When tissue is the issue: A histological review of chronic lung allograft dysfunction

Abstract

At the time of implementation of human allogenic lung transplantation (LTx) by James Hardy in 1963, 1 survival was limited to a maximum of weeks due to surgical and infectious complications. It took until 1971 for a posttransplant survival of 10 months to be reported by Derom et al. 2 Following several episodes of severe acute rejection, 6 months posttransplant their patient developed irreversibly decreased values of forced expiratory volume in 1 second (FEV 1) and FEV 1 /forced vital

Effector immune cells in chronic lung allograft dysfunction: A systematic review

“…acute rejection, infection, non‐specific triggers of lung injury) are shared between BOS and RAS, combined with some similar findings in both entities (e.g. obliterative bronchiolitis lesions in RAS, areas of alveolar fibrosis in BOS) and the fact that patients can transition from one phenotype to another supports the hypothesis that BOS and RAS may be a continuum of the same disease [5–7]. Interestingly, there is considerable overlap between obliterative bronchiolitis after lung transplantation, after allogeneic hematopoietic stem cell transplantation and in clinical settings other than post‐transplant (e.g.…”

CFTR Modulator Therapy and Its Impact on Lung Transplantation in Cystic Fibrosis

“…The post-transplant baseline value is calculated from the mean of the two best postoperative FEV 1 measurements taken more than 3 weeks apart [ 85 ]. The etiology of CLAD is probably multifactorial, its underlying mechanisms are complex, and much of its pathophysiology remains unknown [ 86 ]. The recent advances in the understanding of the pathophysiological mechanisms of CLAD and its different phenotypes were just reviewed in detail by Verleden and colleagues [ 86 ].…”

“…The etiology of CLAD is probably multifactorial, its underlying mechanisms are complex, and much of its pathophysiology remains unknown [ 86 ]. The recent advances in the understanding of the pathophysiological mechanisms of CLAD and its different phenotypes were just reviewed in detail by Verleden and colleagues [ 86 ]. In CLAD-BOS, the most common clinical CLAD phenotype, persistent micro-injuries caused by gastroesophageal reflux, viruses, microbes, etc., to the lung graft epithelium seem to result in chronic airway inflammation and aberrant wound healing with fibroblast activation and migration, eventually leading to small airway obliteration [ 86 ].…”

“…The recent advances in the understanding of the pathophysiological mechanisms of CLAD and its different phenotypes were just reviewed in detail by Verleden and colleagues [ 86 ]. In CLAD-BOS, the most common clinical CLAD phenotype, persistent micro-injuries caused by gastroesophageal reflux, viruses, microbes, etc., to the lung graft epithelium seem to result in chronic airway inflammation and aberrant wound healing with fibroblast activation and migration, eventually leading to small airway obliteration [ 86 ]. To date, no well-proven therapeutic approach is available to successfully treat CLAD in lung transplant recipients, either adults or children, according to a recent systematic review by Benden and colleagues [ 87 ].…”

Activation of Humoral Immunity during the Pathogenesis of Experimental Chronic Lung Allograft Dysfunction

“…Chronic lung allograft dysfunction (CLAD) is the leading cause of allograft failure in the long term [ 1 , 2 , 3 ]. CLAD is an umbrella term describing different subforms of a chronic and persistent decline in pulmonary allograft function [ 1 , 4 ]. Essentially, three subforms have been described, obstructive bronchiolitis obliterans syndrome (BOS), which affects about two-thirds of all CLAD patients, restrictive allograft syndrome (RAS), and mixed forms combining features of BOS and RAS [ 1 , 4 ].…”