ISHLT special report
Report of the ISHLT Working Group on Primary Lung Graft Dysfunction Part IV: Recipient-Related Risk Factors and Markers

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Demographics

Existing evidence does not support an association between recipient age and the risk of PGD.1, 2, 3, 4 Although one study showed a younger mean age of patients with PGD versus those without, there was no adjustment for other potential confounders, such as underlying disease and use of cardiopulmonary bypass.5 The incidence of PGD and risk factors in pediatric lung transplant recipients are also poorly defined.6 Recipient gender (independent of the higher likelihood of sensitization from

Body Weight

Although two studies have identified obesity (body mass index [BMI] >27 to 30) as a significant risk factor for early mortality and longer intensive care unit stay, there are no specific studies of body weight and the incidence of PGD.7, 8

Hepatic Impairment

Among 62 patients with pulmonary arterial hypertension undergoing heart–lung transplantation, the early mortality of those with a serum bilirubin >2.1 mg/dl was 58% compared with 27% for those with a level between 1 and 2 mg/dl, and 16% in those with a normal

Re-transplantation

Short-term mortality is considerably increased for recipients with a second allograft, particularly those transplanted acutely for severe PGD20 and those who are non-ambulatory and ventilator-dependent.21 The occurrence of PGD has not been specifically documented in these reports. Among 15 recipients re-transplanted for obliterative bronchiolitis, only 2 died of PGD, suggesting that the risk of PGD is not substantially elevated.19

General Thoracic Procedures

A cohort of 18 recipients who had undergone earlier pleural

Mechanical ventilation

Pre-transplant mechanical ventilation does not appear to increase the risk of PGD.20, 31, 32

Obstructive Lung Disease

Chronic obstructive pulmonary disease (COPD) patients consistently have the lowest risk of PGD (with a reported incidence as low as 3%).2, 5, 33 In one study, patients with α1-anti-trypsin deficiency had a higher incidence of PGD (9%) and a somewhat longer duration of ventilation and intensive care unit stay compared with those of other emphysema patients. However, bilateral transplantation was also more frequent in the former group, suggesting that confounding variables other than diagnosis

Type of transplant

Most studies of the association between transplant type and PGD are limited by univariate analyses. It is possible that an apparent association between type of transplant and the risk of PGD may be confounded by the indication for lung transplantation and the use of cardiopulmonary bypass.

Role of cardiopulmonary bypass

The role of cardiopulmonary bypass as an independent or contributing factor for PGD remains controversial. Cardiopulmonary bypass causes a systemic, pro-inflammatory response with activation of cytokines, leukocytes and the complement cascade.57, 58, 59 The contribution of this inflammatory response and the requirements for transfusion on early graft function are less well defined. Limited retrospective series supporting both the deleterious and non-deleterious effects of cardiopulmonary bypass

Bleeding and transfusion-related lung injury

Transfusion of blood products may lead to pulmonary dysfunction.66 Free radicals, cytokines and humoral factors that are produced activate neutrophils and facilitate their interaction with the pulmonary endothelium. Activated neutrophils marginate through the endothelium where they are responsible for tissue injury by the release of free radicals and proteases.67

In the early era of lung and heart–lung transplantation, intra-operative and post-operative bleeding were significant causes of early

Surgical complications

Despite improvements in operative techniques, surgical problems may still lead to graft dysfunction in the early post-operative period.86 Technical complications leading to poor graft function generally include vascular anastomotic obstruction or improper orientation of the graft. Mechanical obstruction of the left atrial cuff, pulmonary vein or pulmonary artery due to anastomotic problems and/or subsequent thrombosis is the main source of graft dysfunction after lung transplantation.

Experimental and clinical biologic factors and markers in the recipient

Lung injury begins at least at a sub-clinical level at the time of donor brain-stem death as a result of a generalized inflammatory response, which correlates with subsequent indices of oxygenation in the recipient.118 Experimental and clinical evidence now suggests that reperfusion injury occurs in a biphasic pattern with the early phase of reperfusion injury depending primarily on donor characteristics, and the delayed phase of reperfusion occurring over the ensuing 24 hours depending

Summary

The lack of a clear definition of PGD in many large series of lung transplantation, including the ISHLT registry data, hampers the identification of recipient-related risk factors. Concomitant donor-related variables further confound these analyses. Based on the current body of literature, recipient-related risk factors that would require further study before any association can be stated include the type of procedure, the presence of hepatic dysfunction, and pleural adhesions and/or prior

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