Investigational pharmacological agents for the treatment of ARDS

ABSTRACT

Introduction

Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous form of lung injury with severe hypoxemia and bilateral infiltrates after an inciting event that results in diffuse lung inflammation with a high mortality rate. While research in COVID-related ARDS has resulted in several pharmacotherapeutic agents that have undergone successful investigation, non-COVID ARDS studies have not resulted in many widely accepted pharmacotherapeutic agents despite exhaustive research.

Areas covered

The aim of this review is to discuss adjuvant pharmacotherapies targeting non-COVID Acute Lung Injury (ALI)/ARDS and novel therapeutics in COVID associated ALI/ARDS. In ARDS, variable data may support selective use of neuromuscular blocking agents, corticosteroids and neutrophil elastase inhibitors, but are not yet universally used. COVID-ALI/ARDS has data supporting the use of IL-6 monoclonal antibodies, corticosteroids, and JAK inhibitor therapy.

Expert opinion

Although ALI/ARDS modifying pharmacological agents have been identified in COVID-related disease, the data in non-COVID ALI/ARDS has been less compelling. The increased use of more specific molecular phenotyping based on physiologic parameters and biomarkers, will ensure equipoise between groups, and will likely allow more precision in confirming pharmacological agent efficacy in future studies.

KEYWORDS:

• ARDS
• acute lung injury
• corticosteroids
• tocilizumab
• interferon beta 1a
• neuromuscular blocking agents
• mesenchymal stem cells
• JAK inhibitors

Article highlights

• To date, no drug has been consistently shown to have efficacy in non-COVID-19 ARDS

• Corticosteroids and neuromuscular blocking agents have had shown some efficacy in selective patients and studies in non-COVID ARDS

• ARDS is a syndrome not a single disease with variable onset causes and in patients with variable co-morbidities.

• COVID-19 related ARDS seems to respond to early corticosteroids, the use of JAK inhibitor and the use of monoclonal antibodies that block IL-6 receptors

• The patient variability within syndrome of ARDS adds to the difficulty to demonstrate drug efficacy.

• Novel agents are currently being proposed and studied in ARDS

• Future studies designed to reduce variability (like those focusing on COVID-19 ARDS) coupled with the use of biomarkers should reduce variability and increase the likelihood of demonstrating drug efficacy in ARDS

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was partially funded by NHLBI funded T32 post-doctoral fellowship to Katyayini Aribindi (HL007013).