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

Abstract

Rationale The diffusing capacity of the lung for carbon monoxide corrected for haemoglobin (DLCOcor) measures gas movement across the alveolar-capillary interface. We hypothesised that DLCOcor is a sensitive measure of injurious allograft processes disrupting this interface. Objectives To determine the prognostic significance of the DLCOcor 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 DLCOcor measurements. Low baseline DLCOcor was defined as the failure to achieve a DLCOcor >75% predicted. Drops in DLCOcor were defined as >15% below recent baseline. Results 1259 out of 1492 lung transplant recipients were included. The median (range) time to peak DLCOcor was 354 (181-737) days and the mean±SD DLCOcor was 80.2±21.2% pred. Multivariable analysis demonstrated that low baseline DLCOcor was significantly associated with death (hazrd ratio (HR) 1.68, 95% CI 1.27-2.20; p<0.001). Low baseline DLCOcor was not independently associated with CLAD after adjustment for low baseline forced expiratory volume in 1 s or forced vital capacity. Any DLCOcor declines ≥15% were significantly associated with death, independent of concurrent spirometric decline. Lower percentage predicted DLCOcor values at CLAD onset were associated with shorter post-CLAD survival (HR 0.75 per 10%-unit change, p<0.01). Conclusion Low baseline DLCOcor and post-transplant declines in DLCOcor were significantly associated with survival, independent of spirometric measurements. We propose that DLCOcor 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 DLCOcor after lung transplantation to identify patients at risk of poor outcomes.