# Integrated Analysis of Microbial and Genomic data in Obstructive Lung Disease (I AM GOLD) Study

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $752,810

## Abstract

Project Summary/Abstract
Patients with HIV are at increased risk for chronic obstructive pulmonary disease (COPD), the third leading
cause of death worldwide. In this proposal, our long-term goal is to identify the mechanisms underlying the
increased risk of COPD with HIV infection. Our central hypothesis is that enhanced Th17 driven inflammation
and chronic Gammaproteobacteria-dominated airway microbiota interact to contribute to obstructive lung
disease in HIV+ individuals. This hypothesis is based on the following evidence. First, we have found in HIV-
uninfected COPD patients that a genomic signature of Th17 driven airway inflammation marks a COPD
subgroup with functional small airway disease, which is thought to precede emphysema. Second, Th17 driven
inflammation, a pathway classically thought to defend against bacteria, is enhanced in the airways of HIV+
patients. Third, our group has shown that amongst Ugandan HIV+ patients with pneumonia, a population at
higher risk for lung function decline, there are subgroups characterized by distinct lower airway microbial
communities with differing immune responses. One subgroup had Pseudomonadaceae-dominated airway
microbiota and inflammatory gene expression. Gammaproteobacteria, which includes Pseudomonas, are
commonly found in COPD and, as with Th17 inflammation, are associated with emphysema. Thus, the
Pseudomonadaceae-dominant pneumonia subgroup may be at higher risk for developing chronic disease in
the setting of continued dysbiosis and low level Th17 driven chronic inflammation. Our proposed specific aims
will use existing and newly collected samples from our international multi-center study of HIV-associated
COPD, I AM OLD (Inflammation, Aging, Microbes and Obstructive Lung Disease), in which HIV+ participants in
Uganda and San Francisco are enrolled at the time of acute pneumonia and followed longitudinally. Aim 1 will
identify the airway microbial communities and inflammatory gene expression markers at the time of acute
infection that are associated with subsequent incident COPD and lung function decline in HIV. Aim 2 will
identify the airway microbial communities and inflammatory gene expression markers during chronic stable
disease that are enhanced in HIV+COPD compared to participants without COPD (HIV+COPD-). In Aim 3 we
will perform integrative analyses of the airway microbiome, microbial and human transcriptome, metabolome
and lung radiographic changes in HIV+COPD. We anticipate the following outcomes: 1) identification of the
predominant airway microbiome-host response interactions associated with HIV+COPD in two international at-
risk populations, 2) identification of metabolome alterations associated with specific microbial communities and
inflammatory responses in HIV+COPD, 3) delineation of the range of radiographic abnormalities associated
with microbiome-host response interactions in HIV+COPD. We expect these outcomes to have a positive
impact, providing a new understanding of...

## Key facts

- **NIH application ID:** 10448399
- **Project number:** 5R01HL143998-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Stephanie A Christenson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $752,810
- **Award type:** 5
- **Project period:** 2019-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10448399

## Citation

> US National Institutes of Health, RePORTER application 10448399, Integrated Analysis of Microbial and Genomic data in Obstructive Lung Disease (I AM GOLD) Study (5R01HL143998-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10448399. Licensed CC0.

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