Ignite Creation Date:
2024-05-05 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00147069
Status:
COMPLETED
Last Update Posted:
2019-12-05
First Post:
2005-09-06
Brief Title:
Leukocyte Function in Asthma and COPD
Sponsor:
Imperial College London
Organization:
Imperial College London
Study Overview
Official Title:
Investigation Into Inflammatory Mechanisms in Airway Cells in Smokers and Non-smokers With Inflammatory Lung Disease
Status:
COMPLETED
Status Verified Date:
2019-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The aim of this study is to examine the inflammatory mechanisms involved in the pathogenesis of inflammatory lung disease in particular to compare the inflammatory profile seen in asthma and COPD Evidence for inflammation in asthma and COPD is based on the finding of increased numbers of macrophages and neutrophils in the lungs and respiratory secretions of these patients The inflammatory cells produce proteases as well as reactive oxidant species resulting in a proteaseanti-protease imbalance which favours lung destruction The aim is to examine the inflammatory mediators released by inflammatory cells such as macrophages and lymphocytes in order to determine whether there are differences between non-smoking subjects smoking subjects and patients with asthma or COPD Monocytes are precursors of alveolar macrophages and both monocytes and neutrophils are recruited to the lung from the blood via the action of specific chemoattractants We have evidence that in inflammation there are higher levels of these chemoattractants Therefore these cells might also demonstrate the same changes seen in alveolar macrophages from these patients
We also aim to assess the role of the macrophage precursor monocyte and neutrophils in the blood We will also assess lymphocytemonocyte interaction We will do this as the lymphocyte may be involved in the initial recruitment of inflammatory cells We will also assess the role of cytokines involved with monocytemacrophageneutrophil migration in induced sputum as well as the role of induced sputum in the migration of monocytes and neutrophils into the lung Our aim is to link the initial changes in blood to the changes causing disease in the lungs We aim to examine cellular responses in four groups of subjects namely i non-smoking controls ii smokers without clinical evidence of COPD or asthma iii smokers with COPD iv asthmatic patients
We also aim to assess the role of the macrophage precursor monocyte and neutrophils in the blood We will also assess lymphocytemonocyte interaction We will do this as the lymphocyte may be involved in the initial recruitment of inflammatory cells We will also assess the role of cytokines involved with monocytemacrophageneutrophil migration in induced sputum as well as the role of induced sputum in the migration of monocytes and neutrophils into the lung Our aim is to link the initial changes in blood to the changes causing disease in the lungs We aim to examine cellular responses in four groups of subjects namely i non-smoking controls ii smokers without clinical evidence of COPD or asthma iii smokers with COPD iv asthmatic patients
Detailed Description:
Overall subjects will be characterised into one of four groups normal non-smoking subjects healthy smokers patients with asthma and patients with COPD Subjects will have had to fulfil inclusion and exclusion criteria and give written consent
Recruitment Methods Volunteer subjects healthy non-smokers and healthy smokers will be recruited from within the National Heart and Lung Institute Volunteers will be recruited via advertising using ethically approved advertisements Asthmatic and COPD patients will be recruited from the outpatient clinic at The Royal Brompton Hospital At the screening visit the diagnosis of asthma or COPD will be confirmed from the clinical case notes If the patient is a volunteer they will undergo a full history and examination spirometry Each subject will attend on one study visit only At the first visit a number of investigations will be undertaken including spirometry with reversibility 400 microg ventolin via metered dose inhaler if initial spirometry shows an obstructive picture to exclude asthmatics and sputum induction In addition 50ml of venous blood will be taken
More specifically the following interventions will be undertaken by each subject
1 Medical History and Physical Examination A full medical history and physical examination including height and weight will be performed on the initial screening visit in addition to that recorded in the clinical case notes
2 Respiratory Assessments Forced Expiratory Volume per second FEVI will be measured using a dry wedge spirometer Vitalograph Buckingham UK and expressed as a percent of predicted value Subjects will be trained in the use of the apparatus before beginning the study The baseline value at each visit will be measured after at least fifteen minutes of quiet rest and will be taken as the highest of three readings made at one minute intervals 400 microg ventolin administered via a metered dose inhaler will be given if initial spirometry shows an obstructive picture FEV1 80 predicted FEV1 FVC70 in order to distinguish between the presence of asthma or COPD
3 Sputum Induction Sputum induction will be performed in the Asthma Laboratory The subject will inhale 35 saline at room temperature nebulised via a De Vilbiss 99 Ultrasonic nebuliser set at maximum output using a mouthpiece After five minutes the subject will rinse hisher mouth thoroughly with water and will be asked to cough deeply and expectorate sputum into a pot Samples from this first five minute collection are discarded This procedure will continue for a further ten minutes and the resulting sample will be collected in a polypropylene pot
It is important to explain to the subject that the aim is to obtain sputum and that saliva should be disposed of by spitting into a bowl which is later discarded
In the case of any chest discomfort or shortness of breath the procedure is stopped and spirometry is repeated If the FEV1 has fallen by 10 of the predicted value the subject can rest until the FEV1 has returned to the baseline value or the procedure can be terminated
Sputum samples will be analysed for differential and absolute cell counts eosinophils neutrophils macrophages lymphocytes and columnar epithelial cells Sputum supernatants will be assayed for TNF-alpha IL-8 interferon-gamma and other cytokine levels
Immunohistochemistry will be performed on the induced sputum samples to identify the cellular localisation of factors involved with leukocyte function
Cytospin preparations will be made for differential cell counts and the soluble fraction will be used for cytokine assays
4 Venous Blood Sampling Fifty 50 millilitres of blood shall be venesected at the study visit We will investigate factors involved in leukocyte function and chemotaxis We will also assess cellular distributions of receptors thought to be important in regulation by using FACS analysis
Recruitment Methods Volunteer subjects healthy non-smokers and healthy smokers will be recruited from within the National Heart and Lung Institute Volunteers will be recruited via advertising using ethically approved advertisements Asthmatic and COPD patients will be recruited from the outpatient clinic at The Royal Brompton Hospital At the screening visit the diagnosis of asthma or COPD will be confirmed from the clinical case notes If the patient is a volunteer they will undergo a full history and examination spirometry Each subject will attend on one study visit only At the first visit a number of investigations will be undertaken including spirometry with reversibility 400 microg ventolin via metered dose inhaler if initial spirometry shows an obstructive picture to exclude asthmatics and sputum induction In addition 50ml of venous blood will be taken
More specifically the following interventions will be undertaken by each subject
1 Medical History and Physical Examination A full medical history and physical examination including height and weight will be performed on the initial screening visit in addition to that recorded in the clinical case notes
2 Respiratory Assessments Forced Expiratory Volume per second FEVI will be measured using a dry wedge spirometer Vitalograph Buckingham UK and expressed as a percent of predicted value Subjects will be trained in the use of the apparatus before beginning the study The baseline value at each visit will be measured after at least fifteen minutes of quiet rest and will be taken as the highest of three readings made at one minute intervals 400 microg ventolin administered via a metered dose inhaler will be given if initial spirometry shows an obstructive picture FEV1 80 predicted FEV1 FVC70 in order to distinguish between the presence of asthma or COPD
3 Sputum Induction Sputum induction will be performed in the Asthma Laboratory The subject will inhale 35 saline at room temperature nebulised via a De Vilbiss 99 Ultrasonic nebuliser set at maximum output using a mouthpiece After five minutes the subject will rinse hisher mouth thoroughly with water and will be asked to cough deeply and expectorate sputum into a pot Samples from this first five minute collection are discarded This procedure will continue for a further ten minutes and the resulting sample will be collected in a polypropylene pot
It is important to explain to the subject that the aim is to obtain sputum and that saliva should be disposed of by spitting into a bowl which is later discarded
In the case of any chest discomfort or shortness of breath the procedure is stopped and spirometry is repeated If the FEV1 has fallen by 10 of the predicted value the subject can rest until the FEV1 has returned to the baseline value or the procedure can be terminated
Sputum samples will be analysed for differential and absolute cell counts eosinophils neutrophils macrophages lymphocytes and columnar epithelial cells Sputum supernatants will be assayed for TNF-alpha IL-8 interferon-gamma and other cytokine levels
Immunohistochemistry will be performed on the induced sputum samples to identify the cellular localisation of factors involved with leukocyte function
Cytospin preparations will be made for differential cell counts and the soluble fraction will be used for cytokine assays
4 Venous Blood Sampling Fifty 50 millilitres of blood shall be venesected at the study visit We will investigate factors involved in leukocyte function and chemotaxis We will also assess cellular distributions of receptors thought to be important in regulation by using FACS analysis
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None