COPD progression have not been performed before. Not less importantly, all variables indicative of DNA damage were adjusted for parameters like age, 19088077 gender, BMI, smoking habits and lung function. In the context that COPD is a disease of systemic senescence, the results adjusted for the demographic and clinical parameters point out that the increase in DNA damage is likely to increase accordingly to the advancement of the OS and inflammation from non-smoking controls up to COPD exacerbation, rather than caused by age, by fall in FEV1% or by cigarette smoke alone. Adjustment to gender might be of particular importance, as the PBMC PARP activity has been shown to be significantly lower amongst female subjects compared with male subjects. Moreover, according to rodent and porcine models, the regulation of PARP has been reported to be more profound in males than in females. In addition to the variables provided by the Comet Assay IV, 5 new parameters were introduced and found to reflect the relationship between DNA damage and the progression of the disease even better. Out of the novel or newly introduced parameters, the tail length/cell length ratio and tail migration/cell length ratio were found to show the highest ORs with the development and progression of COPD up to COPD exacerbation. A one unit increase in tail length/cell length ratio and tail migration/cell length ratio was associated with a 7.88-fold or 3.91fold higher probability, respectively, for the process progressing to the next stage and therefore can appear most suitable to describe the DNA damage in PBMC over the evolution of COPD. This is the first report to show that these new parameters are most sensitive for the advancement of COPD and to suggest the tail length/cell length ratio and the tail migration/cell length ratio as new precision tools for 169939-93-9 web independent assessment of the DNA damage in smokers and in 10037488 patients with COPD. Along with the comet assay indices, the current study revealed a strong relationship between the evolution of COPD and PARP activity in PBMC. These data suggest an intensified DNA repair occurring in PBMC of patients with higher COPD stages and adds a valuable adjunct to understanding of the systemic component of COPD. PARP activity was somehow heightened amongst the nonobstructive smokers, as compared to both the non-smoking DNA Damage and PARP Activity in COPD controls on one hand and to patients with mild COPD on the other. This may indicate that those smokers, who do not develop COPD, are still sensitive to various antioxidant influences than do COPD patients, at least those with a milder disease. This suggests that although PARP is a very important player in the DNA repair, it does not represent the only pathway to prevent smokers from developing COPD. In mammalian cells, the basal enzymatic activity of PARP is very low, but oxidative and nitrosative stress can trigger DNA strand breakage, which in turn abruptly stimulates the PARP-1 activity. Moderate activation of PARP is of physiological importance and could be beneficial via facilitating the DNA repair. However, overactivation of PARP is connected to numerous pathological conditions associated with oxidative and nitrosative stress, including COPD. In particular, in parallel with energy depletion by the cells caused 
by PARP over-activation, PARP contributes to the synthesis of inflammatory mediators including cytokines, chemokines and enzymes like inducible nitric oxide synthase, but also up
