A Rapid Breath Test for Invasive Aspergillosis

Project Summary AbstractInvasive aspergillosisIAis a leading cause of morbidity and death in immunocompromised patientswith overmillion individuals at risk for IA and at leastIA cases developing worldwide each yearDespite the development of potent triazole antifungal drugs for the treatment of IAIA associated mortality is stillTimely and accurate diagnosis of IAin conjunction with prompt initiation of appropriate antifungal therapyimproves patient outcomesbut is challenging due to the shortcomings of existing diagnosticsDue to the limitations of IA diagnostics and the potentially severe clinical consequences of not treating IA promptlyclinicians routinely prescribe empiric antifungal therapy to patients with suspected IAexposing many patients who ultimately do not have IA to unnecessary antifungal drugswith their toxicities and costsA major unmet need in the care of immunocompromised patients is a diagnostic that can identify IA rapidly and accuratelywithout requiring invasive proceduresTo address this unmet needwe propose further development of a novel microfluidic gas chromatography differential mobility spectrometryGC DMSbreath analysis device for the rapidnoninvasive diagnosis of IAbased on the scientific premise that patients with IA have a unique Aspergillus volatile sesquiterpene secondary metabolite signature in their breathWe have demonstrated this premise in an initial proof of concept study and subsequent validation study in patients with suspected invasive fungal diseaseCombining our expertise in engineeringdiagnostic product developmentand breath analysiswe have developed an integratedfully functioning GC DMS Microanalyzer prototype for rapid bedside breath analysissuccessfully detecting these breath sesquiterpene metabolites in patients with IA using this deviceThe goal of this Fast Track SBIR proposal is further optimization and development of the GC DMS Microanalyzer breath analysis platform for the rapid diagnosis of IAThe objective of phase I is to optimize the preconcentration of sesquiterpene metabolites in the Microanalyzer devicelowering its limit of detection for these analytes and evaluating its sensitivity in a set of patients with suspected invasive fungal diseaseIn phase IIaims are tocomplete Microanalyzer diagnostic device development for IA under design controlincorporating general and special control measuresdevelop and validate GC DMS peak finding algorithms for the automated identification of the IA breath signatureandperform comprehensive analytical validation studies for this GC DMS Microanalyzer breath test for IAUpon successful completion of these objectivesthe Microanalyzer breath test for IA will be ready for evaluation in a multicenter clinical validation study for FDAkclearance and CE mark certificationThis diagnostic device will transform the care of immunocompromised patients at risk for IAreducing diagnostic delaysfacilitating earlyappropriate antifungal treatmentand improving clinical outcomes in these patients Project NarrativeInvasive aspergillosisIAis a rapidly progressive fungal infection that causes morbidity and death in patients with weakened immune systemsDiagnostic methods for IA have important shortcomingsand patients are often prescribed prolonged courses of antifungal drugs unnecessarily due to this lack of reliable diagnosticsWe propose further development of a noninvasiverapidhighly accurate breath test for the diagnosis of IAthis diagnostic platform will reduce unnecessary use of antifungal drugs and reduce diagnostic delays in patients with IAimproving their clinical outcomes