Trial to Determine Effective Aspirin Dose in COPD

The trial will enroll individuals with chronic obstructive pulmonary disease (COPD). The primary design will be a randomized double-blind 6-sequence, 3-period, 3-treatment sequential crossover trial for which the investigators will randomize participants to receive 81mg, 162mg, and 325mg aspirin in one of six pre-specified sequences with a 14-day washout period between doses. Participants will have three follow-up visits after randomization. Individuals who agree to participate in the clinical trial will be randomized to one of six treatment sequences using a computer algorithm at the baseline study visit. Study drug will be provided by the Johns Hopkins Research Pharmacy and participants instructed to take one pill once per day at the same time. All study drug doses will be compounded to appear identical and placed in identical containers fitted with an electronic cap for monitoring medication adherence. Participants will be scheduled to return for a follow-up visit at two weeks, six weeks, and ten weeks after randomization. Blood and urine samples will be collected at each visit. Data will be collected by the principal investigator or trained study coordinator and will be electronically entered into a database stored on the secure Johns Hopkins servers through an online interface that is password protected. Urine will be collected and analyzed for 11-dehydro-thromboxane B2 at each study visit and constitutes the primary outcome of the study. Secondary outcomes will include measurement of platelet reactivity to U46619, a thromboxane A2 agonist, through identification of platelet surface markers CD62P, CD63, CD154 and PAC1. The following adherence measurements will also be collected: 1. Drug discontinuation rate 2. Date and time of each dose of study medication obtained through electronic monitoring to assess adherence The following clinical data will be collected at randomization: 1\. Spirometry performed before and after administration of albuterol per American Thoracic Society protocol in a certified laboratory The following clinical data will be collected at randomization and each subsequent study visit: 1. Respiratory symptom and quality of life questionnaires 2. Occurrence of COPD flares (exacerbations)