The impact of age on the acute respiratory distress syndrome: From bedside to bench and back

The acute respiratory distress syndrome (ARDS) is characterized by severe hypoxia in critically ill patients. Despite extensive research over the past decades mortality remains high. None of the promising pharmacological interventions have shown to improve outcome. The biological heterogeneity among ARDS patients is a major challenge in the search for effective therapeutic interventions. More knowledge regarding the contribution of specific biological pathways in individual patients or subgroups of patients with ARDS is essential. Interestingly, recent studies indicate important epidemiological differences according to age. This finding could reflect age-related differences in pathophysiology of ARDS. Indeed, maturation and aging are known to affect the host response and may influence biological pathways involved in the pathophysiology of ARDS.
The general aim of this thesis is to investigate whether there is a relation between maturation and aging and ARDS and to examine this relation in several aspects of epidemiology and pathophysiology of ARDS. First, we describe the incidence and mortality of ARDS in children and focus on the differences compared to data reported from adults. Then, we show age-related differences in the pulmonary host response in animal models of ARDS, and confirm some of these finding in ARDS patients. Special attention was given to the pulmonary renin angiotensin system as a potential underlying regulatory mechanism. Furthermore, we investigate the relation between aging, the systemic immune response and adverse outcome in ARDS patients. Finally, we identify two biological-phenotypes which are exclusively based on the systemic host response during ARDS.