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

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $750,787

## Abstract

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 testin...

## Key facts

- **NIH application ID:** 10409643
- **Project number:** 5R01HL128156-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** LAURENCE HUANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $750,787
- **Award type:** 5
- **Project period:** 2015-07-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10409643

## Citation

> US National Institutes of Health, RePORTER application 10409643, Inflammation, Aging, Microbes, Obstructive Lung Disease and Diffusion Abnormalities (I AM OLD-DA) Study (5R01HL128156-07). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10409643. Licensed CC0.

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