Advances in mechanisms of repair and remodelling in acute lung injury

Abstract

Background: Acute respiratory distress syndrome (ARDS) is the most severe manifestation of acute lung injury (ALI). In patients who survive the acute injury the process of repair and remodelling may be an independent risk factor determining morbidity and mortality. This review explores recent advances in the field of fibroproliferative ARDS/ALI, with a special emphasis on (a) the primary contributing factors with a focus on cellular and soluble factors, and (b) mechanisms involved in repair and remodelling as they pertain to the importance of cell death, re-population, and matrix deposition.

Discussion: Factors influencing progression to fibroproliferative ARDS vs. resolution and reconstitution of the normal pulmonary parenchymal architecture are poorly understood. Determinants of persistent injury and abnormal repair and remodelling may be profoundly affected by both environmental and genetic factors. Moreover, cumulative evidence suggests that acute inflammation and fibrosis may be in part independent and interactive processes that are autonomously regulated and thus amenable to individual and specific therapy.

Conclusions: Although our current understanding of these processes is limited by the inability to accurately replicate the complex human physiology in laboratory settings, it has recently become apparent that the process of repair and remodelling begins early in the course of ARDS/ALI and may be determined by the type of pulmonary injury. Understanding the mechanisms leading to and regulating fibroproliferative changes may contribute to the development of novel early therapeutic interventions in ARDS/ALI patients.