Update on Chronic Lung Allograft Dysfunction

Abstract

Chronic lung allograft dysfunction (CLAD) encompasses a range of pathologies that cause a transplanted lung to not achieve or maintain normal function. CLAD manifests as airflow restriction and/or obstruction and is predominantly a result of chronic rejection. Three distinct phenotypes of chronic rejection are now recognized: bronchiolitis obliterans, neutrophilic reversible allograft dysfunction, and restrictive allograft syndrome. Recent investigations have revealed that each phenotype has a unique pathology and histopathological findings, suggesting that treatment regimens should be tailored to the underlying etiology. CLAD is poorly responsive to treatment once diagnosed, and therefore the prevention of the factors that predispose a patient to develop CLAD is critically important. Small and large animal models have contributed significantly to our understanding of CLAD and more studies are needed to develop treatment regimens that are effective in humans.

Epithelial cell death markers in bronchoalveolar lavage correlate with chronic lung allograft dysfunction subtypes and survival in lung transplant recipients—a single‐center retrospective cohort study

“…The pathogenesis of CLAD and its subtypes has been an active area of investigation. Various mechanisms involving both innate and adaptive immune responses and aberrant remodeling and repair processes have been proposed to play a role; however, the exact pathophysiology has yet to be elucidated .…”

A single-center experience of 1500 lung transplant patients

“…Moreover, a distinction between obstructive (ie, BOS) versus restrictive (ie, restrictive allograft syndrome) physiology has been identified. 5 A subset analysis of our larger group was performed. For all patients who demonstrated evidence of chronic dysfunction, 95% had obstructive physiology, whereas only 5% had restrictive physiology.…”

Diagnosis, Pathophysiology and Experimental Models of Chronic Lung Allograft Rejection

“…The term “ chronic lung allograft dysfunction ” (CLAD) has emerged over the last decade as an umbrella term for the diagnosis for patients with chronic lung dysfunction after transplantation [ 12 ]. CLAD comprises 2 phenotypes with some overlap.…”

“…In general, definitions have been based on restrictive ventilatory defects and fibrotic infiltrates on chest imaging. Some have used a definition of FVC ≤ 80% baseline function for ≥ 3 weeks in absence of other allograft pathology [ 12,7 ]. An ISHLT working group is currently developing a standardized definition for RAS to facilitate clinical research across centers.…”