• lung allografts
• lung transplant
• primary graft dysfunction

• Humans
• Primary Graft Dysfunction/etiology
• Complement C4b
• Retrospective Studies
• Lung
• Complement System Proteins
• Lung Transplantation/adverse effects
• Allografts
• Graft Rejection/etiology
• Graft Rejection/pathology

• R01 HL153122 NHLBI NIH HHS
• P01 AG049665 NIA NIH HHS
• U19 AI135964 NIAID NIH HHS
• P01 HL154998 NHLBI NIH HHS
• R01 HL147290 NHLBI NIH HHS
• R01 HL147575 NHLBI NIH HHS
• R01 HL149883 NHLBI NIH HHS
• T32 AI083216 NIAID NIH HHS
• R01 HL145478 NHLBI NIH HHS

• Humans
• Pulmonary Artery
• Primary Graft Dysfunction/etiology
• Lung
• Lung Transplantation/adverse effects
• Risk Factors
• Retrospective Studies

• R01 HL145478 NHLBI NIH HHS
• R01 HL147290 NHLBI NIH HHS
• R01 HL147575 NHLBI NIH HHS
• T32 AI083216 NIAID NIH HHS

• lung transplantation
• prediction
• primary graft dysfunction

• Humans
• Nomograms
• Prognosis
• Primary Graft Dysfunction/diagnosis
• Primary Graft Dysfunction/etiology
• Reproducibility of Results
• Models, Statistical
• Quality of Life
• Retrospective Studies
• Lung Transplantation/adverse effects

• aging
• ischemia reperfusion injury
• lung transplantation
• primary graft dysfunction
• senolytics

• De novo malignancy
• Graft rejection
• Lung transplantation
• Native lung complications
• Primary graft dysfunction
• Single lung transplant
• Technical transplant complications
• Vascular transplant complications

Primary graft dysfunction (PGD) is the most important determinant of morbidity and mortality after lung transplantation, but its definition has evolved over the past decade. The implications of this refinement in clinical definition have not been evaluated. In this single-center study, we compared PGD incidence, risk factors, and outcomes using the 2005 and the updated-2016 International Society of Heart and Lung Transplantation guidelines for PGD grading in lung transplant patients.

In this retrospective study, we extracted data from the medical records of 127 patients who underwent lung transplantation between 1/1/2016–12/31/2018. PGD was defined as PGD3 present at 48 and/or 72 hours post-reperfusion. We used the 2005 and the updated 2016 guidelines to assess clinical risk factors, outcomes, and baseline biomarkers for PGD.

On the basis of the 2016 and 2005 guidelines, we identified PGD in 37% and 26% of patients, respectively. PGD was significantly associated with extracorporeal life support, large body mass index, and restrictive lung disease using the 2016 but not the 2005 guidelines. Based on the 2016 guidelines, pretransplant levels of several biomarkers were associated with PGD; using the 2005 guidelines, only increased interleukin-2 levels were significantly associated with PGD. No preoperative biomarkers were associated with PGD using either guidelines after adjusting for clinical variables. Postoperative morbidity and 1-year mortality were similar regardless of guidelines used.

Our findings suggest that refinements in the PGD scoring system have improved the detection of graft injury and associated risk factors without changing its ability to predict postoperative morbidity and mortality.

• Lung transplantation
• cytokines
• lung disease
• primary graft dysfunction (PGD)
• risk factors

Primary graft dysfunction (PGD) is one of the most common complications in the early postoperative period and is the most common cause of death in the first postoperative month. The underlying pathophysiology is thought to be the ischaemia–reperfusion injury that occurs during the storage and reperfusion of the lung engraftment; this triggers a cascade of pathological changes, which result in pulmonary vascular dysfunction and loss of the normal alveolar architecture. There are a number of surgical and anaesthetic factors which may be related to the development of PGD. To date, although treatment options for PGD are limited, there are several promising experimental therapeutic targets. In this review, we will discuss the pathophysiology, clinical management and potential therapeutic targets of PGD.

• Lung transplantation
• Primary graft dysfunction
• Reperfusion injury
• Therapeutics

• Humans
• Lung
• Lung Transplantation/adverse effects
• Primary Graft Dysfunction/etiology
• Primary Graft Dysfunction/therapy
• Reperfusion Injury/etiology
• Reperfusion Injury/therapy
• Risk Factors

• British Journal of Anaesthesia

Primary graft dysfunction (PGD) is a known acute lung injury (ALI) and a major cause of fatality post-lung transplantation. Though some long non-coding RNAs (lncRNAs) have been studied in ALI through regulation of microRNAs (miRNAs), their effects on PGD remain undefined. The present study aims to explore the underlying mechanism of lncRNA X-inactive specific transcript (XIST) in PGD after lung transplantation.

Initially, the expression of miR-21, IL-12A and XIST was determined by RT-qPCR and western blot analysis. The dual luciferase reporter assay, RNA pull-down and RIP assay were performed to identify the targeting relationship between miR-21 and IL-12A and the binding relationship between miR-21 and XIST. Loss- and gain-of-function investigations were conducted in rats treated with prolonged cold ischemia and polymorphonuclear neutrophils (PMNs).

miR-21 was decreased, whilst XIST and IL-12A were increased in the bronchoalveolar lavage fluid of PGD patients after lung transplantation. Enhanced miR-21 expression in rats and PMNs resulted in downregulated expression of pro-inflammatory factors and chemokines, and enhanced the apoptosis of PMNs. XIST was found to upregulate IL-12A expression in a miR-21-dependent manner. Additionally, XIST silencing enhanced the apoptosis of PMNs and inhibited the neutrophil extracellular trap (NET) formation through upregulation of miR-21 but downregulation of IL-12A in vivo.

In summary, lncRNA XIST upregulates IL-12A by binding to miR-21, thereby inducing NET formation and accelerating PGD after lung transplantation. This suggests that inhibition of XIST and NET may be beneficial for the treatment of PGD.

• Competing endogenous RNA
• Interleukin-12A
• Long non-coding RNA
• MicroRNA-21
• Neutrophil extracellular trap
• Primary graft dysfunction
• X-inactive specific transcript

• lung transplantation
• extracorporeal membrane oxygenation
• hypertension, pulmonary
• pulmonary fibrosis
• heart failure
• diastolic

• Adult
• Aged
• Aged, 80 and over
• Brazil/epidemiology
• Bronchiectasis/epidemiology
• Bronchiectasis/therapy
• Extracorporeal Membrane Oxygenation/methods
• Female
• Humans
• Intensive Care Units
• Length of Stay
• Lung Diseases/epidemiology
• Lung Diseases/therapy
• Lung Transplantation/methods
• Male
• Middle Aged
• Postoperative Complications
• Prospective Studies
• Pulmonary Arterial Hypertension/epidemiology
• Pulmonary Arterial Hypertension/therapy
• Pulmonary Emphysema/epidemiology
• Pulmonary Emphysema/therapy
• Pulmonary Fibrosis/epidemiology
• Pulmonary Fibrosis/therapy
• Retrospective Studies
• Time Factors
• Treatment Outcome

Over 19% of deceased organ donors are labeled increased risk for disease transmission (IRD) for viral blood‐borne disease transmission. Many potential organ recipients need to decide between accepting an IRD organ offer and waiting for a non–IRD organ.

Using machine learning and simulation, we built transplant and waitlist survival models and compared the survival for patients accepting IRD organ offers or waiting for non–IRD organs for the heart, liver, and lung. The simulation consisted of generating 20 000 different scenarios of a recipient either receiving an IRD organ or waiting and receiving a non–IRD organ.

In the simulations, the 5‐year survival probabilities of heart, liver, and lung recipients who accepted IRD organ offers increased on average by 10.2%, 12.7%, and 7.2%, respectively, compared with receiving a non–IRD organ after average wait times (190, 228, and 223 days, respectively). When the estimated waitlist time was at least 5 days for the liver, and 1 day for the heart and lung, 50% or more of the simulations resulted in a higher chance of 5‐year survival when the patient received an IRD organ versus when the patient remained on the waitlist. We also developed a simple equation to estimate the benefits, in terms of 5‐year survival probabilities, of receiving an IRD organ versus waiting for a non–IRD organ, for a particular set of recipient/donor characteristics.

For all three organs, the majority of patients are predicted to have higher 5‐year survival accepting an IRD organ offer compared with waiting for a non–IRD organ.

• Smoking
• Smoking cessation
• Solid organ transplantation
• Transplant outcomes

• ECMO
• extracorporeal membrane oxygenation
• lung transplantation
• mechanical support
• primary graft function

• Acute lung injury
• Ischemia-reperfusion injury
• Lung transplantation
• Primary graft dysfunction

• Humans
• Lung Transplantation/adverse effects
• Lung Transplantation/methods
• Primary Graft Dysfunction/etiology
• Primary Graft Dysfunction/pathology
• Reperfusion Injury/etiology
• Reperfusion Injury/pathology
• Risk Factors

• diastolic heart failure
• left ventricular function
• lung transplant
• primary graft dysfunction
• pulmonary hypertension

• Hypervolemia
• Lung transplant
• Primary graft dysfunction
• Pulmonary edema

• primary graft dysfunction (pgd)
• ischemia-reperfusion injury
• lung transplantation
• acute lung injury

• Acute Lung Injury/immunology
• Animals
• Humans
• Immunity, Innate
• Lung Transplantation/adverse effects
• Primary Graft Dysfunction/immunology
• Risk Factors
• Time Factors

• R01 HL087115 NHLBI NIH HHS
• K24 HL115354 NHLBI NIH HHS
• K23 HL-121406 NHLBI NIH HHS
• T32 HL-007891 NHLBI NIH HHS
• T32 HL007891 NHLBI NIH HHS
• K23 HL121406 NHLBI NIH HHS

• BOS
• acute rejection
• donor specific HLA antibodies
• lung transplantation
• risk factors
• survival

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. Herein, we carried out a systematic review and meta-analysis of published literature to identify recipient-related clinical risk factors associated with PGD development.

A systematic search of electronic databases (PubMed, Embase, Web of Science, Cochrane CENTRAL, and Scopus) for studies published from 1970 to 2013 was performed. Cohort, case-control, or cross-sectional studies that examined recipient-related risk factors of PGD were included. The odds ratios (ORs) or mean differences (MDs) were calculated using random-effects models

Thirteen studies involving 10042 recipients met final inclusion criteria. From the pooled analyses, female gender (OR 1.38, 95% CI 1.09 to 1.75), African American (OR 1.82, 95%CI 1.36 to 2.45), idiopathic pulmonary fibrosis (IPF) (OR 1.78, 95% CI 1.49 to 2.13), sarcoidosis (OR 4.25, 95% CI 1.09 to 16.52), primary pulmonary hypertension (PPH) (OR 3.73, 95%CI 2.16 to 6.46), elevated BMI (BMI≥25 kg/m²) (OR 1.83, 95% CI 1.26 to 2.64), and use of cardiopulmonary bypass (CPB) (OR 2.29, 95%CI 1.43 to 3.65) were significantly associated with increased risk of PGD. Age, cystic fibrosis, secondary pulmonary hypertension (SPH), intra-operative inhaled nitric oxide (NO), or lung transplant type (single or bilateral) were not significantly associated with PGD development (all P>0.05). Moreover, a nearly 4 fold increased risk of short-term mortality was observed in patients with PGD (OR 3.95, 95% CI 2.80 to 5.57).

Our analysis identified several recipient related risk factors for development of PGD. The identification of higher-risk recipients and further research into the underlying mechanisms may lead to selective therapies aimed at reducing this reperfusion injury.

• Female
• Humans
• Lung Diseases/diagnosis
• Lung Diseases/therapy
• Lung Transplantation/adverse effects
• Male
• Mortality
• Odds Ratio
• Patient Outcome Assessment
• Primary Graft Dysfunction/epidemiology
• Primary Graft Dysfunction/etiology
• Publication Bias
• Pulmonary Wedge Pressure
• Risk Factors

• Ex vivo lung perfusion
• Lung reconditioning
• Lung transplantation