Validation of a host response test to distinguish bacterial and viral respiratory infection
Background: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response s...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2019-10-01
|
| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419306449 |
| _version_ | 1818131876551852032 |
|---|---|
| author | Emily C. Lydon Ricardo Henao Thomas W. Burke Mert Aydin Bradly P. Nicholson Seth W. Glickman Vance G. Fowler Eugenia B. Quackenbush Charles B. Cairns Stephen F. Kingsmore Anja K. Jaehne Emanuel P. Rivers Raymond J. Langley Elizabeth Petzold Emily R. Ko Micah T. McClain Geoffrey S. Ginsburg Christopher W. Woods Ephraim L. Tsalik |
| author_facet | Emily C. Lydon Ricardo Henao Thomas W. Burke Mert Aydin Bradly P. Nicholson Seth W. Glickman Vance G. Fowler Eugenia B. Quackenbush Charles B. Cairns Stephen F. Kingsmore Anja K. Jaehne Emanuel P. Rivers Raymond J. Langley Elizabeth Petzold Emily R. Ko Micah T. McClain Geoffrey S. Ginsburg Christopher W. Woods Ephraim L. Tsalik |
| author_sort | Emily C. Lydon |
| collection | DOAJ |
| description | Background: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative and coinfection cases. Methods: Subjects with acute respiratory illness were enrolled in participating emergency departments. Reference standard was an adjudicated diagnosis of bacterial infection, viral infection, both, or neither. An 87-transcript signature for distinguishing bacterial, viral, and noninfectious illness was measured from peripheral blood using RT-PCR. Performance characteristics were evaluated in subjects with confirmed bacterial, viral, or noninfectious illness. Subjects with bacterial-viral coinfection and microbiologically-negative suspected bacterial infection were also evaluated. Performance was compared to procalcitonin. Findings: 151 subjects with microbiologically confirmed, single-etiology illness were tested, yielding AUROCs 0•85–0•89 for bacterial, viral, and noninfectious illness. Accuracy was similar to procalcitonin (88% vs 83%, p = 0•23) for bacterial vs. non-bacterial infection. Whereas procalcitonin cannot distinguish viral from non-infectious illness, the RT-PCR test had 81% accuracy in making this determination. Bacterial-viral coinfection was subdivided. Among 19 subjects with bacterial superinfection, the RT-PCR test identified 95% as bacterial, compared to 68% with procalcitonin (p = 0•13). Among 12 subjects with bacterial infection superimposed on chronic viral infection, the RT-PCR test identified 83% as bacterial, identical to procalcitonin. 39 subjects had suspected bacterial infection; the RT-PCR test identified bacterial infection more frequently than procalcitonin (82% vs 64%, p = 0•02). Interpretation: The RT-PCR test offered similar diagnostic performance to procalcitonin in some subgroups but offered better discrimination in others such as viral vs. non-infectious illness and bacterial/viral coinfection. Gene expression-based tests could impact decision-making for acute respiratory illness as well as a growing number of other infectious and non-infectious diseases. Keywords: Biomarkers, Gene expression, Respiratory tract infections, Coinfection, Diagnosis, Precision medicine |
| first_indexed | 2024-12-11T08:27:54Z |
| format | Article |
| id | doaj.art-24872e5a3d85489aa45fad625b167655 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-12-11T08:27:54Z |
| publishDate | 2019-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-24872e5a3d85489aa45fad625b1676552022-12-22T01:14:31ZengElsevierEBioMedicine2352-39642019-10-0148453461Validation of a host response test to distinguish bacterial and viral respiratory infectionEmily C. Lydon0Ricardo Henao1Thomas W. Burke2Mert Aydin3Bradly P. Nicholson4Seth W. Glickman5Vance G. Fowler6Eugenia B. Quackenbush7Charles B. Cairns8Stephen F. Kingsmore9Anja K. Jaehne10Emanuel P. Rivers11Raymond J. Langley12Elizabeth Petzold13Emily R. Ko14Micah T. McClain15Geoffrey S. Ginsburg16Christopher W. Woods17Ephraim L. Tsalik18Duke University School of Medicine, Durham, NC, USA; Duke University Center for Applied Genomics and Precision Medicine, Durham, NC, USADuke University Department of Biostatistics and Informatics, Durham, NC, USADuke University Center for Applied Genomics and Precision Medicine, Durham, NC, USADuke University Center for Applied Genomics and Precision Medicine, Durham, NC, USAInstitute of Medical Research, Durham Veterans Affairs Medical Center, Durham, NC, USAUniversity of North Carolina Medical Center, Chapel Hill, NC, USADuke University Department of Medicine, Durham, NC, USA; Duke Clinical Research Institute, Durham, NC, USAUniversity of North Carolina Medical Center, Chapel Hill, NC, USAUniversity of North Carolina Medical Center, Chapel Hill, NC, USA; United Arab Emirates University, Al Ain, UAERady Children's Institute for Genomic Medicine, San Diego, CA, USAHenry Ford Hospital System, Detroit, MI, USAHenry Ford Hospital System, Detroit, MI, USAUniversity of South Alabama Health University Hospital, Mobile, AL, USADuke University Center for Applied Genomics and Precision Medicine, Durham, NC, USADuke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA; Department of Hospital Medicine, Duke Regional Hospital, Durham, NC 27705, USADuke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA; Durham Veterans Affairs Health Care System, Durham, NC, USADuke University Center for Applied Genomics and Precision Medicine, Durham, NC, USADuke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA; Durham Veterans Affairs Health Care System, Durham, NC, USA; Co-Corresponding author at: 508 Fulton Street, Service 113,Durham, NC 27710, USADuke University Center for Applied Genomics and Precision Medicine, Durham, NC, USA; Durham Veterans Affairs Health Care System, Durham, NC, USA; Corresponding author at: Duke University Medical Center 102359, Durham, NC 27705, USA.Background: Distinguishing bacterial and viral respiratory infections is challenging. Novel diagnostics based on differential host gene expression patterns are promising but have not been translated to a clinical platform nor extensively tested. Here, we validate a microarray-derived host response signature and explore performance in microbiology-negative and coinfection cases. Methods: Subjects with acute respiratory illness were enrolled in participating emergency departments. Reference standard was an adjudicated diagnosis of bacterial infection, viral infection, both, or neither. An 87-transcript signature for distinguishing bacterial, viral, and noninfectious illness was measured from peripheral blood using RT-PCR. Performance characteristics were evaluated in subjects with confirmed bacterial, viral, or noninfectious illness. Subjects with bacterial-viral coinfection and microbiologically-negative suspected bacterial infection were also evaluated. Performance was compared to procalcitonin. Findings: 151 subjects with microbiologically confirmed, single-etiology illness were tested, yielding AUROCs 0•85–0•89 for bacterial, viral, and noninfectious illness. Accuracy was similar to procalcitonin (88% vs 83%, p = 0•23) for bacterial vs. non-bacterial infection. Whereas procalcitonin cannot distinguish viral from non-infectious illness, the RT-PCR test had 81% accuracy in making this determination. Bacterial-viral coinfection was subdivided. Among 19 subjects with bacterial superinfection, the RT-PCR test identified 95% as bacterial, compared to 68% with procalcitonin (p = 0•13). Among 12 subjects with bacterial infection superimposed on chronic viral infection, the RT-PCR test identified 83% as bacterial, identical to procalcitonin. 39 subjects had suspected bacterial infection; the RT-PCR test identified bacterial infection more frequently than procalcitonin (82% vs 64%, p = 0•02). Interpretation: The RT-PCR test offered similar diagnostic performance to procalcitonin in some subgroups but offered better discrimination in others such as viral vs. non-infectious illness and bacterial/viral coinfection. Gene expression-based tests could impact decision-making for acute respiratory illness as well as a growing number of other infectious and non-infectious diseases. Keywords: Biomarkers, Gene expression, Respiratory tract infections, Coinfection, Diagnosis, Precision medicinehttp://www.sciencedirect.com/science/article/pii/S2352396419306449 |
| spellingShingle | Emily C. Lydon Ricardo Henao Thomas W. Burke Mert Aydin Bradly P. Nicholson Seth W. Glickman Vance G. Fowler Eugenia B. Quackenbush Charles B. Cairns Stephen F. Kingsmore Anja K. Jaehne Emanuel P. Rivers Raymond J. Langley Elizabeth Petzold Emily R. Ko Micah T. McClain Geoffrey S. Ginsburg Christopher W. Woods Ephraim L. Tsalik Validation of a host response test to distinguish bacterial and viral respiratory infection EBioMedicine |
| title | Validation of a host response test to distinguish bacterial and viral respiratory infection |
| title_full | Validation of a host response test to distinguish bacterial and viral respiratory infection |
| title_fullStr | Validation of a host response test to distinguish bacterial and viral respiratory infection |
| title_full_unstemmed | Validation of a host response test to distinguish bacterial and viral respiratory infection |
| title_short | Validation of a host response test to distinguish bacterial and viral respiratory infection |
| title_sort | validation of a host response test to distinguish bacterial and viral respiratory infection |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419306449 |
| work_keys_str_mv | AT emilyclydon validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT ricardohenao validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT thomaswburke validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT mertaydin validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT bradlypnicholson validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT sethwglickman validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT vancegfowler validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT eugeniabquackenbush validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT charlesbcairns validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT stephenfkingsmore validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT anjakjaehne validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT emanuelprivers validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT raymondjlangley validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT elizabethpetzold validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT emilyrko validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT micahtmcclain validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT geoffreysginsburg validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT christopherwwoods validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection AT ephraimltsalik validationofahostresponsetesttodistinguishbacterialandviralrespiratoryinfection |