Background
Severe primary graft dysfunction (PGD) is associated with the development of bronchiolitis
obliterans syndrome (BOS), the most common form of chronic lung allograft dysfunction
(CLAD), in adults. However, PGD associations with long-term outcomes following pediatric
lung transplantation are unknown. We hypothesized that PGD grade 3 (PGD 3) at 48-
or 72-hours would be associated with shorter CLAD-free survival following pediatric
lung transplantation.
Methods
This was a single center retrospective cohort study of patients ≤ 21 years of age
who underwent bilateral lung transplantation between 2005 and 2019 with ≥ 1 year of
follow-up. PGD and CLAD were defined by published criteria. We evaluated the association
of PGD 3 at 48- or 72-hours with CLAD-free survival by using time-to-event analyses.
Results
Fifty-one patients were included (median age 12.7 years; 51% female). The most common
transplant indications were cystic fibrosis (29%) and pulmonary hypertension (20%).
Seventeen patients (33%) had PGD 3 at either 48- or 72-hours. In unadjusted analysis,
PGD 3 was associated with an increased risk of CLAD or mortality (HR 2.10, 95% CI
1.01-4.37, p=0.047). This association remained when adjusting individually for multiple potential
confounders. There was evidence of effect modification by sex (interaction p = 0.055) with the association of PGD 3 and shorter CLAD-free survival driven predominantly
by males (HR 4.73, 95% CI 1.44-15.6) rather than females (HR 1.23, 95% CI 0.47-3.20).
Conclusions
PGD 3 at 48- or 72-hours following pediatric lung transplantation was associated with
shorter CLAD-free survival. Sex may be a modifier of this association.
KEYWORDS
Abbreviations:
BOS (bronchiolitis obliterans syndrome), CARV (community associated respiratory virus), CF (cystic fibrosis), CHOP (Children's Hospital of Philadelphia), CLAD (chronic lung allograft dysfunction), CMV (cytomegalovirus), ECMO (extracorporeal membrane oxygenation), FEV1 (forced expiratory volume in 1 second), HR (hazard ratio), ISHLT (International Society for Heart and Lung Transplantation), IQR (Interquartile Range), PCR (polymerase chain reaction), LV (left ventricle), PGD (primary graft dysfunction), PFT (pulmonary function test), PH (pulmonary hypertension), RAS (restrictive allograft syndrome), RV (right ventricle)To read this article in full you will need to make a payment
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References
- Chronic lung allograft dysfunction: definition, diagnostic criteria, and approaches to treatment-a consensus report from the pulmonary council of the ISHLT.J Heart Lung Transplant. 2019; 38: 493-503https://doi.org/10.1016/j.healun.2019.03.009
- Late primary graft dysfunction after lung transplantation and bronchiolitis obliterans syndrome.Am J of Transplantation. 2008; 8: 2454-2462https://doi.org/10.1111/j.1600-6143.2008.02389.x
- International society for heart and lung transplantation. the international thoracic organ transplant registry of the international society for heart and lung transplantation: twenty-first pediatric lung and heart‒lung transplantation report-2018; focus theme: multiorgan transplantation.J Heart Lung Transplant. 2018; 37: 1196-1206https://doi.org/10.1016/j.healun.2018.07.021
- Lung transplantation in children.Ann Surg. 2002; 236: 270-276https://doi.org/10.1097/00000658-200209000-00003
- Pediatric lung transplantation as standard of care.Clin Transplant. 2021; 35: e14126https://doi.org/10.1111/ctr.14126
- Pediatric lung transplantation.Semin Pediatr Surg. 2017; 26: 213-216https://doi.org/10.1053/j.sempedsurg.2017.07.005
- International society for heart and lung transplantation. the registry of the international society for heart and lung transplantation: nineteenth pediatric lung and heart-lung transplantation report-2016; focus theme: primary diagnostic indications for transplant.J Heart Lung Transplant. 2016; 35: 1196-1205https://doi.org/10.1016/j.healun.2016.08.019
- Primary graft dysfunction and other selected complications of lung transplantation: a single-center experience of 983 patients.J Thorac Cardiovasc Surg. 2005; 129: 1421-1429https://doi.org/10.1016/j.jtcvs.2005.01.022
- The effect of primary graft dysfunction on survival after lung transplantation.Am J Respir Crit Care Med. 2005; 171: 1312-1316https://doi.org/10.1164/rccm.200409-1243OC
- Clinical risk factors for primary graft dysfunction after lung transplantation.Am J Respir Crit Care Med. 2013; 187: 527-534https://doi.org/10.1164/rccm.201210-1865OC
- Report of the international society of heart and lung transplantation working group on primary lung graft dysfunction, part ii: epidemiology, risk factors, and outcomes – a 2016 consensus group statement of the international society for heart and lung transplantation.J Heart Lung Transplant. 2017; 36: 1104-1113https://doi.org/10.1016/j.healun.2017.07.020
- Impact of immediate primary lung allograft dysfunction on bronchiolitis obliterans syndrome.Am J Respir Crit Care Med. 2007; 175: 507-513https://doi.org/10.1164/rccm.200608-1079OC
- Primary graft dysfunction and long-term pulmonary function after lung transplantation.J Heart Lung Transplant. 2007; 26: 1004-1011https://doi.org/10.1016/j.healun.2007.07.018
- Short-and long-term outcomes of 1000 adult lung transplant recipients at a single center.J Thorac Cardiovasc Surg. 2011; 141: 215-222https://doi.org/10.1016/j.jtcvs.2010.09.009
- 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: 371-378https://doi.org/10.1016/j.healun.2005.11.436
- Report of the ISHLT working group on primary lung graft dysfunction, part i: definition and grading – a 2016 consensus group statement of the international society for heart and lung transplantation.J Heart Lung Transplant. 2017; 36: 427-432https://doi.org/10.1016/j.healun.2017.07.021
- Ischemia-reperfusion-induced lung injury.Am J Respir Crit Care Med. 2003; 167: 490-511https://doi.org/10.1164/rccm.200207-670SO
- Immunological link between primary graft dysfunction and chronic lung allograft rejection.Ann Thorac Surg. 2008; 86 (discussion 196-7): 189-195https://doi.org/10.1016/j.athoracsur.2008.03.073
- Immunohistochemical localization of nitric oxide synthase and the oxidant peroxynitrite in lung transplant recipients with obliterative bronchiolitis.Transplantation. 1997; 64: 270-274https://doi.org/10.1097/00007890-199707270-00016
- Cytokine profile after lung transplantation: correlation with allograft injury.Ann Thorac Surg. 2006; 81 (discussion 1849-50): 1844-1849https://doi.org/10.1016/j.athoracsur.2005.11.053
- Recommendations for a standardized pulmonary function report. An official American thoracic society technical statement.Am J Respir Crit Care Med. 2017; 196: 1463-1472https://doi.org/10.1164/rccm.201710-1981ST
- Report of the ISHLT working group on primary lung graft dysfunction, part III: mechanisms – a 2016 consensus group statement of the international society for heart and lung transplantation.J Heart Lung Transplant. 2017; 36: 1114-1120https://doi.org/10.1016/j.healun.2017.07.014
- Preoperative echocardiographic parameters predict primary graft dysfunction following pediatric lung transplantation.Pediatr Transplant. 2021; 25: e13858https://doi.org/10.1111/petr.13858
- Diastolic dysfunction increases the risk of primary graft dysfunction after lung transplant.Am J Resp Crit Care Med. 2016; 193: 1392-1400https://doi.org/10.1164/rccm.201508-1522OC
- Full recovery of right ventricular systolic function in children undergoing bilateral lung transplantation for severe PAH.J Heart Lung Transplant. 2022; 41: 187-198https://doi.org/10.1016/h.healun.2021.10.014
- Lung transplantation in childhood and adolescence: unicentric 14-year experience with sex matching as the main prognosticator.Eur J Cardiothorac Surg. 2016; 49: 810-817https://doi.org/10.1093/ejcts/ezv243
- The international thoracic organ transplant registry of the international society for heart and lung transplantation: twenty-fourth pediatric lung transplantation report –2021; focus on recipient characteristics.J Heart Lung Transplant. 2021; 40: 1023-1034https://doi.org/10.1016/j.healun.2021.07.018
- Outcomes of adolescent recipients after lung transplantation: an analysis of the international society for heart and lung transplantation registry.J Heart Lung Transplant. 2018; 37: 323-331https://doi.org/10.1016/j.healun.2017.02.017
- Indications and outcome after lung transplantation in children under 12 years of age: a 16-year single center experience.J Heart Lung Transplant. 2022; 41: 226-236https://doi.org/10.1016/j.healun.2021.10.012
- Lung clearance index is sensitive to small airway disease in pediatric lung transplant recipients.J Heart Lung Transplant. 2017; 36: 980-984https://doi.org/10.1016/j.healun.2017.05.004
- Early institution of extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation improves outcomes.J Heart Lung Transplant. 2007; 26: 331-338https://doi.org/10.1016/j.healun.2006.12.010
- Extracorporeal membrane oxygenation for primary graft dysfunction after lung transplantation: long-term survival.Ann Thorac Surg. 2009; 87: 854-860https://doi.org/10.1016/j.athoracsur.2008.11.036
- Ex-vivo lung perfusion versus standard protocol lung transplantation-mid-term survival and meta-analysis.Ann Cardiothorac Surg. 2020; 9: 1-9
- Portable normothermic ex-vivo lung perfusion, ventilation, and functional assessment with the Organ Care System in donor lung use for transplantation from extended-criteria donors (EXPAND): a single-arm, pivotal trial.Lancet Resp Med. 2019; 7: 975-984https://doi.org/10.1016/S2213-2600(19)30200-0
- A prospective, randomized crossover pilot study of inhaled nitric oxide versus inhaled prostacyclin in heart transplant and lung transplant recipients.J Thorac Cardiovasc Surg. 2009; 138: 1417-1424https://doi.org/10.1016/j.jtcvs.2009.04.063
- Perioperative statin use is associated with decreased incidence of primary graft dysfunction after lung transplantation.J Heart Lung Transplant. 2017; 36: 948-956https://doi.org/10.1016/j.healun.2017.05.007
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Publication history
Published online: December 26, 2022
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