- Email: [email protected]
Baseline Lung Allograft Dysfunction Negatively Impacts Survival Following Lung Transplantation
Abstracts S117 Survival from onset of CLAD was significantly decreased if patient had persisting infiltrates on thoracic imaging (P< 0.001, fig. 1B). There was a strong correlation between rCLAD diagnosed in any way and persisting infiltrates (P< 0.0001). Conclusion: This study shows that recipients with rCLAD diagnosed with both TLC and FVC decline have impaired survival as compared to BOS. rCLAD diagnosed by a solitary decline in TLC or FVC did not show significantly reduced survival compared to BOS. A strong correlation between infiltrates and rCLAD was observed, and recipients with infiltrates on thoracic imaging had significantly impaired survival after onset of CLAD. Infiltrative findings should be incorporated in rCLAD guidelines.
2( 96)
2( 95) Baseline Lung Allograft Dysfunction Negatively Impacts Survival Following Lung Transplantation J. Liu ,1 K. Jackson,2 J. Weinkauf,1 A. Kapasi,1 A. Hirji,1 B. Laing,2 J. Mullen,2 D. Freed,2 J. Nagendran,2 S. Meyer,2 D. Lien,1 K. Halloran.1 1Medicine, University of Alberta, Edmonton, AB, Canada; 2Surgery, University of Alberta, Edmonton, AB, Canada. Purpose: Survival after lung transplantation is limited by chronic lung allograft dysfunction (CLAD), defined as a loss of lung function from a stable post-transplant baseline. Our objective was to evaluate survival and potential risk factors in recipients with baseline lung allograft dysfunction (BLAD), compared to those who achieve a normal threshold of lung function. Methods: We performed a retrospective cohort study of double lung transplant recipients in our program, 2004 - 2009 (n= 178). Normal threshold was defined as both FEV1 and FVC > 80% predicted, on > 2 consecutive tests post-transplant; BLAD was defined as failure to achieve normal. We used Kaplan-Meier analysis and log-rank testing to assess survival, and multivariable logistic regression to assess potential risk factors for BLAD. We compared time to peak function and CLAD incidence (FEV1 or FVC < 80% of baseline) with Wilcoxon rank sum and Fisher’s exact testing. Results: 75/178 (42%) met criteria for BLAD. BLAD markedly impaired survival (median 6.0 years vs. > 11 years, Figure 1). Regression results are shown in Table 1. Interstitial lung disease (ILD) as indication (p = 0.04) and longer duration of ventilation (p = 0.02) were associated with BLAD. Median time to peak lung function was 536 vs. 263 days for normal and BLAD respectively (p < 0.01). The incidence of CLAD onset was similar (p = 0.17). Conclusion: BLAD negatively impacts survival following lung transplantation and is associated with ILD as indication and prolonged ventilation. The nature of BLAD warrants further study, and we suggest its inclusion in future lung dysfunction phenotyping algorithms.
Evaluation of an FVC-Based Definition of Restrictive Chronic Lung Allograft Dysfunction (CLAD) in a Multi-Center Cohort M.T. Durheim ,1 D.M. Wojdyla,1 C.L. Green,1 S. Keshavjee,2 K. McCurry,3 A.O. Lidor,4 R.D. Davis,5 S.M. Palmer,1 J.L. Todd.1 1Duke Clinical Research Institute, Durham, NC; 2University of Toronto, Toronto, ON, Canada; 3Cleveland Clinic, Cleveland, OH; 4Johns Hopkins University, Baltimore, MD; 5Florida Hospital Transplant Institute, Orlando, FL. Purpose: Evidence suggests a restrictive phenotype of CLAD exists, but the optimal approach to its diagnosis is uncertain. Patients with restrictive allograft syndrome (RAS), defined as CLAD accompanied by a decline in total lung capacity (TLC), have distinct clinical and pathological features when compared to those with preserved TLC, typical of bronchiolitis obliterans syndrome (BOS). As most centers do not routinely monitor posttransplant lung volumes, we proposed a definition of restrictive CLAD (R-CLAD) based upon loss of forced vital capacity (FVC) at CLAD onset, which was associated with poor survival after CLAD. In this study, we aimed to validate the impact of FVC loss on survival in a multicenter cohort. Methods: We analyzed longitudinal data from bilateral lung recipients enrolled in the Reflux Surgery in Lung Transplantation (RESULT) study at four North American centers. CLAD was defined as FEV1 < 80% of the mean of the two best post-transplant FEV1s. R-CLAD was defined by FVC loss at CLAD onset (FVCCLAD/FVCBaseline < 0.8) whereas BOS was defined by preserved FVC at CLAD onset (FVCCLAD/FVCBaseline ≥ 0.8). The mean of the two FVCs that paired with the two best post-transplant FEV1s was used as the FVC baseline. Kaplan-Meier survival estimates were compared using a log-rank test. Results: 211 recipients developed CLAD, of whom 33% (n= 69) met criteria for R-CLAD. These patients had similar age, gender, BMI, lung allocation score, and frequency of grade 2 or 3 primary graft dysfunction when compared to those with BOS, but were more likely to have undergone transplantation for interstitial lung disease. Median survival was 8.1 months following onset of R-CLAD, compared with 20.7 months following onset of BOS (p = 0.003). Similar results were observed when stratified by each of the four enrolling centers. Conclusion: Our results substantiate that clinically meaningful physiologic CLAD phenotypes can be determined using spirometric indices routinely obtained in all lung recipients.
2( 96)
2( 95) Baseline Lung Allograft Dysfunction Negatively Impacts Survival Following Lung Transplantation J. Liu ,1 K. Jackson,2 J. Weinkauf,1 A. Kapasi,1 A. Hirji,1 B. Laing,2 J. Mullen,2 D. Freed,2 J. Nagendran,2 S. Meyer,2 D. Lien,1 K. Halloran.1 1Medicine, University of Alberta, Edmonton, AB, Canada; 2Surgery, University of Alberta, Edmonton, AB, Canada. Purpose: Survival after lung transplantation is limited by chronic lung allograft dysfunction (CLAD), defined as a loss of lung function from a stable post-transplant baseline. Our objective was to evaluate survival and potential risk factors in recipients with baseline lung allograft dysfunction (BLAD), compared to those who achieve a normal threshold of lung function. Methods: We performed a retrospective cohort study of double lung transplant recipients in our program, 2004 - 2009 (n= 178). Normal threshold was defined as both FEV1 and FVC > 80% predicted, on > 2 consecutive tests post-transplant; BLAD was defined as failure to achieve normal. We used Kaplan-Meier analysis and log-rank testing to assess survival, and multivariable logistic regression to assess potential risk factors for BLAD. We compared time to peak function and CLAD incidence (FEV1 or FVC < 80% of baseline) with Wilcoxon rank sum and Fisher’s exact testing. Results: 75/178 (42%) met criteria for BLAD. BLAD markedly impaired survival (median 6.0 years vs. > 11 years, Figure 1). Regression results are shown in Table 1. Interstitial lung disease (ILD) as indication (p = 0.04) and longer duration of ventilation (p = 0.02) were associated with BLAD. Median time to peak lung function was 536 vs. 263 days for normal and BLAD respectively (p < 0.01). The incidence of CLAD onset was similar (p = 0.17). Conclusion: BLAD negatively impacts survival following lung transplantation and is associated with ILD as indication and prolonged ventilation. The nature of BLAD warrants further study, and we suggest its inclusion in future lung dysfunction phenotyping algorithms.
Evaluation of an FVC-Based Definition of Restrictive Chronic Lung Allograft Dysfunction (CLAD) in a Multi-Center Cohort M.T. Durheim ,1 D.M. Wojdyla,1 C.L. Green,1 S. Keshavjee,2 K. McCurry,3 A.O. Lidor,4 R.D. Davis,5 S.M. Palmer,1 J.L. Todd.1 1Duke Clinical Research Institute, Durham, NC; 2University of Toronto, Toronto, ON, Canada; 3Cleveland Clinic, Cleveland, OH; 4Johns Hopkins University, Baltimore, MD; 5Florida Hospital Transplant Institute, Orlando, FL. Purpose: Evidence suggests a restrictive phenotype of CLAD exists, but the optimal approach to its diagnosis is uncertain. Patients with restrictive allograft syndrome (RAS), defined as CLAD accompanied by a decline in total lung capacity (TLC), have distinct clinical and pathological features when compared to those with preserved TLC, typical of bronchiolitis obliterans syndrome (BOS). As most centers do not routinely monitor posttransplant lung volumes, we proposed a definition of restrictive CLAD (R-CLAD) based upon loss of forced vital capacity (FVC) at CLAD onset, which was associated with poor survival after CLAD. In this study, we aimed to validate the impact of FVC loss on survival in a multicenter cohort. Methods: We analyzed longitudinal data from bilateral lung recipients enrolled in the Reflux Surgery in Lung Transplantation (RESULT) study at four North American centers. CLAD was defined as FEV1 < 80% of the mean of the two best post-transplant FEV1s. R-CLAD was defined by FVC loss at CLAD onset (FVCCLAD/FVCBaseline < 0.8) whereas BOS was defined by preserved FVC at CLAD onset (FVCCLAD/FVCBaseline ≥ 0.8). The mean of the two FVCs that paired with the two best post-transplant FEV1s was used as the FVC baseline. Kaplan-Meier survival estimates were compared using a log-rank test. Results: 211 recipients developed CLAD, of whom 33% (n= 69) met criteria for R-CLAD. These patients had similar age, gender, BMI, lung allocation score, and frequency of grade 2 or 3 primary graft dysfunction when compared to those with BOS, but were more likely to have undergone transplantation for interstitial lung disease. Median survival was 8.1 months following onset of R-CLAD, compared with 20.7 months following onset of BOS (p = 0.003). Similar results were observed when stratified by each of the four enrolling centers. Conclusion: Our results substantiate that clinically meaningful physiologic CLAD phenotypes can be determined using spirometric indices routinely obtained in all lung recipients.