Latent Class Analysis Identifies Distinct Phenotypes of Primary Graft Dysfunction After Lung Transplantation

Shah, Rupal J.; Diamond, Joshua M.; Cantu, E.; Lee, James C.; Lederer, David J.; Lama, Vibha N.; Orens, Jonathan B.; Weinacker, Ann; Wilkes, David S.; Bhorade, Sangeeta; Wille, Keith; Ware, Lorraine B.; Palmer, Scott M.; Crespo, Maria; Localio, A. Russell; Demissie, Ejigayehu; Kawut, Steven M.; Bellamy, Scarlett L.; Christie, Jason D.

doi:10.1378/chest.12-1480

Cited by 50 publications

(37 citation statements)

References 19 publications

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“…(27) These models focused exclusively on the timing of onset and resolution of lung dysfunction, using only grades of PGD at various timepoints to generate latent classes, and found that patients with severe persistent dysfunction (one of three identified classes) had the worst clinical outcomes. This approach differs from ours in its focus on repeated measures of one clinical input (grade of PGD) to generate latent class and lack of inclusion of biological markers; whether consideration of additional clinical data points and/or biomarkers as class-defining variables would lead to identification of different PGD subphenotypes remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials

Calfee

Delucchi

Parsons

et al. 2014

The Lancet Respiratory Medicine

1,157

1,213

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Background Subphenotypes have been identified within heterogeneous syndromes such as asthma and breast cancer, with important therapeutic implications. Whether subphenotypes exist within the acute respiratory distress syndrome (ARDS), another heterogeneous syndrome, is unknown. Methods We applied latent class modeling to identify subphenotypes using clinical and biological data from two NHLBI ARDS randomized controlled trials; modeling was conducted independently in each cohort. We then tested the association of subphenotypes with clinical outcomes in both cohorts and with the response to positive end-expiratory pressure (PEEP) in the second cohort. Findings Independent latent class models indicated that a two-class (i.e. two subphenotype) model was optimal for both cohorts. In both cohorts, we identified a hyperinflammatory subphenotype (Phenotype 2) that was characterized by higher plasma levels of inflammatory biomarkers, a higher prevalence of vasopressor use, lower serum bicarbonate, and a higher prevalence of sepsis, compared to Phenotype 1. Subjects in Phenotype 2 had higher mortality and fewer ventilator-free and organ failure-free days in both cohorts. In the second cohort, the effects of ventilation strategy on mortality, ventilator and organ failure-free days differed significantly by phenotype (p=0.003–0.049 for interactions). Interpretation Latent class models identify two subphenotypes within ARDS, one of which is characterized by more severe inflammation, shock, and metabolic acidosis and by significantly worse clinical outcomes. Response to treatment in a randomized trial of PEEP strategies differed based on subphenotype. Identification of ARDS subphenotypes may be useful in selecting patients for clinical trials. Funding National Institutes of Health

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Section: Discussionmentioning

confidence: 99%

Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials

Calfee

Delucchi

Parsons

et al. 2014

The Lancet Respiratory Medicine

1,157

1,213

View full text Add to dashboard Cite

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“…This is an accepted and well validated outcome construct for PGD that we have utilized extensively in the past 11–13 . Chest radiographs from immediately after transplant and from 24, 48 and 72 hours after transplant were assessed for the presence of multifocal infiltrates by two independent readers, with adjudication, similar to previous studies 7,12,14 .…”

Section: Methodsmentioning

confidence: 99%

Peripheral Blood Gene Expression Changes Associated With Primary Graft Dysfunction After Lung Transplantation

Diamond

Cantu

Porteous

et al. 2017

American Journal of Transplantation

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Recipient responses to primary graft dysfunction (PGD) after lung transplantation may have important implications to the fate of the allograft. We therefore evaluated longitudinal differences in peripheral blood gene expression in subjects with PGD. RNA expression was measured throughout the first transplant year in 106 subjects enrolled in the Clinical Trials in Organ Transplantation-03 study using a panel of 100 hypothesis-driven genes. PGD was defined as grade 3 in the first 72 posttransplant hours. Eighteen genes were differentially expressed over the first year based on PGD development, with significant representation from innate and adaptive immunity genes, with most differences identified very early after transplant. Sixteen genes were overexpressed in the blood of patients with PGD compared to those without PGD within 7 days of allograft reperfusion, with most transcripts encoding innate immune/inflammasome-related proteins, including genes previously associated with PGD. Thirteen genes were underexpressed in patients with PGD compared to those without PGD within 7 days of transplant, highlighted by T cell and adaptive immune regulation genes. Differences in gene expression present within 2 hours of reperfusion and persist for days after transplant. Future investigation will focus on the long-term implications of these gene expression differences on the outcome of the allograft.

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“…27 These models focused exclusively on the timing of onset and resolution of lung dysfunction, using only grades of primary graft dysfunction at various timepoints to generate latent classes, and the analyses showed that patients with severe persistent dysfunction (one of three identifi ed classes) had the worst clinical outcomes. Similarly, Reilly and colleagues from the same research group did a latent class analysis of timing of ARDS after severe trauma.…”

Section: Discussionmentioning

confidence: 99%

Latent Class Models Identify Two Subphenotypes in Respiratory Distress Syndrome with Differential Response to Positive End-Expiratory Pressure

Calfee¹,

Delucchi²,

Parsons³

et al. 2015

Annals ATS

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Latent Class Analysis Identifies Distinct Phenotypes of Primary Graft Dysfunction After Lung Transplantation

Cited by 50 publications

References 19 publications

Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials

Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials

Peripheral Blood Gene Expression Changes Associated With Primary Graft Dysfunction After Lung Transplantation

Latent Class Models Identify Two Subphenotypes in Respiratory Distress Syndrome with Differential Response to Positive End-Expiratory Pressure

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