Although much has been learned about the mechanisms leading to acute lung injury, mortality—which is mainly related to sepsis or associated non-pulmonary organ dysfunction1—remains high (around 50%) in patients with adult respiratory distress syndrome (ARDS).2-4 Many new therapeutic approaches aiming to control the inflammatory response accompanying ARDS have been evaluated.5 However, these treatments have had no impact on the mortality stemming from the disease.5 The lack of success with these new interventions is probably multifactorial.6 One possible explanation is that the appropriate patient population had not been enrolled for study.7 In this regard, it is also probably unrealistic to hope that a single treatment will modify the evolution of all ARDS patients who represent a heterogeneous population with very different severities of lung injury. Thus, it is unlikely that the efficacious treatment of patients with mild lung injury will be as efficient in patients with severe lung injury.

Most of the treatments tested recently were targeted to control the inflammatory response.5 Although the development of lung injury is mainly dependent on aggression of endothelial cells by inflammatory cells,8 its severity and recovery also depend on epithelial cell function.9 In fact, the predominant pathological finding in acute lung injury is diffuse alveolar epithelial damage.10 ,11 Furthermore, physiologically it has been shown that the structure and function of the alveolar epithelium are important determinants of lung injury.12Finally, the alveolar epithelium is also the site of alveolar fluid reabsorption and plays a major role in the development of lung fibrosis associated with ARDS.13-15 Treatments aimed at improving epithelial function might therefore become one of the key elements to accelerate recovery and decrease the mortality of patients with ARDS.

In this review we will emphasise the importance of modulating …