Impact of quercetin on inflammatory and oxidative stress markers in COPD

槲皮素对慢性阻塞性肺病炎症和氧化应激标志物的影响

• 批准号: 10677369
• 负责人: Nathaniel Marchetti
• 金额: $ 38.62万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-09 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10677369
• 关键词: Adrenal Cortex Hormones; Agonist; Allium cepa; Anti-Inflammatory Agents; Antihypertensive Agents; Antioxidants; Apple; Asthma; Biological; Biological Availability; Biological Process; Blood; Blood Glucose; Bronchial Hyperreactivity; Bronchoalveolar Lavage; Cause of Death; Chemicals; Chronic; Chronic Disease; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Clinical; Clinical Trials; Data; Development; Diet; Disease; Dose; Environmental Risk Factor; Epithelial; Flavonoids; Food; Future; Goals; Human; Immune response; Incidence; Individual; Inflammation; Inflammatory; Inhalation; Lung; Lung diseases; Measures; MicroRNAs; Morbidity - disease rate; Multi-Institutional Clinical Trial; Mus; Natural Products; Oral; Outcome; Oxidants; Oxidative Stress; Participant; Pathway interactions; Patients; Peptide Hydrolases; Pharmaceutical Preparations; Pharmacotherapy; Phase; Physical Examination; Placebos; Plants; Plasma; Platelet Count measurement; Play; Pre-Clinical Model; Prevalence; Property; Protease Inhibitor; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Inflammation; Pulmonary Sarcoidosis; Quercetin; Questionnaires; Randomized; Research; Rhinovirus; Risk; Role; Running; Safety; Smoking History; Structure of parenchyma of lung; Supplementation; Symptoms; Therapeutic Effect; Tissue-Specific Gene Expression; Tissues; United States; anti-cancer; clinically relevant; comorbidity; design; dietary; disease natural history; disease phenotype; dosage; efficacy evaluation; epidemiology study; inflammatory marker; influenza pneumonia; metabolic profile; mortality; novel; novel therapeutics; participant safety; patient population; prevent; pulmonary function; side effect; volunteer

Chronic obstructive pulmonary disease (COPD) is a major cause of mortality and morbidity in the United States and growing cause of chronic disease globally. At present the treatment options for COPD are limited and new therapies are needed to treat/prevent progression of COPD. Environmental factors and host response leading to imbalance in the ratio of oxidants to antioxidants, and proteases to antiproteases leading to chronic inflammation and tissue destruction is thought to play crucial role in development and progression of COPD. Quercetin is a plant flavonoid and has potent antioxidant and anti-inflammatory properties. Quercetin supplementation decreased markers of oxidative stress and inflammation in the plasma of patients with another chronic lung disease, pulmonary sarcoidosis. Quercetin also decreased both oxidative stress and lung inflammation in a preclinical model of chronic obstructive pulmonary disease (COPD). However the impact of quercetin in altering biological signatures in COPD subjects is yet to be determined. The proposed study is conducted in two phases, R61/R33 to define and confirm the biological effects of quercetin in COPD, bioavailability, safety, identification of the appropriate biological signatures which reflect clinical outcomes in COPD. This study will also define the optimal dose of quercetin required for altering biological signatures favorably. This information is necessary to conduct the future clinical trials with quercetin in COPD patients. In R61 Phase, there will be 15 study participants with moderate COPD with FEV1 ranging between 45 and 70 % of predicted and they will be randomized to receive either placebo or quercetin 2000 mg/day for 6 months. In R33 phase there will be 35 COPD subjects, who will be randomized to receive placebo, or one of the 3 quercetin doses, 500, 1000 or 2000 mg/day. Outcome of R61 phase will determine the feasibility of R33 Phase. In both R61 and R33 phases, all subjects will be characterized using a validated symptom questionnaire, medication and smoking histories, analysis of co-morbidities, and physical examination. All subjects will be asked to go on a low quercetin diet 7 days prior to start of quercetin or placebo supplementation to until the end of trial. Blood and bronchoalveolar lavage (BAL) will be collected after 7 days washout period (run-in) and after study drug treatment. Blood will also be collected at 3 months of study drug treatment. Plasma and BAL quercetin levels, markers of inflammation and oxidative stress in blood and BAL will be measured. Pulmonary function, and blood profiles (CBC and CMP) will be performed at run-in and at 3 and 6 months of study drug treatment to assess the safety. Results from these studies will provide information on biological endpoints, safety, bioavailability, and quercetin dosage required to carry out large clinical trials examining the efficacy of quercetin in COPD patients.

慢性阻塞性肺疾病（COPD）是美国死亡率和发病率的主要原因，也是全球慢性疾病的主要原因。目前COPD的治疗选择有限，需要新的治疗方法来治疗/预防COPD的进展。环境因素和宿主反应导致氧化剂与抗氧化剂、蛋白酶与抗蛋白酶比例失衡，导致慢性炎症和组织破坏，被认为在COPD的发生和进展中起着至关重要的作用。