Cigarette Smoke Nasal and Whole Blood Challenge in Patients With Chronic Obstructive Pulmonary Disease (COPD)

NCT00159341 | Completed Phase 1

• 1 other identifier: 05/Q0404/84
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This is a clinical research study to assess whether after exhaling a single cigarette smoke through the nose there are changes in the inflammatory cells and proteins of nasal secretions. A single blood sample from each subject will be stimulated with cigarette smoke in the laboratory to see the effects on inflammatory blood cells. Comparison of findings between smokers with COPD and "Healthy" smokers will be carried out. We hypothesize that some subjects have amplified inflammatory response to a single cigarette, and these will be those subjects who develop chronic obstructive pulmonary disease (COPD) after decades of smoking. We hope to develop an acute challenge model that relates to the causation of COPD. When studying the effects of new drugs, these may be detected in small numbers of patients in a challenge situation, when we would need to study many more unchallenged patients to demonstrate drug effects. In clinical research on asthma and allergy, the nasal allergen challenge has been a very successful model, and we hope to validate a comparable model for COPD.

Conditions

Lung Diseases, Obstructive

Keywords

cigarette smoke; nasal; whole blood; cytokines; chemokines; nasal fluid; filter paper

Outcome Measures

Primary Outcomes (1)

• Changes in the cytology and inflammatory mediator content of nasal exudates

  Single timepoint

Secondary Outcomes (6)

• Comparison of nasal inflammatory response to smoke in patients with COPD with relevant controls

  Single timepoint

• Comparison of inflammatory response in blood following cigarette smoking in patients with COPD and relevant controls

  Single timepoint

• Comparison of nasal challenge with blood challenge

  Single timepoint

• Develop a nasal challenge model to test novel anti-inflammatoy therapies for COPD

  Single timepoint

• Identification of potential biomarkers for therapeutic trials in COPD

  Single timepoint

Interventions

Nasal lavage PROCEDURE

Nasal lavage was carried out at specified timepoints

Nasal filter paper PROCEDURE

Nasal filter paper was placed at specified timepoints

Blood sampling PROCEDURE

Blood sampling was performed as a routine safety check

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Smokers currently on at least 5 cigarettes per day, with a history of \>10 pack years
• Post-bronchodilator FEV1 \>30% of predicted and \< 80% of predicted
• Pre-bronchodilator FEV1/FVC of \<70%
• With or without chronic simple bronchitis

You may not qualify if:

• History of asthma, allergy (including rhinitis/eczema)
• Reversibility : an increase in FEV1 that is \>400ml from the baseline pre- bronchodilator value (bronchodilate with salbutamol 400g delivered from a metered dose inhaler (MDI) into a spacer).
• Smokers currently on at least 5 cigarettes per day, with a history of \>10 pack years
• FEV1 \>90% of predicted, FEV1/FVC of \>70%
• Cannot have chronic simple bronchitis
• Age, sex, smoking history matched to COPD Smokers
• History of asthma, allergy (including rhinitis/eczema
• Reversibility: an increase in FEV1 that is both \>400ml from the baseline pre-bronchodilator value (bronchodilate with salbutamol 400mcg delivered from a metered dose inhaler (MDI) into a spacer)P
• Pregnancy

Sponsors & Collaborators

• Imperial College London: lead
• Millennium Pharmaceuticals, Inc.: collaborator

Study Sites (1)

National Heart & Lung Institue Clinical Studies Unit, Imperial College London

London, SW3 6HP, United Kingdom

Location

Related Publications (1)

• - Vachier I et al.Inflammatory features of nasal mucosa in smokers with and without COPD. Thorax 2004; 59:303-307. - Naclerio RM et al. Mediator release after nasal airway challenge with allergen. Am Rev Respir Dis 1983; 128:597-602. - Greiff L et al. The 'nasal pool' device applies controlled concentrations of solutes on human nasal airway mucosa and samples its surface exudations/secretions. Clin Exp Allergy 1990; 20:253-259. - Alam R et al. Development of a new technique for recovery of cytokines from inflammatory sites in situ. J Immunol Methods 1992; 155:25-29. - Weido AJ et al. Intranasal fluticasone propionate inhibits recovery of chemokines and other cytokines in nasal secretions in allergen-induced rhinitis. Ann Allergy Asthma Immunol 1996; 77:407-415. - Meltzer EO, Jalowayski AA. Nasal cytology in clinical practice. Am J Rhinol 1988; 2:47-54. - Fishwick D et al. Immunologic response to inhaled endotoxin: changes in peripheral cell surface markers in normal individuals. J Occup Environ Med 2004; 46:467-472. - Mudway IS, Kelly FJ. An investigation of inhaled ozone dose and the magnitude of airway inflammation in healthy adults. Am J Respir Crit Care Med 2004; 169:1089-1095. - Rahman I et al. Glutathione, stress responses, and redox signalling in lung inflammation. Antioxidants & Redox Signalling 2005; 7:42-59. - Koechlin C et al. Does systemic inflammation trigger local exercise-induced oxidative stress in COPD? Eur Respir J 2004; 23:538-544.

  RESULT

Related Links

• Imperial College London website

MeSH Terms

Conditions

Lung Diseases, Obstructive; Cigarette Smoking

Interventions

Nasal Lavage; Blood Specimen Collection

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Tobacco Smoking; Smoking; Behavior; Tobacco Use

Intervention Hierarchy (Ancestors)

Therapeutic Irrigation; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative

Study Officials

• Trevor T Hansel, BSc MSc PhD

  National Heart & Lung Institute, Imperial College London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 8, 2005
• First Posted: September 12, 2005
• Study Start: September 1, 2005
• Primary Completion: December 1, 2006
• Study Completion: December 1, 2006
• Last Updated: September 14, 2023

Record last verified: 2023-09

Locations

GB (1)