Leukocyte Function in Chronic Obstructive Pulmonary Disease (COPD)

Leukocyte Migration and Differentiation in COPD Patients Compared to Healthy Smokers and Healthy Non-smoking Subjects.

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.

Study Overview

• Status: Completed
• Conditions: Emphysema; COPD; Chronic Bronchitis

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

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SW3 6LY
    • Royal Brompton Hospital/NHLI Imperial College London

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who had taken inhaled or oral steroids or who had suffered an exacerbation of their airway disease in the previous 6 weeks were excluded.

Description

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 exclusion criteria:

• Clinically significant findings in the medical history or on physical examination other than those of COPD in the COPD group.
• Pregnant women or mothers who are breastfeeding.
• Subjects who are unable to give informed consent.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
COPD; Patients with COPD - no intervention
Smokers without COPD; Smokers without COPD - no intervention
Non-smokers; Non-smokers with no history of respiratory disease - no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	2 hours
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	2 hours
Effective Concentration of MCP-1	Migration response of PBMC to Chemokine	2 hours

Collaborators and Investigators

• Sponsor: Imperial College London
• Investigators: Principal Investigator: Louise E Donnelly, PhD, Imperial College London

Publications and helpful links

General Publications

• Traves SL, Smith SJ, Barnes PJ, Donnelly LE. Specific CXC but not CC chemokines cause elevated monocyte migration in COPD: a role for CXCR2. J Leukoc Biol. 2004 Aug;76(2):441-50. doi: 10.1189/jlb.1003495. Epub 2004 May 20.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2001
• Primary Completion (Actual): December 1, 2004
• Study Completion (Actual): April 1, 2007

Study Registration Dates

• First Submitted: September 6, 2005
• First Submitted That Met QC Criteria: September 6, 2005
• First Posted (Estimate): September 7, 2005

Study Record Updates

• Last Update Posted (Actual): December 5, 2019
• Last Update Submitted That Met QC Criteria: December 4, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: neutrophil; chemokine; lymphocyte; chemokine receptor; monocyte
• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Emphysema; Bronchitis; Bronchitis, Chronic
• Other Study ID Numbers: 01-024

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No