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Multicenter Study
. 2022 Dec;22(12):3002-3011.
doi: 10.1111/ajt.17183. Epub 2022 Sep 12.

Prognostic implications of and clinical risk factors for acute lung injury and organizing pneumonia after lung transplantation: Data from a multicenter prospective cohort study

Elizabeth N Pavlisko  1 , Megan L Neely  2 , Heather Kopetskie  3 , David M Hwang  4   5 , Carol F Farver  6 , W Dean Wallace  7   8 , Andrea Arrossi  6 , Peter Illei  9 , Michelle L Sever  3   10 , Jerry Kirchner  2 , Courtney W Frankel  11 , Laurie D Snyder  2   11 , Tereza Martinu  5 , Michael Y Shino  8 , Lorenzo Zaffiri  11 , Nikki Williams  12 , Mark A Robien  12 , Lianne G Singer  5 , Marie Budev  6 , Wayne Tsuang  6 , Pali D Shah  9 , John M Reynolds  11 , S Sam Weigt  8 , John A Belperio  8 , Scott M Palmer  2   11 , Jamie L Todd  2   11
Affiliations
Multicenter Study

Prognostic implications of and clinical risk factors for acute lung injury and organizing pneumonia after lung transplantation: Data from a multicenter prospective cohort study

Elizabeth N Pavlisko et al. Am J Transplant. 2022 Dec.

Abstract

We determined prognostic implications of acute lung injury (ALI) and organizing pneumonia (OP), including timing relative to transplantation, in a multicenter lung recipient cohort. We sought to understand clinical risks that contribute to development of ALI/OP. We analyzed prospective, histologic diagnoses of ALI and OP in 4786 lung biopsies from 803 adult lung recipients. Univariable Cox regression was used to evaluate the impact of early (≤90 days) or late (>90 days) posttransplant ALI or OP on risk for chronic lung allograft dysfunction (CLAD) or death/retransplantation. These analyses demonstrated late ALI/OP conferred a two- to threefold increase in the hazards of CLAD or death/retransplantation; there was no association between early ALI/OP and these outcomes. To determine risk factors for late ALI/OP, we used univariable Cox models considering donor/recipient characteristics and posttransplant events as candidate risks. Grade 3 primary graft dysfunction, higher degree of donor/recipient human leukocyte antigen mismatch, bacterial or viral respiratory infection, and an early ALI/OP event were significantly associated with increased late ALI/OP risk. These data from a contemporary, multicenter cohort underscore the prognostic implications of ALI/OP on lung recipient outcomes, clarify the importance of the timing of these events, and identify clinical risks to target for ALI/OP prevention.

Keywords: acute lung injury; lung transplantation; organizing pneumonia.

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Conflict of interest statement

Disclosures

The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation.

Elizabeth N. Pavlisko acknowledges consulting fees from Agilent.

Megan L. Neely has nothing to report.

Heather Kopetskie acknowledges employment by Rho Inc, which served as the statistical and coordinating center under grant UM2AI117870 (NIAID DAIT SACCC).

David M. Hwang has nothing to report.

Carol F. Farver has nothing to report.

W. Dean Wallace has nothing to report.

Andrea Arrossi has nothing to report.

Peter Illei has nothing to report.

Michelle L. Sever acknowledges employment by Rho Inc, which served as the statistical and data coordinating center under grant UM2AI117870 (NIAID DAIT SACCC).

Jerry Kirchner acknowledges institutional grant funding from NIAID for the project which supported part of my salary, and support for attending meetings and/or travel from NIAID.

Courtney W. Frankel acknowledges institutional grant funding from NIAID for the project which supported part of my salary, and support for attending meetings and/or travel from NIAID.

Laurie D. Snyder acknowledges research grants from the NIH; and US patent for Immune monitoring.

Tereza Martinu acknowledges research grants from APCBio Innovations, Inc.; receipt of equipment, materials, drugs, medical writing, gifts, or other services from Trove Therapeutics.

Michael Y. Shino has nothing to report.

Lorenzo Zaffiri has nothing to report.

Nikki Williams has nothing to report.

Mark A. Robien acknowledges that as part of his duties as a US Federal employee, he attends/participates in (open) sessions of NIAID transplantation data safety monitoring board.

Lianne G. Singer acknowledges institutional research grant from Incyte Corp; consulting fees from Altavant Sciences and Grifols; participation on a data safety monitoring or advisory board for Breath Therapeutics/Zambon Spa; and author royalties from UpToDate.

Marie Budev acknowledges research grants from NIH (NIH U01 Grant AI113315 and NIH UM2AI117870). She also acknowledges advisory board participation for CareDx and Altavant Sciences in addition to consultant work for Boston Scientific.

Wayne Tsuang has nothing to report.

Pali D. Shah acknowledges research grant funding from the NIH.

John M. Reynolds has nothing to report.

S. Sam Weigt acknowledges the institutional grant CTOT-20 from NIH/NIAID; advisory board participation for CareDx and Natera; and non-branded speaker’s bureau honoraria from Boehringer Ingelheim and Genentech.

John A. Belperio has nothing to report.

Scott M. Palmer acknowledges research grant funding from the NIH-NIAID for the current work; research grants from AstraZeneca, Care Dx, Incyte, Bristol Myers Squibb, Boehringer Ingelheim; royalties from UptoDate; and consulting fees from Altavant, Natera, Theravance, Mereo BioPharma, Bristol Myers Squibb, Incyte

Jamie L. Todd acknowledges institutional grants from the National Institutes of Health, AstraZeneca, Boehringer Ingelheim, and CareDx; and advisory board participation for Natera and Altavant Sciences.

Figures

Figure 1.
Figure 1.
Photomicrographs demonstrate patterns of acute lung injury (A-C) and organizing pneumonia (D). A) Diffuse alveolar damage, exudative/acute phase, with eosinophilic hyaline membranes lining alveolar septa (arrow). B) Acute fibrinous and organizing pneumonia (AFOP) with aggregates of eosinophilic fibrin filling alveolar spaces (arrow). C) Acute pneumonia with intraalveolar aggregates of neutrophils accompanied by fibrin (arrow). D) Organizing pneumonia with intraalveolar organizing plugs of fibroblast (arrow). Hematoxylin-eosin (H&E), original magnifications ×100 [A-B, D] and ×200 [C].
Figure 2.
Figure 2.
Forest plot of univariable associations from Cox models evaluating the impact of select donor and recipient factors on the time to development of first late (>90 days posttransplant) acute lung injury (ALI) or (organizing pneumonia (OP) event after lung transplantation. Enrolling center is included as a random effect. ALI/OP-free survival was censored for death, retransplant, and study termination. CI = confidence interval; DSA = donor specific antibody; HLA= human leukocyte antigen; HR = hazard ratio; PGD = primary graft dysfunction; UNOS = United Network for Organ Sharing
See this image and copyright information in PMC

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