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Longitudinal changes of the sputum microbiome in adult asthma and its association with asthma exacerbations

Award Number: R21AI178627
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Abstract About 18.7 million adults have asthma in the United States. The airway microbiome has emerged as an essential regulatory factor in asthma immune responses. Patients with asthma harbor altered bacterial compositions in their airways compared to healthy individuals; the most important alteration is a decrease in beneficial commensals and an increase in pathogenic bacteria. Our study that compared sputum bacterial compositions between adult asthma patients and healthy individuals revealed that asthma was associated with microbial alterations at the community and taxa levels, including changes in the abundances of Streptococcus salivarius, Lactobacillus species, and Haemophilus species. These results are consistent with those of previous independent human studies and have plausible biological mechanisms. However, current data on the airway microbiome in adult patients with asthma are predominantly derived from case-control and cross-sectional studies, which cannot evaluate temporal relationships between airway microbiota alterations and longitudinal asthma morbidity. There is strong evidence from multiple longitudinal studies on chronic obstructive pulmonary disease (COPD) suggesting that the airway microbial composition is closely correlated with asthma exacerbations and immune responses. However, it remains to be established whether these states are correlated in asthma. New study approaches are needed to fill this important knowledge gap. Here, we will perform a longitudinal cohort study with adult patients with asthma and healthy controls. We will collect induced sputum samples at several time points over 6 months and additional sputum samples during asthma exacerbations. We will utilize an FDA-approved electronic inhaler sensor system that will be attached to a rescue inhaler to identify asthma exacerbations and collect induced sputum soon after these exacerbations (within 24 hours). We will perform 16S ribosome RNA gene sequencing and shotgun metagenomic sequencing to identify the sputum bacterial community and relative abundance of different species. We have two aims in this study. Aim 1 is to evaluate compositional fluctuations of the sputum microbiome over time. Aim 2 is to Characterize temporal relationships of the sputum microbiome with asthma exacerbations. This proposed study will enable us to longitudinally evaluate the relationship of airway bacteria with asthma morbidity and characterize the changing dynamic patterns of the airway microbial community during asthma exacerbations. Successful completion of this study could provide valuable insights and evidence for a scaled study to include immune biomarkers and clinical indicators for further investigation.


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 = $209,925 )
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	000	1	12/6/2023	NEW	$209,925
2024	2024	WASHINGTON UNIVERSITY, THE	ONE BROOKINGS DR	SAINT LOUIS	MO	63110	SAINT LOUIS CITY	USA	Allergy and Infectious Diseases Research	001	1	2/6/2024	NEW	$0
														Subtotal = $209,925

Grand Total All Awards = $209,925

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Longitudinal changes of the sputum microbiome in adult asthma and its association with asthma exacerbations

Award Number: R21AI178627

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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