Aspirin and Zileuton and Biomarker Expression in Nasal Tissue of Current Smokers

Inclusion Criteria

• Current tobacco smokers with >= 20 pack years of self-reported smoking exposure and an average use of >= 10 cigarettes/day
• Karnofsky >= 70%
• Leukocytes >= 3,000/microliter
• Absolute neutrophil count >= 1,500/microliter
• Hematocrit >= the lower institutional limit
• Platelets >= the lower institutional limits
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) within normal institutional limits
• Creatinine =< the upper institutional limits
• Prothrombin time (PT)/partial thromboplastin time (PTT) within normal institutional limits
• Fertile subjects must use adequate contraception (abstinence, barrier methods, or birth control pills) prior to study entry and for the duration of study participation; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Participants may have a history of indeterminate pulmonary nodule(s) by chest imaging if nodule follow-up has been completed or the study procedures would not interfere with nodule follow-up
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• History of allergic reaction to aspirin or attributed to compounds of similar chemical or biologic composition to aspirin, including other nonsteroidal anti-inflammatory drugs (NSAIDs)
• Gastric intolerance attributable to ASA or NSAIDs
• History of gastric ulcer within the past 5 years (with or without bleeding)
• Use of ASA or NSAIDs for more than 5 days per month within 3 months of enrollment
• Not willing or are unable to refrain from use of any non-study ASA, NSAIDs and leukotriene antagonists during the study period
• Adult asthma
• Chronic, current or recent (within the past three months) use of leukotriene antagonists
• Require chronic anticoagulation or anti-platelet therapy
• History of bleeding disorder or hemorrhagic stroke
• Chronic, current or recent (within the past three months) use of glucocorticoids (systemic, topical and/or nasal sprays or steroid topical creams to large body surface area); use of steroid topical creams for small body areas (=< 10% body surface) during study intervention is allowed
• History of chronic sinusitis or recent nasal polyps
• History of, or current, active or chronic liver disease even if transaminases have normalized
• History of allergic reaction to zileuton or attributed to compounds of similar chemical or biologic composition to zileuton
• Are taking drugs known to interact with zileuton, including theophylline, warfarin, and propranolol
• Not willing or are unable to limit alcohol consumption to =< 2 alcoholic beverages a day during the study period
• Pregnant or lactating women; breastfeeding should be discontinued if the mother is treated with aspirin; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her study physician immediately
• Participants may not be receiving any other investigational agents
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Have a known history of inability to absorb an oral agent
• Invasive cancer within the past five years except non-melanoma skin cancer
• Urine cotinine level, if collected at screening, does not confirm active smoking status