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A host gene expression approach for identifying triggers of asthma exacerbations.

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Date
2019-01
Authors
Lydon, Emily C
Bullard, Charles
Aydin, Mert
Better, Olga M
Mazur, Anna
Nicholson, Bradly P
Ko, Emily R
McClain, Micah T
Ginsburg, Geoffrey S
Woods, Chris W
Burke, Thomas W
Henao, Ricardo
Tsalik, Ephraim L
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Abstract
RATIONALE:Asthma exacerbations often occur due to infectious triggers, but determining whether infection is present and whether it is bacterial or viral remains clinically challenging. A diagnostic strategy that clarifies these uncertainties could enable personalized asthma treatment and mitigate antibiotic overuse. OBJECTIVES:To explore the performance of validated peripheral blood gene expression signatures in discriminating bacterial, viral, and noninfectious triggers in subjects with asthma exacerbations. METHODS:Subjects with suspected asthma exacerbations of various etiologies were retrospectively selected for peripheral blood gene expression analysis from a pool of subjects previously enrolled in emergency departments with acute respiratory illness. RT-PCR quantified 87 gene targets, selected from microarray-based studies, followed by logistic regression modeling to define bacterial, viral, or noninfectious class. The model-predicted class was compared to clinical adjudication and procalcitonin. RESULTS:Of 46 subjects enrolled, 7 were clinically adjudicated as bacterial, 18 as viral, and 21 as noninfectious. Model prediction was congruent with clinical adjudication in 15/18 viral and 13/21 noninfectious cases, but only 1/7 bacterial cases. None of the adjudicated bacterial cases had confirmatory microbiology; the precise etiology in this group was uncertain. Procalcitonin classified only one subject in the cohort as bacterial. 47.8% of subjects received antibiotics. CONCLUSIONS:Our model classified asthma exacerbations by the underlying bacterial, viral, and noninfectious host response. Compared to clinical adjudication, the majority of discordances occurred in the bacterial group, due to either imperfect adjudication or model misclassification. Bacterial infection was identified infrequently by all classification schemes, but nearly half of subjects were prescribed antibiotics. A gene expression-based approach may offer useful diagnostic information in this population and guide appropriate antibiotic use.
Type
Journal article
Subject
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
COMMUNITY-ACQUIRED PNEUMONIA
REQUIRING HOSPITALIZATION
PERIPHERAL-BLOOD
PROCALCITONIN
ANTIBIOTICS
SIGNATURE
CHILDREN
ETIOLOGY
INFECTIONS
BACTERIAL
Permalink
https://hdl.handle.net/10161/19463
Published Version (Please cite this version)
10.1371/journal.pone.0214871
Publication Info
Lydon, Emily C; Bullard, Charles; Aydin, Mert; Better, Olga M; Mazur, Anna; Nicholson, Bradly P; ... Tsalik, Ephraim L (2019). A host gene expression approach for identifying triggers of asthma exacerbations. PloS one, 14(4). pp. e0214871. 10.1371/journal.pone.0214871. Retrieved from https://hdl.handle.net/10161/19463.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Burke

Thomas Burke

Manager, Systems Project
Ginsburg

Geoffrey Steven Ginsburg

Professor of Medicine
Dr. Geoffrey S. Ginsburg's research interests are in the development of novel paradigms for developing and translating genomic information into medical practice and the integration of personalized medicine into health care.
Henao

Ricardo Henao

Assistant Professor in Biostatistics and Bioinformatics
Ko

Emily Ray Ko

Assistant Professor of Medicine
McClain

Micah Thomas McClain

Associate Professor of Medicine
Tsalik

Ephraim Tsalik

Associate Professor of Medicine
My research is focused on understanding the dynamic between host and pathogen so as to discover and develop host-response markers that can diagnose and predict health and disease.  This new and evolving approach to diagnosing illness has the potential to significantly impact individual as well as public health considering the rise of antibiotic resistance. With any potential infectious disease diagnosis, it is difficult, if not impossible, to determine at the time of presentation
Woods

Christopher Wildrick Woods

Professor of Medicine
1. Emerging Infections 2. Global Health 3. Epidemiology of infectious diseases 4. Clinical microbiology and diagnostics 5. Bioterrorism Preparedness 6. Surveillance for communicable diseases 7. Antimicrobial resistance
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