Treatment of adult respiratory distress syndrome: plea for rescue therapy of the alveolar epithelium

Although much has been learned about the mechanisms leading to acute lung i njury, mortality-which is mainly related to sepsis or associated non-pulmon ary organ dysfunction(1)-remains high (around 50%) in patients with adult r espiratory distress syndrome (ARDS).(2-4) Many new therapeutic approaches a iming to control the inflammatory response accompanying ARDS have been eval uated.(5) Hoc-ever, these treatments have had no impact on the mortality st emming from the disease.(5) The lack of success with these new intervention s is probably multifactorial.(6) One possible explanation is that the appro priate patient population had not been enrolled for study.(7) In this regar d, it is also probably unrealistic to hope that a single treatment will mod ify the evolution of all ARDS patients who represent a heterogeneous popula tion with very different severities of lung injury. Thus, it is unlikely th at the efficacious treatment of patients with mild lung injury will be as e fficient in patients with severe lung injury Most of the treatments tested recently were targeted to control the inflamm atory response.(5) Although the development of lung injury is mainly depend ent on aggression of endothelial cells by inflammatory cells,(5) its severi ty and recovery also depend on epithelial cell function.(9) In fact, the pr edominant pathological finding in acute lung injury is diffuse alveolar epi thelial damage.(10 11) Furthermore, physiologically it has been shown that the structure and function of the alveolar epithelium are important determi nants of lung injury.(12) Finally, the alveolar epithelium is also the site of alveolar fluid reabsorption and plays a major role in the development o f lung fibrosis associated with ARDS.(13-15) Treatments aimed at improving epithelial function might therefore become one of the key elements to accel erate recovery and decrease the mortality of patients with ARDS. In this review we will emphasise the importance of modulating two of the ma ny functions of the alveolar epithelium which we consider to be strategical ly necessary for quicker recovery from ARDS. After reviewing the characteri stics of ARDS lesions, we will determine how we can stimulate the alveolar epithelium to increase oedema clearance and hasten epithelial repair.