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

• Published in: Transplant immunology Vol. 62; p. 101321
• Main Authors: Coiffard, Benjamin, Reynaud-Gaubert, Martine, Rey, Jean-Baptiste, Cousin, Elissa, Grosdidier, Charlotte, Nicolino-Brunet, Corinne, Dignat-George, Françoise, Papazian, Laurent, Thomas, Pascal Alexandre, Barbolosi, Dominique, Serre, Raphaël
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2020; Elsevier
• Subjects: Adult; Allografts - immunology; Bacteriology; Blood; Cardiology and cardiovascular system; Chronic Disease; Computational Biology - methods; Emerging diseases; Female; Graft rejection; Graft Rejection - diagnosis; Graft Survival; Human health and pathology; Humans; Infectious diseases; Life Sciences; Lung Transplantation; Male; Mathematical Modeling; Microbiology and Parasitology; Middle Aged; Models, Theoretical; Neutrophils; Neutrophils - immunology; Parasitology; Prognosis; Retrospective Studies; Virology; RAS; Lung transplantation; Neutrophils; BOS; TLC; IQR; BAL; CMV; Blood; Graft rejection; LTx; FVC; CLAD; Mathematical Modeling; FEV1
• ISSN: 0966-3274; 1878-5492; 1878-5492
• DOI: 10.1016/j.trim.2020.101321

The 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. We 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. 103 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). A slower return to the normal range of blood neutrophils was early associated with CLAD occurrence. •Neutrophils in the lung is a known factor associated with CLAD.•Blood neutrophils were never studied in this specific context of CLAD.•This study aimed to model the kinetics of blood neutrophils after lung transplant.•Slower return to the normal range of blood neutrophils was early associated with CLAD.