Mathematical modeling of peripheral blood neutrophil kinetics to predict CLAD after lung transplantation

Abstract

BackgroundThe presence of neutrophils in the lung was identified as a factor associated with CLAD but requires invasive samples. The aim of this study was to assess the kinetics of peripheral blood neutrophils after lung transplantation as early predictor of CLAD. MethodsWe retrospectively included all recipients transplanted in our center between 2009 and 2014. Kinetics of blood neutrophils were evaluated to predict early CLAD by mathematical modeling using unadjusted and adjusted analyses. Results103 patients were included, 80 in the stable group and 23 in the CLAD group. Bacterial infections at 1 year were associated with CLAD occurrence. Neutrophils demonstrated a high increase postoperatively and then a progressive decrease until normal range. Recipients with CLAD had higher neutrophil counts (mixed effect coefficient beta over 3 years = +1.36 G/L, 95% Confidence Interval [0.99–1.92], p < .001). A coefficient of celerity (S for speed) was calculated to model the kinetics of return to the norm before CLAD occurrence. After adjustment, lower values of S (slower decrease of neutrophils) were associated with CLAD (Odds Ratio = 0.26, 95% Confidence Interval [0.08–0.66], p = .01). ConclusionA slower return to the normal range of blood neutrophils was early associated with CLAD occurrence.