Increased Indoleamine-2, 3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study. (25th October 2017)

• Record Type: Journal Article
• Authors: Pett, Sarah L; Kunisaki, Ken M; Wentworth, Deborah; Griffin, Timothy J; Kalomenidis, Ioannis; Nahra, Raquel; Montejano Sanchez, Rocio; Hodgson, Shane W; Ruxrungtham, Kiat; Dwyer, Dominic; Davey, Richard T; Wendt, Chris H
• Is Part Of: Open forum infectious diseases. Volume 5:Number 1(2018)
• Publication Date: 2017-10-25
• Subjects: influenza -- indoleamine-2, 3-dioxygenase -- kynurenine -- outcome -- tryptophan; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofx228
• Languages: English
• ISSNs: 2328-8957

Abstract

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. ClinicalTrials.gov Identifier: NCT01056185.