Irritant vocal cord dysfunction and occupational bronchial asthma: differential diagnosis in a health care worker.

IJOMEH 2009;22(4) 401
C A S E R E P O R T S
International Journal of Occupational Medicine and Environmental Health 2009;22(4):401 – 406
DOI 10.2478/v10001-009-0038-z
IRRITANT VOCAL CORD DYSFUNCTION
AND OCCUPATIONAL BRONCHIAL ASTHMA:
DIFFERENTIAL DIAGNOSIS
IN A HEALTH CARE WORKER
STEFANO TONINI1,2, ANTONIO DELLABIANCA1,2, CRISTINA M. COSTA1,2, ANDREA LANFRANCO1,2,
FABRIZIO SCAFA1,2, and STEFANO M. CANDURA1,2
1 University of Pavia, Pavia, Italy
Department of Preventive, Occupational and Community Medicine
2 Salvatore Maugeri Foundation, Work and Rehabilitation, IRCCS,
Scientific Institute of Pavia, Pavia, Italy
Division of Occupational Medicine
Abstract
Objectives: Vocal cord dysfunction (VCD) is an uncommon respiratory disease characterized by the paradoxical adduction
of vocal cords during inspiration, that may mimic bronchial asthma. The pathogenesis of VCD has not been clearly defined
but it is possible to recognize non-psychologic and psychologic causes. The majority of patients are female but, interestingly,
a high incidence of VCD has been documented in health care workers. A misdiagnosis with asthma leads to hospitalisation,
unnecessary use of systemic steroids with related adverse effects, and sometimes tracheostomy and intubation. In a subset
of VCD patients, the disease can be attributed to occupational or environmental exposure to inhaled irritants. Materials
and Methods: We report the case of a 45-year-old woman, working as a nurse, who complained of wheezing, cough, dysp-
noea related to inhalation of irritating agents (isopropylic alcohol, formaldehyde, peracetic acid). She underwent chest radi-
ography, pulmonary function assessment both in the presence and in the absence of symptoms, bronchial provocation with
methacholine and bronchodilation test with salbutamol to recognize asthma’s features, allergy evaluation by skin prick tests
and patch tests and video-laryngoscopy. Results: VCD diagnosis was made on the basis of video-laryngoscopy, that visual-
ized the paradoxical motion of the vocal cords during symptoms, in the absence of other pathologic processes. Conclusions:
This case fulfils the proposed criteria for the diagnosis of irritant VCD (IVCD). This is the first report of VCD onset
following exposure to several irritants: formaldehyde, glutaraldehyde, isopropylic alcohol, peracetic acid-hydrogen per-
oxide mixture. These substances are used as cleaning and antiseptic agents in healthcare settings and some ones can also
be found in many indoor environments. A correct diagnosis is important both to give the appropriate treatment and for
medical legal implications.
Key words:
Vocal cord, Asthma, Irritant
Received: September 18, 2009. Accepted: December 3, 2009.
Address reprint request to S. Tonini, Department of Preventive, Occupational and Community Medicine, Occupational Medicine Section I, University of Pavia,
Via Maugeri, 10, 27100 Pavia, Italy (e-mail: stefano.tonini23@libero.it).
INTRODUCTION
Vocal cord dysfunction (VCD) syndrome, which is due to
inappropriate movement of vocal cords during inspiration
with resultant airflow limitation [1,2], is an uncommon dis-
order of the larynx that may mimic or coexist with bron-
chial asthma [3]. Wheezing, dysphonia, choking feeling,
throat tightness, stridor, dyspnoea, suprasternal and neck
muscle retraction, anxiety and cough are typical symptoms
of VCD [4–6]. Wheezing, in particular, is typically mono-
phasic, in contrast to asthma wheezing, which is polyphasic.
The pathogenesis of VCD has not been clearly defined but
it is possible to recognize non-psychologic and psychologic

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IJOMEH 2009;22(4)402
peroxide mixture, d) rinsing, e) cold chemical sterilization
by isopropylic alcohol and hydrogen peroxide. All these
activities were carried out for 8 hours a day, Monday to
Friday every week, in the absence of environmental air as-
pirators. The first episode, which included headache and
throat tightness, quickly evolved into cough with cyanosis,
inspiratory stridor and dyspnoea. These symptoms also oc-
curred at home when using house-cleaning products, and
even when the patient was permanently relocated to an-
other hospital unit. An antiasthmatic therapy with inhaled
budesonide (80 μg bid) was started, following a spirometry
suggesting a minimal upper airway obstruction.
Due to the persistence of symptoms, the patient was admit-
ted to our clinical setting with a suspicion of occupational
asthma [17], in order to undergo a complete diagnostic
procedure. On admission day, routine blood and urine
tests, as well as the levels of total IgE (79.6 kU/l), were in
the normal range. The patient had no history of chronic
rhinitis, angioedema or sinus infection. A concurrent pul-
monary flogistic process, hyperinflation or peribronchial
thickening were ruled out by chest radiography. A com-
plete spirometric test, including the evaluation of alveolo/
capillary diffusion capacity (DLCO) and emogas analysis,
was carried out. Although spirometric manoeuvres were
often hampered by closing glottis episodes, in association
with cough (Fig. 1), static lung volumes (VC, RV, TLC)
causes. Among the first ones are neurologic disorders [7],
gastroesophageal reflux (GER) [5,8] and post-nasal drip syn-
drome [9], whereas the other ones include depression, anxiety
and subconscious conversion reaction [7,10]. The majority of
patients are female between the second and fourth decade of
life, but the syndrome is also common among children and
adolescents. Interestingly, a high incidence of VCD has been
documented in health care workers [11,12]. Fast and appro-
priate diagnosis of VCD is very important because a misdiag-
nosis with asthma leads to hospitalisation, unnecessary use of
systemic steroids with related adverse effects, and sometimes
tracheostomy and intubation as a result of severe dyspnoeic
crisis [13]. The diagnosis is essentially based on the care-
ful collection of the clinical history elements, the exclusion
of alternative/similar disorders, and the close collaboration
with pneumologists and otorhinolaryngology (ORL) special-
ists. Patient education, speech therapy to decrease laryngeal
muscle tone and psychologic counselling are the therapeutic
tools for treatment [1,4,14]. In some patients, during acute
attacks, the administration of helium and oxygen seems to
relieve the symptoms [15].
In a subset of VCD patients, the disease can be attributed to oc-
cupational or environmental exposure to inhaled irritants [16].
The pathogenesis of VCD, and of irritant-induced VCD
(IVCD) in particular, has not yet been defined.
MATERIALS AND METHODS
We report the case of a 45-year-old woman, working as
a nurse in a general hospital, who was hospitalised with
a history of dyspnoea, cough and stridor that lasted for
several months. In particular, the patient reported her
symptoms began approximately one week after moving
to a gastroenterology unit, where she was in charge of
cleaning endoscopy instruments with products contain-
ing irritants, such as peracetic acid, sodium hypochlorite,
formaldehyde, glutaraldehyde and isopropylic alcohol
(40/50 washes a day). The cleaning cycle consists of the
following steps: a) washing with cleansing agents (isopro-
pylic alcohol), b) rinsing, c) disinfection of the lumen of
the endoscopes with products containing formaldehyde
or glutaraldehyde and then with peracetic acid-hydrogen
Fig. 1. Flow-volume curve showing two closing glottis episodes.
These episodes, together with cough, hampered achieving
satisfactory spirometric measures.

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IJOMEH 2009;22(4) 403
aspecific inflammatory process. Sputum examination was
performed at a time when the patient was currently symp-
tomatic and in the presence of ongoing exposure, at least to
some of the chemicals that were able to trigger symptoms.
Chest physical examination performed in the presence of
symptoms did not detect the typical asthmatic wheezing.
On the other hand, a stridor was detected by auscultation
on the trachea. Based on our instrumental results, a diagno-
sis of bronchial asthma could not be confirmed and a VCD
syndrome was suspected. We did not perform a specifi c in-
halation challenge with glutaraldehyde, or with the other
chemicals to which the patient was exposed, because she did
not show any of the functional and inflammatory features of
bronchial asthma. ORL examination, excluded alterations of
nasal mucosa, nasal polyps, submucosal oedema and nasal
discharge. A papilloma on the soft palate was found.
RESULTS
Video-laryngoscopy examination (after provocation by
appropriate respiratory manoeuvres) revealed an adduc-
tion motion of the vocal cords during the inspiratory cycle,
with a typical posterior chinking of the glottis (Fig. 3), as
usually observed in the VCD syndrome. Considering the
were in the normal range, as well as forced expired volume
(FEV1 = 75% of predicted, FEV/VC = 107%), even in
the presence of symptoms (Fig. 2).
Only a slight reduction in terminal forced expiratory flow
(observed/expected FEF75 = 64%), as in bronchiolar ob-
struction syndromes, was detected. A significant hypocap-
nia (pCO2 = 27.5 mmHg) and an alkaline blood pH (7.515),
as observed in hyperventilation of emotional nature, were
also observed. A bronchodilation test with salbutamol was
negative. A bronchial provocation test with methacholine
was not performed because a 22% fall in FEV1 occurred
after inhaling the buffer solution only. We did not consider
this finding as indicating non-specific bronchial hyperre-
sponsiveness because the test was not reliable, due to the
patient’s poor control of respiratory movements.
Skin prick tests with common inhalant allergens showed
a sensitisation to Dermatophagoides pteronyssinus and Der-
matophagoides farinae (both ++). Patch tests with workplace
substances (SIDAPA — Società Italiana di Dermatologia
Allergologica, Professionale e Ambientale — and health
workers series) were negative. Sputum was induced by in-
halation of 4.5% hypertonic saline, after premedication with
salbutamol. Cytologic analysis did not show the characteristic
asthmatic eosinophilia in the induced sputum. Conversely,
an increased total cell number, and an increased neutrophil
percentage (74%) were observed, as in the presence of an
Fig. 2. Satisfactory flow-volume curve showing expiratory
dynamic volumes and flows within the normal range. The
inspiratory loop shows a slight reduction of inspiratory flows,
as observed in extrathoracic airway obstruction.
Fig. 3. Video-laryngoscopy shows adduction of the vocal
cords during inspiration. A characteristic posterior chinking
is partially visible.

C A S E R E P O R T S S. TONINI ET AL.
IJOMEH 2009;22(4)404
careful, in order to avoid misinterpretation of functional
data. A strict compliance with the ATS criteria for spirom-
etry standardization [23], together with flow-volume curve
morphologic analysis may help to avoid misleading con-
clusions.
Some IVCD causing agents can be encountered both in
the working and domestic environment. In our case, the
patient did not show a clearly positive stop-resume work
test because of irritant exposure at home, mainly related
to the presence of bleach and isopropylic alcohol in home
cleansing products, stain removers and deodorants. Be-
sides hindering the identification of the occupational cause
of the disease, the widespread diffusion of some irritants
can also complicate the management of the diagnosed
cases. The patients should be given detailed directions on
how to avoid unexpected or even inadvertent exposure to
substances that can trigger their symptoms.
Although the pathogenesis of VCD is not elucidated, the
temporal association between the onset of symptoms and
irritant exposure in IVCD suggests a direct inflammatory
effect on the vocal cords. The paradoxical adduction of the
vocal cords during inspiration has been found to be associ-
ated with reddening, oedema, when histamine was used as
a provoking agent [24]. By analogy, the irritants involved
in our IVCD case may cause local laryngeal inflammation.
For example, formaldehyde and glutaraldehyde are highly
water-soluble irritants of the mucous membranes in the
upper respiratory tract.
The biological plausibility of irritant exposures as a cause
of VCD is further supported by evidence in the medical
literature that irritants cause other diseases of the upper
airways. Occupational laryngitis has been reported after
exposure to certain chemicals. Many irritants in the work-
place are known to cause occupational rhinitis, and the
lower airways can become hyperreactive after irritant ex-
posure, leading to occupational asthma without latency
period [25].
The involvement of immunologic mechanisms, that has
been explored and finally excluded in the case of VCD in-
duced by Eucalyptus exposure [22] seems unlikely in our
case as well. In fact, some chemicals to which our patient
was exposed can act both as irritants and sensitisers, but
initial suspicion of asthma and the psychologic component
often described for VCD, the patient underwent CBA
(Cognitive Behavioural Assessment) psychological test,
that gave normal results. Thus, an important psychogenic
component of the dysfunction seemed unlikely.
Based on video-laryngoscopic findings and on clinical and
occupational history, a diagnosis of occupational irritant-
induced VCD (IVCD) was made. The patient was advised
to avoid irritant exposure both in the working and non-
working environment. Furthermore, she was addressed to
speech therapy rehabilitation sessions for laryngeal relax-
ation and psychological counselling.
DISCUSSION
VCD is an under-recognized disorder, initially described
by Dunglison in the first half of XIX century [18], affecting
more people than previously thought.
This is the first report of VCD onset following exposure
to several well-known irritants, namely formaldehyde, glu-
taraldehyde, isopropylic alcohol, peracetic acid/hydrogen
peroxide mixture, sodium hypochlorite vapour. These sub-
stances are widely used as cleaning and antiseptic agents
in healthcare settings and some ones (e.g. formaldehyde
and isopropylic alcohol) can also be found in many indoor
environments. These irritants are recognized as a possible
cause of asthma [19–21]. Very few cases of IVCD have
been described so far [16,22]. In 1996 Perkner et al. [16]
reviewed eleven cases of VCD attributable to occupa-
tional irritant exposure and prepared a list of clinical cri-
teria for IVCD: 1) absence of prior VCD or laryngeal dis-
ease, 2) onset of symptoms after a single specific exposure
or accident, 3) exposure to an irritant gas, smoke, fume,
vapour, mist or dust, 4) onset of symptoms within 24 hours
after exposure, 5) symptoms of wheezing, stridor, dyspnoea,
cough, or throat tightness, 6) abnormal direct laryngoscopy
for VCD and 7) exclusion of other vocal cord diseases. Our
case meets all diagnostic criteria proposed in that study.
Since in VCD patients clinical history may often mimic
bronchial asthma, pulmonary function tests are usually
performed in the diagnostic assessment of these patients.
Technical evaluation of spirometry must be particularly

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specific mechanism.
Although asthmatic patients can have normal spirometry
between symptomatic episodes, normal airflow in a dys-
pnoeic and wheezing patient should raise the index of
suspicion for VCD masquerading as asthma. The flow-
volume loop may provide additional clues to the diagnosis
of VCD, although, in our case, the classic truncation of the
inspiratory portion was not much evident.
Further studies are needed to elucidate the mechanisms
leading to IVCD and its similarities and differences with
irritant-induced asthma and rhinitis.
ACKNOwLEDgMENTS
The authors thank the pulmonology technicians for their ser-
vice, Dr. Faniglione M. and Dr. Bernieri S. for their graphic sup-
port, and Prof. Tonini M. for his suggestions.
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