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