Rev. Med. Chir. Soc. Med. Nat., Iai 2012 vol. 116, no.

INTERNAL MEDICINE - PEDIATRICS

ORIGINAL PAPERS

LARYNGEAL MORPHOLOGICAL CHANGES DUE

TO GASTROESOPHAGEAL REFLUX DISEASE
M. D. Cobzeanu1 , Monica Voineag2, V. L. Drug3, Anca Ciubotaru4,
B. M. Cobzeanu1 , O. D. Palade1
University of Medicine and Pharmacy Grigore T. Popa - Iasi
Faculty of Medicine
1. Discipline of ENT
3. Discipline of Medical Semiolgy IGH
4. University of Arts George Enescu - Iasi
2. ENT Outpatients Siegen, Germany
LARYNGEAL MORPHOLOGICAL CHANGES DUE TO GASTROESOPHAGEAL REFLUX DISEASE (GERD) (Abstract): Chronic laryngitis may have life impact on professional voice users. Besides smoking and excessive alcohol intake, GERD is a determining
factor in the etiology of dysphonia. Aim: To evaluate the laryngeal alteration due to GERD
in professional voice users. Material and methods: The study included 96 vocal professionals (teachers, actors, singers and priests), 58 males and 38 females, with a mean age of 38.3
7.5 years, presented for chronic laryngeal symptoms. The patients filled out a standardized
questionnaire and were examined laryngoscopically. Results: Laryngeal changes were scaled
0 (absence) to 7 (maximum) arytenoid edema (5.071.08), interarytenoid edema
(6.181.12), vocal folds edema (5.671.04), ventricular bands edema (4.960.97), laryngeal
edema 4.120.83). Conclusions: Laryngoscopic changes may suggest the concomitance of
GERD in professional voice users with dysphonia. Keywords: GERD, DYSPHONIA, VOCAL PROFESSIONALS.

Even though most otolaryngologists are

aware of the pathology induced by gastroesophageal reflux disease (GERD), this
relationship was more intensely studied
during the last two decades (13, 14). Otolaryngologists have become extremely cautious
when performing the clinical ENT examination and look for reflux signs (rashes, edema
in the arytenoid mucosa and interarytenoidian area) even when they prescribe treatment
for chronic laryngitis. According to the most
recent surveys, laryngopharyngeal reflux
(LPR) displays a complex spectrum of
pathological signs (1, 2, 3, 5).

Reflux laryngitis occurs as a result of a

backward flow of acid and other stomach
contents into the esophagus to the larynx,
resulting in a chemical burn of the lining.
The diagnosis of LPR is based on a
combination of symptoms and findings in
the larynx during physical examination (4,
7, 8).
The opening of the esophagus sits behind the arytenoids in the posterior part of
the larynx, and that is why these areas are
the most affected by reflux. The larynx
shows signs of irritation and inflammation,
as evidenced by the presence of redness

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M.D. Cobzeanu et al.

(erythema) and swelling (edema) of the

arytenoids, interarytenoid region (the area
between the arytenoids, also referred to as
the posterior glottis, or, incorrectly, as the
posterior commissure), and the post-cricoid
region (the area behind the arytenoids that
separates the larynx from the esophageal
opening).
In severe cases, the reflux material can
contact other parts of the larynx causing
erythema and edema of the folds.
The presence of edema of the true vocal
cords is highly suggestive of LPR, even in
the absence of laryngeal erythema (6, 9, 10,
11).
Any activity that increases intraabdominal pressure may exacerbate the
symptoms of LPR. Such activities may
include weight lifting, sit-ups, abdominal
crunches, sexual intercourse, running,
dancing, aerobics, public speaking, acting,
and singing.
Reflux-related symptoms and clinical
presentation have been identified in 4 to10% of all the patients seen by otolaryngologists (15, 16, 17), and most likely, asthese estimates are not accurate, the percentage could be even much higher. Re-garding the patients with laryngeal pathology, LPR is related with these conditions
or represents an etiological factor in approximately 50% of the cases (11, 13).
The most common symptoms and clinical presentations of the reflux laryngitis
are:
- morning hoarseness
- the voice warms in more than 20-30
minutes
- halitosis
- throat clearing
- oral dryness
- white tongue
- globus faringeus

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dysphagia
regurgitations of the gastric content
recurrent cough
laryngospasm,
complication of asthma
acute upper airways infection in children.
In addition to longer vocal warm up
time, the vocal professionals and actors
may also suffer other interferences in their
vocal practice frequent throat clearing,
abundant expectoration, especially during
the first 10-20 minutes of vocal training
(16).
Some authors noticed that LPR patients
do not present esophagitis-related changes,
so dyspepsia and heartburn are usually
absent (8, 12, 17).
The prevalence of esophagitis is relatively low, as the esophageal mucosa of the
distal esophagus has its own antacid protection mechanisms which include the following:
peristalsis (quickly pushing the acid off the
surface of the esophageal mucosa)
structure of the mucosa (tolerating the
intermittent contact with the gastric acid)
capacity of the saliva to neutralize the acid
However, the larynx and the pharynx do
not have such protective mechanisms, thus
exposure to acid and pepsin may cause
substantial changes at this level, whereas
the esophagus may not be affected at all.
According to the preliminary data reported
by Axford (14), the lining of the larynx has
a cell defense mechanism which is different
from the esophageal mucosa and there are
specific differences in the expression of the
MUC genes and carbonic anhydrase in the
larynx and pharynx (1, 3, 8).
If the mucosa is affected, either directly
or through secondary mechanisms, changes
in the laryngeal mucosa may result. Thus, it

Laryngeal morphological changes due to gastroesophageal reflux disease

may be directly affected by the contact

with the laryngeal lining with acid and
pepsin, which results in mucosal lesions.
Alternatively, the irritation of the distal
esophagus by the gastric acid may activate
a reflex mediated by the vagus nerve,
which leads to chronic cough and throat
clearing, affecting the larynx lining as well
(16, 17).
The bile reflux may also affect the larynx. Additionally, according to recent surveys, there are a lot of question marks concerning the pathophysiology of reflux laryngitis. Some authors consider that the
decrease in salivary epidermal growth factor may be associated with reflux laryngitis
(14, 15, 17).
The aim of this research study was to
evaluate the laryngeal alterations due to
gastroesophageal reflux disease in professional voice users

(chronic dysphonia)
- absence of laryngeal benign or malignant lesions
- no drug treatment that could alter the
esophageal motor function or acid secretion
(anticholinergics, sedatives, prostaglandins,
calcium channel blockers, potassium, antibiotics, NSAIDs)
- symptomatic GERD
Exclusion criteria:
- active smokers
- chronic alcohol intake
- upper airways infections during the
last month (before inclusion in the research
study)
- prior history of anti-reflux surgery
- asthma
Statistical analysis
Statistical analysis was performed using
SPSS 16.0, on Windows XP Professional
platform.

MATERIAL AND METHODS

Selection of patients groups
The cases included in the research study
were selected among the patients of the Sf.
Spiridon Emergency Hospital Iasi, ENT
Department. As study material, we used a
group of 96 vocal professionals (teachers,
actors, singers, priests) diagnosed with
chronic laryngitis between 2008 and 2010.
All patients filled out a standardized questionnaire and patient meeting the clinical
criteria of gastroesophageal reflux disease
were included in the study. A written informed consent was obtained from all patients. The control group included 54 age-,
sex- and profession- matched ENT patients
with no laryngeal complaints (16,17).
Selection criteria:
- vocal professionals (teachers, actors,
singers, priests)
- dysphonia for at least 3 months

RESULTS
This research survey included 58 males
and 38 females, aged between 21 and 60
years, mean age 38.3 years (7.56) and
median age 39 years.
The most affected professionals considering laryngeal changes - were teachers
(37.5%), followed by singers (28.12%).
There was no statistically significant difference between priests and actors, considering that priests are a male-only category.
The analysis of laryngeal changes revealed the prevalence of changes in the true
vocal folds, as well as in the interarytenoid
area (p<0.001), closely followed by changes at arytenoid level, false vocal folds, and
laryngeal mucosa in general (table I).
Diagnostic sensitivity of laryngoscopy
for laryngeal changes was of over 50% for
8 of the 10 laryngeal signs suspected to
occur following the action of the reflux.

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M.D. Cobzeanu et al.

Interarytenoid and arytenoid edema followed by vocal folds edema and erythema

were the changes with the highest sensitivity (83-97%).

TABLE I
Laryngeal changes (flexible endoscopic laryngoscopy)
Research group

Laryngeal change

Control group

SD

SD

Arytenoid edema/ erythema

5.07

1.08

1.15

0.92

Interarytenoid edema/ erythema

6.18*

1.12

0.93

0.89

Vocal folds edema/ erythema

5.67*

1.04

0.98

0.91

Ventricular bands edema/ erythema

4.96

0.97

0.87

0.73

Laryngeal edema/ erythema

4.12

0.83

0.77

0.69

-arithmetic mean

SD-standard deviation

Specificity was highest in the patients

with true vocal folds and ventricular bands
erythema, followed by ventricular bands
edema and laryngeal erythema (90-94%).
DISCUSSION
According to our findings, laryngeal
changes were more common at the level of
the vocal and interarytenoid folds
(p<0.001), followed by arytenoid area and
ventricular bands both before, as well as
after treatment. Interarytenoid and arytenoid edemas, followed by edema and erythema of the vocal folds were found to be
the changes with the highest sensitivity (83
- 97%) (16, 17).
Despite numerous studies on reflux
symptoms, those mentioned above as well
as many others (16, 17), there is no objective data to support the significance of the
various patient complaints and changes (as
a result of the performed tests) in terms of
diagnosis. This issue arose as there has not
been any consensus as regards normal
among the groups of patients included in
the survey. Interdisciplinary debates (most

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*p<0.001

particularly, otorhinolaryngology and gastroenterology), as well as multicentric surveys are necessary to accurately determine
the sensitivity and specificity of the results
frequently associated with laryngopharyngeal reflux, as well as the impact of
LPR on the quality of life and general
health status.
CONCLUSIONS
Patients presenting with laryngeal reflux symptoms must be treated in multidisciplinary way (otolaryngologist/gastroenterologist). The positive diagnostic requires
modern and accurate testing methods: flexible endoscopic laryngoscopy, pH monitoring, esophageal impedance study, upper
gastro intestinal endoscopy (UGIE).
Because there is no consensus on diagnosis and treatment, this condition is frequently either over diagnosed (resulting in
various invasive, useless and expensive
tests, as well as the application of inefficient treatment plans), or under diagnosed
(resulting in the progression of symptoms
because of the lack of adequate treatment).

Laryngeal morphological changes due to gastroesophageal reflux disease

REFERENCES
1. Book DT, Rhees JS, Toohill RJ, Smith TL. Perpectives in laryngopharyngeal reflux: an international
survey. Laryngoscope 2002; 112: 1399-1406.
2. Lenderking WR, Hillson E, Crawley JA, Moore D, Berzon R, Pashos CL. The clinical charactheristics and impact of laryngopharyngeal reflux disease on health-related quality of life. Value Health
2003; 6: 560-565.
3. Carrau RL, Khdir A, Crawkley JA, Hillson EM, Davis JK, Pashos CL. The impact of laryngopharyngeal reflux on patient-reported quality of life. Laryngoscope. In press.
4. Halum SL, Postma GN, Johnston, Belafsky PC, Koufman JA. Patients with isolated laryngopharyngeal reflux are not obese. Laryngoscope 2005; 115(6): 1042-1045.
5. Koufman JA, Amin MR, Panetti M. Prevalence of reflux in 113 consecutive patients with laryngeal
and voice disorders. Otolaryngol Head Neck Surg 2000; 123: 385-388.
6. Book DT, Rhee JS, Toohill RJ, Smith TL. Perspective in laryngopharyngeal reflux: an international
survey. Laryngoscope 2002; 112(8 pt 1): 1399-1406.
7. Vaezi MF. Ear, nose, and throat manifestations of gastroesophageal reflux disease. Clin Perspect
Gastroeneterol 2002; 5(6): 324-328.
8. Siupsinskiene N, Adamonis K, Toohill RJ. Quality of life in laryngopharyngeal reflux patients.
Laryngoscope 2007; 117: 480-4.
9. Roy N, Merril RM, Thibeault S, Parsa RA, Gray SD, Smith EM. Prevalence of voice disorders in
teachers and the general population. J Speech Lang Hear Res 2004; 47(2): 281-293.
10. Smit CF, van Leeuwen JA, Mathus-Vliegen LM et al. Gastropharyngeal and gastroesophageal reflux
in globus and hoarseness. Arch Otolaryngol Head Neck Surg 2000; 126: 827-830.
11. Johnston N, Bulmer D, gill GA, et al. cell biology of laryngeal epithelial defenses in health and disease: further studies. Ann Otol Rhinol Laryngol 2003; 112: 481-491.
12. Adhami T, Goldblum JR, Richter JE, Vaezi MF. The role of gastric and duodenal agents in laryngeal
injury: an experimental canine model. Am J Gastroenterol 2004; 99(11): 2098-2106.
13. Shaker R, Bardan E, Gu C et al. Intrapharyngeal distribution of gastric acid refluxate. Laryngoscope
2003; 113: 1182-1191.
14. Axford SE, Sharp N, Ross PE, et al. Cell biology of laryngeal epithelial defenses in health and disease: preliminary studies. Ann Otol Rhinol Laryngol 2001; 110: 1099-1108.
15. Galli J, Calo L, Agostino S et al. Bile reflux as possible risk factor in laryngopharyngeal inflammatory and neoplastic lesions. Acta Otorhinolaryngol Ital 2003; 23: 377-382.
16. Monica Voineag, V. Costinescu, M. D. Cobzeanu. Management of pharyngolaryngeal reflux at voice
professionals. Analele Universitatii Dunarea de Jos Galati, Medicina 2011; XVII(2): 77-83.
17. Voineag M. A. Diagnosis and Treatment of Dysphonias Caused by the Gastroesophageal Reflux
Disease (Case of Vocal Professionals). PhD Thesis, 2011.

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