Tom Ziegler, MD; Vin Tangpricha, MD, PhD; and Greg Martin, MD, investigators in EPICC, were among the first to investigate the relationship of vitamin D to antimicrobial peptide expression (particularly LL-37 or cathelicidin) in humans. In this study, critically ill subjects had significantly lower vitamin D levels and cathelicidin/LL-37 levels compared to healthy controls and there was a strong association between the two mediators.
This initial work laid the foundation for large-scale epidemiology studies of vitamin D in acutely and critically ill patients and prospective cohort studies to determine the relationship of vitamin D and antimicrobial peptides to infectious and other clinical outcomes in critically ill patients. In a prospective cohort of medical ICU patients, Jordan Kempker, MD found no relationship between vitamin D and infectious complications during hospitalization. Expanding from an institutional cohort towards large scale epidemiology, Kempker expanded into health services research by integrating data from the National Health and Nutritional Examination (NHANES) with hospitalization data from the Centers for Medicare/Medicaid Services (CMS) to study the association between vitamin D and infectious or non-infectious hospitalizations. Our group has also completed an NHLBI-funded randomized controlled trial of vitamin D supplementation in ICU patients (NCT01372995) and demonstrated that high dose vitamin D therapy can be safely increase vitamin D levels even in critically ill patients and this treatment may lead to improvements in organ function and important patient-centered clinical outcomes.