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[Dysphagia] Laryngeal Cough Reflex Test

The cough reflex is tested consistently mainly by
pharmacology - to test antitussive medication-
anesthesiology, and, sometimes ENT/respirology. The
most usual method for decades has been the inhalation
of distilled water, followed by mild solutions of
irritatnts such as capsaicin or citric acid. This is a
common test (see following) and water is sufficient to
stimulate a cough. It has also been used to identify
diffee\rences in cough sensitivity related to ACE
inhibitors and to gender:
Nakajoh K; Nakagawa T; Sekizawa K; Matsui T; Arai H;
Sasaki H. Relation between incidence of pneumonia and
protective reflexes in post-stroke patients with oral
or tube feeding. J Intern Med 2000 Jan;247(1):39-42   
The incidence of pneumonia was prospectively analysed
for 1 year in three groups of post-stroke patients on
the basis of the following clinical conditions: oral
feeding without dysphagia (n = 43); oral feeding with
dysphagia (n = 48); and nasogastric tube feeding with
dysphagia (n = 52). We also studied the incidence of
pneumonia in bedridden patients with nasogastric tube
feeding (n = 14). Before the start of the study, the
swallowing and cough reflexes of each patient were
measured. The swallowing reflex was evaluated
according to latency of response, which was timed from
the injection of 1 mL of distilled water into the
pharynx through a nasal catheter to the onset of
swallowing. The cough threshold of citric acid
aerosols was defined as the concentration at which the
patient coughed five times. Cough reflex is
traditionally tested by inhalation of nebulized
distilled water, capsaicin, citric acid, vanilloids.
These tests are widely used by manufacturers of cough
medications. CONCLUSIONS: The state of protective
reflexes had a significant relation to the incidence
of pneumonia. Feeding tube placement may have a
beneficial role in preventing aspiration pneumonia in
mildly or moderately disabled post-stroke patients
with attenuated protective reflexes. Bedridden
patients who were tube-fed had the highest incidence
of pneumonia.
Morice AH .Inhalation cough challenge in the
investigation of the cough reflex and antitussives.
Pulm Pharmacol 1996 Oct-Dec;9(5-6):281-4   .Inhalation
cough challenge is a useful tool in the physiological
and pharmacological investigation of the cough reflex.
There are three types of challenge used, capsaicin and
the vanilloids, organic acids, and distilled water
challenge. In addition, challenge may be administered
in a single dose or cumulative dose fashion. The
correct combination of inhalation technology and
tussive stimulus produces a sensitive and specific
method for estimating the cough reflex.
Morice AH; Higgins KS; Yeo WW.  Adaptation of cough
reflex with different types of stimulation. Eur Respir
J 1992 Jul;5(7):841-7    
Inhalation cough challenge has become an accepted
method of investigating antitussive agents. It is,
therefore, important to examine the degree of
tachyphylaxis (adaptation) seen with repeated cough
challenge. In addition, different types of challenge
may reveal important differences in the neuronal
pathways involved in the cough reflex. Citric acid,
distilled water and capsaicin were examined to
determine adaptation of the cough response during
acute and long-term inhalation studies in healthy
subjects. To study acute tachyphylaxis two separate
one minute continuous inhalation challenges (n = 13)
were performed. Long-term tachyphylaxis (n = 10) was
examined using citric acid and capsaicin inhalation at
10 min intervals for 40 min, and at 4 and 6 h.
Cross-tachyphylaxis to citric acid and capsaicin was
examined in a separate randomized crossover study (n =
10). Highly significant adaptation occurred between
the first and last 10 s of the one minute challenge
with citric acid (90-100%) and distilled water
(74-84%), but was less pronounced with capsaicin
(37-49%, at 2 microM). Cough during the whole of the
second test was significantly reduced for citric acid
(50%). During long-term challenge cough was attenuated
over 40 min both with citric acid (100 mM, p less than
0.05; 300 mM, p less than 0.001; 1 M, p less than
0.001) and with capsaicin (3 microM, p less than 0.01;
10, 30, 100 microM, p less than 0.001 each). With
higher doses, tachyphylaxis was still present at 180
min with both citric acid (300 mM, p less than 0.05)
and capsaicin (100 microM, p less than 0.008).
Fuller RW . Pharmacology of inhaled capsaicin in
humans. Respir Med 1991 Jan;85 Suppl A:31-4  
Inhaled capsaicin in humans causes cough and transient
increase in airways resistance: both these effects
appear to be through stimulation of sensory nerves in
the airway. It has therefore been possible to study
the effect of pharmacological agents on these two
reflexes. The induced cough can be modulated by using
opiates and local anaesthetics and the increase in
airways resistance by anticholinergic agents. The use
of inhaled capsaicin has therefore proved a useful
human model for the study of novel treatments of

Dicpinigaitis PV; Rauf K. The influence of gender on
cough reflex sensitivity. Chest 1998
BACKGROUND: The more common occurrence in women of
cough due to angiotensin-converting enzyme inhibitors
raises the possibility of gender-related differences
in the sensitivity of the cough reflex. Of two recent
studies that evaluated cough response to inhaled
capsaicin in normal subjects, one demonstrated
heightened sensitivity of the cough reflex in women
compared with men, while the other revealed no
gender-related differences. To further investigate
this question, we reviewed our experience with cough
challenge testing in normal volunteers. STUDY
OBJECTIVE: To compare cough reflex sensitivity in
healthy adult female and male subjects. DESIGN:
Retrospective data analysis. SETTING: Academic medical
center. PARTICIPANTS: One hundred healthy volunteers
(50 male, 50 female). Interventions: Subjects inhaled
capsaicin in ascending, doubling concentrations until
the concentration inducing five or more coughs (C5)
was reached. In addition, the concentration inducing
two or more coughs (C2; cough threshold) was measured.
Results: Mean log C5 was significantly lower in women
than in men: 1.02+/-0.09 (SEM) microM vs 1.41+/-0.08
microM, respectively (p=0.002). Log C2 (cough
threshold) was also significantly lower in female
subjects: 0.534+/-0.068 microM vs 0.870+/-0.065 microM
in male subjects (p=0.00058). CONCLUSION: Healthy
women have a more sensitive cough reflex than do
healthy men. The reasons for this significant gender
difference remain to be elucidated, but may involve a
heightened sensitivity, in women, of the sensory
receptors within the respiratory tract that mediate
Newnham DM; Hamilton SJ. Sensitivity of the cough
reflex in young and elderly subjects. Age Ageing 1997
OBJECTIVE: To compare the sensitivity of the cough
reflex--which is said to be normal in elderly
people--in elderly and young subjects. SUBJECTS: 20
elderly (14 female) subjects, mean (SEM) age 83 (1)
years and 20 young (nine female) subjects, mean (SEM)
age 27 (1) years, who were all non-smokers. None of
the subjects was taking antitussive drugs and none
suffered from clinically evident lung, cardiac or
neurological disease. Five elderly subjects were
unable to perform adequate spirometry and were
excluded from analysis. DESIGN AND OUTCOME MEASURES:
Each subject inhaled 10 ml of nebulized distilled
water and isotonic saline (as placebo) for 30 s, 10
min apart in a randomized double-blind crossover
fashion. The cough frequency induced with each
treatment was recorded on a click counter. RESULTS:
Cough frequency on inhaling distilled water was
significantly lower in the elderly group than in the
younger group, with a difference of 9.53 (95%
confidence intervals: 3.63, 15.4; P < 0.001). None of
the subjects coughed when inhaling placebo solution,
resulting in significant differences in cough
frequencies between distilled water and placebo of
5.87 (2.82, 8.92; P < 0.05) for the elderly group and
15.4 (11.0, 19.8; P < 0.0005) for the younger group.
CONCLUSIONS: The sensitivity of the cough reflex
appears to be significantly reduced in elderly
subjects. This may increase the risk of aspiration and
bronchopulmonary infection in old age, even in the
absence of respiratory disease.
Morice AH; Turley AJ; Linton TK. Human ACE gene
polymorphism and distilled water induced cough. 
Thorax 1997 Feb;52(2):111-3   
BACKGROUND: Inhibitors of angiotensin converting
enzyme (ACE) cause a non-productive cough. The
insertion/deletion polymorphism of ACE was used as a
genetic marker to investigate the relationship between
ACE genotype and cough sensitivity. METHODS: A double
blind cough challenge was performed in 66 normotensive
subjects (34 men) of mean age 34.8 years (range 18-80)
using aerosols of distilled water. The number of
coughs during the one minute exposure to water was
recorded. DNA samples from venous blood were amplified
by the polymerase chain reaction and resolved on a 1%
agarose gel. They were analysed for the presence of a
polymorphism in intron 16 of the ACE gene consisting
of an insertion (I) or deletion (D) of an Alu
repetitive sequence 287 base pairs long. RESULTS: The
distribution of genotypes was 20 II, 26 ID, and 20 DD.
The cough response was significantly (p < 0.01)
related to the ACE genotype, the mean number of coughs
being 15.8, 11.3, and 9.6, respectively, in subjects
with the II, ID, and DD genotypes. CONCLUSIONS: The
observation that cough challenge is dependent on ACE
genotype in normal subjects is evidence of a link
between ACE activity and the cough reflex.
Nishino T; Tagaito Y; Isono S. Cough and other
reflexes on irritation of airway mucosa in man. Pulm
Pharmacol 1996 Oct-Dec;9(5-6):285-92
Both human and animal studies show that irritation of
airway mucosa elicits a variety of reflex responses
such as coughing, apnoea, and laryngeal closure. Most
of the information concerning these reflex responses
were obtained in anesthetized conditions with little
applicability to awake conditions. Various aspects of
cough and other reflexes on irritation of the airway
mucosa are discussed. Studies on awake humans showed
that stimulation of the laryngeal mucosa with a small
amount of distilled water during wakefulness causes
elicitation of the expiration reflex, cough reflex,
and swallowing reflex while other types of responses
are scarcely observed. In addition, the duration of
these responses is remarkably short. In contrast, the
same stimulation causes more variant, prolonged, and
exaggerated responses during a light depth of
anesthesia. An increase in depth of anesthesia
abolishes expiratory efforts such as coughing and the
expiration reflex whereas the apnoeic reflex and
laryngeal closure reflex are resistant to the
depressant effect of anesthesia. Also, the respiratory
reflex responses to airway irritation varied,
depending on the site of stimulation: both laryngeal
and tracheal stimulation cause vigorous respiratory
responses whereas bronchial stimulation causes little
or no respiratory responses. These results indicate
not only that the types and magnitude of reflex
responses is greatly modified by the central nervous
state but also that the site of stimulation is crucial
for determining the pattern of respiratory responses
elicited by airway stimulation in humans.
Fontana GA; Pantaleo T; Lavorini F; Benvenuti F;
Gangemi S. Defective motor control of coughing in
Parkinson's disease.  Am J Respir Crit Care Med 1998
Aug;158(2):458-64 The high incidence of serious chest
infections in patients with Parkinson's disease is
unexplained, but an impairment in cough reflex may
have a role. Maximal voluntary cough (MVC) and reflex
cough (RC) to inhalation of ultrasonically nebulized
distilled water were analyzed in patients with
Parkinson's disease and age-matched control subjects
by monitoring the integrated electromyographic
activity (IEMG) of abdominal muscles. The peak
amplitude of IEMG activity (IEMGP) was expressed as a
fraction of the highest IEMGP value observed during
MVC corrected to account for possible losses in
abdominal muscle force due to reduced central muscle
activation. Cough intensity was indexed in terms of
both the IEMGP and the ratio of IEMGP to the duration
of the expiratory ramp (TEC), i.e., the rate of rise
of IEMG activity. Cough threshold was slightly higher
in patients than in control subjects, but the
difference failed to reach statistical significance.
Compared with control subjects, patients displayed a
lower IEMGP during maximal expiratory pressure
maneuvers (PEmax), MVC, and RC (p always < 0.01); TEC
during RC was longer (p < 0.01) than in controls.
Consequently, the rate of rise of IEMG activity during
cough was always lower in patients (p < 0. 01),
especially during RC. Finally, PEmax, and both the
peak and rate of rise of IEMG activity during RC were
inversely related to the level of clinical disability
(Spearman rank correlation coefficient, rs = -0.88,
-0.86, and -0.85, respectively, p always < 0.01). The
results indicate that the central neural mechanisms
subserving the recruitment of motor units and/or the
increase in their frequency of discharge during
voluntary and, even more markedly, RC are impaired in
patients with Parkinson's disease.
Morice AH; Lowry R; Brown MJ; Higenbottam T
Angiotensin-converting enzyme and the cough reflex.
Lancet 1987 Nov 14;2(8568):1116-8   
The effect of inhibition of angiotensin-converting
enzyme (ACE) on standard cough challenge was
investigated in a double-blind, randomised study in
sixteen normal volunteers. Captopril (25 mg) or
matched placebo was given by mouth 2 h before
inhalation of nebulised distilled water, citric acid,
and incremental doses of capsaicin (0.5-20 mumol/l).
Distilled water and citric acid challenge were not
significantly changed by captopril pretreatment.
However, captopril significantly shifted the
dose-response curve to capsaicin inhalation. The
geometric mean dose of capsaicin causing 20 coughs/min
was 1.3 mumol/l for captopril and 2.8 mumol/l for
placebo pretreatment (p = 0.04). Cough is a recognised
side-effect of ACE inhibitors; the observation that
cough challenge is changed by these drugs in normal
subjects implies a role for ACE in the cough reflex,
possibly by metabolism of substrates other than
angiotensin I.
Fontana GA; Pantaleo T; Lavorini F; Mutolo D; Polli G;
Pistolesi M. Coughing in laryngectomized patients.  
Am J Respir Crit Care Med 1999 Nov;160(5 Pt 1):1578-84
Ablation of the larynx implies withdrawal of afferent
information from receptors involved both in the
control of expiratory flow and in the genesis of
protective airway reflexes including coughing. To
investigate the effects of laryngectomy on the sensory
and motor component of coughing, maximal voluntary
cough (MVC) efforts as well as the reflex cough (RC)
responses at threshold (T) and suprathreshold (1.8 x
T, ST) levels induced by inhalation of progressively
increasing concentrations of ultrasonically nebulized
distilled water (fog) were analyzed in 10
laryngectomized patients and 10 control subjects..
Cough volume acceleration, i. e., the ratio of cough
peak flow to the corresponding time to cough peak flow
was also significantly reduced in the patients,
especially during RCT (p < 0.01). The results suggest
that the lack of signals arising from the larynx may
result in a reduction of cough volume acceleration as
well as in the intensity of abdominal muscle
contractions during RCT. These factors may contribute
to facilitate the onset and/or the persistence of
chest infections in laryngectomized patients.


--- MarcM225@aol.com wrote:
> Does anyone do a laryngeal cough reflex test with
> tartaric acid/nebulizer 
> when they are doing a dysphagia bedside evaluation? 
> Can you explain the 
> steps involved in preparing the mixture and what
> type of results are we 
> expecting?  
> Thanks,
> Marc, SLP


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