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-- Head and Neck Surgery

Cough and Paradoxical Vocal Fold Motion

Kenneth W. Altman, C. Blake Simpson, Milan R. Amin, Mona Abaza, Ron Balkissoon and Roy R. Casiano
Otolaryngology -- Head and Neck Surgery 2002 127: 501
DOI: 10.1067/mhn.2002.127589
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Cough and paradoxical vocal fold motion

KENNETH W. ALTMAN, MD, PhD, C. BLAKE SIMPSON, MD, MILAN R. AMIN, MD, MONA ABAZA, MD, RON BALKISSOON,
ROY R. CASIANO, MD, Chicago, Illinois, San Antonio, Texas, Philadelphia, Pennsylvania, Denver, Colorado,

MD,

and

and Miami, Florida

OBJECTIVES: The differential diagnosis and treatment of patients with chronic cough, paradoxical
vocal fold motion, and disordered breathing can
be a challenge to most practicing otolaryngologists. Tracheobronchial (ie, asthma, bronchitis, and
tracheal stenosis), laryngeal (ie, vocal fold paralysis and neoplasms), and rhinologic (ie, allergies
and rhinosinusitis) etiologies are commonly diagnosed and treated effectively. However, occasionally one is faced with patients who are refractory to
medical treatment and have no obvious rhinologic,
laryngeal or pulmonary cause.
STUDY DESIGN AND SETTING: We conducted a review of the literature.
METHODS: We present a thorough review of the current medical literature exploring the complex neurologic mechanisms involved in the production of
cough and the relationship between gastroesophageal reflux disease, vagal neurapathy, and paradoxical vocal fold motion.
RESULTS: The diagnosis and successful treatment of
chronic cough can be complex. It requires a thorough understanding of the neurologic mechanisms

From the Department of Otolaryngology, Northwestern University Medical School, Chicago (Dr Altman), Department
of Otolaryngology, University of Texas Medical Center,
San Antonio (Dr Simpson), Department of Otolaryngology, Medical College of Philadelphia, Ahanemann University, Philadelphia (Dr Amin), Department of Otolaryngology, University of Colorado School of Medicine, Denver
(Dr Abaza), Departments of Medicine and Department of
Biometrics and Preventive Medicine, University of Colorado Health Sciences Center (Dr Balkissoon), and Department of Otolaryngology, University of Miami School of
Medicine, Miami (Dr Casiano).
Presented at the Annual Meeting of the American Academy
of OtolaryngologyHead and Neck Surgery, Neurolaryngology Subcommittee Panel, Denver, CO, September 9-12,
2001.
Reprint requests: Roy R. Casiano, MD, Department of Otolaryngology, University of Miami Hospital and Clinics,
1475 NW 12th Ave, Suite 4025, Miami, FL 33136; e-mail,
rcasiano@med.miami.edu.
Copyright 2002 by the American Academy of OtolaryngologyHead and Neck Surgery Foundation, Inc.
0194-5998/2002/$35.00 0 23/1/127589
doi:10.1067/mhn.2002.127589

behind cough excitation and suppression. Successful treatment strategies include aggressive
management of the patients reactive airway disease, gastroesophageal reflux disease, and, in select cases, paradoxical vocal fold motion. This may
involve a well-coordinated effort among pulmonologists, otolaryngologists, gastroenterologists,
and speech pathologists.
CONCLUSION: Gastroesophageal reflux disease,
vagal neuropathy, and paradoxical vocal fold motion are additional causes of chronic cough and
disordered breathing that need to be considered,
in the absence of obvious laryngotracheal and/or
rhinologic pathology. A high index of suspicion is
essential in making the diagnosis and formulating
an effective multidisciplinary treatment plan for
these patients. (Otolaryngol Head Neck Surg 2002;
127:501-11.)

ough is one of the most common presenting

complaint of adults seeking medical treatment in
an ambulatory setting.1 Although cough is generally due to a brief, self-limiting illness, it can
become a persistent symptom in some cases. The
etiology of chronic cough (persisting for 3
weeks) is extensive and can be explained by the
myriad of afferent pathways involved in the cough
reflex.
Chronic cough often represents a difficult diagnostic, as well as therapeutic, problem. Common
causes of chronic cough include asthma, chronic
bronchitis, and chronic sinusitis and/or allergies.
Treatment for these entities is generally effective
in reducing or eliminating cough. However, there
remains a subset of patients for whom there is no
discernible diagnosis or treatment. These patients
present a diagnostic challenge to the practicing
otolaryngologist.
In this report the neurologic mechanisms of
cough and the current understanding regarding the
pathogenesis of vagal neuropathy and gastroesophageal reflux disease as potential causes of
chronic cough are reviewed. In addition, the
pathogenesis, diagnosis, and treatment for paradoxical vocal fold motion as a common nonpul501

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502 ALTMAN et al

Table 1. Common causes of chronic cough

Table 2. Agents that induce cough3

Most
Cigarette smoking, postnasal drip syndrome,
common
gastroesophageal reflux, chronic bronchitis,
asthma
Less
Bronchiectasis, angiotensin-converting enzyme
common
(ACE) inhibitors, bronchogenic carcinoma,
chronic interstitial pulmonary disease, cystic
fibrosis, congestive heart failure

Chemical
irritants

monary cause of disordered breathing and cough

are discussed.
NEUROLOGIC MECHANISMS OF
COUGH: EXCITATION AND
SUPPRESSION
To understand the pathophysiology behind
chronic cough production, one needs to be familiar
with the neurophysiology of a normal cough. Its
relationship to respiratory physiology and disordered breathing is at its relative infancy. However,
there are common components to both cough and
disordered breathing, beginning at the level of
sensory input from the aerodigestive tract. Although cough may be produced voluntarily, the
reflexive cough is a stronger model for the complex interplay between the sensory and motor
mechanisms producing the cough.
The cough reflex begins with an adverse stimulus in the upper aerodigestive tract that excites
sensory receptors to send afferent information to
the brainstem, mediated through sensory neuropeptides. Integration of this information with
motor instruction from the brain and brainstem
results in the efferent limb, producing the cough.
The common causes of chronic cough are listed in
Table 1. However, there may be a multifactorial
etiology in as many as 62% of patients.1
Sensory Receptors
There are 5 different types of vagal intraepithelial sensory receptors. Slowly adapting pulmonary stretch receptors influence bronchodilation and are not directly involved in the cough.
Receptors that are responsible for the cough
reflex are predominantly the rapidly adapting
stretch receptors (RARs) associated with small
diameter myelinated fibers and the pulmonary
and bronchial C-fiber receptors associated with
nonmyelinated afferent fibers (both of which also

Mechanical
agents

Capsaicin, citric acid, acetic acid, tartaric

acid, acetylcholine, nicotine, sulfur
dioxide, volatile anesthetics, irritant
gases
Instrumentation, lactose, aerosols, dust,
bronchoconstriction, mucus, foreign
bodies, inflation

mediate bronchoconstriction).2 These 3 groups of

receptors generally respond to the same groups of
stimuli, with different sensitivities. Stimuli include chemical irritants and mechanical agents
(Table 2), as well as inflammatory mediators, and
certain disease states (such as pulmonary edema).
The C-fiber receptors can cause neurogenic inflammation that further stimulates the RARs to
enhance cough. However, strong stimuli of the
C-fiber receptors can inhibit cough by a central
reflex action, so there is a complex neurophysiologic interplay. In general, the distribution of receptors is more mechanosensitive toward the larynx and more chemosensitive in the distal/
bronchial airway.
Sensory Neuropeptides
It is now believed that tachykinins play an important role in enhancing cough, based on multiple
studies exploring the induced cough reflex in subjects given tachykinin antagonists.2 Tachykinins
are a class of sensory neuropeptides released from
C-fiber receptors that includes substance P (SP),
neurokinin A (NKA), and calcitonin generelated
peptide (CGRP). These neuropeptides induce
neurogenic inflammation, characterized by vasodilation, plasma exudate, epithelial damage,
submucosal gland secretion, and further sensory
receptor stimulation. Angiotensin-converting enzyme (ACE) inhibitors cause cough in as many as
10% of patients by preventing the breakdown of
tachykinins and bradykinin. NKA mediates contraction of airway smooth muscle, and SP is more
specific to stimulating mucus secretion. Neuropeptides also play a role in activating T- and Blymphocytes, cytokine release, and chemotaxis of
other inflammatory cells.
Sensory Afferents
The afferent limb of the vagus nerves innervates
diffuse structures of the aerodigestive tract and is

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ALTMAN et al

responsible for the origin of the cough reflex.

These include Arnolds nerve from the external
ear canal and tympanic membrane, pharyngeal
branches, superior laryngeal branches, pulmonary
branches, gastric branches from the stomach, cardiac and esophageal branches, and vagally innervated viscera (which may elicit cough in diaphragmatic disease). Although bilateral block of the
superior laryngeal nerves in humans makes little
difference to the cough reflex, there is the suggestion that an afferent supply from the larynx may
inhibit cough whose function is affected by the
presence of irritants.3
Central Integration
Airway sensory afferents terminate in the brainstem at the level of the nucleus tractus solitarius
(NTS).4 The RARs and bronchial and pulmonary
C-fiber receptors project to medial aspects of the
NTS at the obex, but the RARs also project to the
ventrolateral nuclei and pons.4 This is significant
because the carotid chemoreceptor afferent fibers
similarly project to the ventrolateral nuclei, and
this common pathway may explain why palpation
of a carotid body tumor may evoke a cough. The
cough center is influenced by voluntary cortical
control, and the cough reflex is diminished when
the conscious state is depressed.5 Second-order
neurons communicate the sensory brainstem information to the efferent limb of the cough reflex.
The Efferent Limb
The efferent limb begins with instruction/mediation of cortex and cerebellum integrated at the
brainstem to produce sequentially (1) a deep inspiration, (2) glottal closure, (3) relaxation of the
diaphragm, (4) increased thoracic muscle contraction to increase airway pressure, (5) narrowing of
the trachea, (6) glottal opening, and (7) dramatically increased airway flow rates to facilitate
shearing forces for the expulsion of mucus and
foreign material. It is possible that the coordination of this sequence is accomplished by a preprogrammed motor sequence, similar to swallowing and vomiting. The motor neurons generating
the cough are located in ventral respiratory group.
Within this group is the nucleus ambiguous innervating the larynx (via the recurrent laryngeal
nerve) and trachea and the nucleus retroambigua-

503

lis innervating the inspiratory and expiratory muscles (via the phrenic and spinal intercostal motor
neurons).4 The velocity of flow from the cough is
enhanced by vagal efferents that mediate bronchial smooth muscle constriction.
Relationship to Respiratory Physiology
Cough and respiration share common muscle
groups in function, as well as central neurologic
pathways. Respiration is primarily generated in
the medulla (through the NTS dorsally and a ventral nuclei group). However, the cough center is
more diffusely located and is probably distinct
from the medullary respiratory center.1 In support
of centrally distinct centers in the brainstem for
cough and respiration, animal models have demonstrated that although general anesthesia may
depress the respiratory rhythm generator, the
cough reflex remains intact. Also, drugs that suppress the cough reflex may have little effect on
depressing respiration.3 Laryngospasm is also related to the brain respiratory centers because sustained cricothyroid and thyroarytenoid activity is
produced when SP is stereotactically injected into
the NTS in experimental animals.6
Another relationship between cough and respiratory physiology may exist at the level of the
bronchial airway, as manifested in cough-variant
asthma, where cough may be the only presenting
symptom in as many as 57% of patients with
chronic cough due to asthma.1 However, the concept of neurogenic inflammation causing cough
variant asthma is still controversial. It is possible
that the same trigger that leads to airway hyperresponsiveness also triggers neuropeptide release to
initiate cough.5
Pharmacologic Management
Pharmacologic management of cough is ideally
directed toward the underlying disease process.
Although protussive therapy is helpful in clearing
the airways of infectious or stagnant mucus, antitussive therapy is important in reducing the repeated laryngeal trauma of the explosive cough.
Individual agents that may suppress cough are
shown in Table 3. Many agents listed in this table
act locally for specific disease processes, such as
ipatropium bromide to decrease mucus secretion
in patients with bronchitis. The agents that work

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504 ALTMAN et al

Table 3. Agents that suppress cough

Proven to suppress cough

Unproven
effectiveness

Ineffective or
inconsistent

Ipatropium bromide, dexbrompheniramine/pseudoephedrine, guaimesal,

levodropropizine, naproxen, codeine,
dextromethorphan, glaucine, diphenhydramine, caramiphen, viminol
Ammonium chloride, potassium iodide,
hydration, aromatic chest rubs, theophylline, benzonatate, menthol
vapor
Carbocystine, bromhexine, levopropoxyphene

From Irwin et al.1

centrally to elevate the cough threshold generally

act on opiate and serotinergic receptors independent of a sedative effect.7,8
COUGH AND GASTROESOPHAGEAL
REFLUX DISEASE
Allergic rhinitis and rhinosinusitis, cough-variant asthma, and gastroesophageal reflux disease
(GERD) are the cause of chronic cough in 86% of
adult patients. This percentage increases to over
99% when one considers only immunocompetent
nonsmokers with normal chest radiographic findings and no history of ACE inhibitor use.9 Therefore, in the vast majority of otherwise healthy
adult patients who are referred for chronic cough,
the diagnostic choices are limited. If allergy testing, sinus computed tomography scans, and pulmonary function tests are normal, the patient with
a chronic cough almost invariably has GERD as
the primary causative factor of the symptom.10 In
fact, the prevalence of GERD-associated cough
may be as high as 40%.11 This underscores the
need for otolaryngologists to maintain a high index of suspicion for GERD when evaluating complaints of a chronic cough. As pointed out by Irwin
et al,12 chronic cough can be the only symptom
present in a GERD patient, and GERD-induced
cough should be suspected even in the absence of
heartburn or other gastrointestinal symptoms.
Pathophysiology of GERD-associated cough has
been postulated to occur via 2 mechanisms: (1)
acid exposure in the distal esophagus stimulating
an esophagotracheobronchial cough reflex via the
vagus nerve and (2) microaspiration of esophageal
contents into the laryngopharynx and tracheobronchial tree. The first mechanism occurs with tradi-

tional distal GERD, and the second mechanism is

due to proximal GERD or laryngopharyngeal reflux (LPR). Experimental and clinical studies provide support for both mechanisms, so both distal
and proximal reflux appear to play at least some
role in chronic cough. A study by Irwin et al13
using dual-channel pH monitoring demonstrated a
higher correlation of cough with distal esophageal
acid exposure (28%) than proximal esophageal
acid exposure (6%). In addition, Ing et al14 demonstrated that patients with GERD-induced cough
had a significant increase in cough frequency with
acid versus saline infusions into the distal esophagus. The acid-induced cough reflex arc could be
blocked with esophageal lidocaine infusion. The
studies by Irwin et al and Ing et al support the
importance of a vagally mediated esophageal-tracheobronchial cough reflex. Another common
finding in patients with GERD-associated cough is
ineffective esophageal motility and prolonged
esophageal acid clearance. More extensive exposure of acid to the esophagus seems to support
distal esophageal reflex mechanisms in cough production as well.15
It is unlikely that esophageal acid exposure is
the sole cause of cough, however. More recent
evidence using dual-channel pH monitoring
showed that a significant number of patients with
GERD-associated cough had proximal reflux disease in the absence of pathologic distal reflux
disease. Schnatz et al16 demonstrated that 17% of
patients whose pulmonary symptoms (cough and
asthma) responded to antireflux therapy would not
have been recognized as having abnormal reflux if
the proximal pH probe data had not been obtained.
In addition, others have observed acid reflux events
into the hypopharynx in 9 of 15 cough patients.17
Bronchoscopy performed in patients with
GERD-associated cough has failed to show any
evidence of acid-related tracheobronchial injury;
therefore the exact mechanism of microaspiration
and cough is not known.12 The overall importance
of laryngopharyngeal reflux and microaspiration
in the development of chronic cough is unknown
but seems to play a role in at least some patients.
Diagnosis of GERD-Associated Cough
A high index of suspicion for GERD as the
primary etiology of chronic cough must be main-

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tained. It has been estimated that GERD may be

clinically silent (i.e., no heartburn) in as many as
75% of patients who are referred for chronic
cough. Clues in the patients history may include
concomitant LPR symptoms such as globus sensation, throat clearing, and hoarseness (especially
in the morning). In addition, the patient may relate
worsening of the cough with substances that decrease the lower esophageal sphincter (LES) tone
such as caffeine, mints, chocolate, fatty foods,
cigarettes, or alcohol.11 The diagnosis of LPR can
be made fairly reliably using either empiric medical therapy with proton pump inhibitors (PPIs) or
dual-channel 24-hour pH monitoring.18 If a patient
with suspected GERD-associated chronic cough is
found to have signs of posterior laryngitis, pachydermia, or pseudosulcus on laryngoscopy, it is
reasonable to assume that reflux disease is causally related to their cough.19 In these instances,
empiric therapy with PPIs (e.g., omeprazole 20 mg
BID) and reflux precautions are reasonable, using
the patients response to therapy as proof of disease.18 One should be cautioned that chronic
cough because of GERD is fairly slow to respond
to antireflux therapy, taking an average of almost
2 months to resolve with PPIs and 6 months when
treated with H2 blockers.11 A great deal of patience and encouragement may be required by the
treating physician. Another approach to the diagnosis of GERD-associated cough is to test suspected patients with 24-hour, dual-channel pH
monitoring. Although this method is scientifically
more rigorous than empiric therapy, pH probe
monitoring is not foolproof. In cases where evidence of proximal reflux disease is absent on laryngoscopy (lack of posterior laryngitis or
pseudosulcus), pH probe testing should be
strongly considered. GERD-associated cough can
occur exclusively via distal esophageal acid exposure, as previously stated; therefore LPR associated laryngeal signs may be absent. If it is determined that pH probe testing is necessary, the
referring physician should ensure that the person
administering the test instructs the patient to log in
all episodes of cough during the test period so that
cough and reflux events can be correlated. Evidence of pathologic reflux disease by either the
distal or proximal pH probe data warrants treat-

505

ment of the patient with PPIs and reflux precautions as outlined earlier.
Caution must be observed in interpreting pH
probe data. A negative study for reflux disease
should be examined carefully to see if there is a
correlation between reflux events and the patients
cough. If a strong correlation exists between reflux
events and the onset of cough, this may be considered pathological reflux disease, even if all
other parameters indicate a negative test.12
Treatment of GERD-Associated Cough
Medical treatment for chronic cough due to
GERD should consist of PPI administration until
symptoms resolve or are under control and should
continue for an additional 3 months thereafter.20
After this, the medications may be gradually discontinued. Because GERD is a chronic intermittent disease, cough may return if treatment is
stopped, so episodic or long-term therapy may be
indicated. In the authors experience, it is not
unusual for patients with GERD-associated cough
to require more aggressive medical therapy with
antireflux medications. Doubling the dose of PPIs
(omeprazole 40 mg BID, for example) and the
addition of a nighttime H2 blocker (ranitidine 300
mg) to cover suspected nocturnal acid breakthrough (NAB) may be necessary.18 NAB is related to a high nocturnal histamine concentration
in subjects taking PPIs and seems to be respond
better to H2 blockers than PPIs.21 Patients are
strongly advised to discontinue the use foods containing caffeine or chocolate. Laying down immediately after eating is also avoided. Also, raising
the head of ones bed with wedges may complement medical therapy. Laparoscopic Nissen fundoplication is the surgical procedure of choice for
GERD, but there are no data that examine the
long-term results of this procedure for extraesophageal manifestations of GERD, such as
chronic cough. The ideal candidate is a young
patient with pH probeproved GERD-associated
cough who needs lifetime treatment with PPIs.
Those patients who respond favorably to PPIs
would expect a similar amount of improvement in
their symptoms after Nissen fundoplication. However, patients should be cautioned that lack of
improvement in their cough while on adequate

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506 ALTMAN et al

acid suppression may not translate to a surgical

cure.18
VAGAL NEUROPATHY AND COUGH
Postviral vagal neuropathy is a potential cause
of chronic cough when all other possibilities have
been ruled out. Recent evidence supports the concept that some of these patients may have sustained vagal injury as a result of a viral infection.22
A careful history in these patients often reveals
that the coughing started after an upper respiratory
infection (URI) and persisted long after the resolution of the other symptoms. As a result, they
may have airway hyperresponsiveness that persists beyond the resolution of the acute URI. This
hypersensitivity may manifest as a decrease in the
cough threshold in response to irritating stimuli.
This hyperreactivity can cause patients to be more
susceptible to chemical or mechanical stimulation
of the cough reflex. In addition to eliminating
irritative stimuli, these patients may require symptomatic therapy.
PATHOGENESIS
The fact that viruses can damage nerves is not a
new concept. There are many examples of virusinduced neuropathies, including postherpetic neuralgia, HIV neuropathy, herpes-zoster infection,
and Guillain-Barre syndrome (GBS). Two mechanisms by which viral infection may cause neuritis/neuropathy have been proposed: (1) direct infection/inflammation of a nerve or (2) induction of
a nonspecific inflammatory response that secondarily involves a nerve.
The demonstration that viruses may infect
nerves directly has been studied in relation to the
herpes simplex virus (HSV) (e.g., postherpetic
neuralgia). Notably, it has been shown that the
vagus nerve can be infected by HSV.23 Gesser et
al24 were able to demonstrate the presence of HSV
in vagal sensory ganglia after oral and esophageal
inoculation of the virus in mice. They postulated
that the virus directly entered nerve endings during the mucosal infection stage and then traveled
via axonal transport to the proximal ganglia.
The other potential mechanism, nerve injury as
a result of the inflammatory cascade, has been
studied as it relates to Guillain-Barre syndrome.25
Presumably, the proximity of the nerve to the site

of infection allows exposure to various inflammatory mediators such as cytokines. These may cause
indiscriminate damage to the nerve or lead to the
production of cross-reacting antibodies, which
may subsequently damage the nerve.
In patients with prolonged cough after an URI,
the presumptive injury occurs at the muscarinic
receptors of the vagus nerve, specifically the M2
receptors. These receptors, when stimulated, normally inhibit airway reactivity. Damage to these
receptors therefore produces airway hypersensitivity.22 Animal studies have demonstrated that administration of gallamine triethiodide (a specific
M2 receptor antagonist) augments vagally mediated bronchoconstriction.26 Other experiments
have shown that viruses can cause specific damage
to the M2 receptors, leading to airway hyperresponsiveness.22,27 This damage has been demonstrated to far outlast resolution of the viral infection.28 It is possible that at least in some cases, the
damage is permanent, leading to a permanent condition of airway hyperactivity.
Diagnosis of a Vagal
NeuropathyInduced Cough
Ideally, diagnosis of this problem could be obtained by vagal nerve biopsy. However, this is not
always possible or practical. Therefore, the diagnosis relies on a careful history, detailing the onset
of the cough and relating it to a viral infection.
Recent-onset airway hyperresponsiveness after an
URI raises the suspicion of a vagal injury. The
cough is typically nonproductive. If not already
done, patients be sent should for pulmonary function testing to examine airway reactivity, via a
methacholine challenge test.
Treatment of a Vagal
NeuropathyInduced Cough
Patients with airway hypersensitivity are more
prone to develop cough secondary to a variety of
irritative factors, within both the upper and lower
airways. These may include allergens, hot or cold
air, acid reflux, or particulate matter. Initial treatment should therefore be aimed at reducing these
factors. Avoidance of exposure to allergens, hot or
cold air, and particulate matter such as dust or
smoke may help reduce the frequency of coughing
episodes.

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Adjunctive treatments for allergies and acid reflux disease are also important in reducing the
impact of these factors on airway irritation. Allergy therapy may include the use of antihistamines, steroids, bronchial inhalers, or immunotherapy. Treatment for acid reflux disease includes
high-dose PPI therapy (as noted previously), in
addition to lifestyle and dietary modifications.
If patients have persistent cough despite these
measures, symptomatic therapy should be considered. Antitussive medication such as codeine or
dextromethorphan may be of benefit. Tramadol, in
addition, has been highly successful in our experience in treating patients with chronic cough.
Tramadol is a weak opiate, which appears to have
enhanced antitussive effects compared with codeine.29
Ultimately, the treatment of these patients may
entail specific activation of M2 receptors on the
vagal nerve endings or prevention of M2 receptor
loss. Research in the production of drugs capable
of targeting this area is ongoing.30,31
PARADOXICAL VOCAL FOLD MOTION
Paradoxical vocal fold motion (PVFM), or the
abnormal, involuntary, adductory motion of the
vocal folds during respiration, described by Christopher et al32,33 as vocal cord dysfunction (VCD),
was reported initially as Munchausens stridor in
1974. The diversity of terminology in both the
otolaryngology and pulmonary literature, including factitious asthma, hysterical or psychogenic
asthma, steroid-resistant asthma, irritable larynx
syndrome, episodic paroxysmal laryngospasm,
functional laryngeal stridor, laryngeal dyskinesia,
and functional airway obstruction, underlies the
lack of uniformity in describing or understanding
the etiology of this disorder.34 Generally presenting as a treatment-resistant, upper airway obstruction mimicking asthma, the impact of this disorder
cannot be underestimated, because serious airway
interventions, including intubation and tracheostomy, have occurred in some patients.34
PVFM is typically seen in predominantly young
female medical professionals. Its association with
a number of psychogenic cofactors has led to the
consideration that a component of this dysfunction
may represent a conversion disorder.35 The significant role of associated stress and emotional trig-

507

gers, dysfunctional respiratory and phonatory behavior, medical comorbidities and a variety of
airborne irritant inductions, underscore the need
for a multidisciplinary approach to the proper diagnosis and treatment of this disorder. A high
proportion of these patients also have an association with gastroesphogeal reflux signs and symptoms. The data supporting the presence of laryngospasm in the setting of vocal fold acid exposure
in animal models contribute to the likelihood that
reflux disease is a potential cofactor that needs to
be addressed in these patients.36
Classification schemes for PVFM have been
proposed; most are based on the potential mechanisms for PVFM or the pattern of laryngeal dysfunction. Maschaka et al37 defined 5 organic and 2
nonorganic categories by etiology, including
brainstem, upper motor neuron, lower motor neuron, movement, gastroesphogeal reflux, malingering, and conversion disorders. Morrison et al38
described a subclassification scheme of hyperkinetic laryngeal function, consisting of muscular
tension dysphonia, episodic laryngospasm,
chronic cough, throat clearing, and globus or foreign body sensation. It has been proposed that the
severity of the symptoms is related to the degree
and duration of glottic closure for an individual
patient, suggesting that this disorder may represent
a point on a continuum of laryngeal hyperactivity.
Pathophysiology of Paradoxical Vocal
Fold Motion: Accentuation of the
Normal Glottic Closure Reflex
The larynx has 3 major physiological functions:
maintenance of an airway, protection of the airway, and phonation. The cough reflex and laryngeal closure reflex are not only important for protecting the airway during deglutition but also in
response to potentially noxious inhaled stimuli.
Sensory perception from the larynx is received
by way of general visceral afferents. The sensory
nerve endings/receptors that can stimulate vocal
cord closure and cough as part of the glottic closure reflex are found in the larynx, trachea, and
larger airways. These may respond not only to
pressure but also irritant stimuli.
Perkner et al39 described a series of patients
with occupational irritant-induced PVFM who
were initially diagnosed with reactive airways

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dysfunction syndrome (RADS), a form of irritantinduced occupational asthma. These patients typically reported the initiation of symptoms after
high-level exposures to workplace irritant fumes,
vapors, or odors (smoke inhalation, ammonia or
chlorine, dust). Associated eye and nasal symptoms, headache, nausea, and lightheadedness were
often reported supporting the irritant nature of
these exposures. A feature that distinguished this
group from the non occupationally associated
PVFM cases was central chest pain. A series of
patients with irritant-induced PVFM without evidence for asthma after chlorine and ammonia exposures have been recently been studied. They had
lower airway injuries with biopsy-proved chronic
lymphocytic inflammation.40-42 The histologic pattern is distinct from the typical pattern seen is
asthma. It has been proposed that the airway injury
renders these individuals with a hypersensitive
glottic closure reflex. The exact mechanism requires further elucidation.
These observations have lead to the hypothesis
that the glottic closure reflex is somehow accentuated in those patients with PVFM such that
various extrinsic and intrinsic stimuli can trigger
reflex closure of the vocal cords as an adaptive
protective response. This may be an augmentation
of a normal physiologic response by lowering the
threshold levels for initiation compared with normal individuals. Furthermore, chronic irritation of
the larynx from GERD, allergies and rhinosinusitis, or inhaled irritant exposures, with the consequent frequent throat clearing and cough, predisposes the larynx to being more sensitive to various
external stimuli triggering PVFM attacks.38,39,43
Diagnosis of Paradoxical Vocal Fold
Motion
The common presenting symptoms include stridor, wheezing, choking sensation, acute episodic
dyspnea, aphonia, dysphonia, dysphagia, and
chronic cough, frequently triggered by exposure to
irritants or with exertion.34 Many PVFM patients
will point to or grab their throat while they describe the sensation. Inspiratory stridor and greater
difficulty getting air in than out are symptoms
often reported by these patients. Subsequent to
their initial exposure, patients report developing a
sensitivity to various nonspecific triggers such

as cigarette smoke, cold air, exercise, perfume,

cleaning agents, various other chemical odors, and
emotional stress. This clinical presentation often
leads to the erroneous diagnoses of asthma or
multiple chemical sensitivity. In fact many of
them report that the metered dose and/or powder
inhalers can trigger their cough, shortness of
breath, and wheezing, whereas nebulized medications provide significant relief. The duration of
this disorder is often extended, an average of 40.5
months in one study by Murray et al,44 as most
patients were unsuccessfully treated for asthma
and other comorbidities before their diagnosis.
When possible it is useful to perform laryngoscopy at the time of an acute attack to show the
patient what is happening with their vocal cords.
Classically described laryngoscopic findings include the paradoxical inspiratory adduction of the
membranous portion of the vocal folds and the
presence of a diamond-shaped posterior glottic
chink.32 Although considered pathognomonic,
these findings are not uniformly present and the
intermittent symptomatology of the disorder may
lead to relatively normal examinations between
episodes. It should be noted that Treole et al45 did
demonstrate abnormal adductory vocal fold movement during asymptomatic periods of normal
breathing, suggesting that a more chronic, rather
than episodic, pattern may actually be present.
Repetitive laryngeal motions such as panting,
rapid deep respiration, and certain phonatory tasks
may precipitate the onset of an event during examination. Relaxation of abnormal adductory motion can also be induced by examination maneuvers such as sniffing, whistling, and breath
holding.44
Complaints of dysphonia have shown documented changes in objective voice measurements,
such as increased shimmer and noise-to-harmonic
ratio. Murray et al44 postulated that voice changes
may be related to vocal fold edema caused by
GERD or the vocal trauma of coughing itself.
Routine imaging studies are generally unhelpful
in the evaluation of PVFM. Patients with pure
PVFM will have normal chest radiographs with no
evidence of hyperinflation. Recent studies have
looked at fluoroscopic and ultrasound imaging
during stridorous events and have demonstrated
vocal cord adduction during inspiration.46,47

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ALTMAN et al 509

Fig 1. Flow diagram outlining the neurologic sequence of

the reflexive cough. RAR, rapidly adapting stretch receptors. Note C-fiber receptors have excitatory effect (), but
inhibitory effect () with strong stimuli.

Pulmonary function tests may or may not show

significant improvement (12% increase in
FEV1) after inhaled bronchodilator medications.
Their FEV1 and FEV1/FVC ratio may be in the
normal, low, or high range. FEF50/FIF50, the ratio
of mid-expiratory and mid-inspiratory flows during maximal inspiratory and expiratory efforts,
may be significantly greater than 1 if they have
predominantly inspiratory PVFM. However, it is
now recognized that many individuals have both
inspiratory and expiratory PVFM, rendering this
ratio unhelpful (Fig 1). In many cases there is a
normal airway response to methacholine challenge
with PC20 FEV1 values of greater than 8 mg/mL.
However, the flow-volume loops may be truncated. Recently, Bucca and coworkers48 demonstrated that a greater than 25% drop in the maximum inspiratory flow (MIF) during histamine
inhalation challenge best reflected changes in midinspiratory glottic area.
In cases where methacholine testing fails to
elicit PVFM in individuals with a compelling history, one may consider irritant provocation tests
with agents reported to cause symptoms. Such
exposures may elicit symptoms in addition to
characteristic changes in the flow-volume loop.

Fig 2. A, A normal flow volume loop. B, Extrathoracic

airflow obstruction with truncation of the inspiratory loop.
This is consistent with symptomatic PVFM but may be seen
in other laryngeal diseases. FVC, forced vital capacity;
FIF50, forced inspiratory flow at 50% forced vital capacity;
FEF50, forced expiratory flow at 50% forced vital capacity.
(Reproduced with permission from Perkner J, Fennelly K,
Balkissoon R, et al. Irritant associated vocal cord dysfunction. J Occup Environ Med 1998;40:136-43, copyright
American College of Occupational and Environmental
Medicine.)

Treatment of Paradoxical Vocal Fold

Motion
Patients with PVFM are a diverse group with
many cofactors contributing to a disorder that is
currently defined by symptomatology and not eti-

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Otolaryngology
Head and Neck Surgery
December 2002

510 ALTMAN et al

ology. It may be that the abnormal adductory

function represents the potential outcome of many
varied processes, from mechanical to psychogenic. The multidisciplinary approach to these patients is often successful, but the morbidity in
recalcitrant patients (emergency department visits,
extensive pharmacotherapy, intubations, and tracheotomy) underscores the need for a better understanding of the mechanism, as well as improvement in treatment options. The need for a team
management for these patients, including speech
pathology, pulmonology, psychology, and laryngology at a minimum, cannot be overemphasized.
Options for treatment include explanation and
reassurance, speech and/or psychiatric therapy, sedation, oxygen, heliox (80% helium/20% oxygen),
constant positive airway pressure (CPAP), antireflux regimens, and antiallergy therapy.49,50 Although asthmatic medications are not usually useful, the significant contribution of GERD in this
disorder leads to the common use of antireflux
therapy as part of the treatment.44 The controlling
of allergic and/or irritant stimuli can be dealt with
by a combination of pharmacotherapy and avoidance.
The mainstay of treatment has been a speech
therapy program that focuses on respiratory reeducation.51 Patients should be referred to speech
pathologists who are familiar with the treatment of
this disorder. Reassurance to the patients that their
condition is treatable and that it generally will
improve over time assists in encouraging them to
return to work and regular social activities. Discontinuing unnecessary medications such as bronchodilators and steroids is often a positive reinforcement that should be used to motivate people
to follow through with speech therapy. Concentrating on a rhythmic, active, and supported expiration, the result is to remove the patients focus
from the inspiratory phase of respiration during
the episodes. Speech therapy often also includes
other vocal treatments such as vocal onset ease,
upper body relaxation, and resonant voice techniques. Murray et al44 reported symptomatic improvement in 88% of their patients when multidisciplinary individualized treatment protocols
were used. Improvement in pulmonary functions,
voice handicap index scores, and objective measurements was also shown in these patients.

The role of psychiatric intervention as an important component of the overall management of

PVFM has been well described.32,33,34,44 Gavin et
al52 showed higher levels of anxiety and anxiety
related diagnoses in adolescents with PCVM, but
whether this was a result or cause of the disorder
was difficult to discern.
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