Macrophage Regulation of Ozone-Induced Lung Inflammation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Change in the abundance of monocyte-derived alveolar macrophages
研究概览
简要总结
The purpose of this research study to understand how prior respiratory infections affect the susceptibility to lung inflammation following environmental exposures.
详细描述
Study participants will undergo a 1-day screening that includes a blood draw and breathing testing, return for a two-day series of testing to include blood draw, and brief breathing test before and after an inhaled challenge with either filtered air (FA) or ozone (O3). Participants return the next day for a brief breathing test, a blood draw and a procedure called bronchoscopy to evaluate the lung after the challenge.
Participants then return 18 - 20 days later to repeat the two-day series of testing to be challenged with the exposure not received on the first series, (FA or O3). Each visit will take about 3 - 3.5 hours. Follow-up phone calls from the study team will occur at 24 hours after each 2-day test series.
Total study duration is about one to one-and a half months.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Individuals between 18-55 yrs. of age (No subject will be excluded from the study on the basis of gender or ethnicity)
- •Individuals with knowledge of prior respiratory viral infection history allowing them to be segregated into one of three cohorts
- •Cohort 1 - No history of respiratory viral infection (defined as no symptoms consistent with respiratory viral infection nor history of a positive respiratory viral test)
- •Cohort 2 - Documented mild respiratory viral infection (a positive test, either PCR- or antigen-based) but with mild to no symptoms and no evidence of a lower respiratory tract infection (including no hospitalization, and no oxygen use)
- •Cohort 3 - History of respiratory viral infection and symptoms/imaging consistent with a lower respiratory tract infection who have recovered, are >6 months out from their infection, and have normal lung function (spirometry with FVC, FEV1 and FEV1/FVC)
- •There will be no maximal period from respiratory viral infection for inclusion in the study, the minimal period will be >6 months out from infection
排除标准
- •Individuals with prior respiratory viral pneumonia who have ongoing respiratory symptoms, are still using supplemental oxygen, or have abnormal lung function
- •Current smokers of tobacco products including e-cigarettes or those with previous smoking history within the prior 5 years
- •Pregnant women and women who are presently lactating.
- •Subjects that have received antibiotic administration or an upper respiratory infection within the previous 4 weeks
- •College and graduate students or employees who are under direct supervision by any of the investigators in this protocol
- •Alcohol or illicit substance abuse
- •Chronic cardio/pulmonary respiratory disorders or other medical conditions as determined by the investigator
- •Increased airway hyperresponsiveness at baseline as measured by a positive methacholine challenge response (methacholine PC20 FEV1 < 4 mg/ml)
- •Subjects will be requested to refrain from antihistamines, nonsteroidal anti-inflammatory agents, antioxidants (e.g. beta-carotene, selenium, and lutein) and supplemental vitamins (e.g. C and E), for 1 week prior to, and during testing.
研究组 & 干预措施
Cohort 2
Documented mild respiratory viral infection
干预措施: Ozone (Drug)
Cohort 1
no history of respiratory viral infection
干预措施: Ozone (Drug)
Cohort 3
Respiratory viral pneumonia
干预措施: Ozone (Drug)
结局指标
主要结局
Change in the abundance of monocyte-derived alveolar macrophages
时间窗: Baseline, Day 18-20
Change in the abundance of monocyte-derived alveolar macrophages and association to measures of O3-induced inflammation (BAL cell neutrophils, albumin and cytokine production)
Change in the abundance of monocyte-derived alveolar macrophages
时间窗: Baseline, Day 18-20
\- Change in the abundance of monocyte-derived alveolar macrophages and association to measures of O3-induced inflammation (BAL cell neutrophils, albumin and cytokine production)
次要结局
- Change in the abundance of autonomous CSF-1 expression in alveolar macrophages(Baseline, Day 18-20)
- Association between prior evidence of respiratory viral pneumonia(Baseline, Day 18-20)
- Association between prior evidence of respiratory viral infection without pneumonia(Baseline, Day 18-20)
- Change in the abundance of autonomous CSF-1 expression in alveolar macrophages(Baseline, Day 18-20)
- Association between prior evidence of COVID pneumonia(Baseline, Day 18-20)
- Association between prior evidence of COVID infection without pneumonia(Baseline, Day 18-20)
研究者
Robert Tighe, MD
Associate Professor of Medicine
Duke University