Rationale: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Objectives: We sought to identify donor, recipient, and perioperative risk factors for PGD. Methods: We performed a 10-center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD at 48 or 72 hours posttransplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression. Measurements and Main Results: A total of 1,255 patients from 10 centers were enrolled; 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.6; P ¼ 0.002); FI O 2 during allograft reperfusion (OR, 1.1 per 10% increase in FI O 2 ; 95% CI, 1.0-1.2; P ¼ 0.01); single lung transplant (OR, 2; 95% CI, 1.2-3.3; P ¼ 0.008); use of cardiopulmonary bypass (OR, 3.4; 95% CI, 2.2-5.3; P , 0.001); overweight (OR, 1.8; 95% CI, 1.2-2.7; P ¼ 0.01) and obese (OR, 2.3; 95% CI, 1.3-3.9; P ¼ 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1-5.6; P ¼ 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6-7.7; P ¼ 0.002); and mean pulmonary artery pressure (OR, 1.3 per 10 mm Hg increase; 95% CI, 1.1-1.5; P , 0.001). PGD was significantly associated with 90-day (relative risk, 4.8; absolute risk increase, 18%; P , 0.001) and 1-year (relative risk, 3; absolute risk increase, 23%; P , 0.001) mortality. Conclusions: We identified grade 3 PGD risk factors, several of which are potentially modifiable and should be prioritized for future research aimed at preventative strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 00552357). What This Study Adds to the FieldWe performed a multicenter, prospective cohort study of 1,255 lung transplant recipients across 10 US transplant centers. We identified receipt of an organ from a donor with any smoking history, elevated FI O 2 during allograft reperfusion, preoperative sarcoidosis or pulmonary arterial hypertension, use of cardiopulmonary bypass, single lung transplant, large-volume blood product transfusion, elevated pulmonary arterial pressures, and overweight or obese recipient body habitus as risk factors for grade 3 PGD. Several of these risk factors are potentially modifiable, and thus may suggest preventative strategies, whereas other risk factors should be prioritized for future mechanistic research efforts.

Rationale: Primary graft dysfunction (PGD) is the main cause of early morbidity and mortality after lung transplantation. Previous studies have yielded conflicting results for PGD risk factors. Objectives: We sought to identify donor, recipient, and perioperative risk factors for PGD. Methods: We performed a 10-center prospective cohort study enrolled between March 2002 and December 2010 (the Lung Transplant Outcomes Group). The primary outcome was International Society for Heart and Lung Transplantation grade 3 PGD at 48 or 72 hours posttransplant. The association of potential risk factors with PGD was analyzed using multivariable conditional logistic regression. Measurements and Main Results: A total of 1,255 patients from 10 centers were enrolled; 211 subjects (16.8%) developed grade 3 PGD. In multivariable models, independent risk factors for PGD were any history of donor smoking (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.2-2.6; P ¼ 0.002); FI O 2 during allograft reperfusion (OR, 1.1 per 10% increase in FI O 2 ; 95% CI, 1.0-1.2; P ¼ 0.01); single lung transplant (OR, 2; 95% CI, 1.2-3.3; P ¼ 0.008); use of cardiopulmonary bypass (OR, 3.4; 95% CI, 2.2-5.3; P , 0.001); overweight (OR, 1.8; 95% CI, 1.2-2.7; P ¼ 0.01) and obese (OR, 2.3; 95% CI, 1.3-3.9; P ¼ 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1-5.6; P ¼ 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6-7.7; P ¼ 0.002); and mean pulmonary artery pressure (OR, 1.3 per 10 mm Hg increase; 95% CI, 1.1-1.5; P , 0.001). PGD was significantly associated with 90-day (relative risk, 4.8; absolute risk increase, 18%; P , 0.001) and 1-year (relative risk, 3; absolute risk increase, 23%; P , 0.001) mortality. Conclusions: We identified grade 3 PGD risk factors, several of which are potentially modifiable and should be prioritized for future research aimed at preventative strategies. Clinical trial registered with www.clinicaltrials.gov (NCT 00552357). What This Study Adds to the FieldWe performed a multicenter, prospective cohort study of 1,255 lung transplant recipients across 10 US transplant centers. We identified receipt of an organ from a donor with any smoking history, elevated FI O 2 during allograft reperfusion, preoperative sarcoidosis or pulmonary arterial hypertension, use of cardiopulmonary bypass, single lung transplant, large-volume blood product transfusion, elevated pulmonary arterial pressures, and overweight or obese recipient body habitus as risk factors for grade 3 PGD. Several of these risk factors are potentially modifiable, and thus may suggest preventative strategies, whereas other risk factors should be prioritized for future mechanistic research efforts.

No abstract

Few studies have examined the lung virome in health and disease. Outcomes of lung transplantation are known to be influenced by several recognized respiratory viruses, but global understanding of the virome of the transplanted lung is incomplete. To define the DNA virome within the respiratory tract following lung transplantation we carried out metagenomic analysis of allograft bronchoalveolar lavage (BAL), and compared to healthy and HIV+ subjects. Viral concentrates were purified from BAL and analyzed by shotgun DNA sequencing. All of the BAL samples contained reads mapping to anelloviruses, with high proportions in lung transplant samples. Anellovirus populations in transplant recipients were complex, with multiple concurrent variants. Q-PCR quantification revealed that anellovirus sequences were 56-fold more abundant in BAL from lung transplant recipients compared with healthy controls or HIV+ subjects (p<0.0001). Anellovirus sequences were also more abundant in upper respiratory tract specimens from lung transplant recipients than controls (p=0.006). Comparison to metagenomic data on bacterial populations showed that high anellovirus loads correlated with dysbiotic bacterial communities in allograft BAL (p=0.00816). Thus the respiratory tracts of lung transplant recipients contain high levels and complex populations of anelloviruses, warranting studies of anellovirus lung infection and transplant outcome.

Primary graft dysfunction (PGD) is a syndrome encompassing a spectrum of mild to severe lung injury that occurs within the first 72 hours after lung transplantation. PGD is characterized by pulmonary edema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. In recent years, new knowledge has been generated on risks and mechanisms of PGD. Following ischemia and reperfusion, inflammatory and immunological injury-repair responses appear to be key controlling mechanisms. In addition, PGD has significant impact on short- and long-term outcomes; therefore, the choice of donor organ is impacted by this potential adverse consequence. Improved methods of reducing PGD risk and efforts to safely expand the pool are being developed. Ex-vivo lung perfusion is a strategy which may improve risk assessment and become a promising platform to implement treatment interventions to prevent PGD. This review will detail recent updates in the epidemiology, pathophysiology, molecular and genetic biomarkers and state-of-the-art technical developments affecting PGD. (158 words)