The Role of Lung Volumes in Nocturnal Asthma

肺容量在夜间哮喘中的作用

基本信息

批准号：
8516089
负责人：
Robert Llewellyn Owens
金额：
$ 15.68万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2014-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8516089
关键词：
Affect Air Airway Resistance Allergic American Anti-Inflammatory Agents Anti-inflammatory Apnea Area Asthma Body Weight decreased Breathing Bronchoconstriction Bronchodilation Chemical Engineering Chronic Clinical Clinical Research Clinical Trials Clinical Trials Design Collaborations Commit Continuous Positive Airway Pressure Contracts Critical Care Data Development Disease Environment Environmental air flow Esophageal Faculty Foundations Funding Future Grant Health Care Costs Hospitals Immunologics Incidence Individual Inflammatory Internal Medicine Investigation Israel Knowledge Laboratories Lead Link Lung Lung diseases Manometry Measurement Measures Mechanics Medical center Medicine Mentors Methodology Metric Monitor Nocturnal Asthma Obesity Obstruction Obstructive Sleep Apnea Outcome Overweight Pathogenesis Pathology Patients Pharmaceutical Preparations Physicians Physiological Prevalence Public Health Schools Publications Randomized Research Research Personnel Research Training Respiration Respiratory Mechanics Respiratory physiology Role Scientist Series Severities Sleep Spasm Stretching Symptoms Techniques Testing Therapeutic Therapeutic Intervention Tidal Volume Time Training Tube Weight Gain Wheezing Woman Work Writing airway hyperresponsiveness airway inflammation asthma inhaler base career development falls improved insight instrument lung volume pandemic disease pressure prevent productivity loss research study respiratory responsible research conduct statistics sucking tool

项目摘要

DESCRIPTION (provided by applicant): Robert L. Owens, MD is a clinical and research fellow in the Divisions of Sleep and Pulmonary/Critical Care Medicine at the Brigham and Women's Hospital. He has a background in Chemical Engineering, Internal Medicine, Pulmonary and Critical Care, and Sleep Medicine. His research efforts have focused on respiratory mechanics, with two projects to date resulting in first author publications. The most recent work quantified the influence of lung volumes on upper airway collapsibility, and helps explain the role of lung volumes in obstructive sleep apnea. Completion of the project required careful measurements made during sleep using techniques perfected in the lab of Dr. Atul Malhotra, the proposed mentor. Using some of these tools, Dr. Owens will now focus on respiratory mechanics during sleep in patients with asthma and study the pathogenesis of nocturnal asthma. He will test the hypotheses that 1) lung volumes are important in lower airway mechanics in people with asthma, and 2) that manipulation of lung volumes (using positive airway pressure) will improve nocturnal asthma severity. Although prior work has been done in this area, methodological issues may have contributed to some of the negative prior results. In order to accomplish this task, further training in respiratory mechanics, statistics, and clinical trial design will be necessary. A mentored K23 grant will provide the support necessary to pursue the ongoing training and research. Ultimately, the career development grant will form the foundation for Dr. Owens to become a successful independent investigator. Environment Dr. Atul Malhotra will serve as Dr. Owens's mentor. Dr. Malhotra has a proven track record of research, obtaining considerable independent funding, and development of junior faculty. His laboratory is known for obtaining physiological data in heavily instrumented, yet sleeping, subjects. His laboratory has ongoing collaborations with renowned respiratory physiologists (such as Drs. Steven Loring and Jeffrey Fredberg), and asthma clinical researchers (Dr. Jeffrey Drazen and the Asthma Clinical Research Network). Furthermore, James Butler, another expert in respiratory physiology has recently joined the lab. The Brigham and Women's Hospital is in close proximity to the Harvard School of Public Health and the Beth Israel Deaconess Medical Center, among others, which provides a rich intellectual environment. The BWH is committed to training future physician-scientists, and provides training in many areas, including the responsible conduct of research. Research Asthma is a chronic respiratory disease characterized by airway inflammation and airway hyper- responsiveness, which causes airflow obstruction. It is extremely prevalent, affecting an estimated 22 million Americans, and costly with loss of productivity and direct healthcare costs in the billions of dollars. The incidence and prevalence of asthma are increasing, both in the US and around the world. This increase comes despite greater understanding of the inflammatory and allergic basis for asthma, and despite better anti- inflammatory medications. One explanation for the increasing prevalence of asthma is the concomitant increase in obesity, with the majority of Americans now overweight or obese. Numerous studies have convincingly linked asthma and obesity, and demonstrated increased obstruction with weight gain and decreased obstruction with weight loss. However, the mechanisms that underlie this linkage are not known. We believe that low lung volumes contribute to the pathogenesis and severity of asthma. End-expiratory lung volume is decreased in obesity, and likely falls further during sleep, particularly in overweight and obese patients. Both upper and lower airway resistance increase with decreasing lung volumes, as airways become smaller. However, prior work has shown that lower airway resistance increases out of proportion to the decrease in lung volume that occurs during sleep in asthma patients. This difference between controls and people with asthma has not been further explored, yet may provide insight into asthma pathogenesis and provide potential targets for therapy. Therefore, we propose a series of experiments to define the impact of lung volumes during sleep on airway resistance. Methodologies already in use in our lab will be applied to patients with asthma and controls. Nocturnal airway resistance will be measured continuously using the forced oscillation technique (FOT), a non- invasive measurement that is ideal for use during sleep. Lung volumes can be monitored with magnetometers, and esophageal manometry will be used to estimate transpulmonary pressures. Finally, we will test the hypothesis that lung stretch can be used therapeutically by tonically and dynamically increasing lung volumes during sleep using bi-level positive airway pressure. This research can help delineate asthma pathogenesis and may help improve therapeutic options in this exceedingly common disease.

描述（由申请人提供）：医学博士Robert L. Owens是Brigham and妇女医院的睡眠和肺/重症监护医学分区的临床和研究人员。他具有化学工程，内科，肺部和重症监护以及睡眠医学背景。他的研究工作集中在呼吸机械上，迄今为止，两个项目导致了第一作者出版物。最近的工作量化了肺体积对上气道可折叠性的影响，并有助于解释肺体积在阻塞性睡眠呼吸暂停中的作用。该项目的完成需要在拟议的导师Atul Malhotra博士的实验室中使用完善的技术进行仔细的测量。使用其中一些工具，欧文斯博士现在将在哮喘患者的睡眠期间专注于呼吸机械，并研究夜间哮喘的发病机理。他将检验以下假设：1）哮喘患者的低气道力学对肺部体积很重要，以及2）操纵肺体积（使用正气道压力）将改善夜间哮喘的严重程度。尽管在这一领域已经完成了先前的工作，但方法论问题可能导致了一些负面的先前结果。为了完成这项任务，将需要进一步的呼吸机械，统计和临床试验设计培训。指导的K23赠款将为进行持续的培训和研究提供必要的支持。最终，职业发展赠款将为欧文斯博士成为成功的独立调查员奠定基础。环境Atul Malhotra博士将担任Owens博士的导师。 Malhotra博士在研究方面拥有可靠的记录，获得了相当大的独立资金和初级教师的发展。他的实验室以在富有工具但睡觉的受试者中获得生理数据而闻名。他的实验室与著名的呼吸生理学家（例如史蒂文·洛林（Steven Loring）和杰弗里·弗雷德伯格（Jeffrey Fredberg））和哮喘临床研究人员（Jeffrey Drazen博士和哮喘临床研究网络）进行了持续的合作。此外，另一位呼吸生理学专家詹姆斯·巴特勒（James Butler）最近加入了实验室。杨百翰和妇女医院靠近哈佛公共卫生学院和贝丝以色列执事医疗中心等，提供了丰富的知识环境。 BWH致力于培训未来的医师科学家，并在许多领域提供培训，包括负责任的研究。研究哮喘是一种慢性呼吸道疾病，其特征是气道炎症和气道超反应性，导致气流阻塞。它极为普遍，影响了约2200万美国人，并且成本高昂，生产率损失和直接医疗保健成本（数十亿美元）。在美国和世界各地，哮喘的发病率和患病率都在增加。尽管对哮喘的炎症性和过敏性基础有更大的了解，并且尽管有更好的抗炎药。哮喘患病率增加的一种解释是肥胖的同时增加，大多数美国人现在超重或肥胖。许多研究令人信服地联系了哮喘和肥胖症，并证明随着体重增加而增加的阻塞增加，随着体重减轻而减少阻塞。但是，尚不清楚这种联系的基础的机制。我们认为，低肺体积有助于哮喘的发病机理和严重程度。肥胖症的端肺肺体积减少，在睡眠期间，尤其是超重和肥胖的患者，可能会进一步降低。随着气道变小，上和下气道阻力随着肺部的减少而增加。但是，先前的工作表明，较低的气道阻力与哮喘患者在睡眠期间发生的肺部体积减少成比例。对照组和患有哮喘患者之间的这种差异尚未进一步探索，但可以提供对哮喘发病机理的见识，并为治疗提供潜在的靶标。因此，我们提出了一系列实验，以定义睡眠期间肺体积对气道阻力的影响。我们实验室中已经使用的方法将应用于哮喘和对照患者。夜间气道电阻将使用强制振荡技术（FOT）连续测量，这是一种非侵入性测量，非常适合在睡眠期间使用。可以用磁力计监测肺部体积，并将使用食管测量法来估计转肺压力。最后，我们将检验以下假设：肺拉伸可以通过双层正气道压力在睡眠过程中通过音调和动态增加肺体积进行治疗使用。这项研究可以帮助描述哮喘发病机理，并有助于改善这种极为常见的疾病的治疗选择。