Clinical predictors for restrictive allograft syndrome: A nested case-control study

Abstract

Risk factors for restrictive allograft syndrome (RAS), a severe phenotype of chronic lung allograft dysfunction (CLAD) after lung transplantation, are currently not well known. In this retrospective nested case-control-study, we analyzed 69 patients with RAS and 69 matched non-CLAD controls to identify clinical risk factors for RAS. Patients with RAS demonstrated overall higher blood eosinophils (P = .02), increased bronchoalveolar eosinophils (P < .001) and lymphocytes (P = .03), and higher incidence of infections, particularly Pseudomonas species infection (P = .003), invasive fungal disease (P < .001, mainly due to Aspergillus species), SARS-CoV-2 (P < .001), and cytomegalovirus infection (P = .04), compared with non-CLAD controls. Antihuman leukocyte antigen (anti-HLA) antibodies, especially persistent donor-specific antibodies (P < 0.001), specifically targeting HLA-DQ and HLA-DR loci, and antibody-mediated rejection (P < .001), were strongly associated with later RAS. Histopathologic lung injury patterns on transbronchial biopsy (P < .001), and persistent chest computed tomography opacities in absence of pulmonary dysfunction (P < .001) were identified as early indicators of later RAS. Proactive detection and management of these risk factors could help mitigate future decline in allograft function and reduce progression to clinical RAS. Future studies should explore early treatment strategies targeting these modifiable factors to preserve allograft function and improve long-term outcomes for lung transplant recipients.