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The Journal of Heart and Lung Transplantation
International Society for Heart and Lung Transplantation.

Primary graft dysfunction grade 3 following pediatric lung transplantation is associated with chronic lung allograft dysfunction

  • Author Footnotes
    ⁎ During the study design, data collection, and data analysis phases.
    Wai Wong
    Correspondence
    Reprint requests: Wai Wong, MD, Division of Pulmonary Medicine and Respiratory Diseases, Boston Children's Hospital, 300 Longwood Avenue, BCH3121, Boston, MA, 02115. Telephone: +617-355-1900. Fax: +617-730-0084
    Footnotes
    ⁎ During the study design, data collection, and data analysis phases.
    Affiliations
    Department of Pediatrics, Division of Pulmonary Medicine and Respiratory Diseases, Harvard Medical School, Boston Children's Hospital, Boston, Massachusetts

    Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Brandy Johnson
    Affiliations
    Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Author Footnotes
    ⁎ During the study design, data collection, and data analysis phases.
    Pi Chun Cheng
    Footnotes
    ⁎ During the study design, data collection, and data analysis phases.
    Affiliations
    Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania

    Department of Pediatrics, Division of Pediatric Pulmonology, Allergy, and Sleep Medicine, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, Indiana
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  • Maureen B. Josephson
    Affiliations
    Department of Pediatrics, Division of Pulmonary and Sleep Medicine, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Katsuhide Maeda
    Affiliations
    Department of Surgery, Division of Cardiothoracic Surgery, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Robert A. Berg
    Affiliations
    Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Steven M. Kawut
    Affiliations
    Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Michael O. Harhay
    Affiliations
    Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
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  • Samuel B. Goldfarb
    Affiliations
    Department of Pediatrics, Division of Pulmonary and Sleep Medicine, University of Minnesota, Masonic Children's Hospital, Minneapolis, Minnesota
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  • Nadir Yehya
    Affiliations
    Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Adam S. Himebauch
    Affiliations
    Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Perelman School of Medicine at the University of Pennsylvania, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania
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  • Author Footnotes
    ⁎ During the study design, data collection, and data analysis phases.
Published:December 26, 2022DOI:https://doi.org/10.1016/j.healun.2022.12.014

      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)
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