Increased indoleamine-2,3-dioxygenase activity is associated with poor clinical outcome in adults hospitalized with influenza in the INSIGHT FLU003Plus study
© The Author(s) 2018. 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.
Pett, SL; Kunisaki, KM; Wentworth, D; Griffin, TJ; Kalomenidis, I; Nahra, R; Sanchez, RM; Hodgson, SW; Ruxrungtham, K; Dwyer, D; Davey, RT; Wendt, CH; Lundgren, J; Jansson, P; Pearson, M; Aagaard, B; Hudson, F; Bennet, R; Pacciarini, F; Angus, B; Paton, N; Collaco Moraes, Y; Cooper, D; Emery, S; Courtney-Rogers, D; Robson, R; Gordin, F; Sanchez, A; Standridge, B; Vjecha, M; Moricz, A; Delfino, M; Belloso, W; Losso, M; Tillmann, K; Touloumi, G; Gioukari, V; Anagnostou, O; La Rosa, A; Saenz, MJ; Lopez, P; Herrero, P; Portas, B; Kaewon, P; Ubolyam, S; Brekke, K; Campbell, M; Denning, E; DuChene, A; Engen, N; George, M; Harrison, M; Neaton, JD; Nelson, R; Quan, SF; Schultz, T; Baxter, J; Brown, S; Hoover, M; Beigel, J; Dewar, R; Gover, E; McConnell, R; Metcalf, J; Natarajan, V; Rehman, T; Voell, J; Dwyer, DE; Kok, J; Uyeki, T; Munroe, D; Paez, A; Bertrand, M; Temesgen, Z; Rizza, S; Wolfe, C; Carbonneau, J; Novak, R; Schwarber, M; Polenakovik, H; Clark, L; Patil, N; Riska, P; Omotosho, J; Faber, L; Markowitz, N; Glesby, M; Ham, K; Parenti, D; Simon, G; Coburn, P; Freiberg, M; Koerbel, G; Dharan, N; Paez-Quinde, M; Gunter, J; Beilke, M; Lu, Z; Gunderson, E; Baker, J
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