Pulmonary Biomarkers of Inflammation in Chronic Tetraplegia

慢性四肢瘫痪的肺部炎症生物标志物

• 批准号: 7750488
• 负责人: Miroslav Radulovic
• 金额: --
• 依托单位: JAMES J PETERS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7750488
• 关键词: Acute; Address; Adenosine; Affect; Ammonia; Animal Model; Anti-Inflammatory Agents; Asthma; Atelectasis; Biochemical; Biological Markers; Blood; Blood Pressure; Body measure procedure; Breathing; Bronchoconstriction; Bronchodilator Agents; Caliber; Caring; Cause of Death; Cells; Cervical; Cervical spinal cord injury; Chronic; Clinical; Cost Savings; Coughing; Data; Development; Diagnosis; Dinoprostone; Disease; Economic Burden; Environmental air flow; Exercise; Exhalation; Exhibits; Extravasation; Failure; Functional disorder; Future; Healthcare Systems; Histamine; Hospitalization; Hydrogen Peroxide; Impairment; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Injury; Institutes; Interleukin-6; Interruption; Intervention; Investigation; Isoprostanes; Knowledge; Laboratories; Lead; Lesion; Leukotriene B4; Life Style; Link; Liquid substance; Longevity; Lung; Measurement; Measures; Mediator of activation protein; Methodology; Methods; Mission; Modeling; Morbidity - disease rate; Muscle Weakness; NG-Nitroarginine Methyl Ester; Neurologic; Nitric Oxide; Oscillometry; Paralysed; Patient Care; Patients; Peptides; Persons; Phase; Physiology; Play; Plethysmography; Pneumonia; Population; Prevention; Process; Prostaglandins; Pulmonary Circulation; Pulmonary Embolism; Pulmonary function tests; Quadriplegia; Quality of life; Reflex action; Rehabilitation Research; Rehabilitation therapy; Reporting; Resistance; Resort; Respiratory Failure; Respiratory Muscles; Respiratory Paralysis; Respiratory System; Respiratory physiology; Respiratory tract structure; Risk; Role; Rosa; Screening procedure; Serum; Spinal cord injury; Spirometry; Sputum; Steroids; Structure of thoracic nerve; Surrogate Markers; System; Techniques; Therapeutic; Therapeutic Uses; Training; Translating; Treatment Cost; Tumor Necrosis Factor-alpha; Veterans; Water; Work; aerosolized; airway hyperresponsiveness; airway inflammation; alternative treatment; care systems; chemokine; clinical care; cost; cost effective; cytokine; disability; human TNF protein; improved; inflammatory marker; isoprostaglandin F2alpha type-III; methacholine; mortality; nerve supply; novel therapeutics; public health relevance; pulmonary function; respiratory; restoration; socioeconomics; tool

DESCRIPTION (provided by applicant): Persons with tetraplegia exhibit pulmonary dysfunction attributed to paralysis of respiratory muscles leading to inadequate ventilation and inability to clear secretions, predisposing this population to be more susceptible to repeated pulmonary infections. In addition to restrictive pulmonary dysfunction observed, individuals with high cervical lesion often exhibit obstructive respiratory physiology similar to that seen in asthmatics and believed to be due to unopposed parasympathetic innervation to the airways and, possibly, the loss of sympathetic innervation to the lungs. Underlying airway inflammation is the major pathophysiological mechanism in individuals with asthma. Similarly, airway inflammation may play a role in the obstructive physiology observed in individuals with tetraplegia. Our preliminary data from project entitled "The Effect of Nitric Oxide on Pulmonary Resistances and Blood Pressure in Persons with Tetraplegia" (RCDA #B4162C-Radulovic) has demonstrated that individuals with chronic stable tetraplegia have increased levels of fractional exhaled nitric oxide (FeNO) comparable to levels in mild asthmatic subjects, suggesting the presence of underlying airway inflammation. Measurement of more specific biomarkers of airway inflammation that are found in exhaled breath condensates (EBC) will enable better definition of the presence of and, potentially, address contributing factors leading to underlying airway inflammation in the respiratory tract of individuals with chronic tetraplegia. Thus, in turn, can result in development of new therapeutic strategies, such as use of inhaled steroids in this population, and potentially decrease the rate of respiratory complications, decreasing the number of re-hospitalizations and improving the quality of life of affected individuals. The purpose of this study is to determine the presence/absence of exhaled biomarkers of inflammation in individuals with chronic stable tetraplegia and their relationship with FeNO and overall pulmonary function. Understanding the underlying mechanisms involved in pulmonary dysfunction observed in persons with chronic cervical SCI may identify treatment options, such as use of inhaled steroids. This approach would be expected to ultimately improve quality of life in affected individuals, decreasing the rate of re-hospitalizations due to respiratory complications and the socioeconomic burden placed on these with SCI and the health care system. PUBLIC HEALTH RELEVANCE: Relevance of the Proposed Work to the VA Patient Care Mission. The Mission of the Department of Veterans Affairs is to provide optimal clinical care for all patients. Compared with able-bodied veterans, persons with SCI require specialized care directly related to the degree of neurologic impairment. It is important to recognize and address the secondary complications of paralysis to improve the longevity and quality of life of persons with SCI. This study may facilitate the development of new cost effective therapeutic approaches for the treatment and prevention of respiratory complications. Significant system- wide cost-savings may result from improvements in our approach to veterans with higher cord lesions. Increasing our understanding of the underlying mechanisms of obstructive respiratory dysfunction observed in individuals with chronic cervical SCI is of utmost importance for guiding future clinical interventions. The finding of underlying inflammation would suggest therapeutic use of specific anti-inflammatory agents. Failing to find markers of inflammation would, in turn, suggest neurological impairment and raise the possibility of alternative treatments, such as inhaled L-NAME. Reduction of underlying airway inflammation in persons with chronic tetraplegia would be expected to reduce the mortality and morbidity associated with respiratory complications, which are the leading cause of mortality during the acute phase of SCI and third leading cause of re-hospitalization in persons with chronic cervical SCI. Apart from decreasing respiratory complications, improvement of overall respiratory function would be expected to increase the quality of life, with potential implications on employability, personal activities, and exercise training. Advances in pulmonary care would be expected to translate into more productive, active and independent lifestyles for affected individuals. Decreasing the rates of hospitalization for individuals with chronic cervical SCI would significantly decrease the financial burden of providing care.

描述（由申请人提供）： 四肢瘫痪者因呼吸肌麻痹而表现出肺功能障碍，导致通气不足和无法清除分泌物，使该人群更容易反复肺部感染。除了观察到的限制性肺功能障碍外，患有高位颈椎病变的个体通常表现出与哮喘患者相似的阻塞性呼吸生理学，并被认为是由于气道的副交感神经支配不受对抗，并且可能是由于肺部的交感神经支配丧失所致。潜在的气道炎症是哮喘患者的主要病理生理机制。同样，气道炎症可能在四肢瘫痪患者的阻塞性生理学中发挥作用。我们题为“一氧化氮对四肢瘫痪患者肺阻力和血压的影响”项目（RCDA #B4162C-Radulovic）的初步数据表明，慢性稳定四肢瘫痪患者的呼出一氧化氮 (FeNO) 水平升高，与轻度哮喘受试者的水平相当，表明存在潜在气道 炎症。对呼出气冷凝物 (EBC) 中发现的更具体的气道炎症生物标志物进行测量，将能够更好地定义慢性四肢瘫痪患者呼吸道中潜在气道炎症的存在，并可能解决导致潜在气道炎症的影响因素。因此，反过来可以导致新的治疗策略的开发，例如在该人群中使用吸入类固醇，并可能降低呼吸系统并发症的发生率，减少再住院的次数并改善受影响个体的生活质量。本研究的目的是确定慢性稳定性四肢瘫痪患者呼出的炎症生物标志物是否存在，以及它们与 FeNO 和整体肺功能的关系。了解慢性颈椎 SCI 患者观察到的肺功能障碍的潜在机制可能会确定治疗方案，例如使用吸入类固醇。这种方法预计将最终改善受影响个体的生活质量，降低因呼吸系统并发症而再次住院的比率以及脊髓损伤患者和医疗保健系统所承受的社会经济负担。 公共卫生相关性： 拟议工作与 VA 患者护理任务的相关性。 退伍军人事务部的使命是为所有患者提供最佳的临床护理。与身体健全的退伍军人相比，脊髓损伤患者需要与神经损伤程度直接相关的专门护理。认识并解决瘫痪的继发并发症对于延长 SCI 患者的寿命和生活质量非常重要。这项研究可能有助于开发新的成本有效的治疗方法来治疗和预防呼吸系统并发症。我们对脊髓损伤程度较高的退伍军人的治疗方法的改进可能会显着节省全系统的成本。 增加我们对慢性颈椎 SCI 患者观察到的阻塞性呼吸功能障碍的潜在机制的了解，对于指导未来的临床干预至关重要。潜在炎症的发现建议使用特定的抗炎药物进行治疗。如果未能找到炎症标志物，则表明神经系统受损，并提高了替代治疗的可能性，例如吸入 L-NAME。减少慢性四肢瘫痪患者的潜在气道炎症有望降低与呼吸系统并发症相关的死亡率和发病率，呼吸系统并发症是 SCI 急性期死亡的主要原因，也是慢性颈椎 SCI 患者再住院的第三大原因。除了减少呼吸系统并发症外，整体呼吸功能的改善有望提高生活质量，并对就业能力、个人活动和运动训练产生潜在影响。肺部护理的进步预计将为受影响的个人带来更有生产力、更积极和更独立的生活方式。降低慢性颈椎 SCI 患者的住院率将显着减轻提供护理的经济负担。