# Asthma Inflammation Research > **NIH NIH P01** · CLEVELAND CLINIC LERNER COM-CWRU · 2020 · $2,731,369 ## Abstract ABSTRACT – OVERALL PROGRAM More than 25 million Americans suffer from asthma, and nearly half do not have their asthma under control. Standard treatment is limited, and a stepped care approach is applied uniformly to all patients regardless of the underlying mechanisms of asthma. Our Asthma Inflammation Research [AIR] Program aims to uncover fundamental mechanisms of asthma and identify biomarkers of those pathways that will define mechanistic endotypes of asthma in order to target therapies in a precision medicine approach of care. In Cycle I of the TPPG, we uncovered new mechanisms of airway inflammation and hyper-reactivity. In Cycle II, we apply the fundamental discoveries to precisely target pathways for bronchodilation (Project 3) and inflammation (Projects 1 and 2). Based on findings that oxidative metabolism mechanistically contributes to asthma, Project 1 investigates whether diet can modulate inflammatory responses, gene expression, and airway reactivity. Metabolic endotypes will be elucidated, and a specific biomarker of eosinophil activation, bromotytrosine (BrTyr) is tested in asthma control and biologic-based therapies of asthma. Project 2 has identified T-Helper 17 [TH17] pathways in origins of severe asthma. In Cycle II, Project 2 determines if, and how, TH17 cytokines drive pathologic inflammation, and uses the information to develop serum biomarkers of this endotype, and small molecule inhibitors and peptidomimetics of IL-17A for treatment of asthma. Project 3 shows that high levels of nitric oxide (NO) and oxidants in asthmatic airways damage soluble guanylate cyclase (sGC), making it NO-insensitive and diminishing the NO-sGC pathway from acting in bronchodilation. In Cycle II, Project 3 develops bronchodilator drug response profiling to identify sGC endotypes, and tests sGC activators and stimulators in asthma preclinical models to support a new indication for sGC drugs as bronchodilators. The projects benefit from model systems and efficiencies of cores, including a new Technology Development and Commercialization Core B, and innovative murine models of asthma and airflow imaging in Core C. Partnerships with Pharmaceutical & Biotechnology, Nutrition, Health & Wellness companies, and strategic leveraging of Cleveland-based NHLBI National Centers for Accelerating Innovation (NCAI-CC) and the NSF Innovations Corps at Cleveland Clinic ensure that our discoveries will be implemented over the next 5 years. Altogether, the program provides an unparalleled opportunity for efficient progression of personalized asthma care products to the marketplace for patients. ## Key facts - **NIH application ID:** 9986002 - **Project number:** 5P01HL103453-10 - **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU - **Principal Investigator:** Serpil C. Erzurum - **Activity code:** P01 (R01, R21, SBIR, etc.) - **Funding institute:** NIH - **Fiscal year:** 2020 - **Award amount:** $2,731,369 - **Award type:** 5 - **Project period:** 2011-08-02 → 2022-06-30 ## Primary source NIH RePORTER: https://reporter.nih.gov/project-details/9986002 ## Citation > US National Institutes of Health, RePORTER application 9986002, Asthma Inflammation Research (5P01HL103453-10). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9986002. Licensed CC0. --- *[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*