Leukocyte Function in Asthma and COPD

NCT00147069 | Completed Results

• 1 other identifier: 04-059
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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 protease/anti-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 lymphocyte/monocyte 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 monocyte/macrophage/neutrophil 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.

Conditions

Asthma; COPD; Emphysema; Chronic Bronchitis

Keywords

sputum; macrophage; neutrophil

Outcome Measures

Primary Outcomes (4)

• Total Number of Inflammatory Cells Recovered in Sputum

  Sputum was induced via inhalation of hypertonic saline as previously described, and was processed for differential counts of inflammatory cells.

  1 year

• Number of Matrix Metalloproteases (MMPs) MMP1

  MMPs determined using paired antibody quantitative ELISAs

  1 year

• Number of Matrix Metalloproteases (MMPs) MMP3

  MMPs determined using paired antibody quantitative ELISAs

  1 year

• Number of Matrix Metalloproteases (MMPs) MMP8

  MMPs determined using paired antibody quantitative ELISAs

  1 year

Study Arms (4)

Controls

Non-smoking control subjects without lung disease

Asthmatics

Non-smokers patients with asthma

Non-COPD smokers

Current smokers without airways obstruction, FEV1 \>80% predicted

COPD smokers

Patients with COPD and cigarette smokers

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Four groups of subjects were recruited: patients with COPD (cigarette smokers), diagnosed according to current standard criteria, patients with asthma (non-smokers), diagnosed according to current standard criteria, including a personal history of asthma, current smokers without airways obstruction (FEV1480% predicted) and non-smoking control subjects without lung disease

You may qualify if:

• Asthmatic patients:
• Age 21-79 years of both sexes (females will be taking adequate contraceptive measures).
• Increase in FEV1 \>15% and \>200ml following beta2 agonist inhalation, either at the time of study or previously documented
• COPD patients:
• Stable patients with a post-salbutamol FEV1 30-70% predicted normal of \>1L
• Increase in FEV1 \< 15% and \< 200 ml following beta2 agonist inhalation, either at the time of study or previously documented
• Age 21-79 years of both sexes (females will be taking adequate contraceptive measures )
• Smokers
• No history of allergic or respiratory disease.
• Normal Volunteers
• Age 21-79 years of both sexes (females will be taking adequate contraceptive measures )
• Non-smokers
• Normal lung function
• No upper respiratory tract infection within the last 4 weeks
• No history of allergic or respiratory disease.

You may not qualify if:

• Asthmatic patients with FEV1 less than 40% predicted value
• Alcohol abuse
• Any history or evidence of hepatic, cardiovascular or renal disease
• Any history or evidence of neuropsychiatric disease
• Drug abuse or any other condition associated with poor compliance
• Pregnancy or breast feeding
• Patients are unable to provide written informed consent
• COPD patients:
• \. Any other active lung diseases 2. Upper respiratory infection within the last 4 weeks 3. Pregnancy or breast feeding 4. Any mental condition rendering the patient unable to understand the nature, scope and possible consequences of the study 5. Subjects unable to give informed consent

Sponsors & Collaborators

• Imperial College London: lead

Study Sites (1)

Royal Brompton Hospital/NHLI Imperial College London

London, SW3 6LY, United Kingdom

Location

Related Publications (1)

• Culpitt SV, Rogers DF, Traves SL, Barnes PJ, Donnelly LE. Sputum matrix metalloproteases: comparison between chronic obstructive pulmonary disease and asthma. Respir Med. 2005 Jun;99(6):703-10. doi: 10.1016/j.rmed.2004.10.022. Epub 2004 Dec 13.

  PMID: 15878486 RESULT

Biospecimen

Retention: SAMPLES WITHOUT DNA

sputum

MeSH Terms

Conditions

Asthma; Pulmonary Disease, Chronic Obstructive; Emphysema; Bronchitis, Chronic

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bronchitis; Respiratory Tract Infections; Infections

Results Point of Contact

• Title: Professor Louise Donnelly
• Organization: Imperial College London

l.donnelly@imperial.ac.uk

+44 (0)20 7594 7895

Study Officials

• Louise E Donnelly, PhD

  Imperial College London

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2005
• First Posted: September 7, 2005
• Study Start: April 1, 2004
• Primary Completion: April 1, 2007
• Study Completion: April 1, 2007
• Last Updated: December 5, 2019
• Results First Posted: December 5, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)