Treatment for acute respiratory distress syndrome in adults: a narrative review of phase 2 and 3 trials

ABSTRACT

Introduction

Ventilatory management and general supportive care of acute respiratory distress syndrome (ARDS) in the adult population have led to significant clinical improvements, but morbidity and mortality remain high. Pharmacologic strategies acting on the coagulation cascade, inflammation, oxidative stress, and endothelial cell injury have been targeted in the last decade for patients with ARDS, but only a few of these have shown potential benefits with a meaningful clinical response and improved patient outcomes. The lack of availability of specific pharmacologic treatments for ARDS can be attributed to its complex pathophysiology, different risk factors, huge heterogeneity, and difficult classification into specific biological phenotypes and genotypes.

Areas covered

In this narrative review, we briefly discuss the relevance and current advances in pharmacologic treatments for ARDS in adults and the need for the development of new pharmacological strategies.

Expert opinion

Identification of ARDS phenotypes, risk factors, heterogeneity, and pathophysiology may help to design clinical trials personalized according to ARDS-specific features, thus hopefully decreasing the rate of failed clinical pharmacologic trials. This concept is still under clinical investigation and needs further development.

KEYWORDS:

• Acute lung injury
• acute respiratory distress syndrome
• pharmacologic treatment
• phenotypes
• trials

Article highlights

• Ventilatory management and supportive care of ARDS have improved, but pharmacologic therapeutic strategies remain mainly supportive.

• ARDS presents with heterogeneous causative risk factors, different sub-phenotypes, and genetic variability, which may influence the results of clinical pharmacologic trials. The accurate selection of inclusion criteria for a clinical trial might allow more efficient therapies, hopefully avoiding premature discard of potentially useful pharmacologic treatments.

• Applications of personalized medicine to ARDS are attractive but still need extensive work, organizational structuring, investments, validation of models, and large samples of well-selected patients.

Declaration to 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 work was funded by the Brazilian Council for Scientific and Technological Development (COVID-19-CNPq; 401700/2020-8 and 403485/2020-7); Rio de Janeiro State Research Foundation (COVID-19-FAPERJ; E-26/210.181/2020); \Funding Authority for Studies and Projects (01200008.00); and Foundation Carlos Chagas Filho Research Support of the State of Rio de Janeiro (FAPERJ) and BRAZILIAN NATIONAL COUNCIL FOR SCIENTIFIC AND TECHNOLOGICAL DEVELOPMENT (CNPq)