A host gene expression approach for identifying triggers of asthma exacerbations.
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 articleSubject
Science & TechnologyMultidisciplinary Sciences
Science & Technology - Other Topics
COMMUNITY-ACQUIRED PNEUMONIA
REQUIRING HOSPITALIZATION
PERIPHERAL-BLOOD
PROCALCITONIN
ANTIBIOTICS
SIGNATURE
CHILDREN
ETIOLOGY
INFECTIONS
BACTERIAL
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https://hdl.handle.net/10161/19463Published Version (Please cite this version)
10.1371/journal.pone.0214871Publication 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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Show full item recordScholars@Duke
Thomas Burke
Manager, Systems Project
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.
Ricardo Henao
Assistant Professor in Biostatistics and Bioinformatics
Emily Ray Ko
Assistant Professor of Medicine
Micah Thomas McClain
Associate Professor of Medicine
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
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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