Significance of phenotype change after chronic lung allograft dysfunction onset

Eyal Fuchs, Liran Levy, Ella Huszti, Benjamin Renaud-Picard, Gregory Berra, Mitsuaki Kawashima, Akihiro Takahagi, Rasheed Ghany, Jan Havlin, Micheal C. McInnis, Shaf Keshavjee, Lianne G. Singer, Jussi Tikkanen, Chung Wai Chow, Tereza Martinu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Definitions for chronic lung allograft dysfunction (CLAD) phenotypes were recently revised (2019 ISHLT consensus). Post-CLAD onset phenotype transition may occur as a result of change in obstruction, restriction, or RAS-like opacities (RLO). We aimed to assess the prevalence and prognostic implications of these transitions. This was a single-center, retrospective cohort study of bilateral lung transplants performed in 2009–2015. CLAD phenotypes were determined per ISHLT guidelines. CLAD phenotype transition was defined as a sustained change in obstruction, restriction or RLO. We specifically focused on phenotype changes based on RLO emergence. Association of RLO development with time to death or retransplant were assessed using Kaplan–Meier and Cox proportional hazards models. Among 211 patients with CLAD, 47 (22.2%) experienced a phenotype transition. Nineteen patients developed RLO. Development of RLO phenotype after CLAD onset was associated with a shorter time to death/retransplant when considering the entire CLAD patient cohort (HR = 4.00, CI 2.74–5.83, P < 0.001) and also when restricting the analysis to only patients with a Non-RLO phenotype at CLAD onset (HR 9.64, CI 5.52–16.84, P < 0.0001). CLAD phenotype change based on emergence of RAS-like opacities implies a worse outcome. This highlights the clinical importance of imaging follow-up to monitor for phenotype transitions after CLAD onset.

Original languageEnglish
Pages (from-to)2620-2632
Number of pages13
JournalTransplant International
Issue number12
StatePublished - Dec 2021


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