Clinical Risk Factors for Primary Graft Dysfunction after Lung Transplantation

Abstract

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.

Ex-vivo Lung Perfusion and Its Role in Experimental Studies

“…Despite the improvements on management strategies, rate of primary graft dysfunction (PGD) (ischemia reperfusion injury) after lung transplantation is 10%-30% and still affects the mortality and morbidity largely (20). A 30-day mortality rate in patients with PGD ranges between 24.5% and 36.4% according to its severity (21).…”

Ozone and Acute Respiratory Distress Syndrome. It’s in the Air We Breathe

“…The interaction between cigarette smoke exposure and ozone is also interesting. Cigarette smoke has recently been identified as an independent risk factor for ARDS in several at-risk populations (11)(12)(13), and is believed to have many of the same pathophysiologic effects on the lung as air pollution. It is possible that cigarette smoke and ozone have synergistic effects on the lung.…”

Lung Size Mismatch and Primary Graft Dysfunction after Bilateral Lung Transplantation

“…Details of the LTOG cohort have been described previously 2 . In this LTOG ancillary study, we included patients aged 18-80 years undergoing bilateral lung transplantation (BLT) at 10 US transplant centers between March 2002 and December 2010.…”

“…Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplantation (LTx) and is associated with the development of bronchiolitis obliterans, which is a major cause of long-term mortality 1,2 . Improved survival associated with graft oversizing in bilateral lung transplants (BLT) has been demonstrated in several studies [3][4][5][6][7][8][9] .…”

“…It is conceivable that differences in PGD rates are responsible for these early survival differences and that lung undersizing predisposes to PGD through mechanisms involving both the pulmonary vasculature, as well as through potentially injurious tidal volumes during mechanical ventilation. A significantly undersized pulmonary vasculature could result in higher pulmonary arterial pressure at reperfusion, which is a risk factor for PGD 2,10 . Alternately, variability in size matching could result in different rates of PGD through differences in mechanical ventilation tidal volumes compared to donor lung size during the period of mechanical ventilation during and after lung transplantation.…”