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

Award Number: R01HL143998
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2019
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Integrated Analysis of Microbial and Genomic data in Obstructive Lung Disease (I AM GOLD) Study - 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 the biology underlying the enhanced risk for COPD amongst the HIV- infected population which could direct therapeutic interventions.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Lung Diseases Research	000	4	1/10/2024	NON-COMPETING CONTINUATION	$0
2024	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94103	SAN FRANCISCO	USA	Lung Diseases Research	001	4	6/17/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $752,810 )
2022	2022	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Lung Diseases Research	000	4	7/13/2022	NON-COMPETING CONTINUATION	$752,810
														Subtotal = $752,810

Issue Date FY: 2021 ( Subtotal = $842,772 )
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cardiovascular Diseases Research	002	3	7/14/2021	SUPPLEMENT FOR EXPANSION	$0
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Cardiovascular Diseases Research	001	3	7/12/2021	SUPPLEMENT FOR EXPANSION	$89,962
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Lung Diseases Research	003	3	7/30/2021	NON-COMPETING CONTINUATION	$0
2021	2021	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Lung Diseases Research	000	3	7/9/2021	NON-COMPETING CONTINUATION	$752,810
														Subtotal = $842,772

Issue Date FY: 2020 ( Subtotal = $842,772 )
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Lung Diseases Research	001	2	8/19/2020	SUPPLEMENT FOR EXPANSION	$89,962
2020	2020	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Lung Diseases Research	000	2	7/8/2020	NON-COMPETING CONTINUATION	$752,810
														Subtotal = $842,772

Issue Date FY: 2019 ( Subtotal = $774,747 )
2019	2019	REGENTS OF THE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, THE	1855 FOLSOM ST STE 425	SAN FRANCISCO	CA	94143	SAN FRANCISCO	USA	Lung Diseases Research	000	1	9/12/2019	NEW	$774,747
														Subtotal = $774,747

Grand Total All Awards = $3,213,101

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

Award Number: R01HL143998

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2019

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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