Difficulties in modelling ARDS (2017 Grover Conference Series)

Area of Science:

• Pulmonary Medicine
• Translational Research
• Animal Modeling

Background:

• Acute Respiratory Distress Syndrome (ARDS) lacks successful drug treatments despite decades of research.
• Animal models often fail to replicate critical ARDS features like hypoxemia and cardiovascular instability.
• Reproducing ARDS pathophysiology in animal models presents significant challenges.

Purpose of the Study:

• To critically evaluate the limitations of current animal models for ARDS.
• To discuss the role of intensive care unit (ICU) interventions in ARDS modeling.
• To propose improvements for developing more clinically relevant ARDS animal models.

Main Methods:

• Review of existing ARDS animal studies and their translational outcomes.
• Analysis of physiological parameters and endpoints in ARDS models.
• Consideration of species-specific factors, including environmental temperature and metabolic changes.

Main Results:

• Many ARDS drug studies successful in animals have failed in human clinical trials.
• Animal models easily induce lung inflammation but struggle to reliably induce hypoxemia.
• Hypoxemia in models is often confounded by cardiovascular failure, necessitating ICU interventions.

Conclusions:

• Clinically relevant ARDS models must better recapitulate disease properties, including hypoxemia and hyperinflammation.
• The impact of ICU measures (ventilation, fluid support) as a 'second hit' needs careful consideration.
• Standardized, comparable endpoints (e.g., PaO2/FiO2 ratio) and control for environmental confounders are crucial for robust ARDS modeling.