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EBV Related BOS Development Is Not Associated with Over-Immunosupression
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The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017
antifungal prophylaxis, respondents believed it would significantly increase the use of echinocandins as first-line (55%; 31/56) and second-line (75%; 42/56) prophylaxis. 70% (39/56) of respondents believed a subcutaneous formulation would significantly increase its use over an IV infusion. Conclusion: These findings suggest that echinocandins have the potential to play a larger role as antifungal prophylaxis agents in lung transplant recipients, especially if a subcutaneous formulation becomes available. 6( 22) Voriconazole Therapeutic Drug Monitoring Among Lung Transplant Recipients Receiving Targeted Therapy for Invasive Aspergillosis G. Butler-Laporte ,1 C. Poirier,2 P. Ferraro,3 M. Langevin,3 C. Lemieux,3 Y. Theoret,4 M. Luong.5 1McGill University, Montreal, QC, Canada; 2Medicine, Division Respirology, Hopital Notre Dame, Montreal, QC, Canada; 3Hopital Notre Dame, Montreal, QC, Canada; 4Hopital SteJustine, Montreal, QC, Canada; 5St. Luc Hospital, Montreal, QC, Canada. Purpose: Voriconazole is the recommended treatment for invasive aspergillosis (IA) in lung transplant recipients (LTR). The use of voriconazole therapeutic drug monitoring (TDM) is increasingly recommended but its use remains controversial. We conducted a study to explore the association between voriconazole serum concentration and clinical outcome of LTR receiving targeted therapy for IA. Methods: We conducted a retrospective study of all lung transplant recipients receiving IA voriconazole targeted mono-therapy who underwent serum TDM between January 2013 and December 2015 at Notre-Dame Hospital, CHUM, Montreal, Canada. Chart review was performed to collect demographic, clinical and laboratory data. Clinical outcome and mortality were assessed at 12 weeks after initation of therapy. Classification and regression tree (CART) analysis was used to find the most predictive voriconazole level thresholds for successful outcome. Results: Among the 111 LTR during the study period, 11 received voriconazole monotherapy for targeted therapy and underwent TDM during therapy. All 11 patients had pulmonary involvement, without dissemination. At 12 weeks of therapy, 6 patients achieved successful outcome while 5 patients did not. The median TDM value among patients who achieved successful outcome vs patients who failed therapy were 0.9 (0.3-7.3) µg/mL and 0.6 (0.05-4.9) µg/mL respectively. Two separate CART analyses were performed; one was based on the median voriconazole TDM concentration, the other was based on minimal voriconazole TDM concentration for each patient. Successful outcome were more likely attained among patients with median TDM concentration > 0.645 µg/mL (P= 0.06) or minimal TDM concentration > 0.415 µg/mL (P= 0.02). None of the patient died during the study period. Conclusion: Our study demonstrates that voriconazole targeted therapy among lung transplant recipients with invasive aspergillosis is associated with a better treatment response when median TDM concentration are greater than 0.645 µg/mL or when minimal TDM concentration are greater than 0.415 µg/mL. 6 ( 23) EBV Related BOS Development Is Not Associated with OverImmunosupression J. Magnusson ,1 J. Westin,2 R. Nordén,2 L. Andersson,3 G. Riise.1 1Pulmonary Medcine and Allergology, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 2Infectious Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 3Infectious Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg, Sweden. Purpose: Quantification of EBV-DNA in whole blood(B-EBV) has been suggested as a marker for immunosuppression and that elevated levels is associated with over-immunosuppression. Here, we tested if repeat elevated EBV-DNA (REED) levels could predict infectious complications and thus be used as a marker for patients at risk for BOS(grade 1 or higher). Methods: In this prospective cohort study, adult lung transplant recipients (N= 93 ), that underwent surgery and were planned for on-site follow-up during Jan 1st 2009- Apr 1st 2012, were included. Elevated CMV causing preemptive treatment, airway bacterial and fungal infections, and B-EBV levels were recorded. REED was defined as elevated EBV DNA over log
3.1, at more than one occasion with an interval of > one month. BOS-free survival was analyzed using Kaplan-Meier and differences in the distribution was analyzed using the Log rank test. A p-value < 0.05 was considered significant. Uni- and multivariate cox regression models to compare other infections (p< 0.2, multivariate inclusion threshold) were used. Results: All 93 subjects had at least 36 months followup. At end of follow up 38 patients had died or been re-transplanted. There was no difference in incidence of infectious events between the groups with REED and no REED (Table 1). Repeated high level of EBV was associated with a shorter time to BOS-development (p= 0,03) (Figure 1). This was verified in a cox regression model (table 2).There were no cases of post transplant lymphoproliferative disorder during the first 6 months of followup. Conclusion: We found that elevated levels of EBV-DNA at more than one occasion during the initial 6 months post LtX is associated with a shorter time to development of BOS. We did not find any statistically significant differences in the incidence of infectious complications between REED and non-REED groups. Therefore, another mechanism for shortened time to BOS development than effects of over-immunosuppression, must be considered.
6( 24) Characteristics of Perioperative Airway Pathogens in Living and Cadaveric Lung Transplantation H. Oda , T.F. Chen-Yoshikawa, Y. Goda, H. Kayawake, S. Ueda, M. Hamaji, H. Motoyama, K. Hijiya, A. Aoyama, H. Date. Thoracic Surgery, Kyoto University Hospital, Kyoto City, Japan. Purpose: Infection is one of the leading mortalities within 1 month after lung transplantation. Respiratory tract infection before and after lung transplantation might possibly effect on the clinical course of the patients. To understand the effects of pathogenic bacteria in the respiratory tract, we investigated perioperative airway pathogens of recipients and donors in living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT). Methods: Between Jun. 2008 and Aug. 2016, 143 lung transplantations were performed at Kyoto University Hospital. There were 72 LDLLTs involving 131 living donors, while there were 71 CLTs involving 71 brain-dead donors. We investigated pathogenic bacteria in the respiratory tract of the recipients before transplantation and within 1 month after transplantation. Furthermore, we also investigated pathogenic bacteria in the respiratory tract of the donors before transplantation. Results: In LDLLT, pathogenic bacteria in the respiratory tract were found 16 recipients (22.2%) before transplantation. Only pathogenic bacteria were found in 3 living donors (2.3%), but those bacteria were not detected continuously from the recipient’s sputum culture after transplantation. In CLT, pathogenic bacteria were found in 22 recipients (31.0%) before transplantation. Pathogenic bacteria were found in 48 cadaveric donors (67.6%); however, donor’s bacteria were continuously detected in the recipient’s sputum culture after transplantation in only 4 recipients. There were no recipients who died of the infectious disease caused by the bacteria derived from donors. Of note, within 1 month after lung transplantation, in the recipient’s respiratory
The Journal of Heart and Lung Transplantation, Vol 36, No 4S, April 2017
antifungal prophylaxis, respondents believed it would significantly increase the use of echinocandins as first-line (55%; 31/56) and second-line (75%; 42/56) prophylaxis. 70% (39/56) of respondents believed a subcutaneous formulation would significantly increase its use over an IV infusion. Conclusion: These findings suggest that echinocandins have the potential to play a larger role as antifungal prophylaxis agents in lung transplant recipients, especially if a subcutaneous formulation becomes available. 6( 22) Voriconazole Therapeutic Drug Monitoring Among Lung Transplant Recipients Receiving Targeted Therapy for Invasive Aspergillosis G. Butler-Laporte ,1 C. Poirier,2 P. Ferraro,3 M. Langevin,3 C. Lemieux,3 Y. Theoret,4 M. Luong.5 1McGill University, Montreal, QC, Canada; 2Medicine, Division Respirology, Hopital Notre Dame, Montreal, QC, Canada; 3Hopital Notre Dame, Montreal, QC, Canada; 4Hopital SteJustine, Montreal, QC, Canada; 5St. Luc Hospital, Montreal, QC, Canada. Purpose: Voriconazole is the recommended treatment for invasive aspergillosis (IA) in lung transplant recipients (LTR). The use of voriconazole therapeutic drug monitoring (TDM) is increasingly recommended but its use remains controversial. We conducted a study to explore the association between voriconazole serum concentration and clinical outcome of LTR receiving targeted therapy for IA. Methods: We conducted a retrospective study of all lung transplant recipients receiving IA voriconazole targeted mono-therapy who underwent serum TDM between January 2013 and December 2015 at Notre-Dame Hospital, CHUM, Montreal, Canada. Chart review was performed to collect demographic, clinical and laboratory data. Clinical outcome and mortality were assessed at 12 weeks after initation of therapy. Classification and regression tree (CART) analysis was used to find the most predictive voriconazole level thresholds for successful outcome. Results: Among the 111 LTR during the study period, 11 received voriconazole monotherapy for targeted therapy and underwent TDM during therapy. All 11 patients had pulmonary involvement, without dissemination. At 12 weeks of therapy, 6 patients achieved successful outcome while 5 patients did not. The median TDM value among patients who achieved successful outcome vs patients who failed therapy were 0.9 (0.3-7.3) µg/mL and 0.6 (0.05-4.9) µg/mL respectively. Two separate CART analyses were performed; one was based on the median voriconazole TDM concentration, the other was based on minimal voriconazole TDM concentration for each patient. Successful outcome were more likely attained among patients with median TDM concentration > 0.645 µg/mL (P= 0.06) or minimal TDM concentration > 0.415 µg/mL (P= 0.02). None of the patient died during the study period. Conclusion: Our study demonstrates that voriconazole targeted therapy among lung transplant recipients with invasive aspergillosis is associated with a better treatment response when median TDM concentration are greater than 0.645 µg/mL or when minimal TDM concentration are greater than 0.415 µg/mL. 6 ( 23) EBV Related BOS Development Is Not Associated with OverImmunosupression J. Magnusson ,1 J. Westin,2 R. Nordén,2 L. Andersson,3 G. Riise.1 1Pulmonary Medcine and Allergology, Institute of Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 2Infectious Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg, Sweden; 3Infectious Medicine, Institute of Biomedicine, Sahlgrenska University Hospital, Gothenburg, Sweden. Purpose: Quantification of EBV-DNA in whole blood(B-EBV) has been suggested as a marker for immunosuppression and that elevated levels is associated with over-immunosuppression. Here, we tested if repeat elevated EBV-DNA (REED) levels could predict infectious complications and thus be used as a marker for patients at risk for BOS(grade 1 or higher). Methods: In this prospective cohort study, adult lung transplant recipients (N= 93 ), that underwent surgery and were planned for on-site follow-up during Jan 1st 2009- Apr 1st 2012, were included. Elevated CMV causing preemptive treatment, airway bacterial and fungal infections, and B-EBV levels were recorded. REED was defined as elevated EBV DNA over log
3.1, at more than one occasion with an interval of > one month. BOS-free survival was analyzed using Kaplan-Meier and differences in the distribution was analyzed using the Log rank test. A p-value < 0.05 was considered significant. Uni- and multivariate cox regression models to compare other infections (p< 0.2, multivariate inclusion threshold) were used. Results: All 93 subjects had at least 36 months followup. At end of follow up 38 patients had died or been re-transplanted. There was no difference in incidence of infectious events between the groups with REED and no REED (Table 1). Repeated high level of EBV was associated with a shorter time to BOS-development (p= 0,03) (Figure 1). This was verified in a cox regression model (table 2).There were no cases of post transplant lymphoproliferative disorder during the first 6 months of followup. Conclusion: We found that elevated levels of EBV-DNA at more than one occasion during the initial 6 months post LtX is associated with a shorter time to development of BOS. We did not find any statistically significant differences in the incidence of infectious complications between REED and non-REED groups. Therefore, another mechanism for shortened time to BOS development than effects of over-immunosuppression, must be considered.
6( 24) Characteristics of Perioperative Airway Pathogens in Living and Cadaveric Lung Transplantation H. Oda , T.F. Chen-Yoshikawa, Y. Goda, H. Kayawake, S. Ueda, M. Hamaji, H. Motoyama, K. Hijiya, A. Aoyama, H. Date. Thoracic Surgery, Kyoto University Hospital, Kyoto City, Japan. Purpose: Infection is one of the leading mortalities within 1 month after lung transplantation. Respiratory tract infection before and after lung transplantation might possibly effect on the clinical course of the patients. To understand the effects of pathogenic bacteria in the respiratory tract, we investigated perioperative airway pathogens of recipients and donors in living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT). Methods: Between Jun. 2008 and Aug. 2016, 143 lung transplantations were performed at Kyoto University Hospital. There were 72 LDLLTs involving 131 living donors, while there were 71 CLTs involving 71 brain-dead donors. We investigated pathogenic bacteria in the respiratory tract of the recipients before transplantation and within 1 month after transplantation. Furthermore, we also investigated pathogenic bacteria in the respiratory tract of the donors before transplantation. Results: In LDLLT, pathogenic bacteria in the respiratory tract were found 16 recipients (22.2%) before transplantation. Only pathogenic bacteria were found in 3 living donors (2.3%), but those bacteria were not detected continuously from the recipient’s sputum culture after transplantation. In CLT, pathogenic bacteria were found in 22 recipients (31.0%) before transplantation. Pathogenic bacteria were found in 48 cadaveric donors (67.6%); however, donor’s bacteria were continuously detected in the recipient’s sputum culture after transplantation in only 4 recipients. There were no recipients who died of the infectious disease caused by the bacteria derived from donors. Of note, within 1 month after lung transplantation, in the recipient’s respiratory