Novel biomarkers of chronic lung allograft dysfunction: is there anything reliable?

Abstract

Purpose of reviewChronic lung allograft dysfunction (CLAD) remains a major barrier preventing long-term survival following lung transplantation. As our clinical knowledge regarding its definition and presentation has significantly improved over the last years, adequate biomarkers to predict development of CLAD, phenotype of CLAD or prognosis post-CLAD diagnosis are definitely needed. Recent findingsRadiological and physiological markers are gradually entering routine clinical practice. In-depth investigation of biological samples including broncho-alveolar lavage, biopsy and serum has generated potential biomarkers involved in fibrogenesis, airway injury and inflammation but none of these are universally accepted or implemented although progress has been made, specifically regarding donorderived cell-free DNA and donor-specific antibodies.

Systems prediction of chronic lung allograft dysfunction: Results and perspectives from the Cohort of Lung Transplantation and Systems prediction of Chronic Lung Allograft Dysfunction cohorts

“…Six studies are discussed which successively addressed the activation of dendritic cells ( 19 ), secretion of matrix metaloproteinase-9 by activated T cells ( 22 , 24 ), and three for the blood of T and B subpopulations to predict BOS ( 26 , 27 , 31 ). All these studies explored mechanisms and finally immune biomarkers as candidates are able to predict CLAD after LT ( 3 , 12 , 13 , 42 ).…”

“…Although the pathophysiological mechanisms and the risk factors implicated in BOS and RAS are far from being fully elucidated, literature provides increasing evidence and novel insights, especially regarding auto-antibodies ( 4 , 6 , 10 , 11 ). Identification of risk factors associated with specific CLAD phenotypes together with relevant biomarkers ( 12 , 13 ) is of crucial importance as it may assist patient risk stratification, optimize follow-up, and allow prevention and early intervention for potentially modifiable factors. In the field of kidney transplantation, this objective has been reached in 2021 by an international consortium ( 14 ).…”

Thoracic Ultrasound in Lung Transplantation—Insights in the Field

“…Though TUS might be regarded as a novel modality for clinical guidance in the management of lung transplantation (LTx), its wide range of applications within the different fields of LTx has received increased recognition [ 13 , 14 ]. However, due to LTx being a rare condition, the evidence for TUS use in all stages of LTx is restricted to a few studies that are very often based on observations from a limited number of lung transplant recipients.…”

Monitoring practices of chronic lung allograft dysfunction in pediatric lung transplantation

“…11 Other proposed methods include the multiple breath washout (MBW) technique, lung magnetic resonance imaging (MRI), infant/preschool spirometric methods, and biomarkers like cell-free DNA have been proposed. [12][13][14][15] Regardless, despite limitations to the current adultfocused definition of CLAD/Bronchiolitis obliterans syndrome (BOS), there is no pediatric-specific consensus on CLAD detection and monitoring strategies. We sought to determine CLAD detection and monitoring practices at pediatric lung transplant programs, aiming to better understand international practices and potential variability in approaches to testing for CLAD in pediatrics.…”

“…Therefore, supplemental or novel methods for CLAD diagnosis have been proposed, especially for younger children, including chest computed tomography (CT) imaging and histopathology from lung tissue biopsies 11 . Other proposed methods include the multiple breath washout (MBW) technique, lung magnetic resonance imaging (MRI), infant/preschool spirometric methods, and biomarkers like cell‐free DNA have been proposed 12–15 . Regardless, despite limitations to the current adult‐focused definition of CLAD/Bronchiolitis obliterans syndrome (BOS), there is no pediatric‐specific consensus on CLAD detection and monitoring strategies.…”