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Principal Investigator: Tara F Carr
Organization: UNIVERSITY OF ARIZONA
Fiscal Year: 2023
Award: $255,048
Funding agency: National Institute of Allergy and Infectious Diseases
The overall goal of this Asthma and Allergic Diseases Cooperative Research Center (AADCRC) proposal is to
elucidate the mechanisms by which the innate immune system affords protection against viral-induced
exacerbations in asthma. In the renewal of our AADCRC program, we will continue to focus on the critical
and often understudied innate immune factors the anion lipids of surfactant, (palmitoyl-oleoyl-
phosphatidylglycerol (POPG) and phosphatidylinositol (PI)) and Toll interacting protein (Tollip) and
surfactant protein-A (SP-A). Three inter-related projects are proposed in this application; the program will
employ use of biologic airway and peripheral systemic specimen samples obtained from well-phenotyped
participants with and without type 2 asthma and atopy through Core B, the Clinical Core. We hypothesize that
POPG/PI, Tollip and SP-A function as unique immune modulators which attenuate the effects of viral
infections in type 2 asthma, specifically RV-C, influenza A and SARS-CoV-2. Supplementation of
functional POPG/PI, SP-A and the IL-33 decoy receptor sST2 offer novel alternatives to reduce
exacerbations due to viral infections in asthma. Use of human samples is critical as animal models of SARS-
CoV-2, influenza and RVC are limited, and translational of findings to human disease can be variable. Therefore,
the goal of the Clinical Core is to provide services for our AADCRC investigators to perform safe, consistent
procedures in research participants for phenotyping and standardized, high quality collection of biologic airway
and peripheral systemic specimens, cost effective sample processing and data collection, with robust data
management and statistical analysis to test the hypotheses presented in each project. This Clinical Core will
extensively phenotype 100 participants comprised of 60 asthma (30 mild, and 30 severe) patients and 40 controls
(25 atopic, 15 non-atopic) for lung function testing, type 2 phenotyping, genotyping, nasal sampling, and to
participate in the bronchoscopy studies to understand the effectiveness of these innate immune modulators in
asthma and atopy, and in mild and severe asthma. The Clinical Core will coordinate and perform bronchoscopy
with bronchoalveolar lavage, nasal and epithelial cell brushings, and endobronchial biopsy on all participants.
The Clinical Core will be responsible for processing, storing, and distributing all samples collected from
participants, to each of the three projects. In this capacity, the Core will allow each clinical sample to be utilized
to its full potential and serve all projects equally. For all of the studies within the AADCRC utilizing human subject
samples, the Clinical Core will also be responsible for assuring patient safety, data confidentiality and full
regulatory compliance. A Biostatistics Unit is embedded in this core to integrate the clinical data with the
molecular/biomarker data to effectively model relationships between cellular features and clinical phenotypes in
asthma.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ACE2><Alleles><Allelomorphs><Allergic Disease><Alveolar Macrophages><Animal Model><Animal Models and Related Studies><Anions><Asthma><Atopic Allergy><Attenuated><B cell differentiation factor><B cell stimulating factor 2><B-Cell Differentiation Factor><B-Cell Differentiation Factor-2><B-Cell Stimulatory Factor-2><BCDF><BSF-2><BSF2><Biological><Biological Markers><Biological Response Modifiers><Biometrics><Biometry><Biomodulators><Biopsy><Biostatistics><Blood><Blood Reticuloendothelial System><Body Tissues><Bronchial Asthma><Bronchoalveolar Lavage Fluid><Bronchoscopy><Bronchoscopy with Bronchoalveolar Lavage><Brush Cell><COVID-19 infection><COVID-19 virus><COVID-19 virus infection><COVID19 infection><COVID19 virus><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Clinical><Clinical Data><Clinical Research><Clinical Study><CoV-2><CoV2><Collaborations><Collection><Consent><DNA><Data><Data Analyses><Data 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Differentiation-Inducing Protein><Nasal><Nasal Epithelium><Nasal Passages Nose><Native Immunity><Natural Immunity><Non-Specific Immunity><Nonspecific Immunity><Nose><Orthomyxovirus Type A><Participant><Patient Recruitments><Patients><Peripheral><Phase><Phenotype><Phosphatidyl Inositol><Phosphatidylglycerols><Phosphatidylinositols><Phosphoinositides><Plasmacytoma Growth Factor><Procedures><Process><Production><Protocol><Protocols documentation><PtdIns><Pulmonary Macrophages><Pulmonary Surfactant-Associated Protein A><Pulmonary function tests><RIP1><RIPK1><RIPK1 gene><RNA Expression><Receptor Protein><Receptor-Interacting Protein><Receptor-Interacting Serine/Threonine Kinase 1><Research><Research Personnel><Research Specimen><Researchers><Respiratory Epithelium><Respiratory System, Nose, Nasal Passages><Rhinovirus><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SP-A Protein><Safety><Sampling><Services><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome related corona virus 2><Signal Transduction><Signal Transduction Systems><Signaling><Specimen><Standardization><Statistical Data Analyses><Statistical Data Analysis><Statistical Data Interpretation><Structure of respiratory epithelium><Supplementation><Surfactant Protein A><TLR protein><TOLLIP><TOLLIP gene><Testing><Tissues><Toll-Interacting Protein><Toll-Like Receptor Family Gene><Toll-like receptors><Transcription><Type A Influenza><Viral><Viral Diseases><Virus Diseases><Work><Wuhan coronavirus><airway epithelium><angiotensin converting enzyme 2><angiotensin converting enzyme II><asthma attack><asthma exacerbation><asthmatic><atopic triad><atopy><attenuate><attenuates><bio-markers><biobank><biologic><biologic marker><biological signal transduction><biomarker><biorepository><clinical phenotype><coronavirus disease 2019 infection><coronavirus disease 2019 virus><coronavirus disease-19 virus><cost effective><cytokine><data interpretation><data management><exacerbation in asthma><exacerbation prone asthma><exacerbation prone asthmatic><experience><experiment><experimental research><experimental study><experiments><fluid><hCoV19><host response><human disease><human subject><immune modulators><immune system response><immunologic substance><immunological substance><immunomodulatory biologics><immunoresponse><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inflammatory modulation><influenzavirus><interferon beta 2><liquid><model of animal><nCoV2><novel><participant recruitment><patient safety><phosphatidyl glycerol><programs><receptor><receptor binding><receptor bound><recruit><respiratory tract epithelium><sample collection><screening><screenings><specimen collection><statistical analysis><surfactant><synergism><viral infection><virus infection><virus-induced disease>