Title: Acute respiratory distress syndrome – epidemiology, biomarkers and phenotypes

Main supervisor: Attila Frigyesi           

Co-supervisor: Hans Friberg

Reviewers: Ulf Schött and Pyotr Platonov

Abstract

Background

Acute respiratory distress syndrome (ARDS) is an inflammatory condition characterized by intra-alveolar oedema, resulting in loss of aerated lung tissue leading to severe hypoxia resistant to oxygen treatment. Common causes of ARDS are pneumonia, aspiration of gastric contents, and sepsis. In epidemiological studies, ARDS-incidence is around 10% among patients in the intensive care unit (ICU), and up to 23% among patients requiring invasive mechanical ventilation. Mortality is high, up to 45% in severe disease. Diagnosis is frequently delayed or missed, preventing the timely use of potentially life-saving interventions. Also, current treatment is supportive only, and specific treatment options are lacking. Recently many ARDS cases worldwide have been caused by the novel SARS-CoV-2 virus.

Research questions

1. Is bioactive circulating adrenomedullin associated with ARDS development and ARDS mortality among ICU patients?
2. Is bio-ADM associated with mortality in critically ill COVID-19 patients?
3. Are intracellular adhesion molecule 1 (ICAM-1) and vascular adhesion molecule 1 (VCAM-1) associated with hyperinflammatory ARDS phenotyped among ICU-patients?
4. Can proteomics identify clinically significant ARDS phenotypes, and identify new diagnostic biomarkers for ARDS among ICU-patients?

Preliminary results

In study I, increasing bio-ADM levels were shown to be associated with the presence of ARDS (OR 1.8) and both low (OR 3.4) and high (OR 3.1) levels of bio-ADM were associated with ARDS-mortality.

Significance

New biomarkers in ARDS can improve diagnosis and lead to more timely interventions, thus reducing mortality. Identifying clinically relevant ARDS phenotypes can lead to more personalised treatment and improve outcomes. Novel biomarkers can be used as potential therapeutic target in future treatments.

Published studies

Johnsson P, Fredriksson A, Tung C, Friberg H, Frigyesi A. Plasma bioactive adrenomedullin on intensive care unit admission is associated with acute respiratory distress syndrome: an observational study. Intensive Care Med Exp. 2023 Mar 3;11(1):10. doi: 10.1186/s40635-023-00494-7. PMID: 36864354; PMCID: PMC9981258.

In writing

Johnsson P, Sievert T, Didriksson I, Friberg H, Frigyesi A. Plasma bioactive adrenomedullin during critical COVID-19 predicts mortality and need for renal replacement therapy.