Asthma Inflammation Research

Overview

The overall goal of the Asthma Inflammation Research \[AIR\] Translational Program is to create an integrated multidisciplinary team for the focused purpose of development of diagnostic and prognostic tests informative for airway inflammation, and for the design of innovative, targeted biologic therapeutics. The overarching aims of the AIR program are to conceptualize, develop, and test the next-generation therapeutics, and novel asthma diagnostic and prognostic tools that will allow us to improve the standard of asthma care.

More than 20 million Americans suffer from asthma, and nearly half of asthma sufferers do not have their asthma under control. Although commonly diagnosed using physiological measures of airflow and bronchial hyperreactivity, asthma pathophysiology is related to chronic inflammation of the airway. Current diagnostic evaluation and monitoring are inadequate for proposed practice guidelines. The most commonly used test for evaluation of asthma is the measurement of airflow obstruction by spirometry. The National Asthma Education Prevention Program (NAEPP) and Expert Panel Reports set forth grading of asthma severity based on the frequency of symptoms, airflow, and the need for inhaled beta-agonists. Practice guidelines outline that the goals of therapy for asthma are to: maintain normal activity with near normal parameters of lung function, prevent exacerbations that lead to tissue injury, and avoid medication toxicity. In order to facilitate these goals, NAEPP defines key components for management including disease monitoring and stepped care pharmacotherapy. Unfortunately, there is no optimal plan for monitoring inflammation, which causes us to fail in key components in management of asthma. Limited options for anti-inflammatory treatments to control asthma likewise often lead to substantial morbidities due to treatment with high doses of corticosteroids. Our AIR program plans to develop novel asthma monitoring tests and design targeted therapeutics, which altogether may reduce toxicities and improve the long-term health of patients. Impact on broad scientific advancement. Our cumulative studies provide fundamental information on the molecular mechanisms that contribute to unresolving and excessive inflammation that leads to tissue remodeling. This mechanistic knowledge is of broad scientific importance as nearly all chronic human diseases are defined by prolonged and active inflammation, with tissue destruction, and failed attempts at healing. Thus, our investigations will provide comprehensive knowledge and consequent translational deliverables that may be widely applicable as diagnostic strategies and therapies in other chronic inflammatory diseases.

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