Leukocyte Function in Chronic Obstructive Pulmonary Disease (COPD)
Leukocyte Function in Chronic Obstructive Pulmonary Disease (COPD)
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.
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
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.