Clinical Risk Factors for Primary Graft Dysfunction After Lung Transplantation

Overview

Journal Am J Respir Crit Care Med

Specialty Critical Care

Date 2013 Jan 12

PMID 23306540

Citations 226

Authors

Joshua M Diamond

James C Lee

Steven M Kawut

Rupal J Shah

A Russell Localio

Scarlett L Bellamy

David J Lederer

Edward Cantu

Benjamin A Kohl

Vibha N Lama

Sangeeta M Bhorade

Maria Crespo

Ejigayehu Demissie

Joshua Sonett

Keith Wille

Jonathan Orens

Ashish S Shah

Ann Weinacker

Selim Arcasoy

Pali D Shah

David S Wilkes

Lorraine B Ware

Scott M Palmer

Jason D Christie

Affiliations

Soon will be listed here.

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 post-transplant. 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 = 0.002); FiO2 during allograft reperfusion (OR, 1.1 per 10% increase in FiO2; 95% CI, 1.0-1.2; P = 0.01); single lung transplant (OR, 2; 95% CI, 1.2-3.3; P = 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 = 0.01) and obese (OR, 2.3; 95% CI, 1.3-3.9; P = 0.004) recipient body mass index; preoperative sarcoidosis (OR, 2.5; 95% CI, 1.1-5.6; P = 0.03) or pulmonary arterial hypertension (OR, 3.5; 95% CI, 1.6-7.7; P = 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).

Citing Articles

Differentially expressed microRNAs in pre-transplant lung biopsies target immune checkpoint proteins and can predict primary graft dysfunction in lung transplantation.

Miceli V, Ferrigno P, Centi C, Carcione C, Iannolo G, Agnese V Heliyon. 2025; 11(4):e42515.

PMID: 40028527 PMC: 11869042. DOI: 10.1016/j.heliyon.2025.e42515.

Activation of Nrf2 pathway by 4-Octyl itaconate enhances donor lung function in cold preservation settings.

Gao X, Tang M, Li J, Ma J, Liu Z, Liu W Respir Res. 2025; 26(1):69.

PMID: 40016745 PMC: 11869626. DOI: 10.1186/s12931-025-03151-7.

Longitudinal single-cell profiles of lung regeneration after viral infection reveal persistent injury-associated cell states.

Niethamer T, Planer J, Morley M, Babu A, Zhao G, Basil M Cell Stem Cell. 2025; 32(2):302-321.e6.

PMID: 39818203 PMC: 11805657. DOI: 10.1016/j.stem.2024.12.002.

Transcatheter mitral valve repair with MitraClip® enabling single lung transplantation: A case report.

Carlier F, Dumonceaux M, Plante-Bordeneuve T, Evrard P, Marchand E, Belhaj A Heliyon. 2025; 11(1):e41222.

PMID: 39802031 PMC: 11721235. DOI: 10.1016/j.heliyon.2024.e41222.

The Risk of Pretransplant Blood Transfusion for Primary Graft Dysfunction After Lung Transplant.

Kaihou T, Toyoda T, Cerier E, Yagi Y, Manerikar A, Thomae B Ann Thorac Surg Short Rep. 2025; 2(3):573-577.

PMID: 39790394 PMC: 11708632. DOI: 10.1016/j.atssr.2024.02.004.

References

Meyer D, Bennett L, Novick R, Hosenpud J . Effect of donor age and ischemic time on intermediate survival and morbidity after lung transplantation. Chest. 2000; 118(5):1255-62. DOI: 10.1378/chest.118.5.1255. View

Daud S, Yusen R, Meyers B, Chakinala M, Walter M, Aloush A . Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome. Am J Respir Crit Care Med. 2006; 175(5):507-13. DOI: 10.1164/rccm.200608-1079OC. View

Gajic O, Rana R, Winters J, Yilmaz M, Mendez J, Rickman O . Transfusion-related acute lung injury in the critically ill: prospective nested case-control study. Am J Respir Crit Care Med. 2007; 176(9):886-91. PMC: 2048675. DOI: 10.1164/rccm.200702-271OC. View

Christie J, Edwards L, Kucheryavaya A, Benden C, Dipchand A, Dobbels F . The Registry of the International Society for Heart and Lung Transplantation: 29th adult lung and heart-lung transplant report-2012. J Heart Lung Transplant. 2012; 31(10):1073-86. DOI: 10.1016/j.healun.2012.08.004. View

Calfee C, Matthay M, Eisner M, Benowitz N, Call M, Pittet J . Active and passive cigarette smoking and acute lung injury after severe blunt trauma. Am J Respir Crit Care Med. 2011; 183(12):1660-5. PMC: 3136993. DOI: 10.1164/rccm.201011-1802OC. View

Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P . Meta-analysis: ventilation strategies and outcomes of the acute respiratory distress syndrome and acute lung injury. Ann Intern Med. 2009; 151(8):566-76. DOI: 10.7326/0003-4819-151-8-200910200-00011. View

Eisner M, Thompson T, Hudson L, Luce J, Hayden D, Schoenfeld D . Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome. Am J Respir Crit Care Med. 2001; 164(2):231-6. DOI: 10.1164/ajrccm.164.2.2011093. View

Sims M, Beers M, Ahya V, Kawut S, Sims K, Lederer D . Effect of single vs bilateral lung transplantation on plasma surfactant protein D levels in idiopathic pulmonary fibrosis. Chest. 2011; 140(2):489-496. PMC: 3148793. DOI: 10.1378/chest.10-2065. View

Whitson B, Nath D, Johnson A, Walker A, Prekker M, Radosevich D . Risk factors for primary graft dysfunction after lung transplantation. J Thorac Cardiovasc Surg. 2006; 131(1):73-80. DOI: 10.1016/j.jtcvs.2005.08.039. View

10.

Sommers K, Griffith B, Hardesty R, Keenan R . Early lung allograft function in twin recipients from the same donor: risk factor analysis. Ann Thorac Surg. 1996; 62(3):784-90. DOI: 10.1016/s0003-4975(96)00371-2. View

11.

de Perrot M, Bonser R, Dark J, Kelly R, McGiffin D, Menza R . Report of the ISHLT Working Group on Primary Lung Graft Dysfunction part III: donor-related risk factors and markers. J Heart Lung Transplant. 2005; 24(10):1460-7. DOI: 10.1016/j.healun.2005.02.017. View

12.

Prekker M, Nath D, Walker A, Johnson A, Hertz M, Herrington C . Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation. J Heart Lung Transplant. 2006; 25(4):371-8. DOI: 10.1016/j.healun.2005.11.436. View

13.

Kuntz C, Hadjiliadis D, Ahya V, Kotloff R, Pochettino A, Lewis J . Risk factors for early primary graft dysfunction after lung transplantation: a registry study. Clin Transplant. 2009; 23(6):819-30. DOI: 10.1111/j.1399-0012.2008.00951.x. View

14.

Stadlmann S, Rieger G, Amberger A, Kuznetsov A, Margreiter R, Gnaiger E . H2O2-mediated oxidative stress versus cold ischemia-reperfusion: mitochondrial respiratory defects in cultured human endothelial cells. Transplantation. 2002; 74(12):1800-3. DOI: 10.1097/00007890-200212270-00029. View

15.

Hsieh S, Ware L, Eisner M, Yu L, Jacob 3rd P, Havel C . Biomarkers increase detection of active smoking and secondhand smoke exposure in critically ill patients. Crit Care Med. 2010; 39(1):40-5. PMC: 3148017. DOI: 10.1097/CCM.0b013e3181fa4196. View

16.

Gammie J, Cheul Lee J, Pham S, Keenan R, Weyant R, HATTLER B . Cardiopulmonary bypass is associated with early allograft dysfunction but not death after double-lung transplantation. J Thorac Cardiovasc Surg. 1998; 115(5):990-7. DOI: 10.1016/s0022-5223(98)70396-4. View

17.

Brower R, Matthay M, Morris A, Schoenfeld D, Thompson B, Wheeler A . Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000; 342(18):1301-8. DOI: 10.1056/NEJM200005043421801. View

18.

Lederer D, Kawut S, Wickersham N, Winterbottom C, Bhorade S, Palmer S . Obesity and primary graft dysfunction after lung transplantation: the Lung Transplant Outcomes Group Obesity Study. Am J Respir Crit Care Med. 2011; 184(9):1055-61. PMC: 3208644. DOI: 10.1164/rccm.201104-0728OC. View

19.

Christie J, Kotloff R, Ahya V, Tino G, Pochettino A, Gaughan C . The effect of primary graft dysfunction on survival after lung transplantation. Am J Respir Crit Care Med. 2005; 171(11):1312-6. PMC: 2718464. DOI: 10.1164/rccm.200409-1243OC. View

20.

Christie J, Keshavjee S, Orens J, Arcasoy S, dePerrot M, Barr M . Potential refinements of the International Society for Heart and Lung Transplantation primary graft dysfunction grading system. J Heart Lung Transplant. 2008; 27(1):138. DOI: 10.1016/j.healun.2007.09.030. View