Dysbiosis Impact on Lung Disease in HIV
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- AEC function
研究概览
简要总结
Despite the high burden of respiratory symptoms in the HIV+ population, causes of chronic obstructive pulmonary disease (COPD) in individuals with HIV are poorly understood. Microbial communities present in the lungs or gut could play an important role in COPD via their ability to stimulate inflammation and oxidative stress and by the interactions of microbial and host gene transcription. By exploring the impact of the structure and function of microbial communities on the host in HIV-associated COPD, this project could lead to discovery of novel therapeutics to treat and prevent COPD. Subjects will be 20 HIV+ individuals with COPD (FEV1/FVC <0.70 and FEV1 and DLco<80% predicted) and 20 HIV+ individuals with normal lung function (controls) and 10 HIV negative individuals recruited from our ongoing cohorts. Controls will be matched to the individuals with COPD based on age, gender, pack-years of smoking, ART use, HIV viral suppression, and history of illicit drug use. Bronchoscopy will be performed on all subjects. The investigator will uncover mechanisms that contribute to COPD in HIV+ individuals, which will lead to interventional therapies. For example, the investigators evaluate the impact of bacteria on lung epithelial cell gene expression and inflammation and test ability of anti-inflammatories to alter responses. Identification of other key pathways or microbes could also lead to testing of pro-biotics, post-biotics (bacterial metabolites), or therapy with bacteria genetically modified for desired function or metabolites.
详细描述
Day one:
Respiratory questionnaires:
The Modified Medical Research Council Dyspnea scale (MMRC) and the St. George's Questionnaire(SGQT) will be administered. These are paper and pencil questionnaires that inquire about respiratory symptoms, quality of life, and other lung related issues. This will take approximately 20 minutes to complete.
Blood Sample collection:
The subject will be asked to provide a blood sample by venipuncture of approximately 110mls (7.4 tablespoon) at this study visit. The purpose of this collection is to have blood processed for serum, plasma, and PBMCS, and a portion stored for RNA to be used for future use. A hemoglobin and carboxyhemoglobin will be done in order to calculate the DLCO only if the participant requires repeat spirometry and DLCO testing. In addition, part of this blood will be used to perform routine clinical blood tests to assure that it is safe to proceed with the bronchoscopy test. (CBC/DIFF/PLT, LYTS, BUN, Creatinine, Glucose, PT/PTT) The de-identified research samples will be processed and stored at -80C. Personal information will not be provided to individual research subjects as Dr. Morris's laboratory is not CLIA certified .
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV-1 infection, documented in medical record at any time prior to study entry.
- •HIV negative who have prior involvement in an HLRC study.
- •Men and women age 18 to
- •Ability and willingness to complete all tests.
- •Participant in HLRC studies,(PRO10060177, PRO09050521, PRO14070355, PRO08030011, PRO00606151, PRO13050229) MACS(Pitt Men's study), Women's Interagency Health Study, PACT or local HIV + clinics.
- •COPD will be defined as Subjects with FEV1/FVC<0.70 or FEV1 and DLco < 80% predicted - this is the same criteria for the other HLRC studies listed in #5.
排除标准
- •Pregnancy or breast-feeding. (urine pregnancy done on all females of child bearing potential-males and females who are at least 1 year post menopausal or surgically sterile will not be tested)
- •Contraindication to pulmonary function testing (i.e. abdominal or cataract surgery within 3 months, recent myocardial infarction, etc.).
- •Increasing respiratory symptoms or febrile (temperature >100.40F [380C]) within 4 weeks of study entry.
- •Acute cardiopulmonary issue in the past 4 months.
- •Uncontrolled hypertension at screening visit (systolic > 180 mm Hg or diastolic > 100 mm Hg) from an average of two or more readings. Subject may return for screening after blood pressure is controlled.
- •Active cancer requiring systemic chemotherapy or radiation.
- •Active infection of lungs, brain, or abdomen.
- •Intravenous drug use or alcohol use that will impair ability to complete study investigations in the opinion of the investigator.
- •subjects with an upper or lower respiratory tract infection
- •Individuals with a Primary diagnosis of vocal cord dysfunction, or those with significant or uncontrolled systemic diseases, for example; uncontrolled diabetes or uncontrolled hypertension.
- •on antibiotics in the past 3 months for an acute infection (prophylaxis OK)
- •FEV1 less than 30% predicted
- •Allergy to any drug needed to perform testing and no alternative available (albuterol, atropine, lidocaine, fentanyl, versed, Demerol)
结局指标
主要结局
AEC function
时间窗: 5 years
Trans-epithelial electrical resistance (TEER) will be measured hourly during bacterial co-culture with ALI AECs in the various experimental conditions using an Ag/AgCl electrode106
AEC supernatant cytokines and cell gene expression
时间窗: 5 years
Basolateral supernatant cytokines and MMPs will be measured by ELISA, and AEC cytokine and MMP gene expression by rtPCR. We will determine if IgG- or IgM-bound bacteria from HIV+ individuals with COPD generate a greater inflammatory response in co-culture than bacteria from HIV+ individuals without COPD and if this response can be decreased by anti-inflammatories.
Comparison of Ig-bound and BAL bacteria
时间窗: 5 years
Using 16S sequencing, we will compare unsorted bacteria from BAL to IgG- and IgM-bound and Ig-negative bacteria in HIV+ individuals with and without COPD.
次要结局
未报告次要终点
研究者
Alison Morris
Chief, Pulmonary, Allergy, and Critical Care Medicine
University of Pittsburgh