The Utility of feNO in the Differential Diagnosis of Chronic Cough

Study Overview
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Brief Summary
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In this study the investigators wish to explore the difference in 24 hr. cough counts measured using the Hull Automated Cough Counter (HACC), from baseline and after two weeks treatment with either montelukast or prednisolone in patients with an NO measurement of ≥30 ppb at screening.

Detailed Description
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Patients attending the unit as part of their normal outpatients' appointment will be approached with regards to whether interested in taking part in the study. During an outpatients appointment all new chronic cough patients undertake Demographics assessment, full blood count, spirometry test, FeNO measurement and concomitant medication as part of their standard medical care. If a patient decides to take part in this study then at this visit they will have further tests outside their standard medical care including, sputum induction, completion of Leicester cough questionnaire, cough challenge and 24 hr cough monitoring at the screening visit. All the data collected in terms of the clinic visit and additional tests will be analysed in this study. 40 patients with chronic cough and a FeNO≥30 ppb will be enrolled in to the High FeNO Treatment Groups. They will be randomised on a 1:1 ratio to receive either: Montelukast 10 mg daily for four weeks or Prednisolone 20 mg daily for two weeks followed by two weeks Montelukast 10 mg. 20 subjects with chronic cough and a FeNO≤20 ppb will be enrolled in low FeNO Treatment Group will receive montelukast 10 mg for 28 days. The study consists of five visits to the unit. The first visit will be combined with the patients scheduled clinic appointment. During this visit the investigators will carry out some preliminary assessments such as checking medical history, physical examination, full blood count and vital signs. Demographics assessments, spirometry test, FeNO measurement and concomitant medication will be recorded as per their scheduled clinic visit. Further testing will be conducted with regards to the study, these tests include: sputum induction, cough challenge, Hull Airways Reflux Questionnaire (HARQ), Leicester Cough Questionnaire (LCQ) and 24h cough monitoring all these tests will be operated at baseline and after 2 weeks and 4 weeks treatment. Also pregnancy test for women of child bearing potential is required in this study. At the end of visit 1, patients will receive 14 or 28 days' supply of the randomised study medication. Visit 2 (13th day) and visit 4 (27th day): Participants will be asked to come to the unit where The Hull Automated Cough Counter will be applied to measure their cough frequency for 24 hours at the end of their treatment. Visit 3 (14th day) and visit 5 (28th day): Patients will be assessed for any adverse events and any changes in concomitant medication use during the trial and also their vital signs will be checked. After that the FeNo measurement, Pulmonary Function Tests, cough challenge, sputum induction, 24h cough monitoring, Hull Airways Reflux Questionnaire (HARQ) and Leicester Cough Questionnaire (LCQ) will be repeated to compare with the first assessment. At the end of the study all patients will be reviewed by a chronic cough registrar/consultant as per the standard care as a clinic patient.

Official Title
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The Utility of feNO in the Differential Diagnosis of Chronic Cough: The Response to Anti-inflammatory Therapy With Prednisolone and Montelukast

Conditions
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Cough

Intervention / Treatment
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* Drug: Montelukast (High FeNO group)
* Drug: Prednisolon, Montelukast (High FeNO)
* Drug: Montelukast (Low FeNO group)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a history of chronic cough (at least 8 weeks duration) Male and female subjects of at least 18 yrs of age Subjects able to understand the study and co-operate with the study procedures Subjects who consent to their general practitioner (GP) being informed of their study participation. Patients with a FeNO of ≥30ppb at presentation to the Chronic cough clinic.( required for entry on to the high FeNO treatment groups) Patients with FeNO ≤ 20 ppb at presentation to the chronic cough clinic (required for entry as low FeNO treatment group) Exclusion Criteria: Patients with current diagnosis of asthma. Female subjects who are pregnant, or lactating, or who are of child bearing potential but are not using contraceptive measures. Suffering from any concomitant disease (chronic heart, chronic lung such as; COPD, bronchiectasis and cystic fibrosis, chronic renal, chronic liver or neuromuscular disease or immunosuppression; pneumonia and diabetes) which may interfere with study procedures or evaluation. A lower respiratory tract infection 4 weeks prior to entry on to study Systemic infections Live virus immunisation planned within next 3 months Subjects with no previous chickenpox who had a recent (<=28 days) close personal contact with chickenpox OR herpes zoster (high FeNO treatment groups only) Subjects having recent (<=28 days) exposure to measles (high FeNO treatment groups only) Participation in another study (use of investigational product) within 30 days preceding entry on to study. Alcohol or drug abuse Inability to follow study procedures Use of corticosteroids either as inhaled, topical or systemic ≥ 4weeks prior to enrolment Subjects with known allergy to prednisolone, montelukast Subjects who are taking Angiotensin Converting Enzymes (ACE) inhibitors. Current smoker Subjects who are taking bronchodilators should be on it for at least 4 weeks on regular dose and carry on the same dose during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Montelukast (high FeNO)<br>Montelukast 10 mg film-coated tablet contains montelukast sodium equivalent to 10 mg montelukast patients to take one tablet per day for 28 days Montelukast is a Class B medicine | Drug: Montelukast (High FeNO group)<br>* Montelukast 10 mg film-coated tablet contains montelukast sodium equivalent to 10 mg montelukast patients to take (oral use) one tablet per day for 28 days<br>* Other names: Montelukast;|
| Active Comparator: Prednisolone, Montelukast (high FeNO)<br>Prednisolone 5 mg and montelukast 10 mg. Patients to take Prednisolone 5 mg, 4 tablets per day for 14 days patients to take Montelukast 10 mg film-coated tablet per day for another 14 days Prednisolone is a Class A medicine Montelukast is a Class B medicine | Drug: Prednisolon, Montelukast (High FeNO)<br>* Prednisolone 5 mg, patients to take 4 tablets per day for 14 days then take Montelukast 10 mg tablet per day for another 14 days.<br>* Other names: Prednisolone and Montelukast;|
| Active Comparator: Montelukast<br>Montelukast 10 mg film-coated tablet contains montelukast sodium equivalent to 10 mg montelukast patients to take one tablet per day for 28 days Montelukast is a Class B medicine | Drug: Montelukast (Low FeNO group)<br>* Montelukast 10 mg film-coated tablet contains montelukast sodium equivalent to 10 mg montelukast patients to take one tablet per day for 28 days<br>* Other names: Montelukast;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hull Automated Cough counter | To determine the difference in objective measure of cough as demonstrated by 24 hr cough counts at the baseline, after 2 and 4 weeks treatment between three treatment groups with an associated elevated FeNO. | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HARQ and LCQ questionnaires | Compare change in subjective measures on HARQ and LCQ questionnaires of cough between the treatment groups at the baseline and after 2 week and 4 weeks treatment. | 28 days | 
| FVC as measured through spirometry | Compare change in FVC between treatment groups at the baseline and after 2 weeks and 4 weeks treatment. | 28 days | 
| Cough Challenge | Change in cough reflex sensitivity using inhaled citric acid between treatment groups at the baseline and after 2 weeks and 4 weeks treatment. | 28 days | 
| Sputum Induction | Change in Sputum inflammatory markers between treatment groups at the baseline and after 2 weeks and 4 weeks treatment. | 28 days | 
| Blood Count | Assess whether previous history of blood eosinophils may predict therapeutic response to anti-inflammatory medication in cough. | Baseline | 
| FeNO measurement | Assess whether the efficiency of FeNO may help to predict therapeutic response to anti-inflammatory medication in cough. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic