Phenotyping Asthma for Bronchial Thermoplasty: Airway Smooth Muscle Structure and Function

支气管热成形术的哮喘表型分析：气道平滑肌结构和功能

• 批准号: 10205149
• 负责人: Melissa J Suter
• 金额: $ 72.36万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10205149
• 关键词: 3-Dimensional; Adrenal Cortex Hormones; Affect; Agonist; Assessment tool; Asthma; Award; Birefringence; Bronchoconstriction; Bronchodilator Agents; Calibration; Catheters; Clinical; Clinical Research; Complex; Computer software; Custom; Detection; Disease; Economic Burden; Epithelial; Etiology; Evaluation; Exhibits; Extrinsic asthma; Fiber; Fibrosis; Functional disorder; Goals; Human; Hyperplasia; Hypertrophy; Imaging Device; Imaging technology; Individual; Inflammation; Knowledge; Link; Measures; Metaplasia; Monitor; Morbidity - disease rate; Mucous Membrane; Mucous body substance; Multi-Institutional Clinical Trial; Multicenter Studies; Muscle function; Operative Surgical Procedures; Optical Coherence Tomography; Patients; Phenotype; Physiological; Play; Population; Prevalence; Research; Research Proposals; Resected; Role; Severity of illness; Signal Transduction; Structure; Structure of parenchyma of lung; Structure-Activity Relationship; Symptoms; System; Technology; Testing; Therapeutic; Thick; Time; Tissues; Translating; United States; Visualization; airway hyperresponsiveness; airway inflammation; airway obstruction; airway remodeling; asthmatic; asthmatic patient; base; clinical predictors; imaging platform; imaging system; improved; in vivo; individualized medicine; muscular structure; novel; optical imaging; preclinical study; predicting response; prospective; public health relevance; respiratory smooth muscle; response; sheep model; socioeconomics; targeted treatment; three dimensional structure; validation studies

Project Summary Asthma currently affects over 300 million individuals worldwide and the prevalence is continually increasing. Approximately 10% of asthmatics have uncontrolled or poorly controlled symptoms and it is this population that urgently need improved targeted therapies and management strategies in order to reduce the high morbidity and socio-economic burden, estimated to be 14.7 billion dollars annually in the United States alone. The exact mechanisms behind the pathophysiology of asthma remain uncertain. Airway smooth muscle (ASM) is known to play a critical and multifaceted role, yet our knowledge on the role of ASM in asthma is limited due to an inability to directly visualize and study the 3D structure of ASM, and the relationship to functional bronchoconstriction in patients. The real-time evaluation of ASM is critical in furthering our understanding of the pathophysiology of asthma, for classifying asthma phenotypes, for tailoring treatment, and for assessing and monitoring the response to therapy. In this award we will develop a custom optical imaging platform based on polarization-sensitive optical coherence tomography (PS-OCT) that will enable the accurate quantification of ASM hyperplasia and hypertrophy, epithelial disruption and hypertrophy, subepithelial fibrosis, mucosal thickness increases, mucus metaplasia, in vivo. We will develop and validate novel dual-layer calibrating catheters that will enable accurate assessment of tissue fiber orientation and birefringence signal intensity. We will additionally develop and validate automated calibration and processing software that will provide real-time visualization of ASM in vivo. These technological advancements will enable us to begin to answer important questions linking remodeling changes in airway wall structure with physiologic function. We will conduct a preclinical study in a sheep model of allergic asthma to test our hypothesis that remodeling plays both a protective and provocative role in bronchoconstriction, and that the presence of inflammation greatly increases bronchoconstriction. We will further translate this technology into the clinical setting in a multicenter clinical trial aimed at using our PS-OCT imaging system to phenotype asthma and to predict the response to bronchial thermoplasty. The unprecedented ability to study both the 3D structure of airway smooth muscle (ASM) and it’s function in vivo is likely to transform the study of asthma in patients in phenotyping populations, for therapy guidance, and in research endeavors aimed at studying the true role of ASM in asthma.

项目摘要 目前，全世界有超过3亿人患有哮喘，而且患病率还在持续上升。 大约10%的哮喘患者症状未得到控制或控制不佳，正是这一人群 迫切需要改进的靶向治疗和管理策略，以降低高发病率 和社会经济负担，仅在美国每年估计就有147亿美元。完全相同的 哮喘的病理生理学背后的机制仍然不确定。已知的呼吸道平滑肌(ASM) 发挥关键和多方面的作用，但我们对ASM在哮喘中的作用的了解有限，因为 不能直接可视化和研究ASM的三维结构及其与功能的关系 患者出现支气管性收缩。ASM的实时评估对于加深我们对ASM的理解是至关重要的 哮喘的病理生理学，用于哮喘表型的分类，用于定制治疗，以及用于评估 并监测对治疗的反应。在这个奖项中，我们将开发一个定制的光学成像平台 关于偏振敏感光学相干层析成像(PS-OCT)，它将使精确定量 ASM增生和肥大，上皮破裂和肥大，上皮下纤维化，粘膜 增厚，粘液化生，活体内。我们将开发和验证新的双层校准 能够准确评估组织纤维取向和双折射信号强度的导管。我们 将另外开发和验证自动校准和处理软件，以提供实时 活体内ASM的可视化。这些技术进步将使我们能够开始回答重要的问题 气道壁结构重塑变化与生理功能的关系问题。我们将进行一项 在过敏性哮喘绵羊模型上进行的临床前研究，以验证我们的假设，即重塑既在 在支气管收缩中的保护和挑衅作用，炎症的存在大大增加 支气管收缩。我们将在多中心临床试验中进一步将这项技术转化为临床环境 目的：利用我们的PS-OCT成像系统对哮喘进行表型分析，并预测对哮喘的疗效 热成形术。前所未有的能力既研究呼吸道平滑肌(ASM)的三维结构，也研究它的 体内功能很可能改变对哮喘患者表型人群的研究，用于治疗 指导，以及旨在研究ASM在哮喘中的真正作用的研究努力。

项目成果

Polarization mode dispersion correction in endoscopic polarization-sensitive optical coherence tomography with incoherent polarization input states.

具有非相干偏振输入状态的内窥镜偏振敏感光学相干断层扫描中的偏振模式色散校正。

• DOI: 10.1364/boe.457790
• 发表时间: 2022
• 期刊: Biomedical optics express
• 影响因子: 3.4
• 作者: Adams,DavidC;Majid,Adnan;Suter,MelissaJ
• 通讯作者: Suter,MelissaJ

Automated segmentation and quantification of airway mucus with endobronchial optical coherence tomography.

• DOI: 10.1364/boe.8.004729
• 发表时间: 2017-10
• 期刊: Biomedical optics express
• 影响因子: 3.4
• 作者: D. C. Adams;H. Pahlevaninezhad;M. Szabari;Josalyn L. Cho;D. Hamilos;M. Kesimer;R. Boucher;A. Luster;B. Medoff;M. Suter

Human milk H2O2 content: does it benefit preterm infants?

• DOI: 10.1038/pr.2017.303
• 发表时间: 2018-03-01
• 期刊: PEDIATRIC RESEARCH
• 影响因子: 3.6
• 作者: Cieslak, Monika;Ferreira, Cristina H. F.;Belik, Jaques
• 通讯作者: Belik, Jaques