A33-02 Epidermal Growth Factor Associates With Platelet Counts and Clinical Outcomes During Lung Injury

Abstract Rationale Epidermal growth factor (EGF), a platelet protein, may promote epithelial survival and repair after injury. However, little is known about circulating EGF levels in humans during pneumonia and lung injury. We hypothesized that higher circulating EGF levels would associate with higher platelet counts and improved outcomes during pneumonia and lung injury. Methods We utilized two cohorts of hospitalized patients: the observational Pittsburgh Acute Lung Injury Registry cohort (ALIR; n = 313 patients at enrollment, only baseline samples available) with heterogeneous etiologies of severe respiratory failure, and a subset of the Accelerating COVID-19 Therapeutic Interventions and Vaccines 4 (ACTIV-4A) randomized trial (n = 93 patients with 264 total patient time points). Plasma concentrations of EGF were quantified by ELISA. Spearman’s correlation was used to test associations between EGF and platelet levels. The association of EGF with survival was determined using a Kaplan-Meier survival curve. Temporal trends in EGF were assessed in ACTIV-4A using a linear mixed-effects model with a study day x mortality interaction term. Results Median EGF concentrations were higher in ALIR than ACTIV-4A (65.8 vs. 25.7 pg/mL; Wilcoxon p 0.001). EGF had a positive relationship with platelet counts in both ALIR (Figure 1A: Spearman rho= 0.41, p 0.0001) and ACTIV-4A (Figure 1B: Spearman rho=0.21, p = 0.0016). During 90-day follow-up, patients in ACTIV-4A with baseline EGF levels median demonstrated a trend toward improved survival compared to those with baseline EGF median (Figure 1C: HR = 0.51, 95% CI 0.19-1.38, p = 0.19). Using serial samples in the ACTIV-4A cohort, EGF levels significantly declined (Figure 1D) in non-survivors, which was evident by day 3 (p = 0.037) and more pronounced by day 14 (p = 0.001). Conclusions In two independent patient cohorts enriched for respiratory failure due to pneumonia and lung injury, circulating EGF levels positively correlated with platelet counts during illness. Importantly, EGF levels demonstrated a significant temporal decline in non-survivors in ACTIV-4A through day 14. Overall, our findings suggest that circulating EGF levels may be mediated in part by platelet counts and may be a protective factor during acute lung injury. This abstract is funded by: NHLBI