NOVEL DIAGNOSTIC FOR MANAGING ASTHMA AT POINT OF CARE

PROJECT SUMMARY Asthma is a chronic lung disease of heterogenous etiology affecting nearly 8% of the US population. Failure to properly treat asthma is associated with increased risk of morbidity and mortality, resulting in over 4,000 deaths in 2021 and an estimated economic burden over 50 billion dollars in the US. The presence of eosinophils and their granule product, eosinophil peroxidase (EPX), in airways is associated with asthma type and severity. Yet there are no commercially available products to accurately measure EPX in the airways to diagnose and manage asthma in the health care setting. Surrogate methods to define eosinophilic asthma are often too invasive, expensive, complex, unavailable, or only have low or modest correlation with eosinophil levels in the airways. Previously we demonstrated EPX is the most specific protein to identify eosinophils, an important inflammatory cell in asthma, and developed a gold-standard ELISA assay for EPX detection (EPX-ELISA). We demonstrated nasal EPX is a surrogate of airway/lung EPX levels. The overall goal of this project is to develop a rapid diagnostic test (RDT) for the detection of EPX (EPX-RDT) from human nasal swab samples that would provide comparable values of EPX to that of the existing gold standard EPX-ELISA. Such a test will be able to diagnose and guide asthma treatment regimens non-invasively from nasal swabs at the point-of-care. Currently there is no such tool on the market today. The proposal combines three innovations: (1) Unique pre-validated anti-EPX antibodies (not reproduced in over twenty years to match our level of validation and sensitivity); (2) Targeting the truly eosinophil-specific protein (EPX) that ensures we recognize both intact/degranulated eosinophils, and (3) Use of non-invasively collected nasal swab samples instead of currently used invasive collection methods such as blood, sputum or biopsy. In Aim 1 of this phase I study we will develop a novel reader integrated test cartridge to quantify EPX levels (EPX- RDT) device. In Aim 2 we will optimize nasal swab preparation for the EPX-RDT device and use EPX-ELISA as a correlative predicate. In Aim 3 we will perform validation studies with real-world clinical swab samples from people with and without asthma. Here the EPX-RDT test will be compared to the predicate EPX-ELISA. The successful completion of this aim will establish initial clinical performance for the test. At the conclusion of Phase 1, we will have a functional point-of-care device capable of detecting EPX continuum in nasal swabs with high precision and accuracy. In Phase 2, the EXP-RDT will be used to conduct clinical studies to prepare for FDA approval, commercialization, marketing and distribution. The final product will be an easy-to- use and cost-efficient tool to diagnose and treat asthma non-invasively.