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Multicenter Study
. 2013 Aug;144(2):616-622.
doi: 10.1378/chest.12-1480.

Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation

Rupal J Shah  1 , Joshua M Diamond  2 , Edward Cantu  3 , James C Lee  4 , David J Lederer  5 , Vibha N Lama  6 , Jonathan Orens  7 , Ann Weinacker  8 , David S Wilkes  9 , Sangeeta Bhorade  10 , Keith M Wille  11 , Lorraine B Ware  12 , Scott M Palmer  13 , Maria Crespo  14 , A Russell Localio  15 , Ejigayehu Demissie  15 , Steven M Kawut  2 , Scarlett L Bellamy  15 , Jason D Christie  2
Affiliations
Multicenter Study

Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation

Rupal J Shah et al. Chest. 2013 Aug.

Abstract

Background: There is significant heterogeneity within the primary graft dysfunction (PGD) syndrome. We aimed to identify distinct grade 3 PGD phenotypes based on severity of lung dysfunction and patterns of resolution.

Methods: Subjects from the Lung Transplant Outcomes Group (LTOG) cohort study with grade 3 PGD within 72 h after transplantation were included. Latent class analysis (LCA) was used to statistically identify classes based on changes in PGD International Society for Heart & Lung Transplantation grade over time. Construct validity of the classes was assessed by testing for divergence of recipient, donor, and operative characteristics between classes. Predictive validity was assessed using time to death.

Results: Of 1,255 subjects, 361 had grade 3 PGD within the first 72 h after transplantation. LCA identified three distinct phenotypes: (1) severe persistent dysfunction (class 1), (2) complete resolution of dysfunction within 72 h (class 2), and (3) attenuation, without complete resolution within 72 h (class 3). Increased use of cardiopulmonary bypass, greater RBC transfusion, and higher mean pulmonary artery pressure were associated with persistent PGD (class 1). Subjects in class 1 also had the greatest risk of death (hazard ratio, 2.39; 95% CI, 1.57-3.63; P < .001).

Conclusions: There are distinct phenotypes of resolution of dysfunction within the severe PGD syndrome. Subjects with early resolution may represent a different mechanism of lung pathology, such as resolving pulmonary edema, whereas those with persistent PGD may represent a more severe phenotype. Future studies aimed at PGD mechanism or treatment may focus on phenotypes based on resolution of graft dysfunction.

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Figures

Figure 1.
Figure 1.
Three-class model generated from latent class analysis. The y axis indicates the probability of International Society for Heart & Lung Transplantation PGD grade on a given day. The x axis represents the postoperative day. A given probability of PGD grade for each day is represented by symbols connected by corresponding lines (● = grade 3, X = grade 1 or 2, ○ = grade 0). The line with the highest probability generated from the model indicates that members of that class are most likely to have a particular grade on a particular day. A, Latent class 1 (55% of grade 3 PGD population): Grade 3 PGD present on day 0 and persisted to day 3. Grade 3 had the highest probability on all study days in this class. B, Latent class 2 (7% of grade 3 PGD population): Grade 3 PGD present on day 0 that resolved completely to grade 0 by day 3. On day 0, grade 3 had the highest probability, but the probability of grade 3 decreased by day 1, and on days 2 and 3, grade 0 had the highest probability. C, Latent class 3 (39% of grade 3 population): Grade 3 PGD present on day 0 that attenuated to lower grades 1 and 2, but did not completely resolve, by day 3. On day 0, grade 3 had the highest probability, but decreased by day 1, and on days 2 and 3, intermediate grades had the highest probability. PGD = primary graft dysfunction.
Figure 2.
Figure 2.
Relationship of each class with time to death. P value generated from log-rank test.
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References

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    1. Christie JD, Carby M, Bag R, Corris P, Hertz M, Weill D; ISHLT Working Group on Primary Lung Graft Dysfunction 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. J Heart Lung Transplant. 2005;24(10):1454-1459 - PubMed
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    1. Christie JD, Bellamy S, Ware LB, et al. Construct validity of the definition of primary graft dysfunction after lung transplantation. J Heart Lung Transplant. 2010;29(11):1231-1239 - PMC - PubMed

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