U01AI159087

Multi-Omics of the Frequent Exacerbator Asthmatic - Abstract

Asthma is a common, complex, and costly pediatric chronic condition in the U.S., resulting in nearly 2 million acute-care visits and $82 billion in overall costs each year. Children of low-income families in urban communities have the highest prevalence of asthma and the greatest disparities in asthma morbidity and mortality.

In Hamilton County, OH, over 36,000 children have asthma, with more than 14,000 of them being Medicaid-insured, resulting in a 10-fold higher rate of hospitalization. Asthma exacerbations, acute episodes of increased asthma symptoms and deteriorations in lung function, are a major cause of stress for patients and families.

While exacerbations are a prominent feature of poorly controlled and severe asthma, exacerbation rates can be high even in patients with mild asthma, and asthma exacerbation frequency can remain unchanged despite intensive controller therapy. Pediatric studies have revealed that exacerbations continue to occur despite good baseline symptom control.

A frequent exacerbator phenotype of asthma (defined by 2 or more exacerbations/year) has been described, but little is known about this asthma subgroup, which disproportionately affects urban populations and is responsible for considerable asthma morbidity and healthcare costs. No specific clinical characteristics can reliably discriminate between frequent and non-frequent exacerbators, highlighting the need for systems-level approaches.

Our center-specific project will fill this gap in understanding. Our preliminary data reveal differentially expressed and differentially methylated genes in the nasal epithelium of children who are frequent exacerbators and highlight biologic pathways that implicate distinct mechanisms underlying the frequent exacerbator phenotype.

We will test the hypothesis: the frequent exacerbator is a distinct endotype of asthma that is characterized by host nasal epithelial transcriptomic and/or DNA methylomic patterns that distinguish the frequent exacerbator from asthmatic children who are not frequent exacerbators, and that these patterns are, in part, triggered by distinct nasal microbial patterns.

We propose an innovative strategy utilizing multiple systems-based approaches that layer host nasal biome and methylome patterns with nasal epithelial transcriptomics taken during an acute exacerbation (before administration of steroids). We are uniquely poised to conduct this study due to the tremendous infrastructure that we have established as part of the Ohio Pediatric Asthma Repository and our multidisciplinary team.

The overall objective of our studies is to improve the lives of children with asthma from low-income families who live in urban communities. We propose two aims: (1) to contribute to the overall CAUSE goals by conducting network-wide CAUSE clinical research projects and participating in the CAUSE steering committee and other network functions; (2) to conduct a center-specific project aligned with CAUSE goals focused on the frequent exacerbator asthma phenotype.

Childrens Hospital Medical Center

TO ASSIST PUBLIC AND PRIVATE NONPROFIT INSTITUTIONS AND INDIVIDUALS TO ESTABLISH, EXPAND AND IMPROVE BIOMEDICAL RESEARCH AND RESEARCH TRAINING IN INFECTIOUS DISEASES AND RELATED AREAS, TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS. TO ASSIST PUBLIC, PRIVATE AND COMMERCIAL INSTITUTIONS TO CONDUCT DEVELOPMENTAL RESEARCH, TO PRODUCE AND TEST RESEARCH MATERIALS, TO PROVIDE RESEARCH SERVICES AS REQUIRED BY THE AGENCY FOR PROGRAMS IN INFECTIOUS DISEASES, AND CONTROLLING DISEASE CAUSED BY INFECTIOUS OR PARASITIC AGENTS, ALLERGIC AND IMMUNOLOGIC DISEASES AND RELATED AREAS. PROJECTS RANGE FROM STUDIES OF MICROBIAL PHYSIOLOGY AND ANTIGENIC STRUCTURE TO COLLABORATIVE TRIALS OF EXPERIMENTAL DRUGS AND VACCINES, MECHANISMS OF RESISTANCE TO ANTIBIOTICS AS WELL AS RESEARCH DEALING WITH EPIDEMIOLOGICAL OBSERVATIONS IN HOSPITALIZED PATIENTS OR COMMUNITY POPULATIONS AND PROGRESS IN ALLERGIC AND IMMUNOLOGIC DISEASES. BECAUSE OF THIS DUAL FOCUS, THE PROGRAM ENCOMPASSES BOTH BASIC RESEARCH AND CLINICAL RESEARCH. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM EXPANDS AND IMPROVES PRIVATE SECTOR PARTICIPATION IN BIOMEDICAL RESEARCH. THE SBIR PROGRAM INTENDS TO INCREASE AND FACILITATE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATES AND FOSTERS SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. RESEARCH CAREER DEVELOPMENT AWARDS SUPPORT THE DEVELOPMENT OF SCIENTISTS DURING THE FORMATIVE STAGES OF THEIR CAREERS. INDIVIDUAL NATIONAL RESEARCH SERVICE AWARDS (NRSAS) ARE MADE DIRECTLY TO APPROVE APPLICANTS FOR RESEARCH TRAINING IN SPECIFIED BIOMEDICAL SHORTAGE AREAS. IN ADDITION, INSTITUTIONAL NATIONAL RESEARCH SERVICE AWARDS ARE MADE TO ENABLE INSTITUTIONS TO SELECT AND MAKE AWARDS TO INDIVIDUALS TO RECEIVE TRAINING UNDER THE AEGIS OF THEIR INSTITUTIONAL PROGRAM.

93.855 - Allergy and Infectious Diseases Research

National Institute of Allergy and Infectious Diseases (NIAID) [HHS - NIH]

Cincinnati, Ohio 45229 United States

Single Zip Code

Childhood Asthma in Urban Settings -Clinical Research Centers (U01 Clinical Trial Optional) (RFA-AI-19-073)

Amendment Since initial award the total obligations have increased 400% from $452,000 to $2,260,000.