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.