The Impact of Donor Smoking on Primary Graft Dysfunction and Mortality after Lung Transplantation

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012-2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined utilizing accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (NNAL) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11·5% (95%CI 3·8, 19·2) by urinary cotinine, 5·7% (95%CI -3·4, 14·9) by urinary NNAL, and 6·5% (95%CI -2·8, 15·8) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability.