Multistate modelling of baseline lung allograft dysfunction in lung transplant recipients

Baseline lung allograft dysfunction (BLAD) is characterised by the failure to achieve normal baseline lung function after lung transplantation (LTX), affecting over a third of LTX recipients and conveying significant mortality. While previous studies identified BLAD as a risk factor for mortality, evolution, transitions and risk factors influencing transitions from BLAD to normal lung function or death/retransplantation remain unknown.

We conducted a retrospective study of 472 LTX recipients transplanted between 2010 and 2018, using a Markov multistate model to characterise lung function evolution. The model investigated transitions between "indeterminate", "BLAD", "normal baseline lung function" and "death/retransplantation" states. We modelled state transitions, association of BLAD with mortality, and risk factors influencing transitions and mortality through respective states.

Our study confirms a higher mortality risk for BLAD, particularly in single LTX (SLTX) compared to double LTX (DLTX) recipients. DLTX recipients with obstructive underlying disease were more likely to recover from BLAD (hazard ratio (HR) 3.1) but faced higher mortality if remaining in BLAD (HR 2.6). Chronic lung allograft dysfunction had a strong association with mortality in patients with normal baseline lung function (HR 5.1) but also to a lesser extent in BLAD patients (HR 1.8). Longitudinal analysis demonstrated that DLTX recipients often recover from BLAD, while SLTX recipients rarely achieve normal lung function if starting in BLAD.

Our study highlights differences in lung function evolution between SLTX and DLTX recipients and investigates for the first time prevalence and risk factors for transitions between BLAD and non-BLAD states, as well as risk factors influencing BLAD-related mortality in LTX recipients.