Patient reported outcomes in patients with nontuberculous mycobacterial pulmonary disease

项目总结/摘要 非结核分枝杆菌（NTM）是存在于土壤和水中的环境病原体， 慢性、衰弱性疾病，主要发生在伴有基础支气管扩张或慢性阻塞性肺疾病的老年患者中 肺部疾病NTM肺病（NTM-PD）最常见的病因是鸟分枝杆菌 complex（MAC）和M.（MAB）. NTM-PD的主要症状包括咳嗽，极度疲劳， 呼吸急促。NTM-PD的表现是异质性的：结节性支气管扩张病（~60-70%）倾向于 进展缓慢，如果MAC可能不需要立即治疗， （约25%）或MAB需要立即治疗。多药治疗，当开始时，包括3-5抗生素服用 18+个月。NTM治疗具有显著毒性的风险，并且一些患者耐受性差。 虽然大多数患者对治疗有微生物学反应，但许多患者无法产生痰液， 测试，并且治疗成功被评价为主观临床改善。咳嗽率的变化， 模式被认为是重要的，但没有被客观地衡量。此外，在完成 治疗后，大约一半会在3年内重新发展NTM-PD。不像它的“表亲”肺结核， 转换是治愈的替代，培养转换对肺部NTM患者的意义是 不太清楚。患者报告结局（PRO），衡量症状、功能和健康相关质量 是以病人为中心的研究和护理的关键组成部分。改善日常症状， 从病人的角度来看，功能是关键的结果，但在功能的作用方面存在重大的证据差距。 PRO数据可以帮助决定何时治疗不需要立即治疗的患者，如何 测量治疗反应和耐受性，以及如何在治疗后监测患者。 我们建议填补关于NTM-PD PRO指标轨迹的知识空白， 结合客观咳嗽监测器以测量患者咳嗽的速率和模式。这项前瞻性 队列研究利用了我们建立NTM临床试验网络和西北NTM生物库的经验 数据仓库我们将继续与温斯洛普、戴利、弗拉姆、麦克沙恩和 Aksamit为所有提出的目标。在第1-4年期间，我们将招募3个特征良好的患者队列 代表NTM-PD的关键阶段-初始诊断（NTM-WATCH）、治疗开始（NTM-TREAT）和 参与研究中心的治疗结束（NTM-TRACK），并收集最多24个研究中心的PRO和临床结局数据 每个月，每个月，在第3-5年期间，我们将在以下方面对PRO进行描述性和纵向分析： 这些前瞻性队列，评估PRO指标监测疾病活动性和耐受性的能力， 治疗我们的研究结果将为将来临床评估联合结局指标奠定基础。 试验终点，最重要的是在临床实践中纳入PRO指标。

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 for clinical trials endpoints and, most importantly, incorporation of PRO measures in clinical practice.