Diagnosing chronic cough with a capsaicin provocation test

Cough is a common complaint that is often perceived as a nuisance.
Epidemiological studies have indicated that chronic cough is very prevalent in
the community. Approximately 40% of the population will at some point in life
qualify with chronic cough. Cough is called chronic if the symptoms persist for
longer than eight weeks. A persistent cough usually indicates an underlying
condition that requires a causal treatment.
Real idiopathic cough is rare.

For all causes of cough is a test that the disease can be diagnosed, except for
the disease sensory hyperreactivity (SHR). It is important, therefore, to
introduce an test to diagnose this condition or to exclude.

There are a couple of studies that are occupied with the capsaicin provocation
test to diagnose sensory hyperreactivity. It appears that patients with sensory
hyperreactivity do have a higher cough respons on the inhalation of capsaicin
than healthy people.
Capsaicin is a harmless and odorless vanilloid, that stimulates mostly the
afferent unmyelinated C-fibers of the sensory nervous system by the release of
neuropeptide P.

Null hypothesis: The standard execution of a capsaicin provocation test in the
diagnosis of unexplained chronic cough in patients is an added value for the
patient.

Alternative hypothesis: The standard execution of a capsaicin provocation test
in the diagnosis of unexplained chronic cough has no benefit to the patient.

Question: Is it an added value for the patient if there will be a default
capsaicin provocation test to diagnose chronic cough?

It will be investigated or with the aid of the capsaicin provocation test the
diagnosis sensory hyperreactivity (SHR) can be made. SHR is known, but there is
no test to actually diagnose it.

This research is a pilot survey. We start with 30 patients who are known on our
department. As this study shows that it has an added value for the treatment of
chronic cough, we are going to test more patients and over a longer period of
time after this study.

If more than 10 subjects will have a positive capsaicin challenge test, it is
an added value for diagnosing patients with chronic cough. We are going to
expand the study en test more subjects and over a longer period of time .

If fewer than 10 subjects have a positive capsaicin provocation test , it will
not be valuable in the diagnosis of patients with chronic cough .

It is an experimental, quantitative, correlational research.

Two weeks prior to the study, the subjects has to stop with antihistamines.
Two days prior to the study, the subjects has to stop with *2-agonists,
anticholinergics and inhaled or oral steroids.

The following information is extracted from the medical records: gender and age.
All subjects undergo the same protocol. The subjects have to inhale different
concentrations of capsaicine, to start with the lowest concentrations and to
end with the highest concentration. We don't tell this to the subjects. Also we
don't tell them that the result of this research is based on the number of
coughs .

The different concentrations of capsaicin are dissolved in 0,9% NaCl. The
different concentrations of capsaicin are 0 µmol / liter ( pure NaCl), 0,4
µmol / liter, 2,0 µmol / liter and 10,0 µmol / liter.

The values are selected on known values, which have been determined in previous
studies. With these values can be determined whether or not a person has the
disease SHR. The solutions that are used for this study, shall be made for us.

For the test, a flow / volume test is performed to investigate whether the
patients already has a bronchoconstriction before the test. Once the FEV1 is
decreased compared to previous visits with 20%, the capsaicin provocation test
can not carried out and will possibly tried again later.
For the patients safety there will be performed a flow/volume test after the
capsaicin provocation test, even though it has been determined that the
inhalation of the capsaicin does not cause bronchoconstriction. There should be
a bronchodilator available at all times.

For each concentration, an amount of 2 ml is needed. The flow of the inhalation
is 0,25 mL/min with an inhalation time of 4 minutes. The output at each
concentration is than 1 mL. The flow of inhalation is determined by an air
regulator with an adjustable clock. The nebulizer flow is calibrated by
determining the output at different flows. The nebulizer flow has to be 4,3
L/min.

Before and after the inhalation of each concentration of capsaicin, each
subject will be ask to choose a deposit score. They have to choose a deposit
score for symptoms chest pain, hoarseness, throat irritation, runny nose, mucus
and eye irritation on a scale from 0 to 3 (0: no symptoms, 3: severe symptoms).

1. Fill the nebulizer with 2 mL of the first solution , this is pure 0.9% NaCl.
Weigh the nebuliser solution
2. Ask the subject to the deposit score as described above
3. Ask the subjects to cough so often as needed and not to talk during and
after each inhalation
4. Let the subject take the mouthpiece in their mouth and put the nose plug on
their nose
5. Turn the nebulizer to a nebulizer flow of 4.3 L / min and tell the subject
to breath on his of her own pace for 4 minutes. Count the nubmer of coughs.
6. Tell the subject after the 4 minutes of inhalating through the mouthpiece to
take the mouthpiece out of the mouth en the nose plug off their nose en breath
on their own pace for another 4 minutes.
7. Count the number of coughs from the time that the atomization of the
solution starts to the end of step 6, with a totel of eight minutes
8. Weigh the nebulizer. The output should be 1 mL.
9. Ask the subject choose a deposit score for all the symptoms
10. If the number of coughs are above the limit values, the capsaicin challenge
is positive. There is no need to go further with the higher concentrations of
capsaicin. The limit values are for the concentration of 0,4 µmol/liter 10
coughs, for the concentration of 2,0 µmol/liter 35 coughs and for the
concentration 10,0 µmol/liter 55 coughs.
11. Wait between each inhalation minimal 10 minutes before starting with the
next inhalation.
12. Fill the nebulizer now with 2 mL of solution 2.
13. Repeat step 2 to step 11.
14. If the number of cough is not higher than the limit value (see table 2),
step 13 can be repeated for the next solutions.

Time will be the only burden for the subjects. For this test, the subjects need
to come back to the hospital for two more times. At the first appointment they
can ask some questions about the study and they can return the consent form.
This appoinment will take about 30 minutes. The second appointment will take
about 60 to 90 minutes. At the second appointment will take place the research
itself.

Other studies concluded that this provocation test will entail no risks for the
patient.