Phenotyping CLAD after single lung transplant: Limits and prognostic assessment of the 2019 ISHLT classification system

Gregory Berra; Ella Huszti; Liran Levy; Mitsuaki Kawashima; Eyal Fuchs; Benjamin Renaud-Picard; Peter Riddell; Olivia Dias; Srinivas Rajagopala; Ambilly Ulahannan; Rasheed Ghany; Lianne Gail Singer; Jussi Tikkanen; Tereza Martinu

doi:10.1016/j.healun.2022.01.015

Phenotyping CLAD after single lung transplant: Limits and prognostic assessment of the 2019 ISHLT classification system

J Heart Lung Transplant. 2022 May;41(5):599-607. doi: 10.1016/j.healun.2022.01.015. Epub 2022 Jan 23.

Affiliations

¹ Toronto Lung Transplant Program, Toronto General Hospital Research Institute, Toronto, Ontario, Canada.
² Biostatistics Research Unit, University Health Network, University of Toronto, Toronto, Ontario, Canada.
³ Toronto Lung Transplant Program, Toronto General Hospital Research Institute, Toronto, Ontario, Canada. Electronic address: tereza.martinu@uhn.ca.

PMID: 35351385
DOI: 10.1016/j.healun.2022.01.015

Abstract

Background: Phenotyping chronic lung allograft dysfunction (CLAD) in single lung transplant (SLTX) is challenging, due to the native lung contribution to pulmonary function test (PFT). We aimed to assess the applicability and prognostic performance of International Society for Heart and Lung Transplantation (ISHLT) classification in SLTX.

Methods: In this retrospective study of adult, first, SLTX performed 2009-2017, patients with persistent drop in FEV1≥20% were assessed by 2 independent adjudicators to determine CLAD status and phenotype. Interobserver agreement (IOA) was calculated (Cohen's Kappa) for CLAD, phenotype and presence of RAS (resttrictive allograft syndrome)-like opacities (RLO). Association of CLAD phenotypes with time to death or retransplant (ReTx), adjusted for age at SLTX, sex, CMV mismatch and native lung condition, were assessed using Cox proportional hazards models.

Results: Of 172 SLTX recipients, 92 experienced a persistent drop in FEV1>20%. Following adjudication, 67 were diagnosed with CLAD. We noted a moderate IOA for CLAD diagnosis (Kappa 0.69) and poor IOA for phenotype adjudication (Kappa 0.52). The final phenotype adjudication was 31 bronchiolitis obliterans syndrome (BOS) (46.3%), 13 RAS (19.4%), 2 mixed (3%), 2 Undefined (3%), and 19 remained Unclassified (28.3%). Using these adjudicated phenotypes, RAS was significantly associated with a higher risk of death/ReTx compared to other groups (HR 2.98, 95%CI [1.39-6.4]). The adjudication of RLO had the best IOA (Kappa 0.73). The presence of RLO was a strong predictor of death or ReTx (HR 2.37, 95%CI [1.2-4.5]), regardless of the final phenotype.

Conclusions: PFT interpretation is challenging in SLTX. A classification essentially relying on imaging, which harbored good IOA, obtained better prognostic performance than a classification using published physiological cut-offs.

Keywords: chronic lung allograft dysfunction; chronic rejection; lung transplantation; phenotype; single lung transplant; unilateral.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allografts
Bronchiolitis Obliterans* / diagnosis
Follow-Up Studies
Humans
Lung
Lung Transplantation*
Primary Graft Dysfunction* / diagnosis
Prognosis
Retrospective Studies
Risk Factors
Syndrome