Clinical trial NCT02555345: Gene Expression Profile and Inflammation Profile of Classic Asthma, Cough Variant Asthma and Eosinophilic Bronchitis
Official title: Difference in Gene Expression Profile in Peripheral Blood Mononuclear Cells and Inflammation Profile in Patients With Classic Asthma, Cough Variant Asthma, and Eosinophilic Bronchitis Compared With Healthy Controls
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Asthmatic Bronchitis
Keywords: classic asthma, cough variant asthma,eosinophilic bronchitis
Lead sponsor: State Key Laboratory of Respiratory Disease
Sponsor class: OTHER
First posted: 2015-09-21
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: All of subjects with classic asthma, CVA, eosinophilic bronchitis, and healthy volunteers are recruited from respiratory outpatient clinics and from staff at the First Affiliated Hospital of Guangzhou Medical College between October 25, 2014 and January 20,2016.

Brief summary: This study aims to identify and validate the gene expression differentials of peripheral blood mononuclear cells and differential inflammation profiles and other aspects in classic asthma, cough-variant asthma and eosinophilic bronchitis.

Detailed description: Asthma is a common and heterogeneous respiratory disorder affecting millions of people, posing a considerable burden on health care systems globally. The disease is characterized by inflammation of the airways with eosinophils, neutrophils, mast cells, lymphocytes, airway epithelial cells, smooth muscle cells and other cells, by airflow obstruction and by bronchial hyperresponsiveness. The disease is triggered by multiple gene-environment interactions. Asthma heterogeneity is recognized in terms of clinical phenotypes of asthma whereby classic asthma (CA) and cough variant asthma (CVA) are identified. classic asthma is a common phenotype of asthma that presents episodic dyspnoea and wheezing with or without cough. Cough variant asthma is a phenotype of asthma that presents solely cause of chronic cough.

Eosinophilic bronchitis (EB) is a common cause of chronic cough, which like eosinophils asthma is characterized by airway eosinophilic inflammation, but unlike asthma there is no airway hyperresponsiveness or variable airflow obstruction.

Improvement of disease diagnosis and management require a better understanding of disease heterogeneity. A useful biomarker for phenotype recognition will represent underlying pathologic mechanisms of disease, marking heterogeneity and guiding personalized treatment approaches. Our hypothesis was that the different clinical manifestos in patients with eosinophilic bronchitis, classic asthma, and cough-variant asthma could be caused by differential gene expression profiles of peripheral blood mononuclear cells (PBMC) and differential inflammation profiles and other aspects.

Eligibility criteria: Inclusion Criteria:

The patients with classic asthma inclusion criteria Asthmatic patient inclusion criteria

1. Male or female patients aged ≥ 18 and ≤ 65, who have signed an Informed Consent form prior to initiation of any study-related procedure.
2. The patients with classic asthma had a history of episode dyspnea and wheezing with or without cough.
3. Clinical diagnosis of asthma confirmed by a chest physician according to international guidelines (GINA 2014); methacholine airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1(forced expiratory volume at one second )【PD20】),\>12% improvement in FEV1 10 min after inhaling 200ug of salbutamol.
4. None of the patients with classic asthma had used inhaled or oral corticosteroids, long-acting β2-agonists, leukotriene antagonists, sodium cromoglycate,or nedocromil sodium, anticholinergic agents, during four weeks prior to entry into the study.

The patients with CVA inclusion criteria

1. Male or female patients aged ≥ 18 and ≤ 65, who have signed an Informed Consent form prior to initiation of any study-related procedure.
2. The diagnosis of CVA is based on isolated cough lasting for ≥ 8 weeks without wheezing or dyspnea, airway hyperresponsiveness (AHR), and relief of cough with bronchodilators according to recommendations in the Chinese national guidelines on the diagnosis and management of cough.
3. None of the patients with CVA had used inhaled or oral corticosteroids, long-acting β2-agonists, leukotriene antagonists, sodium cromoglycate,or nedocromil sodium, anticholinergic agents, during four weeks prior to entry into the study.

The patients with EB inclusion criteria

1. Male or female patients aged ≥ 18 and ≤ 65, who have signed an Informed Consent form prior to initiation of any study-related procedure.
2. The diagnosis of EB is based on cough lasting for ≥ 8 weeks according to recommendations in the Chinese national guidelines on the diagnosis and management of cough.
3. None of the patients with EB had used inhaled or oral corticosteroids, long-acting β2-agonists, leukotriene antagonists, sodium cromoglycate,or nedocromil sodium, anticholinergic agents, during four weeks prior to entry into the study.

Healthy subjects inclusion criteria

1. Male or female patients aged ≥ 18 and ≤ 65, who have signed an Informed Consent form prior to initiation of any study-related procedure.
2. Normal spirometry: baseline FEV1 ≥ 80% of the predicted normal value, FEV1/FVC(forced vital capacity) \> LLN (lower limit of normal).
3. Normal airways responsiveness.
4. Healthy subjects have no any disease or negative allergen skin prick test results.

Exclusion Criteria:

Patients with classic asthma, CVA and EB exclusion criteria

The presence of any of the following will exclude a subject from study enrolment:

Current smokers, ex-smokers. Individuals with respiratory infection during the previous one month. Clinical history of chronic obstructive pulmonary disease(COPD), bronchiectasis, pulmonary embolism.

Clinical history of haematological, immunologic, renal, neurologic, hepatic, endocrinal or other disease, or any condition that might compromise the results or interpretation of the study.

Asthma exacerbation and unstable asthma . Pregnant or lactating women.

Primary outcomes:
measure: Difference in Gene Expression Profile of Peripheral Blood Mononuclear Cells in Classic Asthma,Cough Variant Asthma and Eosinophilic Bronchitis Compared with Healthy Controls
timeFrame: 15 months
Secondary outcomes:
measure: Induced sputum cytology
timeFrame: 15 months
measure: Airway inflammation indices
timeFrame: 15 months
measure: Fractional exhaled nitric oxide Measurements
timeFrame: 15 months
measure: Peripheral blood eosinophil counts, serum IgE assessment
timeFrame: 15 months
measure: Cumulative provocative dose causing 20% fall in FEV1 measured through the Methacholine bronchial challenge test
timeFrame: 15 months
measure: Using LCQ to evaluate the impact of cough on recruited patients with classic asthma, CVA and EB.
timeFrame: 15 months
measure: Circulating markers of inflammation
timeFrame: 15 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: The First Affiliated Hospital of Guangzhou Medical University
name: Kefang Lai, PHD
role: PRINCIPAL_INVESTIGATOR
References: