Effect of Single vs Bilateral Lung Transplantation on Plasma Surfactant Protein D Levels in Idiopathic Pulmonary Fibrosis

Sims, Michael W.; Beers, Michael F.; Ahya, Vivek N.; Kawut, Steven M.; Sims, Karen; Lederer, David J.; Palmer, Scott M.; Wille, Keith; Lama, Vibha N.; Shah, Pali D.; Orens, Jonathan B.; Bhorade, Sangeeta; Crespo, Maria; Weinacker, Ann; Demissie, Ejigayehu; Bellamy, Scarlett L.; Christie, Jason D.; Ware, Lorraine B.

doi:10.1378/chest.10-2065

Cited by 18 publications

(15 citation statements)

References 34 publications

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“…Overall, subjects with IPF had a significantly higher CC-16 level compared to other pre-transplant diagnoses. The lack of association between CC-16 and PGD in IPF subjects may be that subjects with IPF already had such a strong signal of epithelial injury prior to transplantation that any subsequent injury related to PGD is difficult to detect as levels in IPF patients are so high (25). Alternatively, a recent study demonstrated that COPD patients with high levels of circulating inflammatory markers in a symptom-free period had a greater number of exacerbations (26).…”

Section: Discussionmentioning

confidence: 99%

Preoperative Plasma Club (Clara) Cell Secretory Protein Levels Are Associated With Primary Graft Dysfunction After Lung Transplantation

Shah

Wickersham

Lederer

et al. 2014

American Journal of Transplantation

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Inherent recipient factors, including pre-transplant diagnosis, obesity, and elevated pulmonary pressures are established PGD risks. We evaluated the relationship between pre-operative lung injury biomarkers and PGD to gain further mechanistic insight in recipients. We performed a prospective cohort study of recipients in the lung transplant outcomes group enrolled between 2002 and 2010. Our primary outcome was grade 3 PGD on day 2 or 3. We measured pre-operative plasma levels of 5 biomarkers (CC-16, sRAGE, ICAM-1, IL-8, and Protein C) that were previously associated with PGD when measured at the post-operative timepoint. We used multivariable logistic regression to adjust for potential confounders. Of 714 subjects, 130 (18%) developed PGD. Median CC-16 levels were elevated in subjects with PGD (10.1 vs. 6.0, p<0.001). CC-16 was associated with PGD in non-IPF subjects (OR for highest quartile of CC-16: 2.87, 95% CI: 1.37, 6.00, p=0.005) but not in subjects with IPF (OR 1.38, 95% CI: 0.43, 4.45, p=0.59). After adjustment, pre-operative CC-16 levels remained associated with PGD (OR: 3.03, 95% CI: 1.26, 7.30, p=0.013) in non-IPF subjects. Our study suggests the importance of pre-existing airway epithelial injury in PGD. Markers of airway epithelial injury may be helpful in pre-transplant risk stratification in specific recipients.

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Section: Discussionmentioning

confidence: 99%

Preoperative Plasma Club (Clara) Cell Secretory Protein Levels Are Associated With Primary Graft Dysfunction After Lung Transplantation

Shah

Wickersham

Lederer

et al. 2014

American Journal of Transplantation

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“…LTOG is an NHLBI-funded prospective cohort study of lung transplant recipients with the primary aim of examining clinical and genetic risk factors for PGD at nine United States centers (a full list of investigators and participating centers appears before the REFERENCES section) (22)(23)(24)(25)(26)(27)(28). Based on a reported association between obesity and early mortality after lung transplantation for COPD and ILD (21), we restricted our study sample to 512 adult LTOG participants with COPD or ILD who underwent single or bilateral lung transplantation between March 2002 and July 2009 and who had complete exposure and outcome data.…”

Section: Methods Study Design and Participantsmentioning

confidence: 99%

“…Chest radiograph reviewers were masked to other clinical information. The primary outcome was grade 3 PGD defined as the presence of new parenchymal infiltrates in the lung allografts consistent with pulmonary edema and a PaO 2 to FIO 2 ratio of less than 200 at any time within 72 hours of lung transplantation (1,23,24,26,31). In a secondary analysis, we examined grade 3 PGD present at the 72-hour time point.…”

Section: Outcome Definitionsmentioning

confidence: 99%

Obesity and Primary Graft Dysfunction after Lung Transplantation

Lederer¹,

Kawut

Wickersham

et al. 2011

Am J Respir Crit Care Med

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138

102

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Rationale: Obesity has been linked to acute lung injury and is a risk factor for early mortality after lung transplantation. Objectives: To examine the associations of obesity and plasma adipokines with the risk of primary graft dysfunction after lung transplantation. Methods: We performed a prospective cohort study of 512 adult lung transplant recipients with chronic obstructive pulmonary disease or interstitial lung disease enrolled in the Lung Transplant Outcomes Group Study. In a nested case-control study, we measured plasma leptin, adiponectin, and resistin before lung transplantation and 6 and 24 hours after lung transplantation in 40 cases of primary graft dysfunction and 80 control subjects. Generalized linear mixed models and logistic regression were used to estimate risk ratios and odds ratios. Measurements and Main Results: Grade 3 primary graft dysfunction developed within 72 hours of transplantation in 29% participants. Obesity was associated with a twofold increased risk of primary graft dysfunction (adjusted risk ratio 2.1; 95% confidence interval, 1.7-2.6). The risk of primary graft dysfunction increased by 40% (confidence interval, 30-50%) for each 5 kg/m 2 increase in body mass index after accounting for center, diagnosis, cardiopulmonary bypass, and transplant procedure. Higher plasma leptin levels were associated with a greater risk of primary graft dysfunction (sexadjusted P ¼ 0.02). The associations of both obesity and leptin with primary graft dysfunction tended to be stronger among those who did not undergo cardiopulmonary bypass. Conclusions: Obesity is an independent risk factor for primary graft dysfunction after lung transplantation.

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“…In prior studies, our group studied the association between PAI-1, ICAM-1, and Protein C and PGD in a cohort of 128 subjects and between SP-D and PGD in a cohort of 104 subjects [10, 11, 14]. All subjects in the present study were enrolled in a prior study of sRAGE with PGD [12].…”

Section: Methodsmentioning

confidence: 99%

“…In previous studies, increased post-operative plasma levels of plasminogen activator inhibitor (PAI-1), soluble receptor for advanced glycation end products (sRAGE), intercellular adhesion molecule-1 (ICAM-1) and decreased levels of Protein C have been associated with PGD [10–13]. Plasma surfactant protein-D (SP-D) levels have been associated with PGD in patients with IPF receiving single lung transplants [14]. We determined the utility of biomarkers by assessing discrimination for clinically graded PGD, and evaluating predictive utility for 90-day mortality alone and when added to concurrent clinical PGD grade.…”

Section: Introductionmentioning

confidence: 99%

A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation

Shah

Bellamy

Localio

et al. 2012

The Journal of Heart and Lung Transplantation

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Background We aimed to identify combinations of biomarkers to enhance the definition of PGD for translational research. Methods Biomarkers reflecting lung epithelial injury (sRAGE and SP-D), coagulation cascade (PAI-1 and Protein C), and cell adhesion (ICAM-1) were measured in the plasma of 315 subjects derived from the LTOG cohort at 6 and 24 hours after transplantation. We assessed biomarker utility in two ways: first, we tested the discrimination of grade 3 PGD within 72 hours; second, we tested the predictive utility of plasma biomarkers for 90-day mortality. Results 86/315 subjects (27%) developed PGD. 23 subjects (8%) died within 90 days of transplantation, of which 16 (70%) had PGD. Biomarkers measured at 24 hours had greater discrimination than at 6 hours. Individually, sRAGE (AUC 0.71) and PAI-1 (AUC 0.73) had the best discrimination of PGD. The combinations of sRAGE with PAI-1 (AUC 0.75), PAI-1 with ICAM-1 (AUC 0.75), and PAI-1 with SP-D (AUC 0.76) had the best discrimination. Combinations of greater than 2 biomarkers did not significantly enhance discrimination of PGD. ICAM-1 with PAI-1 (AUC 0.72) and ICAM-1 with sRAGE (AUC of 0.72) had the best prediction for 90-day mortality. The addition of ICAM-1, PAI-1, or sRAGE to the concurrent clinical PGD grade significantly improved prediction of 90-day mortality (p<0.001 each). Conclusions Measurement of the combination of a marker of impaired fibrinolysis with an epithelial injury or cell adhesion marker had the best discrimination for PGD and prediction for early mortality, and may provide an alternative outcome useful in future research.

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Effect of Single vs Bilateral Lung Transplantation on Plasma Surfactant Protein D Levels in Idiopathic Pulmonary Fibrosis

Cited by 18 publications

References 34 publications

Preoperative Plasma Club (Clara) Cell Secretory Protein Levels Are Associated With Primary Graft Dysfunction After Lung Transplantation

Preoperative Plasma Club (Clara) Cell Secretory Protein Levels Are Associated With Primary Graft Dysfunction After Lung Transplantation

Obesity and Primary Graft Dysfunction after Lung Transplantation

A panel of lung injury biomarkers enhances the definition of primary graft dysfunction (PGD) after lung transplantation

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