Gamma tocopherol chemoprevention of wood smoke PM2.5-induced airway inflammation

γ-生育酚化学预防木烟PM2.5引起的气道炎症

• 批准号: 9055845
• 负责人: David B. Peden
• 金额: $ 58.08万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-03-01 至 2021-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9055845
• 关键词: Accounting; Acute; Acute bronchitis; Air; Air Pollutants; Air Pollution; Allergens; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Area; Asthma; Blood Vessels; Breathing; Burn injury; Cardiovascular Diseases; Cardiovascular system; Chemoprevention; Chemopreventive Agent; Coughing; Diesel Exhaust; Dietary Intervention; Dose; Endotoxins; Enrollment; Environmental Pollution; Exposure to; Fire - disasters; Functional disorder; Future; GSTM1 gene; Genotype; Glutathione S-Transferase; Health; Hour; Human; Human Volunteers; In Vitro; Individual; Inflammation; Inflammatory Response; Intervention; Intervention Studies; Left; Link; Lipids; Lung; Lung diseases; Mind; Modeling; Nutraceutical; Nutritional; Oral; Ozone; Particulate Matter; Persons; Placebos; Pneumonia; Predisposition; Process; Protein Isoforms; Protocols documentation; Public Health; Reporting; Respiratory System; Respiratory tract structure; Risk; Role; Site; Sputum; Supplementation; Testing; United States; Variant; Vitamin E; Wildfire; airway inflammation; allergic response; asthmatic; atopy; cardiovascular health; dietary supplements; eosinophil; gamma-Tocopherol; healthy volunteer; heart rate variability; in vivo; monocyte; neutrophil; nitrosative stress; particle; particle exposure; phase 1 study; pollutant; preclinical study; prevent; public health relevance; randomized placebo controlled trial; response; screening; volunteer; wood smoke

 DESCRIPTION (provided by applicant): Wood smoke particles (WSP) derived from wildland and other fires produce a significant fraction of ambient air particulate matter. Health effects associated with WSP include acute bronchitis, asthma exacerbation, pneumonia, cough and systemic inflammation in in healthy persons and those with asthma. Cardiovascular effects have also been reported with WSP exposure. WSP from wildland fires can cause abrupt increases in ambient air PM 2.5 levels, and avoidance of rapidly increasing PM air pollution is not feasible as many residents cannot leave the burn region, and wildland firefighters move into wildland fire sites, often for several consecutive days. As avoidance of PM is not feasible in these settings, there is a clear unmet need for interventions to reduce adverse health effects caused by acute WSP exposure. Our team has developed gamma tocopherol (gT), an isoform of vitamin E with robust anti-inflammatory actions, as a chemopreventive intervention for inflammation caused by environmental contaminants. Our animal studies show that gT inhibits allergen, ozone and endotoxin-induced airway inflammation. Our human phase I studies show that gT decreases inflammatory response of circulating monocytes, decreases nitrosative stress, and inhibits neutrophil (PMN) influx to the airway in vivo after endotoxin challenge. Thus, gT supplementation is an attractive nutritional/nutraceutical approach to decreasing the adverse health effects of inhaled WSP. We have also developed a 500µg/m3 WSP exposure protocol which induces both airway and systemic increases in PMNs in human volunteers. Using this challenge protocol, we will undertake a randomized, placebo-controlled study to determine if of supplementation with 1200 mg of on WSP-induced airway and systemic PMN increases in healthy and asthmatic volunteers. Exploratory endpoints will include non-specific bronchial reactivity (NSBR), and cardiovascular responses reported to be impacted by PM exposure. These studies will also allow us to compare responses of allergic asthmatic (AA) and healthy volunteers (HV) to determine if atopy or other facets of asthma modify risk for inflammatory response to WSP. This study will be the first to test a specific nutritional supplement as a chemopreventive intervention for WSP-induced inflammation in either AAs or NVs, and to specifically compare the response of these groups to WSP-induced inflammation.

 描述（由适用提供）：衍生自野外和其他火灾的木烟颗粒（WSP）产生了很大一部分环境空气颗粒物。与WSP相关的健康作用包括健康人和患有哮喘患者的急性支气管炎，哮喘的出现，肺炎，咳嗽和全身性炎症。还报道了WSP暴露的心血管效应。 Wildland大火的WSP会导致周围空气PM 2.5水平的突然增加，并且避免迅速增加的PM空气污染是不可行的，因为许多居民无法离开烧伤区域，而Wildland Firefighters通常会连续几天进入Wildland Fire站点。由于在这些情况下避免PM是不可行的，因此明显未满足的干预措施可以减少急性WSP暴露造成的不良健康影响。我们的团队已经开发了伽马生育酚（GT），这是一种具有强大的抗炎作用的维生素E的同工型，作为由环境污染物引起的感染的化学预防干预措施。我们的动物研究表明，GT抑制过敏原，臭氧和内毒素诱导的气道感染。我们的人类I期研究表明，GT会降低循环单核细胞的炎症反应，减少硝化应激，并抑制内毒素挑战后体内气道对气道的影响（PMN）。这是GT补充是一种有吸引力的营养/营养方法，可降低遗传WSP的不良健康影响。我们还开发了500µg/m3 WSP暴露方案，该方案诱导了人类志愿者的PMN的气道和全身增加。使用此挑战方案，我们将进行一项随机，安慰剂对照的研究，以确定是否补充了1200 mg的WSP诱导的气道，并且健康和哮喘的志愿者的全身性PMN增加。探索性终点将包括非特异性支气管反应性（NSBR）和据报道受PM暴露影响的心血管反应。这些研究还将使我们能够比较过敏性哮喘（AA）和健康志愿者（HV）的反应，以确定特应性或其他哮喘方面是否改变了对WSP炎症反应的风险。这项研究将是第一个测试特定营养补充剂作为AAS或NVS中WSP诱导的炎症的化学预防干预措施，并专门比较这些组对WSP诱导的炎症的反应。