Biomarkers in Pediatric ARDS: Future Directions

Orwoll, Benjamin E.; Sapru, Anil

Since the initial description of ARDS, there have been widespread investigations into the pathobiology of the syndrome as well as for better ways to care for its victims. Through the increasing use of molecular techniques for the study of the ARDS disease process, we have gained a great deal of knowledge related to the development, progression, and resolution of this devastating condition. One major hope for the application of this knowledge is to further characterize subpopulations within what is widely regarded as an extremely heterogeneous disease, which may then lead to the development of specific therapies tailored toward the pathophysiological changes found in each subpopulation. Preliminary steps in this process were realized recently with the description of a biomarker "panel" for ARDS (83) and the publication of a latent class analysis of two ARDS clinical trials by Calfee et al. who described two subphenotypes, hyper-and hypo-inflammatory, with differential clinical responses to the trial interventions (189) . These findings were based on the analysis of clinical characteristics and multiple biomarkers and hold promise that further subphenotyping might be used to guide the design of future clinical trials, such as those targeting Th2 high vs. Th2 low populations in asthma (190) . Though no clear ARDS subphenotypes have yet been identified in pediatric patients, it would seem that the same principles could reasonably be applied. It is also important to recognize that information from biomarkers in pARDS may provide value both in terms of their ability to improve risk stratification and also to better define the pathophysiology of this heterogeneous condition. Better risk stratification will allow for well-designed trials of pARDS therapies and improved prognostication for families. In counterpoint, improved understanding of the pathological mechanisms that lead to pARDS and regulate its resolution may form the bases for the development of novel therapies.