Validation and Refinement of Chronic Lung Allograft Dysfunction Phenotypes in Bilateral and Single Lung Recipients

Derhovanessian, Ariss; Todd, Jamie L.; Zhang, Alice; Li, Ning; Mayalall, Aradhna; Copeland, Catherine; Shino, Michael Y.; Pavlisko, Elizabeth N.; Wallace, W. Dean; Gregson, Aric L.; Ross, David J.; Saggar, Rajan; Lynch, Joseph P.; Belperio, John A.; Snyder, Laurie D.; Palmer, Scott M.; Weigt, S. Sam

doi:10.1513/annalsats.201510-719oc

Cited by 43 publications

(53 citation statements)

References 21 publications

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“…Over the study period, six subjects dropped out (3%), 31 died (14%), and 40 developed chronic lung allograft dysfunction (19%; [CLAD]) defined by a validated spirometry-based approach that considers both FEV 1 as well as FVC. (46, 47) The overall survey completion rate was 86%; rates ranged from 71% to 92% across time points (Table S1). …”

Section: Resultsmentioning

confidence: 99%

Effect of Lung Transplantation on Health-Related Quality of Life in the Era of the Lung Allocation Score: A U.S. Prospective Cohort Study

Singer

Katz

Soong

et al. 2017

American Journal of Transplantation

100

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Under the U.S. Lung Allocation Score (LAS) system, older and sicker patients are prioritized for lung transplantation (LT). The impact of these changes on health-related quality of life (HRQL) after transplant has not been determined. In a single-center prospective cohort study, from 2010–2016 we assessed HRQL before and repeatedly after LT for up to 3 years using the SF12-Physical and Mental Health, the respiratory-specific Airway Questionnaire 20-Revised, and the Euroqol 5D/Visual Analog Scale utility measures by multivariate linear mixed models jointly modeled with death. We also tested changes in LT-Valued Life Activities disability, BMI, allograft function, and 6-minute walk test exercise capacity as predictors of HRQL change. Amongst 211 initial participants (92% of those eligible), LT improved HRQL by all five measures (p<0.05) and all but SF12-Mental Health improved by three-fold or greater than the minimally clinically important difference. Compared to younger participants, those aged ≥65 improved less in SF12-Physical and Mental Health (p<0.01). Improvements in disability accounted for much of the HRQL improvement. In the LAS era, LT affords meaningful and durable HRQL improvements, mediated by amelioration of disability. Identifying factors limiting HRQL improvement in selected subgroups, especially those aged ≥65, are needed to maximize the net-benefits of LT.

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Section: Resultsmentioning

confidence: 99%

Effect of Lung Transplantation on Health-Related Quality of Life in the Era of the Lung Allocation Score: A U.S. Prospective Cohort Study

Singer

Katz

Soong

et al. 2017

American Journal of Transplantation

100

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show abstract

“…RAS/RCLAD was defined as FVC/FVC baseline > 0.2 and chest CT showing pleural/septal thickening, interstitial reticulation or architectural distortion. (18, 19) Recipients with CLAD who did not fulfill RAS/RCLAD criteria were considered to have the BOS/OCLAD phenotype. Those who did not have a chest CT within 3 months of CLAD diagnosis were excluded from this subset analysis.…”

Section: Methodsmentioning

confidence: 99%

The Prognostic Importance of Bronchoalveolar Lavage Fluid CXCL9 During Minimal Acute Rejection on the Risk of Chronic Lung Allograft Dysfunction

Shino

Weigt

et al. 2018

American Journal of Transplantation

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The clinical significance and treatment strategies for minimal acute rejection (grade A1), the most common form of acute rejection (AR), remain controversial. In this retrospective single-center cohort study of 441 lung transplant recipients, we formally evaluate the association between minimal AR and chronic lung allograft dysfunction (CLAD) and test a novel hypothesis using bronchoalveolar lavage (BAL) CXCL9 concentration during minimal AR as a biomarker of subsequent CLAD development. In univariable and multivariable models adjusted for all histopathologic injury patterns, minimal AR was not associated with CLAD development. However, minimal AR with elevated BAL CXCL9 concentrations markedly increased CLAD risk in a dose-response manner. Minimal AR with CXCL9 concentrations greater than the 25th, 50th, and 75th percentile had adjusted hazard ratios (HRs) for CLAD of 1.1 (95% confidence interval [CI] 0.8-1.6), 1.6 (95% CI 1.1-2.3), and 2.2 (95% CI 1.4-3.4), respectively. Thus we demonstrate the utility of BAL CXCL9 measurement as a prognostic biomarker that allows discrimination of recipients at increased risk of CLAD development after minimal AR. BAL CXCL9 measurement during transbronchial biopsies may provide clinically useful prognostic data and guide treatment decisions for this common form of AR, as a possible strategy to minimize CLAD development.

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“…Suhling et al noted that reticular changes and increase in pulmonary consolidation on chest CT are related to a worse survival in lung transplant patients. DerHovanessian et al investigated CLAD cases with/without FVC loss and with/without fibrosis on CT. They discovered that patients who had lung fibrosis on CT scans even without FVC loss experienced significantly reduced survival.…”

Section: Introductionmentioning

confidence: 99%

Quantitative chest CT for subtyping chronic lung allograft dysfunction and its association with survival

Horie

Salazar²,

Saito

et al. 2018

Clinical Transplantation

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Chronic lung allograft dysfunction (CLAD) is a major cause of mortality in lung transplant recipients. CLAD can be sub-divided into at least 2 subtypes with distinct mortality risk characteristics: restrictive allograft syndrome (RAS), which demonstrates increased overall computed tomography (CT) lung density in contrast with bronchiolitis obliterans syndrome (BOS), which demonstrates reduced overall CT lung density. This study aimed to evaluate a reader-independent quantitative density metric (QDM) derived from CT histograms to associate with CLAD survival. A retrospective study evaluated CT scans corresponding to CLAD onset using pulmonary function tests in 74 patients (23 RAS, 51 BOS). Two different QDM values (QDM1 and QDM2) were calculated using CT lung density histograms. Calculation of QDM1 includes the extreme edges of the histogram. Calculation of QDM2 includes the central region of the histogram. Kaplan-Meier analysis and Cox regression analysis were used for CLAD prognosis. Higher QDM values were significantly associated with decreased survival. The hazard ratio for death was 3.2 times higher at the 75th percentile compared to the 25th percentile using QDM1 in a univariate model. QDM may associate with CLAD patient prognosis.

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Validation and Refinement of Chronic Lung Allograft Dysfunction Phenotypes in Bilateral and Single Lung Recipients

Cited by 43 publications

References 21 publications

Effect of Lung Transplantation on Health-Related Quality of Life in the Era of the Lung Allocation Score: A U.S. Prospective Cohort Study

Effect of Lung Transplantation on Health-Related Quality of Life in the Era of the Lung Allocation Score: A U.S. Prospective Cohort Study

The Prognostic Importance of Bronchoalveolar Lavage Fluid CXCL9 During Minimal Acute Rejection on the Risk of Chronic Lung Allograft Dysfunction

Quantitative chest CT for subtyping chronic lung allograft dysfunction and its association with survival

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