Global approaches to chronic lung allograft dysfunction: Toward evidence-based harmonization.

Abstract

Chronic lung allograft dysfunction (CLAD) remains the leading cause of late graft failure and mortality after lung transplantation, imposing a substantial societal burden. Over the past decade, international efforts have refined diagnostic criteria and phenotypic classification of CLAD, and advanced our understanding of the multifactorial mechanisms underlying CLAD onset. Contemporary international surveys provide valuable insight into real-world CLAD management, demonstrating practice harmonization alongside persistent geographic variation. Diagnostic evaluation of CLAD has converged through international consensus. Most transplant centers now incorporate spirometry, chest CT, bronchoscopy with bronchoalveolar lavage and transbronchial biopsies, and donor-specific antibody testing for CLAD surveillance and work-up. However, greater international standardization is still needed for pulmonary function test reporting, imaging protocols, and pathology workflows. Therapeutic management, however, remains more heterogeneous. Major differences persist in preventive strategies, particularly for azithromycin prophylaxis and gastroesophageal reflux management, as well as the use of corticosteroid pulse therapy, lymphocyte-depleting agents, extracorporeal photopheresis, and adjunctive treatments such as montelukast and inhaled bronchodilators in established CLAD. Similar variability is observed in other aspects of lung transplantation, including infection-directed strategies. Rather than representing a limitation, these practice variations identify priorities for future studies by highlighting areas where comparative evidence is lacking. The next decade of CLAD research should therefore focus on generating evidence needed to harmonize clinical care, while advancing molecular diagnostics-guided precision medicine and tailored treatments for CLAD. Standardizing therapeutic algorithms, studying biomarker-guided disease-modifying interventions, and pragmatic clinical trials are essential to transform experience-based CLAD management to evidence-based care, and to improve long-term transplant outcomes.