Objective Estimates Improve Risk Stratification for Primary Graft Dysfunction after Lung Transplantation

Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in the Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002 to 2010; with separate validation in 382 subjects accrued from 2011 to 2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 h, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed three prediction models, where low‐risk recipients had a normal BMI (18.5–25 kg/m2), chronic obstructive pulmonary disease/cystic fibrosis, and absent or mild pulmonary hypertension (mPAP<40 mmHg). All others were considered higher‐risk. Low‐risk recipients had a predicted PGD risk of 4–7%, and high‐risk a predicted PGD risk of 15–18%. Adding a donor‐smoking lung to a higher‐risk recipient significantly increased PGD risk, although risk did not change in low‐risk recipients. Validation demonstrated that probability estimates were generally accurate and that models worked best at baseline PGD incidences between 5% and 25%. We conclude that valid estimates of PGD risk can be produced using readily available clinical variables.

[1]  J. Bavaria,et al.  Primary graft failure following lung transplantation. , 1998, Chest.

[2]  J. Orens,et al.  Association of protein C and type 1 plasminogen activator inhibitor with primary graft dysfunction. , 2007, American journal of respiratory and critical care medicine.

[3]  J. Pilewski,et al.  Donor Smoking History and Age in Lung Transplantation: A Revisit , 2013, Transplantation.

[4]  A. Localio,et al.  Construct validity of the definition of primary graft dysfunction after lung transplantation. , 2010, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[5]  J. Orens,et al.  Plasma Intercellular Adhesion Molecule‐1 and von Willebrand Factor in Primary Graft Dysfunction After Lung Transplantation , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[6]  A. Localio,et al.  Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation. , 2013, Chest.

[7]  C. Deutschman,et al.  Elevated pulmonary artery pressure is a risk factor for primary graft dysfunction following lung transplantation for idiopathic pulmonary fibrosis. , 2011, Chest.

[8]  A. Rahmel,et al.  The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report-2012. , 2012, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[9]  J. Orens,et al.  Elevated Plasma Clara Cell Secretory Protein Concentration Is Associated with High‐Grade Primary Graft Dysfunction , 2011, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[10]  P. Corris,et al.  Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part II: definition. A consensus statement of the International Society for Heart and Lung Transplantation. , 2005, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[11]  Stephen E Kimmel,et al.  The effect of primary graft dysfunction on survival after lung transplantation. , 2005, American journal of respiratory and critical care medicine.

[12]  S. van Buuren Multiple imputation of discrete and continuous data by fully conditional specification , 2007, Statistical methods in medical research.

[13]  M. Bacchetta,et al.  Obesity and underweight are associated with an increased risk of death after lung transplantation. , 2009, American journal of respiratory and critical care medicine.

[14]  S. Kimmel,et al.  Clinical risk factors for primary graft failure following lung transplantation. , 2003, Chest.

[15]  N. Benowitz,et al.  Active and passive cigarette smoking and acute lung injury after severe blunt trauma. , 2011, American journal of respiratory and critical care medicine.

[16]  C. Deutschman,et al.  Plasma levels of receptor for advanced glycation end products, blood transfusion, and risk of primary graft dysfunction. , 2009, American journal of respiratory and critical care medicine.

[17]  M. Amato,et al.  Expression of acute-phase cytokines, surfactant proteins, and epithelial apoptosis in small airways of human acute respiratory distress syndrome. , 2013, Journal of critical care.

[18]  R. Tibshirani,et al.  Improvements on Cross-Validation: The 632+ Bootstrap Method , 1997 .

[19]  G. Patterson,et al.  Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. , 2007, American journal of respiratory and critical care medicine.

[20]  Xiao-Hua Zhou,et al.  The need for reorientation toward cost‐effective prediction: Comments on ‘Evaluating the added predictive ability of a new marker: From area under the ROC curve to reclassification and beyond’ by Pencina et al., Statistics in Medicine (DOI: 10.1002/sim.2929) , 2008, Statistics in medicine.

[21]  Maria Crespo,et al.  Obesity and primary graft dysfunction after lung transplantation: the Lung Transplant Outcomes Group Obesity Study. , 2011, American journal of respiratory and critical care medicine.

[22]  Theo Stijnen,et al.  Using the outcome for imputation of missing predictor values was preferred. , 2006, Journal of clinical epidemiology.

[23]  E. Elkin,et al.  Decision Curve Analysis: A Novel Method for Evaluating Prediction Models , 2006, Medical decision making : an international journal of the Society for Medical Decision Making.

[24]  David W. Hosmer,et al.  Applied Logistic Regression , 1991 .

[25]  E L Korn,et al.  Predictive Margins with Survey Data , 1999, Biometrics.

[26]  Sander Greenland,et al.  The need for reorientation toward cost‐effective prediction: Comments on ‘Evaluating the added predictive ability of a new marker: From area under the ROC curve to reclassification and beyond’ by M. J. Pencina et al., Statistics in Medicine (DOI: 10.1002/sim.2929) , 2008, Statistics in medicine.

[27]  A. Localio,et al.  Clinical risk factors for primary graft dysfunction after lung transplantation. , 2013, American journal of respiratory and critical care medicine.

[28]  Patrick Royston,et al.  Multiple imputation using chained equations: Issues and guidance for practice , 2011, Statistics in medicine.

[29]  J. Neuberger,et al.  Effect of donor smoking on survival after lung transplantation: a cohort study of a prospective registry , 2012, The Lancet.