Clin Chest Med 25 (2004) 321 – 330

Airway function in women: bronchial hyperresponsiveness,

cough, and vocal cord dysfunction
Joseph M. Parker, MDa,b,*, Melanie L. Guerrero, MDa,b
a
Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA
b
Pulmonary and Critical Care Medicine, Walter Reed Army Medical Center, 6900 Georgia Avenue,
Washington, DC, 20307-5001, USA

Asthma and cough are common medical problems Prevalence in women

that almost all physicians encounter at some time
during their practice of medicine. Vocal cord dys-
function (VCD) is being recognized increasingly as a
problem that may confound the diagnosis of asthma
or cough. Women are diagnosed with asthma and
cough more frequently than men and represent the
preponderance of patients who have VCD that are
reported in the medical literature. Why women suffer
disproportionately from upper and lower airway dis-
orders is not well understood.
Bronchial hyperresponsiveness
Asthma has emerged as a major public health
problem in the United States over the past 20 years.
In 1998, the direct and indirect costs of asthma were
estimated at $12.7 billion; a significant number of
people (f5500) die from asthma each year [1]. Cough,
wheezing, and shortness of breath, the cardinal symp-
toms of airway hyperreactivity, are estimated to occur
in approximately 15 million Americans. Women ac-
count for most of the affected adult population.
* Corresponding author. Pulmonary and Critical Care
Medicine, Walter Reed Army Medical Center, Washington,
DC 20307-5001.
E-mail address: joseph.parker@na.amedd.army.mil
(J.M. Parker).
A female:male prevalence ratio of 1.85:1 was seen
in patients between the ages of 23 and 64 years in a
review of more than 60,000 asthmatic subjects of a
large managed care organization. Women generated
more cost for health care use and required more pre-
scription medications, such as inhaled corticosteroids,
the mainstay for therapy in asthma [2]. The largest
population-based survey on respiratory disease, per-
formed between 1991 and 1993, was the European
Community Respiratory Health Survey (ECRHS).
Thirty-seven centers from 16 countries participated
according to a common protocol. A recent retrospec-
tive analysis of these data from 18,659 subjects
determined the gender differences in the incidence
of reported asthma within their study population [3].
During childhood (younger than 10 years of age), girls
had a lower risk of developing asthma than boys;
however, during puberty (10 – 14 years of age) there
was an almost equal risk between the two sexes. Af-
ter puberty (15 – 44 years of age), the risk in women
was significantly higher than in men, having an age-
adjusted rate ratio which ranged from 1.38:1 (95%
CI 1.01 – 1.88) for ages 15 – 19 to 5.91:1 (95% CI
2.31 – 15.12). The pattern of gender reversal in asthma
symptoms and diagnosis as men and women age has
been consistent in most studies [4]. The true preva-
lence of asthma in girls may be underdiagnosed. A
Norwegian study of 401 adolescent men and women,
who were either self-reported asthmatics or diagnosed

0272-5231/04/$ – see front matter D 2004 Elsevier Inc. All rights reserved.
doi:10.1016/j.ccm.2004.01.008
322 J.M. Parker, M.L. Guerrero / Clin Chest Med 25 (2004) 321–330
with asthma by a physician, and 213 asymptomatic
controls demonstrated a risk of underestimating
asthma among adolescent women when the diagno-
sis of asthma was limited to confirmation by a phy-
sician [5]. In this study, although more adolescent
men had a diagnosis of asthma by a physician than
adolescent women (44% versus 32%), methacholine
challenge testing revealed more airway hyperreac-
tivity in adolescent women than in men (62% versus
50%, p < 0.02).
Morbidity and mortality
A nationwide finding showed that the largest
increases in asthma mortality have occurred among
older women; this is likely due to underdiagno-
sis, undertreatment, and poor adherence to the Na-
tional Asthma Education and Prevention Program’s
(NAEPP) asthma treatment guidelines by patients
and physicians [6,7]. Poor medical compliance is a
particular concern because adult-onset asthma is diag-
nosed in approximately 4% to 8% of the population
that is older than 65 years. The economic implications
of possible poor medication compliance among fe-
male asthmatics are noteworthy. In 1996, a cross-
sectional retrospective analysis of 530,000 Medicaid
recipients found that failing to adhere to NAEPP’s
established treatment guidelines was associated with
an increased risk of an asthma-related hospitaliza-
tion (odds ratio, 1.5) [8]. There is a greater preva-
lence of asthma among women and there seems to
be an increased risk of hospital admission among
women asthmatics who present to the emergency
room [9]. Studies have shown consistently higher ad-
mission rates for women who have self-reported
asthma than men in general. One study of more than
13,000 asthma patients reported an approximately
70% higher risk of women being admitted to the hos-
pital, despite the fact that more of the men were heavy
smokers [10]. Possible reasons for this observed gen-
der disparity include: (1) lower hospital admissions
thresholds for women; (2) lack of subjective improve-
ment in clinical condition among female asthmatics
who present to emergency rooms; and (3) poor out-
patient compliance to prescribed medications by
women. Women also experience longer hospital stays
per admission. A case control study in Britain found
an increase in respiratory mortality in hospitalized
women who had asthma [11,12]. It was suggested that
women who have asthma have worse subjective
severity, despite no objective spirometry differences
when compared with men. In a cross-sectional study
of 967 asthmatic patients aged 16 to 75 years, women
reported lower health-related quality of life in all age
groups, except for those aged 35 to 55 years. They
also reported more severe dyspnea, despite higher
levels of pulmonary function. The difference in per-
ceived severity of illness may lead to an increase in
clinic visits and medication use among female asth-
matics [13].
National estimates of asthma prevalence among
women of childbearing age in the United States
showed a two-fold increase in prevalence in the pe-
riod between 1976 and 1980 (prevalence of 2.9%)
compared with the period from 1988 to 1994 (preva-
lence of 5.8%). Among women who were between
the ages of 18 and 24 years the increase was threefold
(1.8% to 6.0%) [14]. This is of particular concern
because women of childbearing age who have known
maternal asthma have an increased risk of preterm
labor and delivery [15]. In this study, 312 preterm
delivery cases were compared with 424 randomly-
selected women who delivered at term; a maternal
history of asthma was associated with a doubling in
the risk of spontaneous preterm labor and medically-
induced preterm delivery. A retrospective review of
567 women who had asthma and delivered at a major
hospital center between 1992 and 1997 noted that
oligohydramnios, intrauterine growth restriction, and
meconium-stained amniotic fluid were the most com-
mon perinatal complication, particularly in those who
required systemic steroids [16].
Physiologic differences
Apparent sex differences in asthma prevalence
have raised the question of different susceptibility
factors to asthma in men and women. Despite their
smaller lung size, women have higher forced expira-
tory flow rates and forced expiratory volume in one
second:forced vital capacity ratio (FEV1:FVC) than
men [17]. Atopy is an important risk factor for
asthma that is assessed by total and specific serum
IgE levels; the measurements were lower in women
in most, but not all, studies. Despite these objective
advantages, asthma rates in women between the ages
of 15 and 49 years exceed those of men [18]. A
physiologic explanation is that airway flow depends
on the fourth power of the airway radius; any
stimulus that causes obstruction creates more turbu-
lent flow in smaller airways than larger ones [19]. In a
case-control study of 105 patients over a 3-year span
within the original population of the ECRHS study, it
was suggested that women’s greater susceptibility to
 J.M. Parker, M.L. Guerrero / Clin Chest Med 25 (2004) 321–330
asthma is partly explained by their smaller airway
caliber [4]. In that cohort, women had a two-fold
increased risk of having asthma; the risk of develop-
ing asthma seemed to be associated inversely with
airway diameter.
The influence of estrogen and progesterone on air-
way hyperresponsiveness has been invoked as one of
the factors that influences asthma risk in women;
however, it is poorly understood. The literature that de-
scribes the phenomenon of cyclical variation in
women’s airway function in relation to menstrual
cycles, pregnancy, and menopausal and postmeno-
pausal hormone replacement therapy supports the
influence of female hormones in airway behavior.
Premenstrual asthma exacerbation has been reported
in multiple studies, with the loss of lymphocytic B2
adrenoreceptor density and subsequent decrease in
airway responsiveness to AMP challenge as the po-
tential physiologic cause [20]. Premenstrual asthma
exacerbations can be severe, with reported occur-
rences in 13% to 40% of female asthmatics, but fatal
cases are infrequent [21,22]. The use of methacholine
challenge, daily diary cards for symptom recording,
and peak flow measurements have shown significant
airway hyperreactivity among premenstrual women,
especially around the midluteal phase (Day 21) with
decreases in the FEV1 and peak flow rates by 10%
in the late luteal phase (Day 24) [21,23]. The use of
oral contraceptives (OCPs) decreased the cyclical
variability in airway function among asthmatic
females [24]. In this study, there was a four-fold
increase in the provocative concentration that was
needed to produce a 20% decrease in the FEV1
(PC20FEV1) as a measure of airway reactivity to
AMP in the group that was not taking OCPs. These
findings also corresponded to significant increases in
the progesterone and estradiol levels that were mea-
sured during the luteal phase. A noteworthy difference
in diurnal peak expiratory flow rates was seen be-
tween the groups that did and did not take OCPs. In
contrast to these findings, a cross-sectional study of
377 women who were taking OCPs and 458 women
who were on hormone replacement therapy (HRT)
who were selected from the general population dem-
onstrated a weak correlation between HRT use and
self-reported increases in wheezing, cough with exer-
tion, and the use of asthma medications. There was no
correlation between the use of OCPs and asthma
symptoms [25]. A recent review of all original re-
search articles between 1966 and 2001 that studied the
impact of hormonal influence on airway function
revealed that most studies showed improvement in
lung function with OCPs and hormone replacement
therapy among female asthmatics [26]. Recently, a
323
randomized, double-blind, placebo-controlled cross-
over trial of exogenous estradiol that was adminis-
tered to 12 women who had mild, premenstrual
asthma found no significant differences on daily peak
expiratory flow rates, FEV1, or quality-of-life scores
[27]. Further studies regarding the hormonal effects
on women who have poorly-controlled or severe
asthma may be warranted.
Tobacco use
Tobacco exposure has been implicated as a factor in
the increased airway hyperresponsiveness in women.
In a study of 5662 smokers (3556 men, 2106 women)
who were given a methacholine challenge, a sig-
nificantly higher prevalence of airway hyperreactiv-
ity was found in women; this resulted in a calculated
relative risk of 1.75 (95% confidence interval [CI],
1.60 – 1.92) [28,29]. In a recent Korean study of
2467 adult smokers, tobacco smoke was particularly
detrimental in the elderly population; increased air-
way hyperresponsiveness was 7.7% in subjects who
were aged 55 to 64 years and was 12.7% in those
who were 65 years of age or older [30]. There also is
increasing evidence that women are more suscepti-
ble to tobacco; this is manifested by a more rapid
decline in FEV1 than in comparable male smokers
[31,32].
Obesity
There is substantial evidence of an association
between asthma and an increase in body mass index
(BMI), especially among women and girls [33 – 36];
however, an analysis of more than 11,000 patients
from the ECRHS population showed a significant
correlation in men but no correlation in women [37].
In contrast to this analysis, a case control study of
169 patients who had asthma showed an increased
risk of airway hyperreactivity among women who
had a BMI that was at least 28kg/m2 (odds ratio 2.10;
95% CI, 1.31 – 3.36) [38]. More recently, a review of
available studies showed no gender association be-
tween asthma and obesity, although a strong associa-
tion existed across the board. This implied that
obese patients were likely to get diagnosed with
asthma because they presented earlier with respira-
tory symptoms or that gastroesophageal reflux dis-
ease (GERD) secondary to obesity may cause airway
hyperreactivity [39].
324 J.M. Parker, M.L. Guerrero / Clin Chest Med 25 (2004) 321–330
Psychologic factors
Although stress is believed to provoke asthma
exacerbations, no clear evidence of causality has been
found. A prospective study of more than 11,000 pa-
tients in Finland examined psychologic factors, in-
cluding neuroticism and extroversion, and their
association with asthma prevalence; a high extro-
version score was a strong predictor of incident
asthma among women [40]. One case control study
of 77 patients who were admitted to the hospital for
severe, life-threatening asthma and 239 patients who
were admitted for nonlife-threatening asthma exacer-
bation found that pre-existing adverse psychologic
factors, such as depression and anxiety, were risks
for hospitalization [41]. Another study revealed a
decrease in the peak expiratory airflow after viewing
scenes depicting an asthma exacerbation in asthmatic
women who had anxiety disorders, but not among
women who did not have concomitant asthma and
anxiety [42]. Regardless of causal effect, psychologic
factors, particularly anxiety, are important in the mor-
bidity of asthmatics in general [43]. The appropri-
ateness and importance of psychologic treatment in
the overall medical management of asthma among
women who have anxiety disorders and poor symp-
tom control is important.
Implications of treatment
Inhaled corticosteroids (ICSs) are the cornerstone
for the treatment of asthma. Several studies have
looked at its effects on bone mineral density (BMD)
[44,45]. More recently, a large meta-analysis showed
a nonstatistically significant decrease (4.1%) in BMD
among men and women with moderate to long-term
use of ICSs [46]. This is in contrast to an earlier study
of premenopausal women wherein a significant de-
crease in the BMD of the posterior-anterior and lateral
lumbar spine was seen in those who were on ICSs;
previous oral steroid use was not an important con-
founding factor [47]. There is a particular concern in
postmenopausal women who are at the highest risk for
complications from osteoporosis. In a comparison of
106 women on ICSs (average of 8 years of 850 mg/
day) with 674 women who were unexposed to ICSs,
no significant difference in BMD of the forearm was
observed [48]. An earlier study suggested a dosage-
dependent increase in the risk of osteoporosis when
BMD was measured in the hip and lumbar spine
among postmenopausal women who were treated with
medium to high dosages of ICSs; this reinforced the
necessity of vigilant monitoring of BMD periodically
in women who are on ICSs [49].
Cough
Cough is the most common reason for seeking
medical attention in the United States [50]. The
diagnosis and management of cough may be respon-
sible for as much as 38% of outpatient pulmonary
practice [51]. The most common causes of chronic
cough include cough-variant asthma, postnasal drip
syndrome, and GERD. There seems to be a prepon-
derance of women who present to physicians for man-
agement of cough, whether chronic (longer than
3 weeks) or acute. Angiotensin-converting enzyme
inhibitor – related cough was found to affect women
more frequently than men [52]. Psychogenic cough,
a diagnosis of exclusion, although uncommon in
adults, is more common in girls who are younger than
18 years of age [53].
Although more women are seen with a complaint
of cough, a population-based study showed that
women may delay seeking hospital treatment for
chronic cough longer than men. This behavior can
lead to poorer access to health care and delays in
diagnosis of diseases, such as tuberculosis [54].
Capsaicin and citric acid sensitivities have been
used as stimulants of the cough reflex. In a recent
study that tested the hypothesis of increased female
cough reflex sensitivity, it was shown that women
have a lower threshold in cough sensitivity than do
men who have comparable lung function [55]. The
study suggested that sex hormones might regulate
airway inflammation through receptors on inflamma-
tory cells that have been found in patients with
chronic cough. The investigators also postulated that
a cough receptor that is common to citric acid and
capsaicin might be hyperresponsive in patients who
have chronic cough. An increased number of recep-
tors or a higher level of receptor responsiveness may
be found in women, but this is conjecture given avai-
lable research.
Vocal cord dysfunction
VCD is a mimic of asthma that is characterized by
the inappropriate adduction of the vocal cords during
respiration. Patients who have VCD may present with
wheezing, dyspnea, cough, chest tightness, or hyper-
ventilation symptoms. The classic patient who has
VCD is a young woman who has episodic dramatic
presentations to the emergency room or clinic with
 J.M. Parker, M.L. Guerrero / Clin Chest Med 25 (2004) 321–330
stridor and dyspnea. Most of the clinical and demo-
graphic information regarding VCD derives from a
large body of case studies; virtually no prospective
data are available.
Prevalence of vocal cord dysfunction in women
The initial case reports of vocal cord dysfunction
in the 1970s consisted almost exclusively of women.
The seminal description of VCD by Christopher and
colleagues [56] was of five patients who presented
with refractory asthma—four of whom were female.
The largest series of patients was reported from the
National Jewish Center for Immunology and Respi-
ratory Medicine. In a retrospective review, Newman
and colleagues [57] reported on the demographic and
clinical characteristics of 95 patients who were diag-
nosed with VCD between 1983 and 1991. These
patients were compared with a historical control group
of patients who had asthma only. The patients who
had VCD were divided into two groups; 42 patients
had only VCD and 53 patients had VCD and asthma.
Most of the patients (41/42) who had only VCD were
women. Also, a substantial majority (39/53) of the
people who had VCD and asthma were women.
Overall, 80 of the 95 patients (84%) who were
diagnosed with VCD were female. Other smaller
retrospective case series reported that 74% to 80%
of the patients in their series were female [58,59].
VCD has been reported frequently in the military;
however, the reasons for this are unclear. Military
personnel undertake mandatory physical activity and
must pass semiannual or annual physical fitness tests.
If military personnel are unable to participate in
physical fitness training or are unable to pass the
physical fitness requirements, they are referred for a
thorough medical evaluation before consideration for
separation; this may, in part, explain the increased
case finding in the military. Military regulations
stipulate that spirometry and airway challenge testing
be used to confirm asthma. This patient population
is not inconsequential. Approximately 15% of pa-
tients who present with unexplained exertional dysp-
nea or suspected asthma had VCD [60].
A large review of the characteristics of 176 pa-
tients from two Army medical referral centers found
a female predominance of VCD [61]. Data from
the larger institution was primarily retrospective and
was derived from patients who were referred to the
speech pathology service. From this institution, 80 of
122 patients (66%) were female. Data from the
second institution, which was prospectively collected
over a 2-year period, revealed a slight male predomi-
325
nance with 29 (54%) male subjects and 25 (46%)
female subjects. The first institution served a popu-
lation of active duty personnel and their dependents
who worked primarily in administrative positions in
the nation’s capital. The second institution served a
population of active duty personnel and dependents
who were assigned to combat units. The first institu-
tion served a more balanced patient population,
whereas the second institution served a predomi-
nantly male population. This is likely the explanation
for the slight male predominance in VCD that was
reported from this group. Another retrospective study
from a military population in Colorado looked at all
patients who underwent laryngoscopy and identified
20 patients who were given a diagnosis of VCD;
16 of the patients (80%) were female [59].
Vocal cord dysfunction and exertional dyspnea
Morris and colleagues [60] prospectively evalu-
ated 33 military patients who presented to a pulmo-
nary disease clinic with dyspnea on exertion. Five of
the patients (15%) had VCD as the cause of their
dyspnea. Five additional patients were identified as
having VCD as a result of their evaluation. Of these
10 patients, 7 (70%) were female.
VCD has been reported as the cause of exer-
tional dyspnea in competitive athletes. McFadden
and Zawadski [62] evaluated seven young athletes
(ages 15 to 32) who had intermittent dyspnea that
occurred during their respective sports and diagnosed
VCD; four were male and three were female. One
prospective study examined the prevalence of inspira-
tory stridor in elite athletes [63]. Subjects were eval-
uated during and after exercise during competition,
simulated competition, or a 7- to 8-minute free run. If
wheeze or stridor were detected, auscultation of the
chest and larynx were performed. Inspiratory wheeze
that resolved within 5 minutes of exercise was deemed
to be diagnostic of VCD. Three hundred and seventy
subjects were evaluated; 174 were women and
196 were men. Nineteen (5.1%) of the subjects were
believed to have inspiratory stridor during exercise,
18 (95%) of whom were female. VCD was not
confirmed by direct laryngoscopy in this study.
Etiology of vocal cord dysfunction
The etiology of VCD is not understood. One in-
teresting theory posits that laryngeal hyperrespon-
siveness may be due to altered autonomic function
that develops following local inflammation [64]. The
326 J.M. Parker, M.L. Guerrero / Clin Chest Med 25 (2004) 321–330
Fig. 1. Flow volume loop with variable extrathoracic ob-
struction. X axis, Volume (L); Y axis, Flow (L/second).
abnormality in autonomic function may be short-lived
or persistent. This concept is supported by a series of
investigations from Italy [65,66]. The investigators
examined the patterns of response to histamine chal-
lenge in patients who had asthma-like symptoms and
upper airway inflammation (sinusitis, postnasal drain-
age, pharyngitis). Bronchial hyperreactivity (B-HR)
was defined by PC20FEV1 and extrathoracic hyper-
reactivity (EA-HR) was defined as a 25% decrease in
maximal midinspiratory flow at values of 8 mg/mL or
less. Patients could be characterized by one of four
patterns: (1) B-HR only (11.1%); (2) EA-HR only
(26.5%); (3) combined B-HR and EA-HR (40.6%);
and (4) no response (21.8%). The groups who were
characterized by EA-HR only and combined B-HR
and EA-HR had significantly greater probabilities of
having upper airway inflammation (sinusitis, post-
nasal drainage, pharyngitis, laryngitis). Female sex
significantly affected the presence of EA-HR and
B-HR [66]. An earlier study by this same group also
found that EA-HR was much more frequent in women
[67]. Inflammation of the upper airway also may
explain the association of VCD and GERD, but this
area remains open to research.
Fig. 2. False positive methacholine challenge.
Diagnosis and management of vocal cord
dysfunction
There are no accepted diagnostic standards for
VCD although there have been attempts to define
VCD and what constitutes an appropriate evalua-
tion [68].
Patients who have VCD usually present with one
or more of the cardinal symptoms of asthma: dyspnea,
wheezing, cough, and chest tightness [57]. They
frequently are misdiagnosed with asthma and are
overtreated with asthma medications. Clues to the
presence of VCD may be refractory asthma with
normal expiratory spirometry; sudden onset and reso-
lution of symptoms; or association with symptoms
that are referable to the vocal cords, such as hoarse-
ness or changes in character or quality of the patient’s
voice. The presence of possible triggers, such as
chronic rhinitis with postnasal drainage or GERD,
may suggest chronic irritation of the glottis. Hyper-
ventilation symptoms, such as syncope or presyncope,
lightheadedness, or numbness and tingling may occur
[69]. An association with sexual abuse was reported in
the literature [70].
The role of pulmonary function testing to include
or exclude coexistent asthma has not been well
defined. It is well-known that patients who have
VCD may produce striking cutoff of the inspiratory
portion of the flow volume loop that is consistent with
a variable extrathoracic obstruction (Fig. 1), although
this may be present in asymptomatic patients. During
severe episodes, the inspiratory and the expiratory
portions of the flow volume loop may be truncated.
Additionally, VCD may interfere with the interpreta-
tion of airway challenge testing and produce a falsely
positive test when airway inflammation is not present
(Fig. 2). A positive methacholine challenge without
the development of obstruction and abnormal inspi-
ratory loops may be a clue that upper airway, not
 J.M. Parker, M.L. Guerrero / Clin Chest Med 25 (2004) 321–330
Fig. 3. Exercise tidal flow volume loop in a patient who has stridor. X axis, Volume (L); Y axis, Flow (L/second).
lower airway, obstruction may be the cause. Newer
modalities, such as impulse oscillometry, may assist in
the determination of whether airway obstruction
occurs in the small or large airways. Analysis of
expired nitric oxide may be used to determine if
airway inflammation is present [71]. These newer
modalities are areas of possible research for physi-
cians who diagnose and manage patients who have
VCD. For patients who have transient exertional
symptoms, exercise tidal flow volume loops may
hold some promise as a diagnostic entity (Fig. 3) [72].
Demonstration of inappropriate adduction of the
vocal cords by direct visualization in symptomatic
patients remains the gold standard. Apposition of the
anterior portion of the true vocal cords with a
posterior ‘‘chink’’ is the classic appearance of VCD
(Fig. 4). Upper airway obstruction that produces
symptoms also may occur with incomplete adduction
of the vocal cords or hyperadduction of the arytenoid
cartilages. Normal laryngoscopy in the absence of
symptoms does not exclude the diagnosis and has a
reported false negative rate of 40% [57]. Therefore,
Fig. 4. Vocal cord adduction during inspiration with pos-
terior ‘‘chink.’’
327
it may be necessary to provoke symptoms. Exercise
or methacholine challenge are used most commonly.
Hyperventilation maneuvers, forced vital capacity
maneuvers, and pressured speech may be used during
the laryngoscopy [68]. Tobacco smoke, ammonium
nitrate, perfume, or other exposures that are known to
trigger an attack also may be used. An experienced
laryngoscopist who is familiar with this disorder is
important; inexperienced laryngoscopists may mis-
take gagging, laryngospasm, or other laryngeal dis-
orders for VCD.
The management of VCD includes education, the
medical management of triggers and coexistent dis-
eases, speech therapy, and, on occasion, the manage-
ment of stress or other existing psychiatric problems.
Management begins with education and reassurance
of the patient. Allowing the patient to visualize the
abnormal vocal cord motion during laryngoscopy
is helpful for understanding and cooperating with
speech therapy. An educational handout or referral
to appropriate Internet sites that have accurate infor-
mation regarding VCD is important in validating the
diagnosis and obtaining compliance with the manage-
ment plan. Medical management of coexistent asthma
should be based on published guidelines with the
intent of not overtreating the patient. Chronic rhinitis
with postnasal drainage or GERD should be treated
aggressively. Referral to a speech pathologist who has
an interest and training in the management of VCD
has been the mainstay of therapy. Speech therapy in
the appropriate patient has a significant probability of
success [73]. Patients who have significant problems
with stress, emotional or psychiatric problems, or a
history of sexual abuse may benefit from a referral to
an interested psychologist or psychiatrist.
Several problems are inherent when reviewing
the body of literature regarding VCD. Investigators
328 J.M. Parker, M.L. Guerrero / Clin Chest Med 25 (2004) 321–330
apply a variety of different terms to vocal cord dys-
function—‘‘laryngeal dysfunction,’’ ‘‘paroxysmal
vocal cord movement,’’ ‘‘paroxysmal vocal cord dys-
function,’’ ‘‘episodic laryngeal dysfunction,’’ ‘‘irrita-
ble larynx syndrome,’’ and ‘‘extrathoracic airway
dysfunction’’ are just some of the terms that are used.
There is a need for the development of a consensus
regarding the appropriate diagnostic evaluation for
VCD that could be applied to prospective studies of
this entity. Presumably, the diagnosis consists of some
combination of symptoms, pulmonary function test-
ing, and laryngoscopy.
In summary, VCD is a mimic of asthma that is
not uncommon. Although the medical literature is
flawed, VCD seems to occur much more commonly
in women.
Summary
Bronchial hyperreactivity and cough are common
medical problems that occur more frequently in
women. Differences in size, hormonal effects, den-
sity, and sensitivity to receptors and psychologic
factors may all play a role, which results in increased
expression of upper and lower airway disease. The
reason that VCD occurs more commonly in women is
not clear but many of the same explanations regard-
ing bronchial hyperreactivity and cough may apply.
References
[1] Redd SC. Asthma in the United States: burden
and current theories. Environ Health Perspect 2002;
110(Suppl 4):557 – 60.
[2] Camargo Jr CA, Schatz M. The relationship of gender
to asthma prevalence, healthcare utilization, and medi-
cations in a large managed care organization. Acad
Emerg Med 2003;10(15):508.
[3] De Marco R, Locatelli F, Sunyer J, Burney P. Differ-
ences in incidence of reported asthma related to age in
men and women. A retrospective analysis of the data
of the European Respiratory Health Survey. Am J
Respir Crit Care Med 2000;162(1):68 – 74.
[4] Dodge RR, Burrows B. The prevalence and incidence
of asthma-like symptoms in a general population sam-
ple. Am Rev Respir Dis 1980;122:567 – 75.
[5] Henriksen AH, Holmen TL, Bjermer L. Gender dif-
ferences in asthma prevalence may depend on how
asthma is defined. Resp Med 2003;97(5):491 – 7.
[6] Moorman JE, Mannino DM. Increasing US asthma
mortality rates: who is really dying? J Asthma 2001;
38:65 – 71.
[7] Hartert TV, Togias A, Mellen BG, Mitchel EF, Snow-
den MS, Griffin MR. Underutilization of controller and
rescue medications among older adults with asthma
requiring hospital care. J Am Geriatr Soc 2000;48:
651 – 7.
[8] Piecoro LT, Potoski M, Talbert JC, Doherty DE.
Asthma prevalence, cost, and adherence with expert
guidelines on the utilization of health care services
and costs in a state Medicaid population. Health Serv
Res 2001;36(2):357 – 71.
[9] Clark S, Cydulka RK, Emerman CE, Rowe BH,
Camargo Jr CA. Sex differences among adults present-
ing to the emergency department with asthma
and COPD exacerbations. Acad Emerg Med 2001;
8(5):534.
[10] Prescott E, Lange P, Vestbo J. Effect of gender on
hospital admissions for asthma and prevalence of
self-reported asthma: a prospective study based on a
sample of the general population. Thorax 1997;52(3):
287 – 9.
[11] Skobeloff EM, Spivey WH, St Clair SS, Schoffstall
JM. The influence of age and sex on asthma admission.
JAMA 1992;268:3437 – 40.
[12] Markowe HL, Bulpitt CJ, Shipley MJ, Rose G, Crom-
bie DL, Fleming DM. Prognosis in adult asthma:
a national study. BMJ 1987;295:949 – 52.
[13] Wijnhoven HA, Kriegsman DM, Snoek FJ, Hesselink
AE, de Haan M. Gender differences in health-related
quality of life among asthma patients. J Asthma 2003;
40(2):189 – 99.
[14] Kwon HL, Belanger K, Bracken MB. Asthma preva-
lence among pregnant and childbearing-aged women
in the United States: estimates from national health
surveys. Ann Epidemiology 2003;13(5):317 – 24.
[15] Sorensen TK, Dempsey JC, Xiao R, Frederick IO, Lu-
thy DA, Williams MA. Maternal asthma and risk of
preterm delivery. Ann Epidemiol 2003;13(4):267 – 72.
[16] Beckmann CA. The effects of asthma on pregnancy
and perinatal outcomes. J Asthma 2003;40(2):171 – 80.
[17] American Thoracic Society. Lung function testing: se-
lection of reference values and interpretative strategies.
Am Rev Respir Dis 1991;144:1202 – 18.
[18] Becklake MR, Kauffmann F. Gender differences in air-
way behaviour over the human life span. Thorax 1999;
54:1119 – 38.
[19] Tattersfield AE. Measurement of bronchial reactivity:
a question of interpretation. Thorax 1981;36:561 – 5.
[20] Tan KS, McFarlane LC, Lipworth BJ. Paradoxical
down-regulation and desensitization of B2 adrenocep-
tors by exogenous progesterone in female asthmatics.
Chest 1997;111:847 – 51.
[21] Alberts WM. Circadian menstrual rhythmicity and
asthma. Chest 1997;111:840 – 2.
[22] Beynon HL, Garbett ND, Barnes PJ. Severe premen-
strual exacerbations of asthma: effects of intramuscular
progesterone. Lancet 1988;332:370 – 2.
[23] Pauli BD, Reid RL, Munt PW, Wigle RD, Forkert L.
Influence of the menstrual cycle on airway function in
asthmatic and normal subjects. Am Rev Resp Dis 1989;
140:358 – 62.
 J.M. Parker, M.L. Guerrero / Clin Chest Med 25 (2004) 321–330
[24] Tan KS, McFarlane LC, Lipworth BJ. Modulation of
airway reactivity and peak flow variability in asth-
matics receiving the oral contraceptive pill. Am J Resp
Crit Care Med 1997;155:1273 – 7.
[25] Lange P, Parner J. Exogenous female sex steroid hor-
mones and risk of asthma and asthma-like symptoms:
a cross sectional study of the general population.
Thorax 2001;56(8):613 – 6.
[26] Haggerty CL, Ness RB, Kelsey S, Waterer GW. The
impact of estrogen and progesterone on asthma. Ann
Allergy Asthma Immunol 2003;90(3):284 – 91.
[27] Ensom MH, Chong G, Zhou D, Beaudin B, Shalansky
S, Bai TR. Estradiol in premenstrual asthma: a double-
blind, randomized, placebo-controlled, crossover study.
Pharmacotherapy 2003;23(5):561 – 71.
[28] Leynaert B, Bousquet J, Henry C, Liard R, Neukirch F.
Is bronchial hyperresponsiveness more frequent in
women than in men? A population-based study. Am
J Respir Crit Care Med 1997;156(5):1413 – 20.
[29] Kanner RE, Connett JE, Altose MD, Buist AS, Lee
WW, Tashkin DP, Wise RA. Gender difference in air-
way hyperresponsiveness in smokers with mild COPD.
Am J Respir Crit Care Med 1994;150:956 – 61.
[30] Kim YK, Kim SH, Tak YJ, Jee YK, Lee BJ, Kin SH,
et al. High prevalence of current asthma and active
smoking effect among the elderly. Clin Exp Allergy
2002;32(12):1706 – 12.
[31] Xu X, Weiss ST, Rijcken B, Schouten JP. Smoking,
changes in smoking habits, and rate of decline in
FEV1: new insight into gender differences. Eur Resp
J 1994;7(6):1056 – 61.
[32] Prescott E, Bjerg AM, Andersen PK, Lange P, Vestbo
J. Gender difference in smoking effects on lung func-
tion and risk of hospitalization for COPD: results from
a Danish longitudinal population study. Eur Resp J
1997;10(4):822 – 7.
[33] Gennuso J, Epstein LH, Paluch RA, Cerny F. The
relationship between asthma and obesity in urban mi-
nority children and adolescents. Arch Ped Adol Med
1998;152(12):1197 – 200.
[34] Young SY, Gunzenhauser JD, Malone KE, McTiernan
A. Body mass index and asthma in the military popu-
lation of the northwestern United States. Arch Intern
Med 2001;161(13):1605 – 11.
[35] Nathell L, Jensen I, Larsson K. High prevalence of
obesity in asthmatic patients on sick leave. Resp Med
2002;96(8):642 – 50.
[36] Figueroa-Munoz JI, Chinn S, Rona RJ. Association
between obesity and asthma in 4 – 11 year old children
in the UK. Thorax 2001;56(2):133 – 7.
[37] Chinn S, Jarvis D, Burney P. European Community
Respiratory Health Survey. Relation of bronchial re-
sponsiveness to body mass index in the ECRHS.
European Community Respiratory Health Survey. Tho-
rax 2002;57(12):1028 – 33.
[38] Guerra S, Sherrill DL, Bobadilla A, Martinez FD,
Barbee RA. The relation of body mass index to asthma,
chronic bronchitis, and emphysema. Chest 2002;
122(4):1256 – 63.
329
[39] Chinn S. Obesity and asthma: evidence for and against
a causal relation. J Asthma 2003;40(1):1 – 16.
[40] Huovinen E, Kaprio J, Koskenvuo M. Asthma in rela-
tion to personality traits, life satisfaction, and stress:
a prospective study among 11000 adults. Allergy
2001;56(10):971 – 7.
[41] Kolbe J, Fergusson W, Vamos M, Garrett J. Case-con-
trol study of severe life threatening asthma in adults:
psychological factors. Thorax 2002;57(4):317 – 22.
[42] Dorhofer DM, Sigmon ST. Physiological and psycho-
logical reactivity in women with asthma: the effects of
anxiety and menstrual cycle phase. Behav Res Ther
2002;40(1):3 – 17.
[43] Kolbe J. Asthma education, action plans, psychosocial
issues and adherence. Can Respir J 1999;6(3):273 – 80.
[44] Medici TC, Grebski E, Hacki M, Ruegsegger P, Maden
C, Efthimiou J. Effect of one year treatment with in-
haled fluticasone propionate or beclomethasone dipro-
prionate on bone density and bone metabolism:
a randomised parallel group study in adult asthmatic
subjects. Thorax 2000;55(5):375 – 82.
[45] Settipane RA. Defining the effects of an inhaled corti-
costeroid and long-acting beta-agonist on therapeutic
targets. All Asthma Proc 2003;24(2):85 – 9.
[46] Sharma PK, Malhotra S, Pandhi P, Kumar N. Effect of
inhaled steroids on bone mineral density: a meta analy-
sis. J Clin Pharm 2003;43(2):193 – 7.
[47] Wisniewski AF, Lewis SA, Green DJ, Maslanka W,
Burrell H, Tattersfield AE. Cross-sectional investiga-
tion of the effects of inhaled corticosteroids on bone
density and bone metabolism in patients with asthma.
Thorax 1997;52(10):853 – 60.
[48] Elmstahl S, Ekstrom H, Galvard H, Johnell O, Ger-
hardsson de Verdier M, Norjavaara E. Is there an asso-
ciation between inhaled corticosteroids and bone
density in postmenopausal women? J All Clin Immun
2003;111(1):91 – 6.
[49] Bonala SB, Reddy BM, Silverman BA, Bassett CW,
Rao YA, Amara S, et al. Bone mineral density in
women with asthma on long-term inhaled cortico-
steroid therapy. Ann Allergy Asthma Immunol 2000;
85(6 Pt 1):495 – 500.
[50] Irwin RS, Boulet LP, Cloutier MM, Fuller R, Gold PM,
Hoffstein V, et al. Managing cough as a defense
mechanism and as a symptom: a consensus panel re-
port of the ACCP. Chest 1998;114:133S – 81S.
[51] Irwin RS, Curley FJ, French CL. Chronic cough: the
spectrum and frequency of causes, key components of
the diagnostic evaluation and outcomes of specific
therapy. Am Rev Resp Dis 1990;141:640 – 7.
[52] Fuller JW. Cough associated with angiotensin con-
verting enzyme inhibitors. J Hum Hypertens 1989;3:
159 – 61.
[53] Rieger B, Warmouth JE. Psychogenic cough treated
with biofeedback and psychotherapy: a review and
case report. Am J Phys Med Rehab 1995;74:155 – 8.
[54] Thorson A, Hoa NP, Long NH. Health seeking behav-
ior of individuals with a cough of more than three
weeks. Lancet 2001;357(9267):1532 – 3.
330 J.M. Parker, M.L. Guerrero / Clin Chest Med 25 (2004) 321–330
[55] Kastelik JA, Thompson RH, Aziz I, Ojoo JC, Reding-
ton AE, Morice AH. Sex related differences in cough
reflex sensitivity in patients with chronic cough. Am J
Respir Crit Care Med 2002;166(7):961 – 4.
[56] Christopher KL, Wood RP, Eckert RC, Blager FB,
Raney RA, Souhrada JF. Vocal cord dysfunction pre-
senting as asthma. NEJM 1983;308:1566 – 70.
[57] Newman KB, Mason UG, Schmaling KB. Clinical fea-
tures of vocal cord dysfunction. Am J Resp Crit Care
Med 1995;152:1382 – 6.
[58] Andrianopoulos MV, Gallivan GJ, Gallivan KH.
PVCM, PVCD, EPL, and irritable larynx syndrome:
what are we talking about and how do we treat it?
J Voice 2000;14(4):607 – 18.
[59] O’Connell MA, Sklarew PR, Goodman DL. Spectrum
of presentation of paradoxical vocal cord motion in
ambulatory patients. Ann Allergy Asthma Immunol
1995;74:341 – 4.
[60] Morris MJ, Deal LE, Bean DR, Grbach VX, Morgan
JA. Vocal cord dysfunction in patients with exertional
dyspnea. Chest 1999;116:1676 – 82.
[61] Perrello MM, Gurevich J, Fitzpatrick T, Berg BW,
Parker JM. Clinical characteristics of vocal cord dys-
function in two military tertiary care facilities. Am J
Resp Crit Care Med 2003;167:A788.
[62] McFadden ER, Zawadski DK. Vocal cord dysfunction
masquerading as exercise-induced asthma. Am J Crit
Care Med 1996;153:942 – 7.
[63] Rundell KW, Spiering BA. Inspiratory stridor in elite
athletes. Chest 2003;123:468 – 74.
[64] Ayres JG, Gabbott PLA. Vocal cord dysfunction and
laryngeal hyperresponsiveness: a function of altered
autonomic balance. Thorax 2002;57:284 – 5.
[65] Bucca C, Rolla G, Brussino L, DeRose V, Bugliani M.
Are asthma-like symptoms due to bronchial or extra-
thoracic airway dysfunction? Lancet 1995;346:791 – 5.
[66] Bucca C, Rolla G, Scappaticci E, Chiampo F, Bugiani
M, Magnano M, et al. Extrathoracic and intrathoracic
airway responsiveness in sinusitis. J Allergy Clin Im-
munol 1995;95:52 – 9.
[67] Bucca C, Rolla G, Scappaticci E, Baldi S, Caria E,
Oliva A. Histamine hyperresponsiveness of the extra-
thoracic in patients with asthmatic symptoms. Allergy
1991;46:147 – 53.
[68] Wood RP, Milgrom H. Vocal cord dysfunction. J Al-
lergy Clin Immunol 1996;98(3):481 – 5.
[69] Parker JM, Berg BW. Prevalence of hyperventilation
in patients with vocal cord dysfunction. Chest 2002;
122(4):185S.
[70] Freedman MR, Rosenberg SJ, Schmaling K. Child-
hood sexual abuse in patients with paradoxical vocal
cord dysfunction. J Nerv Ment Dis 1991;179:295 – 8.
[71] Johnson BD, Beck KC, Zeballos RJ, Weisman IM. Ad-
vances in pulmonary laboratory testing. Chest 1999;
116:1377 – 87.
[72] Johnson BD, Weisman IM, Zeballos RJ, Beck KC.
Emerging concepts in the evaluation of ventilatory lim-
itation during exercise: the exercise tidal flow volume
loop. Chest 1999;116:488 – 503.
[73] Martin RJ, Blager FB, Gay ML, Wood RP. Paradoxic
vocal cord motion in presumed asthmatics. Sem Respir
Med 1987;8(4):332 – 7.