Validation of Biomarkers of Exposure and Host Response

Study Overview
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Brief Summary
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This study will evaluate biomarkers measured in exhaled breath condensate (EBC) to assess clinical strategies of harm reduction. It will take advantage of a recently developed device that permits collection of exhaled breath condensate reproducibly, with minimal subject effort and with no oral contamination. Samples from asymptomatic smokers before and after inducing a change in their smoking habit (cessation or reduction) with the aid of partial nicotine replacement.

Detailed Description
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The proposed study will evaluate biomarkers measured in exhaled breath condensate (EBC) for the purpose of assessing clinical strategies of harm reduction. It will take advantage of a recently developed device that permits collection of exhaled breath condensate reproducibly, with minimal subject effort and with no oral contamination. The major goal of the trial is to provide evidence to validate biomarkers in EBC. This will be accomplished by collecting samples from asymptomatic smokers before and after inducing a change in their smoking habit (cessation or reduction) with the aid of partial nicotine replacement. Measures to be made in EBC include H2O2, the most widely explored biomarker in this body fluid. Methods that reliably can quantify levels in normal non-smokers and in asymptomatic smokers will be used. Two fold increases in smokers have been reported by in several reports and confirmed in preliminary data by the investigators. In addition, other biomarkers of oxidant stress: TBARs, 8-isoprostane and nitrotyrosine will be quantified using standard methods. Biomarkers quantified in EBC will be assessed for reliability (i.e. reproducibility and for sensitivity) to change and for validity (by comparison to clinically defined endpoints and previously validated measures of exposure). Reproducibility will be assessed by making repeated measurements in the same subjects on different occasions. Sensitivity to change will be assessed by comparing values before and after changing smoking habit. Finally, the validity of the biomarkers will be assessed by comparing them to previous measures of smoke exposure (CO, NNAL and NNAL-glc) and to clinically defined endpoints: symptoms, the St. George's Respiratory Questionnaire and post bronchodilator lung function. With regard to the latter measures, preliminary data indicate that symptoms can be detected in asymptomatic smokers and that these can change with a harm reduction strategy.

Official Title
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Validation of Biomarkers of Exposure and Host Response

Conditions
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Cigarette Smoker

Intervention / Treatment
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* Drug: nicotine polacrilex
* Drug: nicotine transdermal system
* Drug: nicotine inhaler


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be 19 years of age or older Have a stable smoking habit greater than three months Have smoked for at least 5 pack years Be willing to make a serious quit attempt and be willing to use nicotine replacement therapy Be able to give informed consent Exclusion Criteria: regular use of anti-inflammatory medication; presence of any inflammatory *disease of the respiratory tract including moderate or worse COPD (FEV1 < 80% predicted and FEV1/FVC ratio < 0.7) or PFT criteria for asthma (improvement in FEV1>12% of predicted and >200ml). Subjects with normal lung function who meet criteria for diagnosis of chronic bronchitis will be excluded. Subjects with stable medical conditions, excluding inflammatory lung disease, will be permitted to participate, providing anti-inflammatory therapies are not used regularly and providing there has been no change in their clinical status in the two months prior to beginning the study.

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: nicotine polacrilex|nan|
|Drug: nicotine transdermal system|nan|
|Drug: nicotine inhaler|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| exhaled breath hydrogen peroxide |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| health status (SGRQ, CCQ, BCSS, LCQ) |  |  | 
| lung function |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking cessation, harm reduction, biomarker, exhaled breath condensate