Condition category
Signs and Symptoms
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Prof Alyn Morice


Contact details

Respiratory Medicine
Division Cardiovascular and Respiratory Studies
Castle Hill Hospital
Castle Road
HU16 5JQ
United Kingdom

Additional identifiers

EudraCT number number

Protocol/serial number

AcadMed CTU04/05

Study information

Scientific title

Validation of the citric acid cough challenge using the KoKo DigiDoser system in healthy volunteers: a 4-week randomised single centre crossover study


Study hypothesis

The citric acid cough challenge was first reported in humans over 50 years ago. The test was established to allow for the quantification of cough and also as a tool for the assessment of antitussive properties of certain therapies. Since this time many different protocols have been published to measure cough reflex sensitivity these can vary in terms of the nebuliser used, tussive agent, single breath, single dose, dose response and number of coughs required to attain a threshold. In our opinion a definitive method for measuring cough sensitivity needs to be established to allow for standardisation of results from different groups to be compared. The standardisation of this test will lead to a higher quality of research, better drug development and ultimately better patient care.

Ethics approval

Hull and East Riding Local Research Ethics Committee approved on the 26th April 2006 (ref: 06/Q1104/46)

Study design

Randomised single centre crossover study

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Artificially induced cough


Volunteers were randomised for the order methods to induce artificial cough, i.e., whether the Mefar dosimeter was used first or the KoKo DigiDoser.

The following assessments were then performed:
1. Impulse oscillometry
2. Spirometry
3. Citric acid cough challenge

Intervention type



Not Applicable

Drug names

Primary outcome measures

Reproducibility of cough reflex sensitivity to citric acid (measured via inhalation of incremental, doubling concentrations of citric acid until the concentration inducing two or more coughs or five or more coughs is reached)using the modified Devilbiss 646 nebuliser powered by the KoKo DigiDoser. Measured within 1 day comparing baseline challenge and challenges at 1, 2 and 4 hours post-baseline to measure within-day reproducibility.

Secondary outcome measures

To compare the reproducibility of cough reflex sensitivity using the modified Devilbiss 646 nebuliser powered by the KoKo DigiDoser with that of the more commonly used MB2 nebuliser powered by the MB3 mefar dosimeter. Assessed at baseline and then two weeks later to assess between-day reproducibility.

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Healthy male/female volunteers
2. Male and female subjects of at least 18 years of age
3. Non-smokers or, ex-smokers of at least 12 months
4. Forced expiratory volume in one second (FEV1) greater than 80% of predicted

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. Female subjects who are pregnant, or lactating, or who are of child bearing potential but are not using contraceptive measures
2. Suffering from any active seasonal allergies
3. Suffering from concomitant disease which may interfere with study procedures or evaluation.
4. Subjects suffering from gastroesophageal reflux taking proton pump inhibitors or any other regular antacid therapy
5. Subjects suffering from post nasal drip syndrome
6. A recent respiratory tract infection within 6 weeks prior to entry on to study
7. Use of medications known to alter the cough reflex
8. Smoking history of greater than 10 pack years

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Respiratory Medicine
HU16 5JQ
United Kingdom

Sponsor information


Hull and East Yorkshire Hospitals NHS Trust (UK)

Sponsor details

Research and Development Office
Medical Research and Teaching Centre
Daisy Building
Castle Hill Hospital
Castle Road
HU16 5JQ
United Kingdom
+44 (0)1482 461883

Sponsor type




Funder type


Funder name

Hull and East Yorkshire Hospitals NHS Trust (UK) - Research and Development Grant

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

1. 2010 results in

Publication citations

  1. Results

    Wright CE, Jackson J, Thompson RL, Morice AH, Validation of the ERS standard citric acid cough challenge in healthy adult volunteers., Cough, 2010, 6, 8, doi: 10.1186/1745-9974-6-8.

Additional files

Editorial Notes