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
• 负责人: LAURENCE HUANG
• 金额: $ 5.31万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10798953
• 关键词: Abbreviations; Acute; Address; Age; Aging; Biological Markers; Biological Specimen Banks; Biology; Blood; Blood Banks; Blood specimen; Bronchoalveolar Lavage; Bronchodilator Agents; Bronchoscopy; C-reactive protein; Carbon Monoxide; Cell Aging; Cessation of life; Chronic; Chronic Obstructive Pulmonary Disease; Chronic lung disease; Clinical; Coagulation Process; Cytomegalovirus; Data; Diffusion; Enrollment; Fibrin; Foundations; Future; Goals; HIV; HIV Infections; High Prevalence; Immunologic Markers; Inflammation; Interferons; Interleukin-6; Intervention Studies; Lead; Longitudinal Studies; Longitudinal cohort; Longitudinal cohort study; Lung; Lung diseases; Lymphocyte Activation; Macrophage Activation; Measurement; Measures; Mediating; Microbe; Morbidity - disease rate; Names; Obstructive Lung Diseases; Participant; Pathogenicity; Pathway interactions; Persons; Phenotype; Pneumonia; Population; Prevalence; Protein Secretion; Pulmonary Emphysema; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary function tests; Research Design; Risk Factors; Specimen; Spirometry; Telomerase; Testing; Therapeutic Intervention; Time; Uganda; Virus Diseases; Work; biomarker panel; chemokine; clinically significant; co-infection; cohort; immune activation; improved; inflammatory marker; insight; lung injury; monocyte; mortality; novel; novel marker; novel therapeutics; peripheral blood; personalized medicine; prevent; pulmonary function; response; telomere

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.

摘要

项目成果

Feasibility and Sensitivity of Saliva GeneXpert MTB/RIF Ultra for Tuberculosis Diagnosis in Adults in Uganda.

• DOI: 10.1128/spectrum.00860-22
• 发表时间: 2022-10-26
• 期刊: MICROBIOLOGY SPECTRUM
• 影响因子: 3.7
• 作者: Byanyima, Patrick;Kaswabuli, Sylvia;Musisi, Emmanuel;Nabakiibi, Catherine;Zawedde, Josephine;Sanyu, Ingvar;Sessolo, Abdul;Andama, Alfred;Worodria, William;Huang, Laurence;Davis, J. Lucian
• 通讯作者: Davis, J. Lucian

Reproducibility of the Ribosomal RNA Synthesis Ratio in Sputum and Association with Markers of Mycobacterium tuberculosis Burden.

• DOI: 10.1128/spectrum.00481-21
• 发表时间: 2021-10-31
• 期刊: Microbiology spectrum
• 影响因子: 3.7
• 作者: Musisi E;Dide-Agossou C;Al Mubarak R;Rossmassler K;Ssesolo AW;Kaswabuli S;Byanyima P;Sanyu I;Zawedde J;Worodria W;Voskuil MI;Savic RM;Nahid P;Davis JL;Huang L;Moore CM;Walter ND
• 通讯作者: Walter ND

HIV Infection Is Associated with Shortened Telomere Length in Ugandans with Suspected Tuberculosis.

• DOI: 10.1371/journal.pone.0163153
• 发表时间: 2016
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Auld E;Lin J;Chang E;Byanyima P;Ayakaka I;Musisi E;Worodria W;Davis JL;Segal M;Blackburn E;Huang L
• 通讯作者: Huang L

HIV infection is associated with elevated biomarkers of immune activation in Ugandan adults with pneumonia.

乌干达成人肺炎患者的免疫激活生物标志物升高与艾滋病毒感染有关。

• DOI: 10.1371/journal.pone.0216680
• 发表时间: 2019
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Wang,RichardJ;Moore,Julia;Moisi,Daniela;Chang,EmilyG;Byanyima,Patrick;Kaswabuli,Sylvia;Musisi,Emmanuel;Sanyu,Ingvar;Sessolo,Abdulwahab;Lalitha,Rejani;Worodria,William;Davis,JLucian;Crothers,Kristina;Lin,Jue;Lederman,Michael
• 通讯作者: Lederman,Michael

Stress and telomere shortening: Insights from cellular mechanisms.

• DOI: 10.1016/j.arr.2021.101507
• 发表时间: 2022-01
• 期刊: Ageing research reviews
• 影响因子: 13.1
• 作者: Lin J;Epel E
• 通讯作者: Epel E