Inflammation, Aging, Microbes, Obstructive Lung Disease and Diffusion Abnormalities (I AM OLD-DA) Study

炎症、衰老、微生物、阻塞性肺疾病和扩散异常 (I AM OLD-DA) 研究

基本信息

  • 批准号:
    10588459
  • 负责人:
  • 金额:
    $ 9.17万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-07-01 至 2025-04-30
  • 项目状态:
    未结题

项目摘要

ABSTRACT Chronic obstructive pulmonary disease (COPD) is an HIV-associated lung disease and a leading cause of morbidity and mortality, and its clinical significance is increasing as the HIV+ population ages worldwide. Despite this, our understanding of the mechanisms underlying HIV+ COPD is limited but both HIV-related and COPD- specific mechanisms are hypothesized. An improved understanding is critical for developing new therapies to treat or prevent this growing problem. This study builds upon a novel, established multinational (US and Uganda) cohort of HIV+ persons. The study measured selected markers of immune activation, inflammation, lung injury, and cellular aging in both blood and lung specimens. The study also performed lung function testing and examined the associations between the selected markers and lung function. Our data show that different markers are associated with different lung function abnormalities, suggesting that these lung function abnormalities may be due to different underlying mechanisms. Interestingly, cytomegalovirus (CMV), which is a chronic viral infection common in HIV+ persons, has been associated with the three markers most strongly associated with one of the lung function abnormalities. These data lead to the following specific aims: Aims 1 and 2: To test the hypothesis that persistent abnormalities in selected markers of immune activation, inflammation, lung injury, and cellular aging measured in the blood are associated with subsequent changes (declines) in lung function and that the specific markers associated with each lung function abnormality will be different. The longitudinal study design will strengthen the causal inferences from our earlier work and will set the foundation for future trials of therapeutic interventions, including the potential for personalized medicine with potentially novel and/or different therapies for different biomarker and/or different lung function abnormalities. Aim 3. In a cross-sectional subset of HIV+ participants selected to undergo bronchoscopy and collect lung specimens, to test the hypothesis that abnormalities in the same markers but now measured in lung specimens are associated with abnormal lung function and test the hypothesis that asymptomatic CMV co-infection is also associated with lung function abnormalities and is mediated by these markers. This aim will determine whether CMV co-infection is involved in lung function abnormalities and potentially set the stage for trials of anti-CMV therapy in HIV+ COPD. To address these aims, we will conduct a longitudinal study of 400 HIV+ subjects (200 in the US and 200 in Uganda) and collect and bank blood specimens at the same time as lung function testing. We will also perform bronchoscopy in a subset of 80 subjects (40 in the US and 40 in Uganda) and collect and bank lung specimens and specimens to assess for CMV co-infection at the same time as lung function testing. The banked specimens will allow for efficient testing of new and novel markers in the future. Our long-term objective is to improve our mechanistic understanding of lung function abnormalities seen in persons with HIV that would lead to a future study that tests new treatments for this important and growing clinical problem.
ABSTRACT Chronic obstructive pulmonary disease (COPD) is an HIV-associated lung disease and a leading cause of morbidity and mortality, and its clinical significance is increasing as the HIV+ population ages worldwide. Despite this, our understanding of the mechanisms underlying HIV+ COPD is limited but both HIV-related and COPD- specific mechanisms are hypothesized. An improved understanding is critical for developing new therapies to treat or prevent this growing problem. This study builds upon a novel, established multinational (US and Uganda) cohort of HIV+ persons. The study measured selected markers of immune activation, inflammation, lung injury, and cellular aging in both blood and lung specimens. The study also performed lung function testing and examined the associations between the selected markers and lung function. Our data show that different markers are associated with different lung function abnormalities, suggesting that these lung function abnormalities may be due to different underlying mechanisms. Interestingly, cytomegalovirus (CMV), which is a chronic viral infection common in HIV+ persons, has been associated with the three markers most strongly associated with one of the lung function abnormalities. These data lead to the following specific aims: Aims 1 and 2: To test the hypothesis that persistent abnormalities in selected markers of immune activation, inflammation, lung injury, and cellular aging measured in the blood are associated with subsequent changes (declines) in lung function and that the specific markers associated with each lung function abnormality will be different. The longitudinal study design will strengthen the causal inferences from our earlier work and will set the foundation for future trials of therapeutic interventions, including the potential for personalized medicine with potentially novel and/or different therapies for different biomarker and/or different lung function abnormalities. Aim 3. In a cross-sectional subset of HIV+ participants selected to undergo bronchoscopy and collect lung specimens, to test the hypothesis that abnormalities in the same markers but now measured in lung specimens are associated with abnormal lung function and test the hypothesis that asymptomatic CMV co-infection is also associated with lung function abnormalities and is mediated by these markers. This aim will determine whether CMV co-infection is involved in lung function abnormalities and potentially set the stage for trials of anti-CMV therapy in HIV+ COPD. To address these aims, we will conduct a longitudinal study of 400 HIV+ subjects (200 in the US and 200 in Uganda) and collect and bank blood specimens at the same time as lung function testing. We will also perform bronchoscopy in a subset of 80 subjects (40 in the US and 40 in Uganda) and collect and bank lung specimens and specimens to assess for CMV co-infection at the same time as lung function testing. The banked specimens will allow for efficient testing of new and novel markers in the future. Our long-term objective is to improve our mechanistic understanding of lung function abnormalities seen in persons with HIV that would lead to a future study that tests new treatments for this important and growing clinical problem.

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

LAURENCE HUANG其他文献

LAURENCE HUANG的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('LAURENCE HUANG', 18)}}的其他基金

Integrated Analysis of Microbial and Genomic data in Obstructive Lung Disease (I AM GOLD) Study
阻塞性肺疾病(I AM GOLD)研究中微生物和基因组数据的综合分析
  • 批准号:
    10017311
  • 财政年份:
    2019
  • 资助金额:
    $ 9.17万
  • 项目类别:
Enhancing the I AM GOLD study with single-cell deep phenotyping and machine learning meta-analysis
通过单细胞深度表型分析和机器学习荟萃分析加强 I AM GOLD 研究
  • 批准号:
    10177730
  • 财政年份:
    2019
  • 资助金额:
    $ 9.17万
  • 项目类别:
Integrated Analysis of Microbial and Genomic data in Obstructive Lung Disease (I AM GOLD) Study
阻塞性肺疾病(I AM GOLD)研究中微生物和基因组数据的综合分析
  • 批准号:
    10446574
  • 财政年份:
    2019
  • 资助金额:
    $ 9.17万
  • 项目类别:
UCSF Career Development Program in Cardiopulmonary, Hematologic, and Immunologic Comorbidities of HIV (CHIC)
加州大学旧金山分校艾滋病心肺、血液和免疫合并症职业发展计划 (CHIC)
  • 批准号:
    9753769
  • 财政年份:
    2018
  • 资助金额:
    $ 9.17万
  • 项目类别:
UCSF Career Development Program in Cardiopulmonary, Hematologic, and Immunologic Comorbidities of HIV (CHIC)
加州大学旧金山分校艾滋病心肺、血液和免疫合并症职业发展计划 (CHIC)
  • 批准号:
    10413803
  • 财政年份:
    2018
  • 资助金额:
    $ 9.17万
  • 项目类别:
UCSF Career Development Program in Cardiopulmonary, Hematologic, and Immunologic Comorbidities of HIV (CHIC)
加州大学旧金山分校艾滋病心肺、血液和免疫合并症职业发展计划 (CHIC)
  • 批准号:
    10202714
  • 财政年份:
    2018
  • 资助金额:
    $ 9.17万
  • 项目类别:
Inflammation, Aging, Microbes, Obstructive Lung Disease and Diffusion Abnormalities (I AM OLD-DA) Study
炎症、衰老、微生物、阻塞性肺疾病和扩散异常 (I AM OLD-DA) 研究
  • 批准号:
    10014578
  • 财政年份:
    2015
  • 资助金额:
    $ 9.17万
  • 项目类别:
Inflammation, Aging, Microbes, Obstructive Lung Disease, and Diffusion Abnormalities (I AM OLD-DA): Pulmonary function in females, evaluating the menopausal transition and immune activation (pFEMI).
炎症、衰老、微生物、阻塞性肺疾病和扩散异常 (I AM OLD-DA):女性肺功能,评估绝经过渡和免疫激活 (pFEMI)。
  • 批准号:
    10556269
  • 财政年份:
    2015
  • 资助金额:
    $ 9.17万
  • 项目类别:
Inflammation, Aging, Microbes, Obstructive Lung Disease and Diffusion Abnormalities (I AM OLD-DA) Study
炎症、衰老、微生物、阻塞性肺病和扩散异常 (I AM OLD-DA) 研究
  • 批准号:
    10798953
  • 财政年份:
    2015
  • 资助金额:
    $ 9.17万
  • 项目类别:
Inflammation, Aging, Microbes, Obstructive Lung Disease and Diffusion Abnormalities (I AM OLD-DA) Study
炎症、衰老、微生物、阻塞性肺疾病和扩散异常 (I AM OLD-DA) 研究
  • 批准号:
    10613550
  • 财政年份:
    2015
  • 资助金额:
    $ 9.17万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    Fellowship
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    Continuing Grant
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    Research Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    EU-Funded
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    Standard Grant
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 9.17万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了