Chronic Bronchitis, COPD, Emphysema
Conditions
Keywords
chemokine, chemokine receptor, neutrophil, lymphocyte, monocyte
Brief summary
The aim of this study is to investigate the mechanisms whereby leukocytes are recruited to the lung in chronic obstructive pulmonary disease (COPD) and cause tissue destruction. The hypothesis is that in COPD more leukocytes enter the lung and it is these cells that are responsible for the degradation of lung tissue. We, the researchers at Imperial College London, will isolate leukocytes from the blood of patients with COPD, healthy smokers and normal subjects and measure the movement of the leukocytes to chemoattractants. We will examine further, which cell surface receptors are responsible for this trafficking of cells. Furthermore, the differentiation of these cells in vitro will be compared with cells from healthy smokers and normal subjects. Specifically, the expression of enzymes that are responsible for tissue destruction and the cell surface receptors on these cells will be investigated. The objective is to identify the mechanisms whereby leukocytes from COPD patients behave differently to cells from healthy smokers and normal subjects with a view to identify novel targets for drug therapy.
Detailed description
Chemotaxis experiments will be performed in order to ascertain the migratory characteristics of leukocytes towards specific chemoattractants. Comparisons of cells from different subjects will be compared. In addition, the effects of various pharmaceutical interventions on this mechanism will also be addressed and compared within subject groups. In some experiments, cells will be differentiated in vitro and their cellular expression and regulation of inflammatory mediators and chemoattractants examined. Again comparisons will be made between subject groups and the efficacy of various pharmacological agents on these cells
Interventions
None listed
Sponsors
Imperial College London
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
21 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy Non-Smoking Subjects. All normal volunteers will meet the following criteria: * Age 21-70 years. * No history of respiratory or allergic disease. * Normal baseline spirometry as predicted for age, sex and height. * Non-smokers. * No history of upper respiratory tract infection in the preceding six weeks. * Not taking regular medication * COPD Subjects. COPD is diagnosed according to American Thoracic Society, European Respiratory Society and British Thoracic Society guidelines. All COPD volunteers will meet the following criteria: * Age between 40-75 years. * A smoking history of at least 20 pack years. (1 pack year = 20 packs of cigarettes per day for 1 year) * Forced expiratory volume at 1 second : Forced vital capacity (FEV1:FVC) ratio of \<0.7, post-bronchodilator FEV1 of \<85% predicted, reversibility with inhaled beta2-agonist of \<15% of predicted FEV1: all three criteria are required. * Current smokers or smokers who had ceased smoking for at least 6 months. * No history of exacerbation, oral steroid or antibiotic use within the preceding 6 weeks. * Normal serum alpha-1 antitrypsin level. * No history of other respiratory or allergic disease. * No evidence of atopy on skin prick testing to common aeroallergens (grass pollen, cat hair, house dust mite or Aspergillus fumigatus * Healthy Smokers. All healthy smoking volunteers in trials will meet the following criteria: * Age 21-70 years. * Smoking history of at least 10 pack years. (1 pack year = 10 packs of cigarettes per day for 1 year). * No history of respiratory or allergic disease. * Normal baseline spirometry as predicted for age, sex and height. * No history of upper respiratory tract infection in the preceding six weeks. * Not taking regular medication.
Exclusion criteria
Subjects will not be included in this study if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effective Concentration (EC 50) of GRO Alpha | 2 hours | Migration response of PBMC to Chemokine EC 50 represents the concentration of a drug that is required for 50% inhibition in vitro |
| Effective Concentration of IL-8 | 2 hours | Migration response of PBMC to Chemokine EC 50 represents the concentration of a drug that is required for 50% inhibition in vitro |
| Effective Concentration of MCP-1 | 2 hours | Migration response of PBMC to Chemokine |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| COPD Patients with COPD - no intervention | 37 |
| Smokers Without COPD Smokers without COPD - no intervention | 33 |
| Non-smokers Non-smokers with no history of respiratory disease - no intervention | 30 |
| Total | 100 |
Baseline characteristics
| Characteristic | COPD | Smokers Without COPD | Non-smokers | Total |
|---|---|---|---|---|
| Age, Continuous | 65 years STANDARD_DEVIATION 10 | 40 years STANDARD_DEVIATION 12 | 34 years STANDARD_DEVIATION 8 | 47.45 years STANDARD_DEVIATION 10 |
| FEV1 (% predicted) | 47 % predicted STANDARD_DEVIATION 15 | 93 % predicted STANDARD_DEVIATION 21 | 102 % predicted STANDARD_DEVIATION 14 | 78.7 % predicted STANDARD_DEVIATION 17 |
| Race and Ethnicity Not Collected | — | — | — | 0 Participants |
| Region of Enrollment United Kingdom | 37 participants | 33 participants | 30 participants | 100 participants |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 13 Participants | 41 Participants |
| Sex: Female, Male Male | 24 Participants | 18 Participants | 17 Participants | 59 Participants |
| Smoking History | 48 pack/years STANDARD_DEVIATION 27 | 21 pack/years STANDARD_DEVIATION 16 | 0 pack/years STANDARD_DEVIATION 0 | 24.7 pack/years STANDARD_DEVIATION 21 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 33 | 0 / 30 |
| other Total, other adverse events | 0 / 37 | 0 / 33 | 0 / 30 |
| serious Total, serious adverse events | 0 / 37 | 0 / 33 | 0 / 30 |
Outcome results
Primary
Effective Concentration (EC 50) of GRO Alpha
Migration response of PBMC to Chemokine EC 50 represents the concentration of a drug that is required for 50% inhibition in vitro
Time frame: 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COPD | Effective Concentration (EC 50) of GRO Alpha | 1.5 ng/ml | Standard Error 0.9 |
| Smokers Without COPD | Effective Concentration (EC 50) of GRO Alpha | 0.9 ng/ml | Standard Error 0.2 |
| Non-smokers | Effective Concentration (EC 50) of GRO Alpha | 0.6 ng/ml | Standard Error 0.3 |
Comparison: p values were calculatedp-value: 0.05Kruskal-Wallis
Primary
Effective Concentration of IL-8
Migration response of PBMC to Chemokine EC 50 represents the concentration of a drug that is required for 50% inhibition in vitro
Time frame: 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COPD | Effective Concentration of IL-8 | 0.2 ng/ml | Standard Error 0.1 |
| Smokers Without COPD | Effective Concentration of IL-8 | 1.4 ng/ml | Standard Error 0.4 |
| Non-smokers | Effective Concentration of IL-8 | 0.8 ng/ml | Standard Error 0.4 |
Comparison: p value was calculatedp-value: 0.05Kruskal-Wallis
Primary
Effective Concentration of MCP-1
Migration response of PBMC to Chemokine
Time frame: 2 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| COPD | Effective Concentration of MCP-1 | 0.5 ng/ml | Standard Error 0.4 |
| Smokers Without COPD | Effective Concentration of MCP-1 | 0.2 ng/ml | Standard Error 0.2 |
| Non-smokers | Effective Concentration of MCP-1 | 0.3 ng/ml | Standard Error 0.3 |
Comparison: The p value was calculatedp-value: 0.05Kruskal-Wallis