Obesity and primary graft dysfunction after lung transplantation: the Lung Transplant Outcomes Group Obesity Study

Abstract

Rationale: Obesity has been linked to acute lung injury and is a risk factor for early mortality after lung transplantation.

Objectives: To examine the associations of obesity and plasma adipokines with the risk of primary graft dysfunction after lung transplantation.

Methods: We performed a prospective cohort study of 512 adult lung transplant recipients with chronic obstructive pulmonary disease or interstitial lung disease enrolled in the Lung Transplant Outcomes Group Study. In a nested case-control study, we measured plasma leptin, adiponectin, and resistin before lung transplantation and 6 and 24 hours after lung transplantation in 40 cases of primary graft dysfunction and 80 control subjects. Generalized linear mixed models and logistic regression were used to estimate risk ratios and odds ratios.

Measurements and main results: Grade 3 primary graft dysfunction developed within 72 hours of transplantation in 29% participants. Obesity was associated with a twofold increased risk of primary graft dysfunction (adjusted risk ratio 2.1; 95% confidence interval, 1.7-2.6). The risk of primary graft dysfunction increased by 40% (confidence interval, 30–50%) for each 5 kg/m(2) increase in body mass index after accounting for center, diagnosis, cardiopulmonary bypass, and transplant procedure. Higher plasma leptin levels were associated with a greater risk of primary graft dysfunction (sex-adjusted P = 0.02). The associations of both obesity and leptin with primary graft dysfunction tended to be stronger among those who did not undergo cardiopulmonary bypass.

Conclusions: Obesity is an independent risk factor for primary graft dysfunction after lung transplantation.

Figure 1.

Continuous association between body mass index and grade 3 primary graft dysfunction (PGD) adjusted for diagnosis, cardiopulmonary bypass, and transplant procedure type. Dark dotted line = effect estimate. Thin dashed lines = 95% confidence bands. The P value is for the association between body mass index and PGD.

Figure 2.

Box plots of plasma leptin and adiponectin levels in 40 cases with grade 3 primary graft dysfunction (PGD) (red) and 80 control subjects (white) before lung transplantation and 6 and 24 hours after reperfusion. (A) Plasma leptin (overall P = 0.04). (B) Plasma leptin stratified by sex (P for interaction = 0.97; sex-adjusted overall P = 0.02). (C) Plasma leptin stratified by cardiopulmonary bypass (CPB) (P for interaction = 0.02; P value for leptin among those receiving cardiopulmonary bypass = 0.76; P value for leptin among those not receiving cardiopulmonary bypass = 0.003). (D) Plasma adiponectin (overall P = 0.60). Cntl = controls.

Figure 3.

Sex-adjusted continuous association between 24-hour plasma leptin level and primary graft dysfunction (PGD). Dark dotted line = effect estimate. Thin dashed lines = 95% confidence bands. The P value is for the association between plasma leptin and PGD.