Patient reported outcomes in patients with nontuberculous mycobacterial pulmonary disease

项目摘要/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，可引起 以老年为主的潜在支气管扩张症或慢性梗阻性疾病患者的慢性衰弱疾病 肺部疾病。非结核分枝杆菌肺部疾病(NTM-PD)最常见的原因是禽类分枝杆菌 复合体(MAC)和脓肿分支杆菌(MAB)。NTM-PD的主要症状包括咳嗽、极度疲劳和 呼吸急促。NTM-PD表现不一：结节-支气管扩张性疾病(~60%-70%) 进展缓慢，如果MAC可能不需要立即治疗，而那些患有空洞病的人 (~25%)或MAB需要立即治疗。开始多药疗法时，需要服用3-5种抗生素。 18个月以上。NTM治疗有显著毒性风险，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，但许多人无法产生痰用于治疗 测试，治疗成功被评估为主观的临床改善。咳嗽和咳嗽的变化 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，大约一半的人会在3年内重新发展为NTM-PD。不像它的“表亲”结核病，那里的文化 转换是治疗的替代品，培养转换对肺部NTM患者的意义是 不太清楚。患者报告结果(PRO)，衡量症状、功能和与健康相关的质量 生命的价值是以患者为中心的研究和护理的关键组成部分。日常症状的改善和 从患者的角度来看，功能是关键的结果，但在以下方面存在显著的证据差距 PRO数据，为那些不需要立即治疗的人提供关于何时治疗、如何治疗 测量治疗反应和耐受性，以及如何监测患者治疗后的情况。 我们建议填补关于NTM-PD和PRO措施轨迹的关键知识空白 结合一个客观的咳嗽监测器来测量患者的咳嗽频率和模式。这一前景 队列研究利用我们建立NTM临床试验网络和西北NTM生物库的经验 数据存储库。我们将继续与温斯罗普博士、戴利博士、弗卢姆博士、麦克肖恩博士和 所有提议的目标都是阿克萨米特。在1-4年内，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 参与站点的治疗结束(NTM-Track)，并收集多达24个的专业和临床结果数据 每个队列数月。在3-5年中，我们将对专业人员进行描述性和纵向分析 这些前瞻性队列，评估PRO措施监测疾病活动性和耐受性的能力 治疗。我们的发现将为未来对临床综合结果测量的评估奠定基础。 试验的终点，最重要的是，将PRO措施纳入临床实践。

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.