ABSTRACT
Do we need biomarkers of lung damage and infection: For what purpose and how should they be used properly? Biomarkers of lung damage can be used for diagnosis, risk stratification/prediction, treatment surveillance and adjustment of targeted therapy. Additionally, novel "omics" methods may offer a completely different and effective way of improving the understanding of pathogenesis of lung damage and a way to develop new candidate lung damage biomarkers. In the current review, we give an overview within the field of acute lung damage of (i) disease mechanism biomarkers, (ii) of "ready to use" evidence-based biomarker-guided lung infection management, (iii) of novel strategies of inflammatory phenotyping and how this can be used to tailor corticosteroid treatment, (iv) a future perspective of where "omics" technologies and mindsets may become increasingly important in developing new strategies for treatment and for understanding the development of acute lung damage.
ABSTRACT
BACKGROUND: Gelsolin is an actin-scavenger controlling the tissue damage from actin in the blood. Gelsolin levels in circulation drops when tissue damage and corresponding actin release is pronounced due to catabolic conditions. The purpose of this study was to determine if low plasma gelsolin independently predicts a reduced chance of weaning from ventilator-demanding respiratory failure in critically ill patients within 28 days from admission. RESULTS: This cohort study included 746 critically ill patients with ventilator-demanding respiratory failure from the randomized clinical trial, "Procalcitonin And Survival Study (PASS)." Primary end point was successful weaning from mechanical ventilation within 28 days. We used multivariable Cox regression adjusted for age, sepsis, PaO2/FiO2 ratio and other known and suspected predictors of persistent respiratory failure. Follow-up was complete.For medical patients, baseline-gelsolin below the 25th percentile independently predicted a 40% lower chance of successful weaning within 28 days (HR 0.60, 95% CI 0.46-0.79, Pâ=â0.0002); among surgical patients this end point was not predicted. Low gelsolin levels predicted chance of being "alive and out of intensive care at day 14" for both medical and surgical patients (HR 0.69, 95% CI 0.54-0.89, Pâ=â0.004). Gelsolin levels did not predict 28 day mortality for surgical or medical patients. CONCLUSIONS: Low levels of serum gelsolin independently predict a decreased chance of successful weaning from ventilator within 28 days among medical intensive care patients. This finding has implications for identifying patients who need individualized intervention early in intensive care course to prevent unfavorable lung prognosis in acute respiratory failure. TRIAL REGISTRATION: This is a substudy to the PASS, Clinicaltrials.gov ID: NCT00271752, first registered January 1, 2006.
