LIVIVO - Das Suchportal für Lebenswissenschaften

switch to English language
Erweiterte Suche

Ihre letzten Suchen

  1. AU="Thomas W Burke"
  2. AU="Lordello, Sylvia"
  3. AU=Karuppal Raju
  4. AU="Zhang, Hui-Ping"
  5. AU="Sutrave, Tarun"
  6. AU="Cirulli, Vincenzo"
  7. AU="Jabłońska-Trypuć, Agata"
  8. AU="Tsichlis, Philip"
  9. AU="Woods, Bob"
  10. AU="Olivier, L"
  11. AU="Khinevich, N.V."
  12. AU="Sabino, Caetano P"
  13. AU="Osborne, Benjamin"
  14. AU="Mydlak, Dariusz"
  15. AU="Pang, Hua"
  16. AU="Ali FARHOUDIAN"
  17. AU="Sienne, Julia Metsio"
  18. AU="Kanagale, Pritam"
  19. AU=Wang Yupei
  20. AU="Egan, Kathleen M"
  21. AU="Prevezanou, Maria"
  22. AU="Márk, Lili"
  23. AU="Pellman, David S"
  24. AU="Wulf, Sarah"
  25. AU="DeVito, Michael"
  26. AU="Fehérvári, Lajos"
  27. AU="Sompa, Sagarika Adhikary"
  28. AU="Ladkany, Rand"
  29. AU=Jain Gaurav
  30. AU="Maldonado, Alejandra"
  31. AU="Junichi Takagi"
  32. AU="Aitor Rodriguez-Casanova"
  33. AU="Wimpenny, Claire"
  34. AU=Gao W J
  35. AU="Suarez-Almazor, Maria E"
  36. AU="Barciszewski, Jakub"
  37. AU=Madhusoodanan Jyoti
  38. AU="Korbecki, Jan"

Suchergebnis

Treffer 1 - 10 von insgesamt 14

Suchoptionen

  1. Artikel ; Online: Epigenetic and transcriptional responses in circulating leukocytes are associated with future decompensation during SARS-CoV-2 infection

    Micah T. McClain / Ilya Zhbannikov / Lisa L. Satterwhite / Ricardo Henao / Nicholas S. Giroux / Shengli Ding / Thomas W. Burke / Ephraim L. Tsalik / Christina Nix / Jorge Prado Balcazar / Elizabeth A. Petzold / Xiling Shen / Christopher W. Woods

    iScience, Vol 27, Iss 1, Pp 108288- (2024)

    1481  

    Abstract: Summary: To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed ... ...

    Abstract Summary: To elucidate host response elements that define impending decompensation during SARS-CoV-2 infection, we enrolled subjects hospitalized with COVID-19 who were matched for disease severity and comorbidities at the time of admission. We performed combined single-cell RNA sequencing (scRNA-seq) and single-cell assay for transposase-accessible chromatin using sequencing (scATAC-seq) on peripheral blood mononuclear cells (PBMCs) at admission and compared subjects who improved from their moderate disease with those who later clinically decompensated and required invasive mechanical ventilation or died. Chromatin accessibility and transcriptomic immune profiles were markedly altered between the two groups, with strong signals in CD4+ T cells, inflammatory T cells, dendritic cells, and NK cells. Multiomic signature scores at admission were tightly associated with future clinical deterioration (auROC 1.0). Epigenetic and transcriptional changes in PBMCs reveal early, broad immune dysregulation before typical clinical signs of decompensation are apparent and thus may act as biomarkers to predict future severity in COVID-19.
    Schlagwörter Health sciences ; Molecular mechanism of gene regulation ; Epigenetics ; Immune response ; Components of the immune system ; Virology ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2024-01-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

  2. Artikel ; Online: Transcriptional responses define dysregulated immune activation in Hepatitis C (HCV)-naïve recipients of HCV-infected donor kidneys

    Julie M. Steinbrink / Cameron Miller / Rachel A. Myers / Scott Sanoff / Anna Mazur / Thomas W. Burke / Jennifer Byrns / Annette M. Jackson / Xunrong Luo / Micah T. McClain

    PLoS ONE, Vol 18, Iss

    2023  Band 1

    Abstract: Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to ...

    Abstract Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to dysregulated immunologic activation secondary to active inflammation from acute viremia at the time of transplantation. This includes increased rates of cytomegalovirus (CMV) DNAemia and allograft rejection. In this study, we evaluate transcriptional responses in circulating leukocytes to define the character, timing, and resolution of this immune dysregulation and assess for biomarkers of adverse outcomes in transplant patients. We enrolled 67 renal transplant recipients (30 controls, 37 HCV recipients) and performed RNA sequencing on serial samples from one, 3-, and 6-months post-transplant. CMV DNAemia and allograft rejection outcomes were measured. Least absolute shrinkage and selection operator was utilized to develop gene expression classifiers predictive of clinical outcomes. Acute HCV incited a marked transcriptomic response in circulating leukocytes of renal transplant recipients in the acute post-transplant setting, despite the presence of immunosuppression, with 109 genes significantly differentially expressed compared to controls. These HCV infection-associated genes were reflective of antiviral immune pathways and generally resolved by the 3-month timepoint after sustained viral response (SVR) for HCV. Differential gene expression was also noted from patients who developed CMV DNAemia or allograft rejection compared to those who did not, although transcriptomic classifiers could not accurately predict these outcomes, likely due to sample size and variable time-to-event. Acute HCV infection incites evidence of immune activation and canonical antiviral responses in the human host even in the presence of systemic immunosuppression. After treatment of HCV with antiviral therapy and subsequent aviremia, this immune activation resolves. Changes in gene ...
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

  3. Artikel ; Online: Transcriptional responses define dysregulated immune activation in Hepatitis C (HCV)-naïve recipients of HCV-infected donor kidneys.

    Julie M Steinbrink / Cameron Miller / Rachel A Myers / Scott Sanoff / Anna Mazur / Thomas W Burke / Jennifer Byrns / Annette M Jackson / Xunrong Luo / Micah T McClain

    PLoS ONE, Vol 18, Iss 1, p e

    2023  Band 0280602

    Abstract: Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to ...

    Abstract Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to dysregulated immunologic activation secondary to active inflammation from acute viremia at the time of transplantation. This includes increased rates of cytomegalovirus (CMV) DNAemia and allograft rejection. In this study, we evaluate transcriptional responses in circulating leukocytes to define the character, timing, and resolution of this immune dysregulation and assess for biomarkers of adverse outcomes in transplant patients. We enrolled 67 renal transplant recipients (30 controls, 37 HCV recipients) and performed RNA sequencing on serial samples from one, 3-, and 6-months post-transplant. CMV DNAemia and allograft rejection outcomes were measured. Least absolute shrinkage and selection operator was utilized to develop gene expression classifiers predictive of clinical outcomes. Acute HCV incited a marked transcriptomic response in circulating leukocytes of renal transplant recipients in the acute post-transplant setting, despite the presence of immunosuppression, with 109 genes significantly differentially expressed compared to controls. These HCV infection-associated genes were reflective of antiviral immune pathways and generally resolved by the 3-month timepoint after sustained viral response (SVR) for HCV. Differential gene expression was also noted from patients who developed CMV DNAemia or allograft rejection compared to those who did not, although transcriptomic classifiers could not accurately predict these outcomes, likely due to sample size and variable time-to-event. Acute HCV infection incites evidence of immune activation and canonical antiviral responses in the human host even in the presence of systemic immunosuppression. After treatment of HCV with antiviral therapy and subsequent aviremia, this immune activation resolves. Changes in gene ...
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

  4. Artikel ; Online: SARS‐CoV‐2 reinfection across a spectrum of immunological states

    Justine M. McKittrick / Thomas W. Burke / Elizabeth Petzold / Gregory D. Sempowski / Thomas N. Denny / Christopher R. Polage / Ephraim L. Tsalik / Micah T. McClain

    Health Science Reports, Vol 5, Iss 4, Pp n/a-n/a (2022)

    2022  

    Abstract: Abstract Purpose Several cases of symptomatic reinfection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) after full recovery from a prior episode have been reported. As reinfection has become an increasingly common phenomenon, an ... ...

    Abstract Abstract Purpose Several cases of symptomatic reinfection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) after full recovery from a prior episode have been reported. As reinfection has become an increasingly common phenomenon, an improved understanding of the risk factors for reinfection and the character and duration of the serological responses to infection and vaccination is critical for managing the coronavirus disease 2019 (COVID‐19) pandemic. Methods We described four cases of SARS‐CoV‐2 reinfection in individuals representing a spectrum of healthy and immunocompromised states, including (1) a healthy 41‐year‐old pediatrician, (2) an immunocompromised 31‐year‐old with granulomatosis with polyangiitis, (3) a healthy 26‐year‐old pregnant woman, and (4) a 50‐year‐old with hypertension and hyperlipidemia. We performed confirmatory quantitative reverse transcription‐polymerase chain reaction and qualitative immunoglobulin M and quantitative IgG testing on all available patient samples to confirm the presence of infection and serological response to infection. Results Our analysis showed that patients 1 and 2, a healthy and an immunocompromised patient, both failed to mount a robust serologic response to the initial infection. In contrast, patients 3 and 4, with minimal comorbid disease, both mounted a strong serological response to their initial infection, but were still susceptible to reinfection. Conclusion Repeat episodes of COVID‐19 are capable of occurring in patients regardless of the presence of known risk factors for infection or level of serological response to infection, although this did not trigger critical illness in any instance.
    Schlagwörter antibody ; COVID‐19 ; immunity ; reinfection ; SARS‐CoV‐2 ; Medicine ; R
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2022-07-01T00:00:00Z
    Verlag Wiley
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

  5. Artikel ; Online: A comparison of host response strategies to distinguish bacterial and viral infection.

    Melissa Ross / Ricardo Henao / Thomas W Burke / Emily R Ko / Micah T McClain / Geoffrey S Ginsburg / Christopher W Woods / Ephraim L Tsalik

    PLoS ONE, Vol 16, Iss 12, p e

    2021  Band 0261385

    Abstract: Objectives Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). Methods In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene ... ...

    Abstract Objectives Compare three host response strategies to distinguish bacterial and viral etiologies of acute respiratory illness (ARI). Methods In this observational cohort study, procalcitonin, a 3-protein panel (CRP, IP-10, TRAIL), and a host gene expression mRNA panel were measured in 286 subjects with ARI from four emergency departments. Multinomial logistic regression and leave-one-out cross validation were used to evaluate the protein and mRNA tests. Results The mRNA panel performed better than alternative strategies to identify bacterial infection: AUC 0.93 vs. 0.83 for the protein panel and 0.84 for procalcitonin (P<0.02 for each comparison). This corresponded to a sensitivity and specificity of 92% and 83% for the mRNA panel, 81% and 73% for the protein panel, and 68% and 87% for procalcitonin, respectively. A model utilizing all three strategies was the same as mRNA alone. For the diagnosis of viral infection, the AUC was 0.93 for mRNA and 0.84 for the protein panel (p<0.05). This corresponded to a sensitivity and specificity of 89% and 82% for the mRNA panel, and 85% and 62% for the protein panel, respectively. Conclusions A gene expression signature was the most accurate host response strategy for classifying subjects with bacterial, viral, or non-infectious ARI.
    Schlagwörter Medicine ; R ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2021-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

  6. Artikel ; Online: Blood RNA alternative splicing events as diagnostic biomarkers for infectious disease

    Zijun Zhang / Natalie Sauerwald / Antonio Cappuccio / Irene Ramos / Venugopalan D. Nair / German Nudelman / Elena Zaslavsky / Yongchao Ge / Angelo Gaitas / Hui Ren / Joel Brockman / Jennifer Geis / Naveen Ramalingam / David King / Micah T. McClain / Christopher W. Woods / Ricardo Henao / Thomas W. Burke / Ephraim L. Tsalik /
    Carl W. Goforth / Rhonda A. Lizewski / Stephen E. Lizewski / Dawn L. Weir / Andrew G. Letizia / Stuart C. Sealfon / Olga G. Troyanskaya

    Cell Reports: Methods, Vol 3, Iss 2, Pp 100395- (2023)

    2023  

    Abstract: Summary: Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay ... ...

    Abstract Summary: Assays detecting blood transcriptome changes are studied for infectious disease diagnosis. Blood-based RNA alternative splicing (AS) events, which have not been well characterized in pathogen infection, have potential normalization and assay platform stability advantages over gene expression for diagnosis. Here, we present a computational framework for developing AS diagnostic biomarkers. Leveraging a large prospective cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and whole-blood RNA sequencing (RNA-seq) data, we identify a major functional AS program switch upon viral infection. Using an independent cohort, we demonstrate the improved accuracy of AS biomarkers for SARS-CoV-2 diagnosis compared with six reported transcriptome signatures. We then optimize a subset of AS-based biomarkers to develop microfluidic PCR diagnostic assays. This assay achieves nearly perfect test accuracy (61/62 = 98.4%) using a naive principal component classifier, significantly more accurate than a gene expression PCR assay in the same cohort. Therefore, our RNA splicing computational framework enables a promising avenue for host-response diagnosis of infection. Motivation: Host-based response assays (HRAs) can often diagnose infectious disease earlier and more precisely than pathogen-based tests. However, the role of RNA alternative splicing (AS) in HRAs remains unexplored, as existing HRAs are restricted to gene expression signatures. We report a computational framework for the identification, optimization, and evaluation of blood AS-based diagnostic assay development for infectious disease. Using SARS-CoV-2 infection as a case study, we demonstrate the improved accuracy of AS biomarkers for COVID-19 diagnosis when compared against six reported transcriptome signatures and when implemented as a microfluidic PCR diagnostic assay.
    Schlagwörter RNA splicing ; diagnostic biomarker ; host response assays ; infectious disease ; SARS-CoV-2 ; viral infection ; Biotechnology ; TP248.13-248.65 ; Biochemistry ; QD415-436 ; Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2023-02-01T00:00:00Z
    Verlag Elsevier
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

  7. Artikel ; Online: Mast cell activation in lungs during SARS-CoV-2 infection associated with lung pathology and severe COVID-19

    Janessa Y.J. Tan / Danielle E. Anderson / Abhay P.S. Rathore / Aled O’Neill / Chinmay Kumar Mantri / Wilfried A.A. Saron / Cheryl Q.E. Lee / Chu Wern Cui / Adrian E.Z. Kang / Randy Foo / Shirin Kalimuddin / Jenny G. Low / Lena Ho / Paul Tambyah / Thomas W. Burke / Christopher W. Woods / Kuan Rong Chan / Jörn Karhausen / Ashley L. St. John

    The Journal of Clinical Investigation, Vol 133, Iss

    2023  Band 19

    Abstract: Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in patients who are severely ill, and the pathophysiology of disease is thought to be immune mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where ... ...

    Abstract Lung inflammation is a hallmark of Coronavirus disease 2019 (COVID-19) in patients who are severely ill, and the pathophysiology of disease is thought to be immune mediated. Mast cells (MCs) are polyfunctional immune cells present in the airways, where they respond to certain viruses and allergens and often promote inflammation. We observed widespread degranulation of MCs during acute and unresolved airway inflammation in SARS-CoV-2-infected mice and nonhuman primates. Using a mouse model of MC deficiency, MC-dependent interstitial pneumonitis, hemorrhaging, and edema in the lung were observed during SARS-CoV-2 infection. In humans, transcriptional changes in patients requiring oxygen supplementation also implicated cells with a MC phenotype in severe disease. MC activation in humans was confirmed through detection of MC-specific proteases, including chymase, the levels of which were significantly correlated with disease severity and with biomarkers of vascular dysregulation. These results support the involvement of MCs in lung tissue damage during SARS-CoV-2 infection in animal models and the association of MC activation with severe COVID-19 in humans, suggesting potential strategies for intervention.
    Schlagwörter COVID-19 ; Medicine ; R
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2023-10-01T00:00:00Z
    Verlag American Society for Clinical Investigation
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

  8. Artikel ; Online: An atlas connecting shared genetic architecture of human diseases and molecular phenotypes provides insight into COVID-19 susceptibility

    Liuyang Wang / Thomas J. Balmat / Alejandro L. Antonia / Florica J. Constantine / Ricardo Henao / Thomas W. Burke / Andy Ingham / Micah T. McClain / Ephraim L. Tsalik / Emily R. Ko / Geoffrey S. Ginsburg / Mark R. DeLong / Xiling Shen / Christopher W. Woods / Elizabeth R. Hauser / Dennis C. Ko

    Genome Medicine, Vol 13, Iss 1, Pp 1-

    2021  Band 19

    Abstract: Abstract Background While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an ... ...

    Abstract Abstract Background While genome-wide associations studies (GWAS) have successfully elucidated the genetic architecture of complex human traits and diseases, understanding mechanisms that lead from genetic variation to pathophysiology remains an important challenge. Methods are needed to systematically bridge this crucial gap to facilitate experimental testing of hypotheses and translation to clinical utility. Results Here, we leveraged cross-phenotype associations to identify traits with shared genetic architecture, using linkage disequilibrium (LD) information to accurately capture shared SNPs by proxy, and calculate significance of enrichment. This shared genetic architecture was examined across differing biological scales through incorporating data from catalogs of clinical, cellular, and molecular GWAS. We have created an interactive web database (interactive Cross-Phenotype Analysis of GWAS database (iCPAGdb)) to facilitate exploration and allow rapid analysis of user-uploaded GWAS summary statistics. This database revealed well-known relationships among phenotypes, as well as the generation of novel hypotheses to explain the pathophysiology of common diseases. Application of iCPAGdb to a recent GWAS of severe COVID-19 demonstrated unexpected overlap of GWAS signals between COVID-19 and human diseases, including with idiopathic pulmonary fibrosis driven by the DPP9 locus. Transcriptomics from peripheral blood of COVID-19 patients demonstrated that DPP9 was induced in SARS-CoV-2 compared to healthy controls or those with bacterial infection. Further investigation of cross-phenotype SNPs associated with both severe COVID-19 and other human traits demonstrated colocalization of the GWAS signal at the ABO locus with plasma protein levels of a reported receptor of SARS-CoV-2, CD209 (DC-SIGN). This finding points to a possible mechanism whereby glycosylation of CD209 by ABO may regulate COVID-19 disease severity. Conclusions Thus, connecting genetically related traits across phenotypic scales links human ...
    Schlagwörter Pleiotropy ; Cross-phenotype association ; Gout ; LD-score ; Colocalization ; PheWAS ; Medicine ; R ; Genetics ; QH426-470
    Thema/Rubrik (Code) 610
    Sprache Englisch
    Erscheinungsdatum 2021-05-01T00:00:00Z
    Verlag BMC
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

  9. Artikel ; Online: Dysregulated transcriptional responses to SARS-CoV-2 in the periphery

    Micah T. McClain / Florica J. Constantine / Ricardo Henao / Yiling Liu / Ephraim L. Tsalik / Thomas W. Burke / Julie M. Steinbrink / Elizabeth Petzold / Bradly P. Nicholson / Robert Rolfe / Bryan D. Kraft / Matthew S. Kelly / Daniel R. Saban / Chen Yu / Xiling Shen / Emily M. Ko / Gregory D. Sempowski / Thomas N. Denny / Geoffrey S. Ginsburg /
    Christopher W. Woods

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Band 8

    Abstract: The systemic immune features that distinguish COVID-19 from common infections remain incompletely elucidated. Here McClain et al. compare RNA sequencing in peripheral blood between subjects with SARS-CoV-2 and other respiratory infections and demonstrate ...

    Abstract The systemic immune features that distinguish COVID-19 from common infections remain incompletely elucidated. Here McClain et al. compare RNA sequencing in peripheral blood between subjects with SARS-CoV-2 and other respiratory infections and demonstrate dysregulated immune responses in COVID-19 with both heterogeneous and conserved components.
    Schlagwörter Science ; Q
    Sprache Englisch
    Erscheinungsdatum 2021-02-01T00:00:00Z
    Verlag Nature Portfolio
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

  10. Artikel ; Online: A host gene expression approach for identifying triggers of asthma exacerbations.

    Emily C Lydon / Charles Bullard / Mert Aydin / Olga M Better / Anna Mazur / Bradly P Nicholson / Emily R Ko / Micah T McClain / Geoffrey S Ginsburg / Chris W Woods / Thomas W Burke / Ricardo Henao / Ephraim L Tsalik

    PLoS ONE, Vol 14, Iss 4, p e

    2019  Band 0214871

    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 ...

    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.
    Schlagwörter Medicine ; R ; Science ; Q
    Thema/Rubrik (Code) 572 ; 610
    Sprache Englisch
    Erscheinungsdatum 2019-01-01T00:00:00Z
    Verlag Public Library of Science (PLoS)
    Dokumenttyp Artikel ; Online
    Datenquelle BASE - Bielefeld Academic Search Engine (Lebenswissenschaftliche Auswahl)

    Zusatzmaterialien

    Kategorien

Zum Seitenanfang