2015. Host Gene Expression Identifies Infectious Triggers of Asthma Exacerbation

BACKGROUND: Asthma exacerbations often occur due to infectious triggers. However, determining whether an infection is present and whether it is bacterial or viral remains clinically challenging leading to antibiotic overuse. A diagnostic strategy that clarifies these uncertainties can enable personalized asthma treatment and mitigate antibiotic resistance. Host gene expression is a promising alternative to pathogen-detection methods. METHODS: Forty-six patients presenting to the emergency department with asthma exacerbations were enrolled. Cases were clinically adjudicated as having bacterial, viral, or non-infectious etiologies. RT-PCR taqman low density array (TLDA) was used to quantify 87 gene targets, followed by logistic regression modeling to define class. Etiologies were correlated with clinical information including symptoms and antibiotic prescriptions. RESULTS: Most clinical parameters were similar between groups including duration of symptoms, presence of sick contacts, and severity of nasal symptoms, cough, headache, throat discomfort, and malaise. Only fever/chills (P = 0.006) and a composite of all symptoms (P = 0.02) were significantly different. In contrast to clinically adjudicated phenotypes, host response signatures identified very few bacterial triggers. Notably, none of the adjudicated bacterial cases had positive confirmatory microbiology. Instead, 29 and 57% were identified as having a viral infection or no infection, respectively. Despite the absence of bacterial infections identified using host gene expression, antibiotics were prescribed in 47.8% of all cases. CONCLUSION: Host response signatures indicated that asthma exacerbation is infrequently caused by bacterial infections, even when clinical adjudications suggest this to be the case. Instead, most are either of viral or non-infectious etiologies. Despite most cases being classified as nonbacterial, empiric antibiotics were prescribed nearly half the time. A host gene expression approach can offer clinically useful diagnostic information to guide more appropriate antibiotic use among patients with asthma exacerbation. DISCLOSURES: G. S. Ginsburg, Host Response Inc.: Board Member, Founder, Scientific Advisor and Shareholder, Stock (currently worth < $100). C. W. Woods, Host Response: Founder, Licensing agreement or royalty; Qvella: Collaborator, Research support; BioFire: Collaborator, none. E. L. Tsalik, Host Response, Inc.: Founder, Equity.