Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study
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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.
I: Open Forum Infectious Diseases, Bind 5, Nr. 1, ofx228, 2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study
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 - 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 - Brown, S.
AU - Faber, L.
AU - Freiberg, M.
AU - Baker, J.
AU - Kronborg, G.
AU - Nielsen, H.
AU - Gerstoft, J.
AU - For the INSIGHT FLU003 Plus Study Group
PY - 2018
Y1 - 2018
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
U2 - 10.1093/ofid/ofx228
DO - 10.1093/ofid/ofx228
M3 - Journal article
C2 - 29322062
AN - SCOPUS:85040557622
VL - 5
JO - Open Forum Infectious Diseases
JF - Open Forum Infectious Diseases
SN - 2328-8957
IS - 1
M1 - ofx228
ER -
ID: 222099999