The Acute Respiratory Distress Syndrome (ARDS) is a systemic syndrome characterized by severe respiratory failure, inflammation, loss of aerated tissue and high mortality. Recently, significant efforts have been made to phenotype ARDS patients through a wide range of new biomarkers and imaging indices with the goal of developing personalized treatments based on patient's biophenotypization. Recent literature demonstrates, both in vitro and in vivo but not yet in ARDS patients, that the serine protease inhibitor(SERPIN)-B3 plays a crucial role in the pathological mechanism of pulmonary fibrogenesis, and, similarly, protease-activated receptors(PAR2) is highly involved in this aberrant inflammatory response. Consequently, studying the expression of SERPINB3 (including SCCA-PD polymorphism) and PAR2, in association with a detailed clinical and biomolecular phenotypization, could allow new insights into the pathophysiological mechanisms of lung injury during ARDS.