Chronic obstructive pulmonary disease (COPD) is currently the fourth cause of death worldwide.
Cigarette smoking is the most well-established risk factor for COPD, but actually only a part of smokers develop the disease, whereas lifelong nonsmokers can develop COPD.
Even if cigarettes contain many toxic compounds which damage the respiratory system, nicotine itself, beside giving addiction, acts as a mediator of lungs damage both directly and indirectly. Thus we hypothesize that, given the same smoking intensity, inter-individual variability in the nicotine clearance rate may affect the actual nicotine exposure, increasing the risk of smoking related disorders as COPD. The individual rate of nicotine clearance is mainly determined by the level of activity of the polymorphic enzyme CYP2A6, which can be easily assessed using a phenotypic assay, known as the Nicotine Metabolite Ratio (NMR). In this study, NMR will be evaluated in a group of smokers with COPD (N=72) and in a group of smokers without COPD (N=72), and difference between group will be tested. Correlations of NMR with specific clinical and functional parameters in COPD and non-COPD smokers will be also investigated.
Identification of smokers at higher risk to develop COPD by a cost-effective assay as the NMR may help to improve preventive strategies including smoke cessation therapy, and the smoker¿s awareness about risk may represents itself a strong motivation to quit smoking.
To our knowledge, no studies investigating the effect of individual rate of nicotine clearance on susceptibility of smokers to COPD are presently available. There is high inter-individual susceptibility to COPD among smokers, and many smokers would never develop it. Results from this project could provide an easily actionable and cost-effective tool to improve prediction of the individual risk to develop COPD, which represents a progressive disease and a leading cause of death worldwide. Since COPD is preventable and treatable, the possibility to identify precociously subject with higher risk could contribute to reduce the social burden associated with the disease.
According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines, the most important therapy for chronic bronchial obstruction is smoking cessation treatment, and quitting smoking has been shown to slow down the progression of COPD, changing its natural history. Notably, awareness about one¿s individual metabolic rate for nicotine clearance could act as a strong motivation to quit smoking for slow metabolizer, since put the subject in front of the evidence to have a higher risk to develop disease. Indeed, it is well known that who perceived themselves at high risk of experiencing a negative health outcome from smoking, expressed greater interest in quitting. In this picture, NMR would exert a double beneficial effect, since it can be also used to guide the choice of the best cessation therapies, as mentioned above.