Department of Medicine, University of California San Francisco, San Francisco, California, USA.
Center for Genes, Environment, & Health, National Jewish Health, Denver, Colorado, USA.
BMJ Open. 2021 Nov 9;11(11):e056841. doi: 10.1136/bmjopen-2021-056841.
Sarcoidosis is a multiorgan granulomatous disorder thought to be triggered and influenced by gene-environment interactions. Sarcoidosis affects 45-300/100 000 individuals in the USA and has an increasing mortality rate. The greatest gap in knowledge about sarcoidosis pathobiology is a lack of understanding about the underlying immunological mechanisms driving progressive pulmonary disease. The objective of this study is to define the lung-specific and blood-specific longitudinal changes in the adaptive immune response and their relationship to progressive and non-progressive pulmonary outcomes in patients with recently diagnosed sarcoidosis.
The BRonchoscopy at Initial sarcoidosis diagnosis Targeting longitudinal Endpoints study is a US-based, NIH-sponsored longitudinal blood and bronchoscopy study. Enrolment will occur over four centres with a target sample size of 80 eligible participants within 18 months of tissue diagnosis. Participants will undergo six study visits over 18 months. In addition to serial measurement of lung function, symptom surveys and chest X-rays, participants will undergo collection of blood and two bronchoscopies with bronchoalveolar lavage separated by 6 months. Freshly processed samples will be stained and flow-sorted for isolation of CD4 +T helper (Th1, Th17.0 and Th17.1) and T regulatory cell immune populations, followed by next-generation RNA sequencing. We will construct bioinformatic tools using this gene expression to define sarcoidosis endotypes that associate with progressive and non-progressive pulmonary disease outcomes and validate the tools using an independent cohort.
The study protocol has been approved by the Institutional Review Boards at National Jewish Hospital (IRB# HS-3118), University of Iowa (IRB# 201801750), Johns Hopkins University (IRB# 00149513) and University of California, San Francisco (IRB# 17-23432). All participants will be required to provide written informed consent. Findings will be disseminated via journal publications, scientific conferences, patient advocacy group online content and social media platforms.
结节病是一种多器官肉芽肿性疾病，被认为是由基因-环境相互作用引发和影响的。在美国，每 45-300/100000 人中就有一人患有结节病，其死亡率呈上升趋势。人们对结节病病理生物学的认识存在最大的差距，就是缺乏对驱动进行性肺病的潜在免疫学机制的理解。本研究的目的是确定初诊结节病患者肺部和血液中适应性免疫反应的纵向变化，并研究其与进行性和非进行性肺部结局的关系。
BRonchoscopy at Initial sarcoidosis diagnosis Targeting longitudinal Endpoints 研究是一项基于美国、由美国国立卫生研究院（NIH）资助的纵向血液和支气管镜检查研究。该研究将在四个中心进行，在组织诊断后 18 个月内，目标样本量为 80 名符合条件的参与者。参与者将在 18 个月内接受 6 次研究访问。除了连续测量肺功能、症状调查和胸部 X 射线外，参与者还将在 6 个月的时间内进行两次支气管镜检查和支气管肺泡灌洗。新鲜处理的样本将进行染色和流式细胞分选，以分离 CD4+T 辅助（Th1、Th17.0 和 Th17.1）和 T 调节细胞免疫群，然后进行下一代 RNA 测序。我们将使用这些基因表达构建生物信息学工具，定义与进行性和非进行性肺部疾病结局相关的结节病内型，并使用独立队列验证这些工具。
该研究方案已获得美国国家犹太医院（IRB# HS-3118）、爱荷华大学（IRB# 201801750）、约翰霍普金斯大学（IRB# 00149513）和加利福尼亚大学旧金山分校（IRB# 17-23432）的机构审查委员会的批准。所有参与者都将被要求提供书面知情同意书。研究结果将通过期刊文章、科学会议、患者权益组织的在线内容和社交媒体平台进行传播。
