Validation of Biomarkers of Exposure and Host Response

University of Nebraska

Status

Completed

Conditions

Cigarette Smoker

Treatments

Drug: nicotine inhaler

Drug: nicotine polacrilex

Drug: nicotine transdermal system

Study type

Interventional

Funder types

Other

Identifiers

NCT00468234

009-05

Details and patient eligibility

About

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.

Full description

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.

Sex

All

Ages

19+ years old

Volunteers

Accepts Healthy Volunteers

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.