ABSTRACT:
Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) consumed arachidonate for the production of eicosanoids which play a role in the inflammation (like COPD), carcinogenesis (like lung cancer), and cardiovascular diseases. This study was designed to introduce noninvasive biomarkers and therapies that aim to reduce the risk for individuals with greater risk of developing smoking-related lung diseases. During this prospective randomized clinical trial, urinary concentration of prostaglandin E metabolite (PGE-M) and leukotriene E4 (LTE4), as markers of COX and 5-LOX inflammatory process, was measured in former (arm A); current (arm B); and never smoker subjects at zero time. The effect of the three treatment groups: etoricoxib and zileuton as a selective COX-2 and 5-LOX inhibitors, respectively, and their combination on the concentrations of these inflammatory markers were evaluated in the current and former smoking population, after 4 weeks. Analysis of variance (ANOVA), chi-square, and paired t-test were applied to analyze our data. At zero time, concentrations of both inflammatory markers were high and significantly associated with status of smoking, which confirmed by measurement of cotinine levels (p<0.05). Treatment with etoricoxib alone and etoricoxib – zileuton combination significantly reduced urinary PGE-M levels, while zileuton alone significantly elevated this marker, in both former and current smokers, compared with their pretreatment values (p<0.05). In addition, treatment with zileuton alone and etoricoxib – zileuton combination significantly reduced urinary LTE4 levels, while etoricoxib alone significantly elevated this marker, in both former and current smokers, compared with their pretreatment values (p<0.05). Former and current smokers were well tolerated with these therapeutic regimens, with no reports of any serious adverse effects. One can conclude that a subclinical respiratory inflammation may associate with smoking people, reflected by elevated levels of PGE-M and LTE4 within urinary samples. Combining etoricoxib and zileuton was associated with inhibition of both COX-2 and 5-LOX pathways manifested by reduced levels of urinary PGE-M and LTE4, for both former and current smokers.