Asthmatic BronchitisNCT02555345
Gene Expression Profile and Inflammation Profile of Classic Asthma, Cough Variant Asthma and Eosinophilic Bronchitis
An observational study of Asthmatic Bronchitis, run by State Key Laboratory of Respiratory Disease at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Asthmatic Bronchitis
- How many people
- 250 participants
- Where
- 1 siteChina
- Study dates
- Oct 2014to Jan 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- The patients with classic asthma inclusion criteria Asthmatic patient inclusion criteria
- Male or female patients aged ≥ 18 and ≤ 65, who have signed an Informed Consent form prior to initiation of any study-related procedure.
- The patients with classic asthma had a history of episode dyspnea and wheezing with or without cough.
- 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.
- 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
Show all 18Show fewer
- Male or female patients aged ≥ 18 and ≤ 65, who have signed an Informed Consent form prior to initiation of any study-related procedure.
- 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.
- 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
- Male or female patients aged ≥ 18 and ≤ 65, who have signed an Informed Consent form prior to initiation of any study-related procedure.
- 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.
- 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
- Male or female patients aged ≥ 18 and ≤ 65, who have signed an Informed Consent form prior to initiation of any study-related procedure.
- Normal spirometry: baseline FEV1 ≥ 80% of the predicted normal value, FEV1/FVC(forced vital capacity) > LLN (lower limit of normal).
- Normal airways responsiveness.
- Healthy subjects have no any disease or negative allergen skin prick test results.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510120
Kefang Lai, PHD, 8620-83062887, Klai@163.com
Nanshan Zhong, MD, 8620-83062718, nanshan@vip.163.com
About this study
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
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.
Read the 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.
- Conditions
- Asthmatic Bronchitis
- Keywords
- classic asthma, cough variant asthma,eosinophilic bronchitis
- Medical subject headings
- Bronchiolitis, Cough-Variant Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| classic asthma/No intervention | Patients with classic asthma were stable.Chest X-ray or CT scan was normal.Fenofibrate(FeNO) was performed.Spirometry was needed. The leicester cough questionnaire (LCQ) was offered to physicians.Sputum,blood and urine samples were collected to study genetic, inflammation and other aspects of these diseases. | |
| CVA/No intervention | Chest X-ray or CT scan was normal.FeNO was performed. Spirometry was needed. The LCQ was offered to physicians. Sputum,blood and urine samples were collected to study genetic, inflammation and other aspects of these diseases. | |
| EB/No intervention | Chest X-ray or CT scan was normal.FeNO was performed. Spirometry was needed. The LCQ was offered.Sputum,blood and urine samples were collected to study genetic, inflammation and other aspects of these diseases. | |
| Healthy/No intervention | Chest X-ray or CT scan was normal.FeNO was performed.Spirometry was needed. Sputum,blood and urine samples were collected to study genetic, inflammation and other aspects of these diseases. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in Gene Expression Profile of Peripheral Blood Mononuclear Cells in Classic Asthma,Cough Variant Asthma and Eosinophilic Bronchitis Compared with Healthy Controls
Five milliliters of venous blood was collected. The peripheral blood mononuclear cells(PBMC) were isolated by the Ficoll-Paque plus(GE Healthcare Bio-Sciences Corp, NJ ) according to the manufacture's recommendations. RNA from PBMC was extracted. RNA-seq, a high throughput RNA sequencing technology, would characterize the transcriptome by sequencing complementary cDNAs followed by mapping of the sequence reads to the genome.
Measured: 15 months
Secondary outcomes (7)
Induced sputum cytology
Before sputum induction, subjects were instructed to rinse their mouth to remove any cellular debris. Nebulization was conducted using 3% saline via an ultrasonic nebulizer. Following expectoration into the clear sterile plastic pot, the sputum plugs were weighed and treated with 4 aliquots of dithiothreitol to completely dissolve the mucus. The mixture was subsequently vortexed, shaked and centrifuged. The supernatant was stored at -80℃ for inflammation profile analysis. The cell pallets were mounted on a glass slide for fixation with polyaldehyde and Haematoxylin-eosin staining. Samples with 5% or fewer epithelial cells of the total cell count were deemed eligible. This entailed counting of 400 non-squamous cells for cytology assessment. Inflammation phenotype was assigned based on a sputum eosinophil cutoff of greater than 3% and a sputum neutrophil cutoff of greater than 61%.
Measured: 15 months
Airway inflammation indices
Sputum Interleukin-1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, IP-10 (CXCL10), MCP-1 (CCL2), MIP-1β(CCL4) and C-reactive protein (CRP) were measured using Luminex xMAP multiplex technology. Comparison in airway inflammation in patients with classic asthma, cough variant asthma and eosinophilic bronchitis was performed.
Measured: 15 months
Fractional exhaled nitric oxide Measurements
Fractional exhaled nitric oxide Measurements will be performed by using a NIOX MINO device(Aerocrine, Sweden),based on the recommendations of international guidelines. The relationship between FENO levels and eosinophilic airway inflammation was assessed in patients with classic asthma, cough variant asthma and eosinophilic bronchitis.
Measured: 15 months
Peripheral blood eosinophil counts, serum IgE assessment
Blood was drawn for differential and total cell counts.Serum total Immunoglobulin E（IgE） and specific IgE was measured using the Unicap system(Pharmacia Diagnostics, Uppasala, Sweden ).Relationship between peripheral blood eosinophilia and IgE was assessed.Relationship between peripheral blood eosinophilia and sputum eosinophilia was assessed.Relationship between FENO and peripheral blood eosinophilia was assessed.Relationship between FENO and sputum eosinophilia was assessed.
Measured: 15 months
Cumulative provocative dose causing 20% fall in FEV1 measured through the Methacholine bronchial challenge test
Spirometric values at the baseline are referred to as FEV1, FVC, FEV1/FVC and MMEF. Spirometry tests are carried out using a spirometer (Jaeger, Germany). All operation procedures meet the joint recommendation by ATS and ERS.The predicted values are selected based on the reference regression model established by Jinping Zheng and nanshan Zhong.Methacholine bronchial challenge test was performed only in subjects with a baseline FEV1 greater than 60% predicted using hand-squeeze nebulizers.The bronchial challenge was ceased in case of FEV1 fall being 20% or greater, or the maximal cumulative dose of methacholine (2.50mg) had been given. Airway hyperresponsiveness (AHR) was defined as 20% or greater fall in FEV1.The cumulative provocative dose causing 20% fall in FEV1 (PD20FEV1-MCh) was reported in subjects with AHR. Relationship between FENO,serum IgE,airway and systematic inflammation and AHR was assessed.
Measured: 15 months
Using LCQ to evaluate the impact of cough on recruited patients with classic asthma, CVA and EB.
The questionnaire of Leicester Cough Questionnaire(LCQ) comprises 19 questions. Scores range from 3 to 21, with higher scores representing a better quality of life. Comparison in LCQ total scores in patients with classic asthma, cough variant asthma and eosinophilic bronchitis was performed.
Measured: 15 months
Circulating markers of inflammation
Serum was collected for analysis of systematic inflammation.systematic inflammation indices including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-13, IL-17, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1βand CRP.Comparison in systematic inflammation in patients with classic asthma, cough variant asthma and eosinophilic bronchitis was performed.
Measured: 15 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2015 (estimated)
- Study startOct 2014
- Primary completionJan 2016 (estimated)
- Study completionJan 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Asthmatic BronchitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 250 participants (estimated)
Sponsor and investigators
- Lead sponsor
- State Key Laboratory of Respiratory Disease
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rui Zhang, State Key Laboratory of Respiratory Disease
- Investigators
- Kefang Lai, PHD, Principal investigator, The First Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02555345
- Sponsor's protocol ID
- RZ-689
- Status last verified
- Sep 2015
- First submitted
- 7 Sep 2015
- Last updated
- 21 Sep 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02555345
- Acronym / sponsor ID
- RZ-689
- Conditions
- Asthmatic Bronchitis
- Keywords
- classic asthma, cough variant asthma,eosinophilic bronchitis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 250 participants (estimated)
- Lead sponsor
- State Key Laboratory of Respiratory DiseaseUniversity, hospital or other
- Study start
- Oct 2014
- Primary completion
- Jan 2016 (estimated)
- Study completion
- Jan 2016 (estimated)
- First posted
- 21 Sep 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| classic asthma/No intervention | – | –Patients with classic asthma were stable.Chest X-ray or CT scan was normal.Fenofibrate(FeNO) was performed.Spirometry was needed. The leicester cough questionnaire (LCQ) was offered to physicians.Sputum,blood and urine samples were collected to study genetic, inflammation and other aspects of these diseases. |
| CVA/No intervention | – | –Chest X-ray or CT scan was normal.FeNO was performed. Spirometry was needed. The LCQ was offered to physicians. Sputum,blood and urine samples were collected to study genetic, inflammation and other aspects of these diseases. |
| EB/No intervention | – | –Chest X-ray or CT scan was normal.FeNO was performed. Spirometry was needed. The LCQ was offered.Sputum,blood and urine samples were collected to study genetic, inflammation and other aspects of these diseases. |
| Healthy/No intervention | – | –Chest X-ray or CT scan was normal.FeNO was performed.Spirometry was needed. Sputum,blood and urine samples were collected to study genetic, inflammation and other aspects of these diseases. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (18 listed)
- The patients with classic asthma inclusion criteria Asthmatic patient inclusion criteria
- Male or female patients aged ≥ 18 and ≤ 65, who have signed an Informed Consent form prior to initiation of any study-related procedure.
- The patients with classic asthma had a history of episode dyspnea and wheezing with or without cough.
- 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.
- 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.
Key exclusion criteria (5 listed)
- Patients with classic asthma, CVA and EB exclusion criteria
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Difference in Gene Expression Profile of Peripheral Blood Mononuclear Cells in Classic Asthma,Cough Variant Asthma and Eosinophilic Bronchitis Compared with Healthy Controls
Time frame: 15 months
Five milliliters of venous blood was collected. The peripheral blood mononuclear cells(PBMC) were isolated by the Ficoll-Paque plus(GE Healthcare Bio-Sciences Corp, NJ ) according to the manufacture's recommendations. RNA from PBMC was extracted. RNA-seq, a high throughput RNA sequencing technology, would characterize the transcriptome by sequencing complementary cDNAs followed by mapping of the sequence reads to the genome.
7 secondary outcomes
Induced sputum cytology
Time frame: 15 months
Airway inflammation indices
Time frame: 15 months
Fractional exhaled nitric oxide Measurements
Time frame: 15 months
Peripheral blood eosinophil counts, serum IgE assessment
Time frame: 15 months
Cumulative provocative dose causing 20% fall in FEV1 measured through the Methacholine bronchial challenge test
Time frame: 15 months
Using LCQ to evaluate the impact of cough on recruited patients with classic asthma, CVA and EB.
Time frame: 15 months
Circulating markers of inflammation
Time frame: 15 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kefang Lai, PHD principal investigator
The First Affiliated Hospital of Guangzhou Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Asthmatic Bronchitis, run by State Key Laboratory of Respiratory Disease at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Kefang Lai, PHD (8620-83062887, klai@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in Gene Expression Profile of Peripheral Blood Mononuclear Cells in Classic Asthma,Cough Variant Asthma and Eosinophilic Bronchitis Compared with Healthy Controls (time frame: 15 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2015.