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

Publication ,  Journal Article
Lydon, EC; Bullard, C; Aydin, M; Better, OM; Mazur, A; Nicholson, BP; Ko, ER; McClain, MT; Ginsburg, GS; Woods, CW; Burke, TW; Henao, R; Tsalik, EL
Published in: PLoS One
2019

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.

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Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2019

Volume

14

Issue

4

Start / End Page

e0214871

Location

United States

Related Subject Headings

  • Young Adult
  • Virus Diseases
  • Retrospective Studies
  • Procalcitonin
  • Models, Biological
  • Middle Aged
  • Male
  • Humans
  • General Science & Technology
  • Gene Expression
 

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Lydon, E. C., Bullard, C., Aydin, M., Better, O. M., Mazur, A., Nicholson, B. P., … Tsalik, E. L. (2019). A host gene expression approach for identifying triggers of asthma exacerbations. PLoS One, 14(4), e0214871. https://doi.org/10.1371/journal.pone.0214871
Lydon, Emily C., Charles Bullard, Mert Aydin, Olga M. Better, Anna Mazur, Bradly P. Nicholson, Emily R. Ko, et al. “A host gene expression approach for identifying triggers of asthma exacerbations.PLoS One 14, no. 4 (2019): e0214871. https://doi.org/10.1371/journal.pone.0214871.
Lydon EC, Bullard C, Aydin M, Better OM, Mazur A, Nicholson BP, et al. A host gene expression approach for identifying triggers of asthma exacerbations. PLoS One. 2019;14(4):e0214871.
Lydon, Emily C., et al. “A host gene expression approach for identifying triggers of asthma exacerbations.PLoS One, vol. 14, no. 4, 2019, p. e0214871. Pubmed, doi:10.1371/journal.pone.0214871.
Lydon EC, Bullard C, Aydin M, Better OM, Mazur A, Nicholson BP, Ko ER, McClain MT, Ginsburg GS, Woods CW, Burke TW, Henao R, Tsalik EL. A host gene expression approach for identifying triggers of asthma exacerbations. PLoS One. 2019;14(4):e0214871.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2019

Volume

14

Issue

4

Start / End Page

e0214871

Location

United States

Related Subject Headings

  • Young Adult
  • Virus Diseases
  • Retrospective Studies
  • Procalcitonin
  • Models, Biological
  • Middle Aged
  • Male
  • Humans
  • General Science & Technology
  • Gene Expression