 24-h pH test had evidence of EPR with the addition
of a hypopharyngeal probe. Also, Katz (21) found that three
of 10 patients would have been diagnosed as normal had
only a single distal esophageal probe been used; yet pharyngeal acid reflux was detected with the addition of a
hypopharyngeal probe.
Pharyngeal pH monitoring may be the best modality to
establish EPR and GER as the cause of laryngeal disease,
although caution must be exercised in the interpretation of
these results. For example, as mentioned, hypopharyngeal
reflux has been documented in normal healthy controls.
Furthermore, some have speculated that the presence of a
probe in the posterior pharynx may actually precipitate acid
reflux secondary to irritation (39) resulting in possible false
positive results. Likewise, certain foods are associated with
falsepositive results such as citric acid-containing beverages including orange juice and carbonated soft drinks.
Taking these issues into consideration along with the fact
that GER and EPR are intermittent phenomena, reliance on
the results of pharyngeal probe monitoring has the potential
to decrease the diagnostic yield when evaluating patients
with suspected reflux laryngitis.
During pharyngeal pH monitoring, loss of mucosal contact between the pH probe and the cavernous posterior
pharynx may occur with subsequent abnormal pH recordings resulting in pseudoreflux. A gradual drop in pH with
a rapid recovery that is not associated with a preceding drop
in pH measured in the more distal probes may represent

AJG October, 1999

Reflux Laryngitis

2815

Table 3. Results of Studies in the Treatment of Patients With Suspected Reflux Laryngitis

No. of
Patients

Percent of
Patients
With
Heartburn

Percent of
Patients
With
Esophagitis

McNalley
89

11

82%

55%

yes/55%

Kamel
94

12

83%

19%

no

Hanson
95

182

NA

NA

no

Waring
95

27

100%

59%

Jasperson
96

21

100%

100%

Metz 97

10

50%

20%

Shaw 97

96

39%

NA

no

Wo 97

22

55%

NA

no

Study*

pH Testing/
Percent With
Positive
Results

yes/no mention
of % with
pH test
no

yes/60%

Rx/Dose and
Duration

Outcome
Parameters

H2RA 150 mg
b.i.d. 12 wk

symptoms, voice
parameters

prior H2RA-PPI
40 mg/d up to
24 wk
H2RA, PPI or
surgery, dose
and duration
variable
PPI or Nissan
40 mg/d
variable
duration
PPI 40 mg/d 4
wk

symptoms and
laryngoscopic
exam
symptoms and
laryngoscopic
exam

PPI 40 mg/d 4
wk
PPI 40 mg/d 12
wk

PPI 40 mg/d 8
wk

Percent of
Patients With
Improvement in
Symptoms
50% by voice
analysis; 50%
got worse
92%

96%

symptoms

80%

symptoms and
laryngoscopic
exam
symptoms

100%

symptoms,
acoustic voice
analysis, and
laryngoscopic
exam
symptoms,
laryngoscopic
exam

60%

60%

67%

* Not placebo controlled; No baseline laryngeal exam.


NA not available; PPI proton pump inhibitor; H2RA histamine-2 receptor antagonist.

pseudoreflux. Although the issue of pseudoreflux has


not been well studied, the pathophysiology of the pH pattern
is most likely an artifact resulting from the probe either
drying up or moving away from the pharyngeal mucosa.
This gradually disrupts the bipolar circuit, causing a graded
rather than precipitous drop in pH. When the patient swallows or changes position, this then restores the bipolar
nature of the system. The incidence of pseudoreflux with
pharyngeal pH monitoring is felt to occur much less than
previously reported with the use of newer multielectrode
catheters (40, 41).

ANTIREFLUX TREATMENT FOR LARYNGITIS


Treatment of patients with suspected reflux laryngitis with
antireflux medications, such as histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs) has been
shown to be effective although no controlled studies have
been performed. Most studies are not comparable because of
differences in patient selection, research methods, outcome
parameters studied, as well as pharmacological agents and
regimens used. Table 3 summarizes the results of eight
studies.
In seven of the eight studies, the patients were initially

evaluated by an ear, nose, throat specialist and then referred


to a gastroenterologist. The degree of GERD varied between
the studies with the prevalence of heartburn ranging between 39 100%. Three of the studies used pH monitoring
(20, 42, 43), and in the two which mentioned the prevalence
of abnormal GERD, heartburn ranged from 55 60% (42,
43). Of the studies which included upper endoscopy as part
of the evaluation, associated esophagitis ranged from 19%
(34) to 100% (44). All studies except for one included a
baseline laryngeal examination; however, laryngeal abnormalities were not uniformly described between the studies.
In all of the studies except for one (42), PPI therapy was
used though the dose ranged from 20 mg p.o. b.i.d. to 40 mg
q HS. The treatment duration ranged from 4 wk up to 24 wk
(34). In one study, the majority of patients underwent fundoplication (20).
Subjective improvement in symptoms and improvement
in follow-up laryngeal exams were the most common outcome parameters followed in the studies. In addition, two
studies included computerized voice analysis (42, 45).
Overall improvement in symptoms in these eight studies
ranged from 50 100%. Hoarseness and throat burning are
the most common symptoms studied, but there was a lot of
variability. Three of the eight studies followed patients after

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Ormseth and Wong

treatment was stopped and in the majority, symptoms


promptly returned (34, 46, 47). Overall symptom improvement correlated with improvement in laryngoscopic exams
in those studies where follow-up examinations were performed. In the two studies assessing computerized voice
analysis, there was poor correlation with subjective improvement in symptoms (42, 25).
Most of the studies did not identify factors suggestive of
a favorable outcome, although two studies suggested that
improvement in symptoms occurred more commonly with
more mild laryngeal abnormalities (45, 46). In the three
studies that included pH monitoring, there was no good
correlation between the degree of symptomatic improvement and abnormal 24-h pH scores (20, 42, 43).
Based on a review of the studies listed in Table 3, the
optimal dose and duration of treatment remain unknown.
Some otolaryngologists have observed that symptoms may
take as long as 3 months to improve (31, 47). Possible
explanations for this finding include the following: 1) The
development of pachydermia laryngeus. Pachydermia
laryngeus is characterized by thickening of the laryngeal
epithelium (hyperkeratosis), which may result from GER
and in many cases may be exacerbated by chronic throat
clearing. These changes may produce refractory symptoms
despite adequate antireflux therapy, and improvement may
only occur in those who are able to cease chronic throat
clearing behavior. 2) The multifactorial nature of laryngitis
in some reflux laryngitis patients in whom GER may only be
playing a minor role or none at all. 3) Incomplete acid
suppression requiring higher doses of medications such as
PPIs for extended periods of time.
The use of other classes of drugs other than antiacid
secretory drugs such as H2RAs and PPIs in the treatment of
reflux laryngitis has not been studied. In addition to its
promotility effect, cisapride has been shown to increase
significantly salivary secretion including bicarbonate output
(48). Whether this may benefit those with reflux laryngitis,
particularly those with xerostomia is intriguing.

SUMMARY
Reflux laryngitis is a common disease and is probably only
one of several laryngeal manifestations associated with
GERD. The hypothesis that GER causes laryngeal symptoms and conditions remains to be definitively proven. In
many patients, the cause of laryngeal symptoms may well be
multifactorial, and definitively identifying in which patients
GER may be playing a role remains a challenge. Documentation of GER using 24-h pH monitoring in those with
laryngeal findings attributed to GER may assist in identifying such patients. Pharyngeal pH probe monitoring, although not without limitations, may be the optimal method
to evaluate such patients in terms of documenting the presence of EPR.
A suggested algorithm based on the available data in
evaluating and treating patients with suspected reflux laryn-

AJG Vol. 94, No. 10, 1999

gitis is to first perform simultaneous esophageal and pharyngeal pH monitoring, if available, as this test will most
likely establish or rule out the presence of EPR. If pharyngeal pH monitoring is not available or undertaken, empiric
treatment with PPIs has been shown to be effective in the
majority of patients though as mentioned, none of the trials
to date have been placebo-controlled. In any case, whether
PPI treatment is initiated based on the results of pharyngeal
pH monitoring or begun empirically, treatment with high
dose PPIs (i.e., 40 60 mg/day) and for relatively long
periods (i.e., 3 6 months) may be required for laryngeal
injury to heal and symptoms to completely resolve. In addition, some of these patients may benefit from the concept
of total acid blockade requiring supplementation of their
PPI therapy with H2RAs at bedtime (47, 49, 50). Lastly,
patients with other risk factors for chronic laryngitis, such as
voice overuse, may benefit from concomitant voice therapy.
Reprint requests and correspondence: Roy K. H. Wong, COL.,
M.C., Chief, Gastroenterology Service, Building #2, Room 7F47,
Walter Reed Army Medical Center, 6900 Georgia Avenue, N.W.,
Washington, D.C. 20307.
Received Mar. 5, 1999; accepted May 21, 1999.

REFERENCES
1. Cherry J, Margulies SI. Contact ulcer of the larynx. Laryngoscope 1968;78:1937 40.
2. Ohman L, Olofsson J, Tibbling L, et al. Esophageal dysfunction in patients with contact ulcer of the larynx. Ann Otol
Rhinol Laryngol 1978;92:228 30.
3. Koufman JA, Wiener GJ, Wallace CW, et al. Reflux laryngitis
and its sequela: The diagnostic role of ambulatory 24-hour
monitoring. J Voice 1988;2:78 9.
4. Toohill RJ, Mushtag E, Lehman RH. Otolaryngologic manifestations of gastroesophageal reflux. In: Sacristan T, AlvarezVincent JJ, Bartual J, et al., eds. Proceedings of XIV World
Congress of Otololaryngology head and neck surgery.
Amsterdam: Kugler & Ghedini Publications, 1990:30059.
5. Ward PH, Hanson DG. Reflux as an etiological factor of
carcinoma of the laryngopharynx. Laryngoscope 1988;98:
11959.
6. Chen MY, Ott DJ, Casolo BJ, et al. Correlation of laryngeal
and pharyngeal carcinomas and 24-hour pH monitoring of the
esophagus and pharynx. Otolaryngol Head Neck Surg 1998;
119:460 2.
7. Little FB, Koufman JA, Kohut RI, et al. Effect of gastric acid
on the pathogenesis of subglottic stenosis. Ann Otol Rhinol
Laryngol 1985;94:516 9.
8. Gaynor EB. Gastroesophageal reflux as an etiologic factor in
laryngeal complications of intubation. Laryngoscope 1988;98:
9729.
9. Lillemoe KD, Johnson LF, Harmon JW. Role of the components of the gastrodudenal contents in experimental acid
esophagitis. Surgery 1982;92:276 84.
10. Johnson LF, Harmon JW. Experimental esophagitis in a rabbit
model. Clinical relevance. J Clin Gastroenterol 1986;(Suppl)8:
26 44.
11. Ludeman JP, Manoukian J, Shaw K, et al. Effects of simulated
gastroesophageal reflux on the untraumatized rabbit larynx. J
Otololaryngol 1998;27:12731.
12. Kambic V, Radsel Z. Acid posterior laryngitis. Aetiology,

AJG October, 1999

13.
14.
15.
16.
17.
18.
19.
20.

21.
22.
23.
24.
25.
26.
27.
28.

29.
30.

31.

histology, diagnosis and treatment. J Laryngol Otol 1984;98:


1237 41.
Hallewell JD, Cole TB. Isolated head and neck symptoms due
to hiatus hernia. Arch Otololaryngol 1970;92:499 501.
Cherry J, Siegel CI, Margulies SI, et al. Pharyngeal localization of symptoms of gastroesophageal reflux. Ann Otol Rhinol
Laryngol 1970;79:9125.
Ward PH, Berci G. Observations on the pathogenesis of
chronic nonspecific pharyngitis and laryngitis. Laryngoscope
1982;92:1377 82.
Von Leden H, Moore P. Contact ulcer of the larynx. Experimental observations. Arch Otololarygol 1960;72:746 51.
Shaker R, Milbrath M, Junlong R, et al. Esophagopharyngeal
distribution of refluxed gastric acid in patients with reflux
laryngitis. Gastroenterology 1995;109:1575 82.
Jacob P, Kahrilas PJ, Herzon G. Proximal esophageal pHmetry in patients with reflux laryngitis. Gastroenterology
1991;100:30510.
Wo JM, Hunter JG, Waring JP. Dual-channel ambulatory
esophageal pH monitoringA useful diagnostic tool? Dig Dis
Sci 1997;42:2222 6.
Waring JP, Lacayo L, Hunter J, et al. Chronic cough and
hoarseness in patients with severe gastroesophageal reflux
disease: Diagnosis and response to therapy. Dig Dis Sci 1995;
40:10937.
Katz PO. Ambulatory esophageal and hypopharyngeal pH
monitoring in patients with hoarseness. Am J Gastroenterol
1990;85:38 40.
Ulualp S, Toohill R, Hoffmann RC, et al. Revelations about
24-hr. ambulatory pharyngeal pH monitoring. Gastroenterology 1998;G1290:A315 (abstract).
Fouad YM, Hatlebakk PO, Katz PO, et al. Elevated upper
esophageal sphincter (UES) pressure is associated with reflux
laryngitis. Gastroenterology 1998;G0505:A123 (abstract).
Ulualp SO, Tohill RJ, Kern M, et al. Pharygo-UES contractile
reflex in patients with posterior laryngitis. Laryngoscope
1998;108:1354 7.
Shaker R, Dodds WJ, Hogan WJ, et al. Mechanisms of
esophago-pharyngeal acid regurgitation. Gastroenterology
1991;100:A494 (abstract).
Ossakow SJ, Elta G, Colturi T, et al. Esophageal reflux and
dysmotility as the basis for persistent cervical symptoms. Ann
Otol Rhinol Laryngol 1987;96:38792.
Ulualp S, Toohill R, Shaker R, et al. Secondary esophageal
peristalsis is preserved in patients with posterior laryngitis.
Gastroenterology 1998;G1291:A316 (abstract).
Fouad YM, Khoury R, Hatlebakk JG, et al. Ineffective esophageal motility (IEM) is more prevalent in reflux patients with
respiratory symptoms. Gastroenterology 1998;G0506:A123
(abstract).
Toohill RJ, Kuhn JC. Role of refluxed acid in the pathogenesis
of laryngeal disorders. Am J Med 1997;103:100S106S.
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;101:1
78.
Koufman JA. Gastroesophageal reflux and voice disorders. In:
Rubin JS, Sataloff RT, Gould WJ, Korovin GS, eds. Diagnosis
and treatment of voice disorders. New York: Igaku-Shoin,
1995:16575.

Reflux Laryngitis

2817

32. Jamieson GC, Duranceau AC. The development of surgery for


gastro-oesophageal reflux disease. In: Jamieson GC, ed. Surgery of the oesophagus. Edinburgh: Churchill Livingston,
1988:233.
33. Wiener GJ, Copper JB, Wu WC, et al. Is hoarseness an
atypical manifestation of gastroesophageal reflux (GER)? An
ambulatory 24-hour pH study. Gastroenterology 1986;90:
A1691 (abstract).
34. Kamel PL, Hanson D, Kahrilas PJ. Omeprazole for the treatment of posterior laryngitis. Am J Med 1994;96:321 6.
35. Weinbeck M, Barnert J. Epidemiology of reflux disease and
reflux esophagitis. Scand J Gastroenterol 1989;24(Suppl 156):
713.
36. Rasmussen CW. A new endoscopic classification of chronic
esophagitis. Am J Gastroenterol 1976;65:409.
37. Wilson JA, White A, von Haacke NP, et al. Gastroesophageal
reflux and posterior laryngitis. Ann Otol Rhinol Laryngol
1989;98:40510.
38. Koufman JA. pH monitoring in otolaryngology patients with
gastroesophageal reflux disease: When the pharyngeal probe is
essential. (Unpublished data), 1993.
39. Mittal RK, Stewart WR, Schirmer BD. Effect of a catheter in
the pharynx on the frequency of transient lower esophageal
sphincter relaxations. Gastroenterology 1992;103:1236 40.
40. Wiener GJ, Koufman JA, Wu WC, et al. The pharyngoesophageal dual ambulatory pH probe for evaluation of atypical manifestations of gastroesophageal reflux (GER). Gastroenterology 1987;92:1694 (abstract).
41. Koufman JA. The otolaryngologic manifestations of gastroesophageal reflux disease. In: Richter JE, ed. Ambulatory
esophageal pH monitoring: Practical approach and clinical
applications. New York: Igaku-Shoin, 1991:129 49.
42. McNally PR, Maydonovitch CL, Prosek RA, et al. Evaluation
of gastroesophageal reflux disease as a cause of idiopathic
hoarseness. Dig Dis Sci 1989;34:1900 4.
43. Hanson DG, Kamel PL, Kahrilas PJ. Outcomes of antireflux
therapy for the treatment of chronic laryngitis. Ann Otol
Rhinol Laryngol 1995;104:550 5.
44. Jaspersen D, Weber R, Hammar CH, et al. Effect of omeprazole on the course of associated esophagitis and laryngitis. J
Gastroenterol 1996;31:7657.
45. Shaw GY, Searl JP. Laryngeal manifestations of gastroesophageal reflux before and after treatment with omeprazole. S
Med J 1997;90:111522.
46. Wo JM, Grist WJ, Gussack G, et al. Empiric trial of high-dose
omeprazole in patients with posterior laryngitis: A prospective
study. Am J Gastroenterol 1997;92:2160 5.
47. Peghini PL, Katz PO, Bracy NA, et al. Nocturnal recovery of
gastric acid secretion with twice-daily dosing of proton pump
inhibitors. Am J Gastroenterol 1998;93:7637.
48. Goldin GF, Marcinkeiwicz M, Zbroch T, et al. Esophagoprotective potential of cisapride: An additional benefit for gastroesophageal reflux disease. Dig Dis Sci 1997;42:13629.
49. Hatlebakk JG, Katz PO, Kuo B, et al. Nocturnal gastric acidity
and acid breakthrough on different regimens of omeprazole 40
mg daily. Aliment Pharmacol Ther 1998;12:1235 40.
50. Fouad YM, Katz PO, Castell DO. Adding ranitidine at bedtime
controls nocturnal gastroesophageal reflux (GER) in patients
taking proton pump inhibitors twice daily. Gastroenterology
1999;116:A208 (abstract).