# Towards a biological definition of ARDS: are treatable traits the solution?

**Authors:** Lieuwe D. J. Bos, John G. Laffey, Lorraine B. Ware, Nanon F. L. Heijnen, Pratik Sinha, Brijesh Patel, Matthieu Jabaudon, Julie A. Bastarache, Daniel F. McAuley, Charlotte Summers, Carolyn S. Calfee, Manu Shankar-Hari

PMC · DOI: 10.1186/s40635-022-00435-w · 2022-03-11

## TL;DR

This paper explores how biological traits can help redefine ARDS, aiming to address its complex and varied nature for better treatment strategies.

## Contribution

The paper introduces a narrative framework for identifying biological patterns in ARDS to guide future redefinitions and targeted therapies.

## Key findings

- ARDS exhibits substantial biological heterogeneity, complicating treatment effectiveness.
- Three predominant biological patterns are identified for potential targeted interventions.
- Biological tests may help classify ARDS subtypes based on epithelial injury, pulmonary edema, or inflammation.

## Abstract

The pathophysiology of acute respiratory distress syndrome (ARDS) includes the accumulation of protein-rich pulmonary edema in the air spaces and interstitial areas of the lung, variable degrees of epithelial injury, variable degrees of endothelial barrier disruption, transmigration of leukocytes, alongside impaired fluid and ion clearance. These pathophysiological features are different between patients contributing to substantial biological heterogeneity. In this context, it is perhaps unsurprising that a wide range of pharmacological interventions targeting these pathophysiological processes have failed to improve patient outcomes. In this manuscript, our goal is to provide a narrative summary of the potential methods to capture the underlying biological heterogeneity of ARDS and discuss how this information could inform future ARDS redefinitions. We discuss what biological tests are available to identify patients with any of the following predominant biological patterns: (1) epithelial and/or endothelial injury, (2) protein rich pulmonary edema and (3) systemic or within lung inflammatory responses.

## Linked entities

- **Diseases:** acute respiratory distress syndrome (MONDO:0006502), ARDS (MONDO:0006502)

## Full-text entities

- **Genes:** ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, SERPINE1 (serpin family E member 1) [NCBI Gene 5054] {aka PAI, PAI-1, PAI1, PLANH1}, PROC (protein C, inactivator of coagulation factors Va and VIIIa) [NCBI Gene 5624] {aka APC, PC, PROC1, THPH3, THPH4}, ANG (angiogenin) [NCBI Gene 283] {aka ALS9, HEL168, RAA1, RNASE4, RNASE5}, IL5 (interleukin 5) [NCBI Gene 3567] {aka EDF, IL-5, TRF}, ANGPT2 (angiopoietin 2) [NCBI Gene 285] {aka AGPT2, ANG2, LMPHM10}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, VWF (von Willebrand factor) [NCBI Gene 7450] {aka F8VWF, VWD}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, SFTPD (surfactant protein D) [NCBI Gene 6441] {aka COLEC7, PSP-D, SFTP4, SP-D}, CXCL8 (C-X-C motif chemokine ligand 8) [NCBI Gene 3576] {aka GCP-1, GCP1, IL8, LECT, LUCT, LYNAP}, SCGB1A1 (secretoglobin family 1A member 1) [NCBI Gene 7356] {aka CC10, CC16, CCPBP, CCSP, UGB, UP-1}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}
- **Diseases:** effusions (MESH:D000080324), cardiogenic pulmonary edema (MESH:D011654), sequential organ failure (MESH:D009102), lung collapse (MESH:D001261), neutrophilic (MESH:C564275), Respiratory failure (MESH:D012131), hypoxemia (MESH:D000860), biological abnormalities (MESH:D021081), Inflammation (MESH:D007249), DAD (MESH:D000070625), endothelial dysfunction (MESH:D014652), lung injuryNot (MESH:D008171), trauma (MESH:D014947), critical illness (MESH:D016638), pulmonary fibrosis (MESH:D011658), fluid overload (MESH:D019190), ARDS (MESH:D012128), nosocomial infection (MESH:D003428), nodules (MESH:D016606), epithelial and (MESH:D009375), cardiogenic edema (MESH:D004487), sepsis (MESH:D018805), lung   Epithelial injury (MESH:D055370), asthma (MESH:D001249), pancreatitis (MESH:D010195), cardiac dysfunction (MESH:D006331), Endothelial injury (MESH:D057772), COVID-19 (MESH:D000086382), opacities (MESH:D003318), pneumonia (MESH:D011014)
- **Chemicals:** simvastatin (MESH:D019821), oxygen (MESH:D010100), PaO2 (-), steroids (MESH:D013256), nitrite (MESH:D009573), water (MESH:D014867)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8913033/full.md

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Source: https://tomesphere.com/paper/PMC8913033