Elevated ferritin is associated with systemic inflammation, inflammasome activation and mortality in Acute Respiratory Distress Syndrome (ARDS)

Puja Mehta, Romit Samanta, Katherine Wick, Rebecca Coll, Patrick Mcaleavey, Andrew Boyle, John Conlon, Manu Shankar-Hari, Angela Rogers, Carolyn Calfee, Michael Matthay, Charlotte Summers, Rachel Chambers, Daniel Mcauley, Cecilia O'Kane

Research output: Contribution to journalMeeting abstractpeer-review

Abstract

Background: Hyperferritinaemia in sepsis is associated with hyperinflammation, worse clinical outcomes, and may predict response to immunomodulation. The role of hyperferritinaemia in ARDS from all-causes is unknown.

Methods: Baseline plasma ferritin was measured in patients with ARDS from two randomised controlled trials of simvastatin (HARP-2; discovery cohort, UK) and neuromuscular blockade (ROSE; validation cohort, USA). Logistic regression model with restricted cubic splines determined a ferritin threshold associated with 28-day mortality. Samples from HARP-2 were also analysed for inflammasome-associated inflammation.

Results: Ferritin was measured in 511 patients from HARP-2 (95% enrolled) and 847 patients from ROSE (84% enrolled). In HARP-2, 144 patients (28%) had a ferritin >1360 ng/mL, which was associated with an increased 28-day mortality (OR 2.43, 95% CI 1.59-3.72). This hyperferritinaemic subgroup also had fewer ventilator-free days (median difference 16 days, p1360 ng/mL identified ARDS patients with a higher mortality associated with inflammasome activation. These results provide support prospective trials targeting the ferritin-inflammasome axis in this subgroup of patients with ARDS.
Original languageEnglish
Article number118
JournalERJ Open Research
Volume8
Issue numberSuppl. 8
Early online date09 May 2022
DOIs
Publication statusPublished - Oct 2022

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