Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a disease entity that poses a major challenge in the care for patients admitted to the intensive care unit (ICU). ALI/ARDS is defined as a) acute onset; b) severe arterial hypoxemia (PaO 2 /FIO 2 ratio d 300 mmHg for ALI and PaO2/FIO2 ratio d 200 mmHg for ARDS); c) bilateral infiltrates on chest radiograph; and d) no evidence of left atrial hypertension (American-European Consensus Conference criteria 1 ). It can develop due

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... o a wide variety of causes such as pneumonia, sepsis, trauma, burns or multiple transfusion, in patients with underlying diseases, such as cancer or immune disorders, but also in previously healthy individuals 2 . The unifying features of ALI/ARDS are considered to be extensive pulmonary inflammation and diffuse alveolar damage. However, the latter histopathological finding may be present in only half of the patients 3 . Currently, no specific treatment for ALI/ARDS exists, and therefore more insight into its pathophysiology is urgently needed. Children One of the factors that may affect the pathophysiology of lung injury is age. Children appear to be relatively protected in terms of incidence and outcome of ALI/ARDS 4-7 . Large, multicenter studies using the AECC criteria have reported mortality rates of 20-35% for pediatric ALI/ARDS 4;5;8 , as compared to 40-55% for adults 6;9 . Erickson et al. even found a positive correlation between age and ALI/ARDS mortality within a pediatric ICU patient cohort 8 . So far, we can only speculate on what determines this age-related effect on the risk and course of ALI/ARDS. Apart from differences in the physical properties between developing lungs of young children and fully mature lungs in adults, a number of other factors including age-related differential (immune) responses of both structural and myeloid cells in the lungs may play an important role herein. At the same time, there are specific causes of lung injury in young children such as severe infection by respiratory syncytial virus (RSV), and infant (I)RDS of preterm birth that show a number of features overlapping with ALI/ARDS 10;11 , and as such, this adds to the heterogeneity of pediatric ALI/ARDS, making a comparison between children and adults not straight forward. Pathogenesis The studies in this thesis have attempted to extend our insight of ALI/ARDS pathogenesis by focusing on the role of pro-apoptotic pathways in lung epithelial injury and inflammation in children.