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

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.

Diffusing capacity of the lung for carbon monoxide: association with long-term outcomes after lung transplantation in a 20-year longitudinal study.

RATIONALE: The diffusing capacity of the lung for carbon monoxide corrected for haemoglobin (D LCOcor) measures gas movement across the alveolar-capillary interface. We hypothesised that D LCOcor is a sensitive measure of injurious allograft processes disrupting this interface. OBJECTIVES: To determine the prognostic significance of the D LCOcor trajectory on chronic lung allograft dysfunction (CLAD) and survival. METHODS: A retrospective analysis was conducted of all bilateral lung transplant recipients at a single centre, between January 1998 and January 2018, with one or more D LCOcor measurements. Low baseline D LCOcor was defined as the failure to achieve a D LCOcor >75% predicted. Drops in D LCOcor were defined as >15% below recent baseline. RESULTS: 1259 out of 1492 lung transplant recipients were included. The median (range) time to peak D LCOcor was 354 (181-737) days and the mean±sd D LCOcor was 80.2±21.2% pred. Multivariable analysis demonstrated that low baseline D LCOcor was significantly associated with death (hazrd ratio (HR) 1.68, 95% CI 1.27-2.20; p<0.001). Low baseline D LCOcor was not independently associated with CLAD after adjustment for low baseline forced expiratory volume in 1 s or forced vital capacity. Any D LCOcor declines ≥15% were significantly associated with death, independent of concurrent spirometric decline. Lower percentage predicted D LCOcor values at CLAD onset were associated with shorter post-CLAD survival (HR 0.75 per 10%-unit change, p<0.01). CONCLUSION: Low baseline D LCOcor and post-transplant declines in D LCOcor were significantly associated with survival, independent of spirometric measurements. We propose that D LCOcor testing may allow identification of a subphenotype of baseline and chronic allograft dysfunction not captured by spirometry. There may be benefit in routine monitoring of D LCOcor after lung transplantation to identify patients at risk of poor outcomes.