tetano
Editor, Senior Moderator
Open Forum Infect Dis. 2017 Oct 25;5(1)
fx228. doi: 10.1093/ofid/ofx228. eCollection 2018 Jan.
[h=1]Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study.[/h] Pett SL[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Kunisaki KM[SUP]4,[/SUP][SUP]5[/SUP], Wentworth D[SUP]6[/SUP], Griffin TJ[SUP]7[/SUP], Kalomenidis I[SUP]8[/SUP], Nahra R[SUP]9[/SUP], Montejano Sanchez R[SUP]10[/SUP], Hodgson SW[SUP]4[/SUP], Ruxrungtham K[SUP]11,[/SUP][SUP]12[/SUP], Dwyer D[SUP]13[/SUP], Davey RT[SUP]14[/SUP], Wendt CH[SUP]4,[/SUP][SUP]5[/SUP]; INSIGHT FLU003 Plus Study Group.
[h=3]Collaborators (195)[/h]
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Background:[/h] 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.
[h=4]Methods:[/h] 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.
[h=4]Results:[/h] 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).
[h=4]Conclusions:[/h] 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.
[h=4]ClinicalTrialsgov Identifier:[/h] NCT01056185.
[h=4]KEYWORDS:[/h] indoleamine-2,3-dioxygenase; influenza; kynurenine; outcome; tryptophan
PMID: 29322062 PMCID: PMC5753217 DOI: 10.1093/ofid/ofx228
Free PMC Article
fx228. doi: 10.1093/ofid/ofx228. eCollection 2018 Jan.[h=1]Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study.[/h] Pett SL[SUP]1,[/SUP][SUP]2,[/SUP][SUP]3[/SUP], Kunisaki KM[SUP]4,[/SUP][SUP]5[/SUP], Wentworth D[SUP]6[/SUP], Griffin TJ[SUP]7[/SUP], Kalomenidis I[SUP]8[/SUP], Nahra R[SUP]9[/SUP], Montejano Sanchez R[SUP]10[/SUP], Hodgson SW[SUP]4[/SUP], Ruxrungtham K[SUP]11,[/SUP][SUP]12[/SUP], Dwyer D[SUP]13[/SUP], Davey RT[SUP]14[/SUP], Wendt CH[SUP]4,[/SUP][SUP]5[/SUP]; INSIGHT FLU003 Plus Study Group.
[h=3]Collaborators (195)[/h]
[h=3]Author information[/h]
[h=3]Abstract[/h] [h=4]Background:[/h] 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.
[h=4]Methods:[/h] 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.
[h=4]Results:[/h] 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).
[h=4]Conclusions:[/h] 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.
[h=4]ClinicalTrialsgov Identifier:[/h] NCT01056185.
[h=4]KEYWORDS:[/h] indoleamine-2,3-dioxygenase; influenza; kynurenine; outcome; tryptophan
PMID: 29322062 PMCID: PMC5753217 DOI: 10.1093/ofid/ofx228
Free PMC Article