Investigating the Association Between Altered Lung MicroBiome and HIV-associated Chronic Obstructive Pulmonary Disease in a Ugandan Cohort
试验速览
- 阶段
- 不适用
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Operational taxanomical units
研究概览
简要总结
Research question
Is there any association between altered lung bacterial communities and HIV-associated Chronic Obstructive Pulmonary Disease (COPD)?
Rationale
Sub-Saharan Africa has experienced dramatic increases in COPD related-morbidity and mortality. Longitudinal studies have shown that people living with HIV develop worsening airflow obstruction with a prevalence higher than that of the general population (i.e 3.4 to 21% compared to 0.4 to 12.2%). It is still unknown why HIV-infected individuals develop COPD at a prevalence higher than their HIV-negative counterparts. It's been hypothesized that a change in the lung bacterial communities in the setting of HIV drives inflammation leading to lung damage. There is a need to explore the dynamics of lung bacterial communities and elucidate mechanisms responsible for irreversible lung damage that may follow lung disturbances in bacterial richness and diversity. In addition, understanding the bacterial communities of the lung in normal subjects is an essential step in providing negative controls to interpret lung microbe in disease states for-example COPD. Insights from this research will inform efforts to design optimal screening and treatment strategies for COPD in the HIV-infected population in sub Saharan Africa.
Methods
A cross sectional study will be conducted in which lung bacterial communities in 63 HIV infected participants ≥ 35 years with and without COPD will be compared with 63 HIV negative participants with and without COPD. Participants will be recruited from COPD/HIV and LINK Nakaseke cohorts, which were population based studies conducted in the same study setting. Sputum samples will be collected using sputum DNA collection, preservation and isolation Kits. Extracted bacterial DNA will be sequenced and used to determine all bacterial species in the processed samples using available online metagenomics databases.
Analysis plan
A histogram will be used to display the frequencies of the identified bacterial species in the processed samples. Bacterial richness and diversity of samples in the 4 groups will be compared to determine any differences.
详细描述
Background
The improvements in access to antiretroviral therapy (ART) among people living with HIV/AIDs (PLWHA) has resulted in a decrease in HIV-associated morbidity and mortality. This is particularly true in low- and middle-income countries (LMICs), which bear the largest burden of HIV. The reduction in mortality has substantially increased life expectancy, with estimates among PLWHA now approaching that of the general population (Asiki, Reniers et al. 2016). Consequently, there has been increased attention among survivors to the emerging burden of non-communicable diseases (NCD), such as chronic obstructive pulmonary disease (COPD) (Geneau, Stuckler et al. 2010). Sub-Saharan Africa, which has the highest density of PLWHA, has experienced dramatic increases in COPD related-morbidity and mortality (van Zyl Smit, Pai et al. 2010, Asiki, Reniers et al. 2016). Studies are urgently needed to further elucidate the pathogenesis of COPD, and to determine optimal screening and treatment strategies (Asiki, Reniers et al. 2016, Drummond, Kunisaki et al. 2016). Associations between lung dysbiosis and COPD exacerbation phenotypes have been demonstrated in the general population(Wang, Bafadhel et al. 2016). However, it still remains unknown why PLWHA have higher prevalence of COPD compared with the general population (Drummond, Kunisaki et al. 2016). No data currently exists on lung microbiome in the general Sub Saharan African population including Uganda. There is a need to explore the dynamics of the lung microbiome (Cui, Morris et al. 2014, Wang, Bafadhel et al. 2016) and elucidate immune-mediated responses responsible for irreversible lung damage that may follow lung dysbiosis in the setting of HIV infection (Hutchinson, Vlahos et al. 2014, Wang, Bafadhel et al. 2016). Understanding the role of lung dysbiosis in the pathogenesis of HIV-associated COPD is of utmost significance in the African setting with the highest HIV/AIDs burden(Cassol, Cassetta et al. 2010, Morris, George et al. 2011).
Study hypothesis
Altered lung microbiome in HIV infected individuals is associated with chronic obstructive pulmonary disease (COPD).
Specific aims
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 35 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Male and female individuals atleast 35 years of age
- •Both HIV seropositive and seronegative.
- •Spirometry confirmed COPD and no COPD
排除标准
- •Participants with asthma
- •Participants with significant respiratory disease other than COPD
- •Failure to perform spirometry
- •Pulse rate greater than 120 beats per minute
- •Blood pressure greater than 140(systolic)/90( diastolic)
- •History of headaches in the past 6 months
- •History of eye, chest or abdominal surgery
- •History of hernia or chest trauma
- •Pregnant women
- •Bed ridden patients
- •Mentally incapacitated patients
结局指标
主要结局
Operational taxanomical units
时间窗: By Febraury 2020
Operational taxonomic units (OTUs) of the four study groups determined from the bacterial genomic sequences.
次要结局
未报告次要终点