PROJECT SUMMARY/ABSTRACT Nontuberculous mycobacteria (NTM) are environmental pathogens present in the soil and water that can cause chronic, debilitating disease in predominately older patients with underlying bronchiectasis or chronic obstructive pulmonary disease. The most common causes of NTM pulmonary disease (NTM-PD) are Mycobacterium avium complex (MAC) and M. abscessus (MAB). Key symptoms of NTM-PD include cough, extreme fatigue, and shortness of breath. NTM-PD is heterogeneous in presentation: nodular-bronchiectatic disease (~60-70%) tends to be slowly progressing and if MAC may not require immediate treatment, while those with cavitary disease (~25%) or MAB require immediate treatment. Multi-drug therapy, when initiated, consists of 3-5 antibiotics taken for 18+ months. NTM treatment carries risks of significant toxicity and is poorly tolerated by some patients. Although most patients have microbiologic response to treatment, many are unable to produce sputum for testing, and treatment success is evaluated as subjective clinical improvement. Changes in cough rates and patterns are presumed to be important but have not been objectively measured. Further, after completing treatment, around half will re-develop NTM-PD within 3 years. Unlike its “cousin” tuberculosis where culture conversion is a surrogate for cure, the meaningfulness of culture conversion to patients in pulmonary NTM is less clear. Patient-reported outcomes (PROs) which measure symptoms, functioning, and health-related quality of life are key components of patient-centered research and care. Improvements in daily symptoms and functioning are critical outcomes from the patient’s perspective, but significant evidence gaps exist in the role of PRO data to inform decisions about when to treat among those who do not require immediate treatment, how to measure treatment response and tolerability, and how to monitor patients post-treatment. We propose to fill critical gaps in knowledge regarding the trajectory of PRO measures for NTM-PD and incorporate an objective cough monitor to measure rates and patterns of cough in patients. This prospective cohort study leverages our experience establishing an NTM Clinical Trials Network and Northwest NTM Biobank data repository. We will continue longstanding collaborations with Drs. Winthrop, Daley, Flume, McShane, and Aksamit for all proposed aims. During Years 1-4 we will enroll 3 well-characterized cohorts of patients representing key stages of NTM-PD – initial diagnosis (NTM-WATCH), treatment start (NTM-TREAT), and at end of treatment (NTM-TRACK) from participating sites and collect PROs and clinical outcome data for up to 24 months for each cohort. During Years 3-5 we will conduct our descriptive and longitudinal analysis of PROs in these prospective cohorts, evaluating PRO measures’ ability to monitor disease activity and tolerability of treatment. Our findings will lay the groundwork for future evaluation of combined outcome measures...