Acute respiratory distress syndrome is a challenging entity for the intensivist.
The pathological hallmark of the acute phase is diffuse alveolar damage, which
is present in approximately half of living patients with acute respiratory
distress syndrome. It is clear that respiratory support for acute respiratory
distress syndrome has gradually been improving over recent decades. However, it
is also evident that these procedures are beneficial, as they reduce lung injury
and keep the patient alive. This could be interpreted as a time-gaining strategy
until the trigger or causal or risk factor improves, the inflammatory storm
decreases and the lung heals. However, all except two pharmacological treatments
(neuromuscular blockers and steroids) were unable to improve the acute
respiratory distress syndrome outcome. The hypothesis that pharmacological
negative results may be explained by the histological heterogeneity of acute
respiratory distress syndrome has been supported by the recent demonstration
that acute respiratory distress syndrome with diffuse alveolar damage
constitutes a specific clinical-pathological entity. Given that diffuse alveolar
damage is a pathological diagnosis and that open lung biopsy (the most common
technique to obtain lung tissue) has several side effects, it is necessary to
develop surrogate biomarkers for diffuse alveolar damage. The aim of this
narrative review is to address the following three topics related to acute
respiratory distress syndrome: (a) the relationship between acute respiratory
distress syndrome and diffuse alveolar damage, (b) how diffuse alveolar damage
could be surrogated in the clinical setting and (c) how enrichment in diffuse
alveolar damage may improve the results of pharmacological clinical trials tried
out on patients with acute respiratory distress syndrome.