ATP/AMP Challenge in Healthy Non-smokers, Smokers, Patients With Asthma, and Patients With Chronic Obstructive Pulmonary Disease (COPD)

Asthma Clinical Trial

Official title:

Adenosine 5'-Triphosphate (ATP) Challenge in Healthy Non-smokers, Current Smokers and Patients With Mild Asthma and Chronic Obstructive Pulmonary Disease (COPD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00159315
• Other study ID #: DHTABPT0336
• Status: Completed
• Phase: N/A
• Start date: October 2002
• Est. completion date: October 2004

Study information

• Verified date: April 2024
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

In this randomised, cross-over, controlled study, a total of 84 subjects will be included: 12 healthy non-smoking volunteers; 12 current smokers; 30 patients with mild steroid-naïve asthma; and 30 patients with mild-moderate COPD.

Each subject will have 1 screening visit (if necessary) and 2 study visits. At visits 2 and 3 the effects of adenosine 5'-triphosphate (ATP) or adenosine 5'-monophosphate (AMP) challenge, given in a random order, will be tested.

Description:

Background: Extracellular adenosine 5'-triphosphate (ATP) stimulates vagal C and Aδ fibers in the lung, resulting in pronounced bronchoconstriction and cough mediated by P2X2/3 receptors located on vagal sensory nerve terminals. We investigated the effects of nebulized ATP on cough and symptoms in control subjects, healthy smokers, and patients with COPD and compared these responses to the effects of inhaled adenosine, the metabolite of ATP.

Methods: We studied the effects of inhaled ATP and adenosine monophosphate (AMP) on airway caliber, perception of dyspnea assessed by the Borg score, cough sensitivity, and ATP in exhaled breath condensate in healthy nonsmokers (n = 10), healthy smokers (n = 14), and patients with COPD (n = 7).

Results: In comparison with healthy subjects, ATP induced more dyspnea, cough, and throat irritation in smokers and patients with COPD, and the effects of ATP were more pronounced than those of AMP. The concentration of ATP in the exhaled breath condensate of patients with COPD was elevated compared with that of healthy subjects.

Conclusions: Smokers and patients with COPD manifest hypersensitivity to extracellular ATP, which may play a mechanistic role in COPD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: October 2004
• Est. primary completion date: October 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Healthy non-smokers (n=12)

• Normal spirometry

• Forced expiratory volume in 1 second (FEV1) reversibility of < 15% after inhaled beta2-agonists*

2. At risk (current smokers) (n=12)*

• Normal spirometry, chronic symptoms (cough, sputum production)

• FEV1 reversibility of < 15% after inhaled beta2-agonists* (* = Global Strategy for the Diagnosis, Management, and Prevention of COPD)

3. Mild steroid-naïve asthma (n=30)

• FEV1 more than or equal to 80%

4. Mild-moderate COPD (n=30)

• FEV1 50-80%

Exclusion Criteria:

1. Pregnancy, breast-feeding, or planned pregnancy during the study.

2. Fertile women not using acceptable contraceptive measures, as judged by the investigator

3. Upper respiratory infection within the last 4 weeks

4. Subjects who have received research medication within the previous one month

5. Subjects unable to give informed consent

6. Any psychiatric condition rendering the patient unable to understand the nature, scope, and possible consequences of the study.

Related Conditions & MeSH terms

• Asthma
• COPD
• Lung Diseases, Obstructive
• Pulmonary Disease, Chronic Obstructive
• Smoking

Intervention

Procedure:
• Inhalation Challenge with ATP

• Inhalation Challenge with AMP

Locations

Country	Name	City	State
United Kingdom	Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
Imperial College London	Duska Scientific Co.

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

Basoglu OK, Barnes PJ, Kharitonov SA, Pelleg A. Effects of Aerosolized Adenosine 5'-Triphosphate in Smokers and Patients With COPD. Chest. 2015 Aug;148(2):430-435. doi: 10.1378/chest.14-2285. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PC20 of ATP and AMP	PC20 of ATP and AMP	On administration
Primary	Lung function	Spirometry	On administration
Primary	Borg score	Measurement of DYSPNEA	On administration
Primary	Impulse oscillometry (IOS)	Small airway function	On administration