Biomarkers for Predicting the Response to Inhaled Corticosteroid in Patients With Chronic Cough.

Study Overview
=================
Brief Summary
-----------------
To investigate the value of blood eosinophils, FeNO and total IgE in predicting the response to inhaled corticosteroid in patients with chronic cough.

Detailed Description
-----------------
Chronic cough is a frequent complaint in respiratory specialists clinic. CVA, UACS, EB, GERC and AC are common causes of chronic cough, among whom, CVA, EB and AC can be classified as corticosteroid responsive cough. To recognize the eosinophilic airway inflammation and assess the response of inhaled corticosteroid, induced sputum analysis is the most widely used examination but not all the subjects can provide an suitable sample of sputum for measurements and it's time-consuming. Recently, blood eosinophils, FeNO and total IgE were detected to be biomarkers of eosinophilic airway inflammation for asthmatics. However, whether can they predict the response to corticosteroid in chronic cough remains uncertain. The present prospective, multi-center, randomized placebo-controlled study aims to explore the value of blood eosinophils, FeNO and total IgE in predicting the response to inhaled corticosteroid in patients with chronic cough.

Official Title
-----------------
The Value of FeNO, Blood Eosinophils and TIgE in Predicting the Response to Corticosteroid in Patients With Chronic Cough

Conditions
-----------------
Cough

Intervention / Treatment
-----------------
* Drug: Beclometasone Dipropionate and Formoterol Inhalation Aerosol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age: 18-70 years; Coughing lasting ≥ 8 weeks； No abnormality in chest imaging in the past 3 months (or there is abnormality but the investigator judges it not the cause of chronic cough)； FEV1% pred>70%；FEV1/FVC>70%； VAS≥30 in the past 48 hours; Non-smokers or patients smoked less than 10 pack-years; Candidates voluntarily participate in and abide by the relevant regulations of the study, can cooperate with corresponding inspections, follow the follow-up plan, and voluntarily sign written informed consent. Exclusion Criteria: Patients received inhaled or oral corticosteroids or leukotriene receptor antagonist in previous 4 weeks; Patients with history of upper respiratory tract infection in the past 8 weeks; Patients taking angiotensin-converting enzyme inhibitors in previous 8 weeks; Female subjects who are pregnant, breast-feeding or risk of becoming pregnant during the study; Combined with a definite history of pulmonary diseases such as bronchiectasis, pulmonary interstitial disease, and pulmonary hypertension. Combined with other serious diseases (such as cardiovascular system diseases, metabolic system diseases, immune system diseases, nervous system diseases, etc.) that may affect the normal process of this study; Participating in other drug clinical trial projects.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: a multi-center, randomized, double-blind, placebo-controlled trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Foster treatment group<br>Participant inhales Foster (Inhaled Beclometasone Dipropionate and Formoterol Inhalation Aerosol) 1 puff bid for 4 weeks. | Drug: Beclometasone Dipropionate and Formoterol Inhalation Aerosol<br>* Inhaled Foster (Beclometasone Dipropionate and Formoterol Inhalation Aerosol) , 1puff, BID, 4weeks<br>|
| Placebo Comparator: Placebo controlled group<br>Participant inhales matched placebo 1 puff bid for 4 weeks. | Drug: Placebo<br>* Inhaled Placebo, 1puff, BID, 4weeks<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The AUC of blood eosinophils, FeNO and total IgE in predicting the response to inhaled corticosteroid in patients with chronic cough. | The area under the receiver operating curve (AUC) of blood eosinophils in predicting the response to inhaled corticosteroid in patients with chronic cough. The area under the receiver operating curve (AUC) of FeNO in predicting the response to inhaled corticosteroid in patients with chronic cough. The area under the receiver operating curve (AUC) of total IgE in predicting the response to inhaled corticosteroid in patients with chronic cough. | the 4th week | 
| The optimal cut-off value of blood eosinophils in cells/μL-1 in predicting the response to inhaled corticosteroid in patients with chronic cough. | The optimal cut-off value of blood eosinophils in cells/μL-1 in predicting the response to inhaled corticosteroid in patients with chronic cough. | the 4th week | 
| The optimal cut-off value of FeNO in pbb in kU/L in predicting the response to inhaled corticosteroid in patients with chronic cough. | The optimal cut-off value of FeNO in pbb in predicting the response to inhaled corticosteroid in patients with chronic cough. | the 4th week | 
| The optimal cut-off value of total IgE in kU/L in predicting the response to inhaled corticosteroid in patients with chronic cough. | The optimal cut-off value of total IgE in kU/L in predicting the response to inhaled corticosteroid in patients with chronic cough. | the 4th week | 
| The sensitivity and specificity in percentage of blood eosinophils, FeNO and total IgE in predicting the response to inhaled corticosteroid in patients with chronic cough. | The sensitivity and specificity in percentage of blood eosinophils in predicting the response to inhaled corticosteroid in patients with chronic cough. The sensitivity and specificity in percentage of FeNO in predicting the response to inhaled corticosteroid in patients with chronic cough. The sensitivity and specificity in percentage of total IgE in predicting the response to inhaled corticosteroid in patients with chronic cough. | the 4th week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical characteristics of responders and non-responders | Clinical characteristics including gender, age and cough duration would be registered in a specific case report form in baseline. | baseline | 
| LCQ change from baseline to the 4th week | Leicester Cough Questionnaire （LCQ）aims to access the life quality of patients wtih chronic cough, ranging from 19 to 133. Higher scores mean a better outcome. | the 4th week | 
| Cough VAS change from baseline to the 4th week | Cough visual analogue scale (VAS) aims to access the severity of cough, ranging from 0 to 100mm. Higher scores mean a worse outcome. | the 4th week | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
chronic cough, biomarkers