Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study

For the INSIGHT FLU003 Plus Study Group

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background. Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. Methods. We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1) pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. Results. We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25-43.90). Conclusions. High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration.

Original languageEnglish (US)
Article numberofx228
JournalOpen Forum Infectious Diseases
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2018

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Human Influenza
Disease Progression
Tryptophan
Kynurenine
Artificial Respiration
Hospitalization
Biomarkers
Logistic Models
Odds Ratio
Infection

Keywords

  • Indoleamine-2,3-dioxygenase
  • Influenza
  • Kynurenine
  • Outcome
  • Tryptophan

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology

Cite this

Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study. / For the INSIGHT FLU003 Plus Study Group.

In: Open Forum Infectious Diseases, Vol. 5, No. 1, ofx228, 01.01.2018.

Research output: Contribution to journalArticle

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title = "Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study",
abstract = "Background. Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. Methods. We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1) pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. Results. We included 32 cases and 64 controls with a median age of 52 years; 41{\%} were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P ≤ .001). When divided into tertiles, 59{\%} of cases vs 20{\%} of controls had KT ratios in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95{\%} CI, 2.25-43.90). Conclusions. High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration.",
keywords = "Indoleamine-2,3-dioxygenase, Influenza, Kynurenine, Outcome, Tryptophan",
author = "{For the INSIGHT FLU003 Plus Study Group} and Pett, {Sarah L.} and Kunisaki, {Ken M.} and Deborah Wentworth and Griffin, {Timothy J.} and Ioannis Kalomenidis and Raquel Nahra and Sanchez, {Rocio Montejano} and Hodgson, {Shane W.} and Kiat Ruxrungtham and Dominic Dwyer and Davey, {R. T.} and Wendt, {Chris H.} and J. Lundgren and P. Jansson and M. Pearson and B. Aagaard and F. Hudson and R. Bennet and F. Pacciarini and B. Angus and N. Paton and {Collaco Moraes}, Y. and D. Cooper and S. Pett and S. Emery and D. Courtney-Rogers and R. Robson and F. Gordin and A. Sanchez and B. Standridge and M. Vjecha and A. Moricz and M. Delfino and W. Belloso and M. Losso and K. Tillmann and G. Touloumi and V. Gioukari and O. Anagnostou and {La Rosa}, A. and Saenz, {M. J.} and P. Lopez and P. Herrero and B. Portas and A. Avihingsanon and K. Ruxrungtham and P. Kaewon and S. Ubolyam and Zelalem Temesgen and Stacey Rizza",
year = "2018",
month = "1",
day = "1",
doi = "10.1093/ofid/ofx228",
language = "English (US)",
volume = "5",
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TY - JOUR

T1 - Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study

AU - For the INSIGHT FLU003 Plus Study Group

AU - Pett, Sarah L.

AU - Kunisaki, Ken M.

AU - Wentworth, Deborah

AU - Griffin, Timothy J.

AU - Kalomenidis, Ioannis

AU - Nahra, Raquel

AU - Sanchez, Rocio Montejano

AU - Hodgson, Shane W.

AU - Ruxrungtham, Kiat

AU - Dwyer, Dominic

AU - Davey, R. T.

AU - Wendt, Chris H.

AU - Lundgren, J.

AU - Jansson, P.

AU - Pearson, M.

AU - Aagaard, B.

AU - Hudson, F.

AU - Bennet, R.

AU - Pacciarini, F.

AU - Angus, B.

AU - Paton, N.

AU - Collaco Moraes, Y.

AU - Cooper, D.

AU - Pett, S.

AU - Emery, S.

AU - Courtney-Rogers, D.

AU - Robson, R.

AU - Gordin, F.

AU - Sanchez, A.

AU - Standridge, B.

AU - Vjecha, M.

AU - Moricz, A.

AU - Delfino, M.

AU - Belloso, W.

AU - Losso, M.

AU - Tillmann, K.

AU - Touloumi, G.

AU - Gioukari, V.

AU - Anagnostou, O.

AU - La Rosa, A.

AU - Saenz, M. J.

AU - Lopez, P.

AU - Herrero, P.

AU - Portas, B.

AU - Avihingsanon, A.

AU - Ruxrungtham, K.

AU - Kaewon, P.

AU - Ubolyam, S.

AU - Temesgen, Zelalem

AU - Rizza, Stacey

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background. Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. Methods. We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1) pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. Results. We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25-43.90). Conclusions. High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration.

AB - Background. Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. Methods. We performed a case-control (1:2; age and sex matched) analysis of adults hospitalized with influenza A(H1N1) pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. Results. We included 32 cases and 64 controls with a median age of 52 years; 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M; IQR, 0.13-0.40) than controls (0.12; IQR, 0.09-0.17; P ≤ .001). When divided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21-0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25-43.90). Conclusions. High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration.

KW - Indoleamine-2,3-dioxygenase

KW - Influenza

KW - Kynurenine

KW - Outcome

KW - Tryptophan

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UR - http://www.scopus.com/inward/citedby.url?scp=85040557622&partnerID=8YFLogxK

U2 - 10.1093/ofid/ofx228

DO - 10.1093/ofid/ofx228

M3 - Article

AN - SCOPUS:85040557622

VL - 5

JO - Open Forum Infectious Diseases

JF - Open Forum Infectious Diseases

SN - 2328-8957

IS - 1

M1 - ofx228

ER -