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Investigating the role of altered lung microbiome in fueling Th17 mediated airway inflammation in COPD among HIV-infected individual

Award Number: R21TW012354
ORGANIZATION: FOGARTY INTERNATIONAL CENTER
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2025

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Investigating the role of altered lung microbiome in fueling Th17 mediated airway inflammation in COPD among HIV-infected individual - Abstract Chronic obstructive pulmonary disease (COPD) is increasing in prevalence among people living with HIV (PLWH) as widespread use of Antiretroviral Therapy (ART) has increased longevity in this population. In rural Ugandan ART clinics, we report COPD prevalence of 6.22%. Currently, it’s not fully known what drives chronic lung inflammation in PLWH despite being virologically suppressed on ART. There is need to explore factors driving chronic airway inflammation among PLWH. Airway microbiome has been implicated in the pathogenesis of COPD. Using 16S ribosomal RNA gene (rDNA) sequencing on induced sputum samples from 200 adults with equal numbers of participants by HIV and COPD status in our rural Ugandan cohort, we show that among PLWH, airway enrichment with Staphylococcus spp as well as depletion of Pseudopropionibacterium and Porphyromonas spp are associated with COPD. Currently, we don’t fully understand how such genera drive chronic airway inflammation. In this study, we will determine the association between lung microbiome and immune responses (particularly Th17/Treg responses) in the distal airways of PLWH with COPD in a viremically controlled Ugandan cohort using BAL samples. We hypothesize that: (i) a Th17-driven pro-inflammatory immune response predominates in the distal airways of PLWH with COPD and (ii) specific distal airway microbial species (signatures) are associated with Th17-immune response among PLHW with COPD. In this study, we will determine (1): the distal airway immune profile among individuals with HIV and COPD in Uganda and (2) the association between lung microbiome and distal airway immune responses using BAL samples.


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: 2025 ( Subtotal = $0 )
2025	2023	MAKERERE UNIVERSITY COLLEGE OF HEALTH SCIENCES	CLINICAL RESEARCH BUILDING NEW MULAGO HILL ROAD	KAMPALA				UGA	International Research and Research Training	000	2	8/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $423,075 )
2023	2023	MAKERERE UNIVERSITY COLLEGE O F HEALTH SCIENCES	CLINICAL RESEARCH BUILDING NEW MULAGO HILL ROAD	KAMPALA				UGA	International Research and Research Training	002	2	8/31/2023	SUPPLEMENT FOR EXPANSION	$100,000
2023	2023	MAKERERE UNIVERSITY COLLEGE O F HEALTH SCIENCES	CLINICAL RESEARCH BUILDING NEW MULAGO HILL ROAD	KAMPALA				UGA	International Research and Research Training	001	2	8/18/2023	SUPPLEMENT FOR EXPANSION	$199,955
2023	2023	MAKERERE UNIVERSITY COLLEGE O F HEALTH SCIENCES	CLINICAL RESEARCH BUILDING NEW MULAGO HILL ROAD	KAMPALA				UGA	International Research and Research Training	000	2	6/26/2023	NON-COMPETING CONTINUATION	$123,120
														Subtotal = $423,075

Issue Date FY: 2022 ( Subtotal = $150,000 )
2022	2022	MAKERERE UNIVERSITY COLLEGE O F HEALTH SCIENCES	CLINICAL RESEARCH BUILDING NEW MULAGO HILL ROAD	KAMPALA				UGA	International Research and Research Training	000	1	6/24/2022	NEW	$150,000
														Subtotal = $150,000

Grand Total All Awards = $573,075

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Investigating the role of altered lung microbiome in fueling Th17 mediated airway inflammation in COPD among HIV-infected individual

Award Number: R21TW012354

ORGANIZATION: FOGARTY INTERNATIONAL CENTER

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2025

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