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Intraoperative Extracorporeal Membrane Oxygenation as an Alternative to Cardiopulmonary Bypass in Lung Transplantation
Abstracts
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Median wait time to transplant in the region for Status 1A patients in the region Group 1: r30 days Group 2: 430 days (N ¼ 48) (N ¼ 121) Death 15% (7) Transplantation 25% (12) VAD 2% (1) n
22% (26) 7% (8) 18% (21)
p o 0.01
difference in survival but more patients in Group 1 had undergone OHT and more patients in Group 2 had undergone VAD (Table). Conclusions: Triage for advanced heart failure therapies at US centers appears to be driven by geography: centers with shorter median wait time to OHT are more likely to evaluate patients for OHT and less likely to place VADs. As patients at these different centers do not differ clinically, further study is needed to assess whether threshold for considering patients for advanced therapies should be determined by wait time to transplant as well as clinical considerations. 441 Long-Term Survival and Prognostic Markers in 1000 Patients with Advanced Heart Failure. A Single-Center Analysis P. Lesny,1 M. Luknar,1 I. Varga,1 P. Solik,1 S. Wimmerova,2 E. Goncalvesova.1 1Heart Failure and Transplant Department, National Cardiovascular Institute, Bratislava, Slovakia (Slovak Republic); 2 Slovak Medical University, Bratislava, Slovakia (Slovak Republic). Purpose: Heart transplant candidates are a selected group of patients with advanced heart failure (HF). Prognosis estimation is the key determinant of optimal patient management. The aim of the study was to analyze the descriptive characteristics, long-term survival, and mortality predictors in pts with advanced HF hospitalized at a single centre. Methods and Materials: Consecutive patients with HF considered for heart transplantation and hospitalized at the National Cardiovascular Institute Bratislava from January 1, 1998, to January 1, 2010, were retrospectively analyzed. Kaplan-Meier survival analysis was performed. Independent mortality predictors were established using logistic regression analysis. Results: One thousand and two pts were eligible for the analysis. The mean age of pts was 49 years, 86.8% were males, NYHA class was 2.6⫾0.7, and left ventricular ejection fraction was 24.3⫾7.7%. The etiology of HF consisted predominantly of dilated cardiomyopathy (57%), coronary artery disease (27.5%), and arterial hypertension (7.1%). The most important comorbidities included arterial hypertension (43%), atrial fibrillation (24.6%), diabetes mellitus (25.1%), and anemia (17.2%). Cumulative survival was as follows: 1-year survival 83%, 3-year 63%, 5-year 50%, 7-year 39% and 10-year 23%. HF progression was the cause of death in 55.7% of pts and sudden death in 37.5% of pts. Presence of coronary artery disease, left ventricular diastolic diameter of 479 mm, plasma sodium o135 mmol/L, NTproBNP 42297 pg/mL, intravenous treatment, and furosemide dose at discharge 4240 mg/day were independent predictors of 1-year mortality. Conclusions: We present a long-term follow-up of a large and selected cohort of pts from a single centre that reflects the course of HF with severe left ventricular systolic dysfunction, barely modified by comorbidities. Mortality of pts with advanced HF still remains high, with 50% of pts surviving 5 years. This cohort represents the pool of potential assist device implant candidates. 442 Appearance of Posttransplant De Novo Anti-HLA Antibodies in LivingDonor Lobar Lung Transplantation A. Ohsumi,1 F. Chen,1 K. Yurugi,2 T. Maekawa,2 T. Yamada,1 M. Sato,1 A. Aoyama,1 T. Sato,1 M. Sonobe,1 M. Omasa,1 T. Bando,1
I. Matsumoto,1 H. Date.1 1Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Center for Cell and Molecular Therapy, Kyoto University Hospital, Kyoto, Japan. Purpose: Recently, the importance of anti-human leukocyte antigen (HLA) antibodies has been pointed out in kidney and liver transplantation. In 2010, Hachem et al. reported the association of donor-specific anti-HLA antibodies (DSA) with acute and chronic rejection in lung transplantation. We investigated the appearance and the trend of anti-HLA antibodies in living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT) at a single lung transplant center in Japan. Methods and Materials: We performed 30 cases of LDLLT and 21 cases of CLT at Kyoto University between June 2008 and October 2012. Since July 2010, anti-HLA antibodies had been screened periodically, using LABScreen Mixed (One Lambda, CA, USA). In addition, they were also investigated when recipients presented symptoms or abnormal findings. When anti-HLA antibodies were detected, their specificities were identified using LABScreen Single Antigen (One Lambda, CA, USA). Results: Anti-HLA antibodies were measured 3.6 ⫾ 2.0 times in 27 cases of LDLLT and 20 cases of CLT. Anit-HLA antibodies were detected in 4 cases in LDLLT (14%) and 5 cases in CLT (25%). Among them, 2 cases in LDLLT (7%) and 2 cases in CLT (10%) had DSA. In LDLLT, one patient had re-LDLLT because of bilateral bronchiolitis obliterans after ipsilateral antibody-mediated rejection. In other 3 patients, class I and/or class II DSA were detected 2 weeks, 1 month, and 10 months after transplantation. All of them were treated with intravenous immunoglobulin and showed no sign of antibodymediated rejection in a close follow-up. Conclusions: In comparison with the current report by Hachem et al., the frequency of DSA appearance was relatively low in our institution. However, DSA was detected even in the early phase of posttransplant days. Accumulation of more cases and longer follow-up were necessary. 443 Intraoperative Extracorporeal Membrane Oxygenation as an Alternative to Cardiopulmonary Bypass in Lung Transplantation D.D. Odell, J. D’Cunha, N. Shigemura, A. Shiose, J.D., Luketich, J.K. Bhama, C. Bermudez. Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA. Purpose: Extracorporeal membrane oxygenation (ECMO) may be used for intraoperative support as an alternative to cardiopulmonary bypass (CPB) during lung transplantation. We sought to evaluate its efficacy. Methods and Materials: We reviewed lung transplants with intraoperative support (CPB or ECMO) from 8/09-11/12. Patients were stratified into groups by type of support. Postoperative ECMO utilization, graft and overall survival were compared along with blood product utilization and complications. For comparisons, a 2:1 propensity matched cohort of CPB:ECMO was analyzed. Results: 169 patients underwent lung transplantation with mechanical support during the study period (17 ECMO and 152 CPB). Demographic were similar in both groups with higher mean Lung Allocation Score (LAS; 83 vs 56) in the ECMO group. Patients transplanted on ECMO in the overall groups were extubated earlier (0.8 vs 4.8 days; p¼0.11) and had significantly decreased rates of respiratory failure post transplantation (29% vs 6%; p¼0.04) with similar trends in the propensity matched cohort. There were no differences in postoperative ECMO utilization between groups. A trend toward improved overall survival was seen with ECMO at 1 year (100% vs 77%) and 3 years (100% vs 66%; p¼0.13). Graft survival was significantly improved in the ECMO group (p¼0.05). Conclusions: Intraoperative ECMO support for primary lung transplantation is comparable to CPB and is associated with earlier
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extubation, significant reduction in respiratory complications, a trend toward lower transfusion requirement and improved overall survival. Graft survival was significantly improved with the use of ECMO. F1 Further longitudinal data is necessary. 444 Role of HLA-G Expression as a Predictive Marker of a Low Risk of Bronchiolitis Obliterans Syndrome in Lung Transplant Recipients: A 3-Year Prospective Study 1,2 G. Thabut,1 I. Krawice,2 E. Carosella,2 N. Rouas-Freiss.2 O. Brugiere, 1 ˆ Service de Pneumologie B et Transplantation Pulmonaire. Hopital CEA, Bichat, Paris, France; 2Laboratoire d’Hemato-Immunologie, ˆ Hopital Saint-Louis, Paris, France. Purpose: In lung Tx, the graft expression of the tolerogenic HLA-G molecule has been shown to be associated to a stable clinical condition observed at the date of tissue sampling. To evaluate the role of HLA-G as a predictive marker of graft tolerance, we planned a 3-year prospective study in a LTx recipients cohort to analyze if early expression HLA-G is associated to short and long-term functional stability of the graft, that is, a lower incidence of acute rejection (AR) or bronchiolitis obliterans syndrome (BOS). Methods and Materials: 41 LTx recipients were included and followed up 3 years post-LTx. Expression of HLA-G was analyzed by immunohistochemistry in the graft tissues from TBBx and dosage of soluble HLAG (sHLA-G) in plasma was performed by ELISA both at 3 and 12 months post-Tx in stable patients. Patients were classified first as those with or without histological detection of HLA-G in the graft at 3 and/or 12 months (hHLA-Gþ or - patients) and second as those with or without trough level sHLA-G 4 25 ng/ml at 3 and/or 12 months (sHLA-G þ or - patients). Freedom from BOS (by log-rank test) and an AR score were compared between both hHLA-G þ or - and sHLA-G þ or – patients. Results: Freedom from BOS at 3 year post-LTx was significantly higher for hHLA-G þ patients (n ¼ 21) compared to hHLA-G - patients (n ¼ 20) (p o 0.05, Figure 1) but did not differ for sHLA-G þ and sHLA-G – patients. No difference was observed for an ARS between hHLA-G þ or – patients and between sHLA-G þ and sHLA-G- patients (p ¼ ns). In addition, median through levels of sHLA-G was higher in hHLA-G þ patients compared to to hHLA-G – ones (p ¼ 0.02). Conclusions: Expression of HLA-G in the graft of stable LTx recipients seems predictive of a lower risk of BOS in long-term follow-up. An isolated dosage of sHLA-G seems of no clinical value as a predictive marker. 445 IgG Immunologic Monitoring To Identify Lung Recipients at Risk of Oportunistic Infections: Prospective Multicenter Study E. Sarmiento,1 J. Cifrian,2 R. Laporta,3 P. Ussetti,3 C. Bravo,4 S. Lopez,4 P. Morales,5 A. de Pablos,6 M. Jaramillo,1 J. Navarro,1 J. Rodriguez-Molina,1 J. Carbone.1 1Hospital General Universitario de Valdecilla, Gregorio Maran˜on, Madrid, Spain; 2Hospital Marques Santander, Spain; 3Hospital Universitario Puerta de Hierro, Madrid, Spain; 4Hospital Vall de Hebron, Barcelona, Spain; 5Hospital La Fe, Valencia, Spain; 6Hospital Universitario Doce de Octubre, Madrid, Spain. Purpose: Infection is a leading cause of morbidity and mortality in the first year following lung transplantation. However, reliable markers performed at fixed times before and after transplantation to detect patients at risk for developing these complications are lacking. The purpose of this study is to define the kinetics of humoral immunity parameters, and to evaluate the usefulness of assessment of these parameters in the identification of recipients at risk of developing severe infections after transplantation. Methods and Materials: We prospectively analyzed 97 adult lung recipients from May 2009 to May 2011 performed at 5 centers in Spain. Immunological studies were performed before transplantation and at 7 and 30 days after transplantation. The protocol included total immunoglobulin levels (IgG, IgM, IgA, nephelometry), complement factors (C3 and C4, nephelometry) and specific antibody titers to
pneumococcal polysaccharides (anti-PPS, ELISA, IgG: 23 serotypes), and to cytomegalovirus (ELISA, IgG). Clinical follow-up was performed over a 6-month period. Definition of outcomes: A. Opportunistic infections (including fungal and CMV that required IV antimicrobial therapy: Prevalence 21,6%). B. Bacterial infection that required IV antimicrobial therapy (Prevalence 58.8%). Statistics: Logistic regression analysis. Results: IgG, IgA, C3 and anti-PPS were significantly lower at day 7 as compared with the baseline study. At day 30 IgG, IgA and anti-PPS remained significantly lower. Immunological risk factors for opportunistic infections were: Pre-transplant IgGo1100 mg/dl (OR 4.95, CI95% 1.13-21.70, p¼0.038), day 7 IgGo600 mg/dL (OR 4.62; CI 95%: 1.06-20.13, p¼0.04), day 30 IgG o698 mg/dL (median value) (OR 5.44; CI 95%: 1.14-25.95, p¼0.033). Risk factors for bacterial infection: Pre-transplant C4o36 mg/dL (OR 4.90; CI 95%: 1.39-17.30, p¼0.013). Conclusions: Protocolized early immunologic monitoring of IgG is useful to identify lung recipients who are at risk of oportunistic infection. These patients deserve a more careful follow-up. 446 A Phase One, Open Label, Multi-Dose Study To Evaluate the Safety, Tolerability, and Biologic Effects of Three Doses of IW001 in Patients with Idiopathic Pulmonary Fibrosis (IPF) K. Rothhaar,1 T. Chew,1 S. Frye,1 M. Klemsz,1,2 W. Lange,1 D.S. Wilkes.1,2 1ImmuneWorks, Indianapolis, IN; 2Indiana University School of Medicine, Indianapolis, IN. Purpose: IW001, an oral solution of Type V collagen (col(V)), is a therapeutic agent in clinical development for IPF by ImmuneWorks. ImmuneWorks scientists believe that lung injury might result in the exposure of a normally hidden protein to the immune system, such as col(V). The immune system may recognize this sequestered protein as foreign, initiating an autoimmune cascade, resulting in an attack on the lung. As the autoimmune response expands, a fibrotic response would follow in an attempt to heal the lung. Lung transplantation is the only viable treatment that has shown survival benefit for IPF patients but the survival benefit is still complicated by significant early mortality rates, especially within the first year. High incidence of col(V) autoreactivity was found with IPF patients and associated with a higher incidence of PGD. Pre-clinical studies showed that col(V)induced immune tolerance abrogated acute rejection in a rat lung transplant model. Methods and Materials: ImmuneWorks conducted an open label, multicenter, Phase I clinical trial in IPF patients who tested positive for anti-col(V) antibodies. Study was designed to evaluate the safety, tolerability, and biological/clinical effects of a three doses (0.1mg, 0.5mg, 1.0mg) of IW001, when administered once daily orally for 24 weeks. Results: About 40% of IPF patients screened for this study tested positive for anti-Col(V) IgG. A total of 30 IPF patients were enrolled in one of three IW001 dose treatment groups. Absolute changes in %FVC pred from baseline to week 24 were determined and showed a trend toward the stabilization of the lung function with IW001 doses at both 0.5mg and 1.0mg/day. Additional biomarkers will be discussed. Conclusions: Our phase I results have demonstrated that IW001 is safe and well tolerated with no unexpected adverse events. IW001 may lead to a possible stabilization of lung function, underscoring the potential of col(V)-induced tolerance to be an effective therapeutic strategy in IPF. 447 Predicting Lung Transplant Waitlist Survival with the Lung Allocation Score in British Columbia, Canada A. Hirji,1 J. Yee,2 M. Sadatsafavi,3 L.G. Singer,4 R.D. Levy.1 1 Respiratory Division, Department of Medicine and British Columbia Transplant, University of British Columbia, Vancouver, BC, Canada; 2 Department of Thoracic Surgery, University of British Columbia, Vancouver, BC, Canada; 3Faculty of Medicine, University of British
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Median wait time to transplant in the region for Status 1A patients in the region Group 1: r30 days Group 2: 430 days (N ¼ 48) (N ¼ 121) Death 15% (7) Transplantation 25% (12) VAD 2% (1) n
22% (26) 7% (8) 18% (21)
p o 0.01
difference in survival but more patients in Group 1 had undergone OHT and more patients in Group 2 had undergone VAD (Table). Conclusions: Triage for advanced heart failure therapies at US centers appears to be driven by geography: centers with shorter median wait time to OHT are more likely to evaluate patients for OHT and less likely to place VADs. As patients at these different centers do not differ clinically, further study is needed to assess whether threshold for considering patients for advanced therapies should be determined by wait time to transplant as well as clinical considerations. 441 Long-Term Survival and Prognostic Markers in 1000 Patients with Advanced Heart Failure. A Single-Center Analysis P. Lesny,1 M. Luknar,1 I. Varga,1 P. Solik,1 S. Wimmerova,2 E. Goncalvesova.1 1Heart Failure and Transplant Department, National Cardiovascular Institute, Bratislava, Slovakia (Slovak Republic); 2 Slovak Medical University, Bratislava, Slovakia (Slovak Republic). Purpose: Heart transplant candidates are a selected group of patients with advanced heart failure (HF). Prognosis estimation is the key determinant of optimal patient management. The aim of the study was to analyze the descriptive characteristics, long-term survival, and mortality predictors in pts with advanced HF hospitalized at a single centre. Methods and Materials: Consecutive patients with HF considered for heart transplantation and hospitalized at the National Cardiovascular Institute Bratislava from January 1, 1998, to January 1, 2010, were retrospectively analyzed. Kaplan-Meier survival analysis was performed. Independent mortality predictors were established using logistic regression analysis. Results: One thousand and two pts were eligible for the analysis. The mean age of pts was 49 years, 86.8% were males, NYHA class was 2.6⫾0.7, and left ventricular ejection fraction was 24.3⫾7.7%. The etiology of HF consisted predominantly of dilated cardiomyopathy (57%), coronary artery disease (27.5%), and arterial hypertension (7.1%). The most important comorbidities included arterial hypertension (43%), atrial fibrillation (24.6%), diabetes mellitus (25.1%), and anemia (17.2%). Cumulative survival was as follows: 1-year survival 83%, 3-year 63%, 5-year 50%, 7-year 39% and 10-year 23%. HF progression was the cause of death in 55.7% of pts and sudden death in 37.5% of pts. Presence of coronary artery disease, left ventricular diastolic diameter of 479 mm, plasma sodium o135 mmol/L, NTproBNP 42297 pg/mL, intravenous treatment, and furosemide dose at discharge 4240 mg/day were independent predictors of 1-year mortality. Conclusions: We present a long-term follow-up of a large and selected cohort of pts from a single centre that reflects the course of HF with severe left ventricular systolic dysfunction, barely modified by comorbidities. Mortality of pts with advanced HF still remains high, with 50% of pts surviving 5 years. This cohort represents the pool of potential assist device implant candidates. 442 Appearance of Posttransplant De Novo Anti-HLA Antibodies in LivingDonor Lobar Lung Transplantation A. Ohsumi,1 F. Chen,1 K. Yurugi,2 T. Maekawa,2 T. Yamada,1 M. Sato,1 A. Aoyama,1 T. Sato,1 M. Sonobe,1 M. Omasa,1 T. Bando,1
I. Matsumoto,1 H. Date.1 1Thoracic Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Center for Cell and Molecular Therapy, Kyoto University Hospital, Kyoto, Japan. Purpose: Recently, the importance of anti-human leukocyte antigen (HLA) antibodies has been pointed out in kidney and liver transplantation. In 2010, Hachem et al. reported the association of donor-specific anti-HLA antibodies (DSA) with acute and chronic rejection in lung transplantation. We investigated the appearance and the trend of anti-HLA antibodies in living-donor lobar lung transplantation (LDLLT) and cadaveric lung transplantation (CLT) at a single lung transplant center in Japan. Methods and Materials: We performed 30 cases of LDLLT and 21 cases of CLT at Kyoto University between June 2008 and October 2012. Since July 2010, anti-HLA antibodies had been screened periodically, using LABScreen Mixed (One Lambda, CA, USA). In addition, they were also investigated when recipients presented symptoms or abnormal findings. When anti-HLA antibodies were detected, their specificities were identified using LABScreen Single Antigen (One Lambda, CA, USA). Results: Anti-HLA antibodies were measured 3.6 ⫾ 2.0 times in 27 cases of LDLLT and 20 cases of CLT. Anit-HLA antibodies were detected in 4 cases in LDLLT (14%) and 5 cases in CLT (25%). Among them, 2 cases in LDLLT (7%) and 2 cases in CLT (10%) had DSA. In LDLLT, one patient had re-LDLLT because of bilateral bronchiolitis obliterans after ipsilateral antibody-mediated rejection. In other 3 patients, class I and/or class II DSA were detected 2 weeks, 1 month, and 10 months after transplantation. All of them were treated with intravenous immunoglobulin and showed no sign of antibodymediated rejection in a close follow-up. Conclusions: In comparison with the current report by Hachem et al., the frequency of DSA appearance was relatively low in our institution. However, DSA was detected even in the early phase of posttransplant days. Accumulation of more cases and longer follow-up were necessary. 443 Intraoperative Extracorporeal Membrane Oxygenation as an Alternative to Cardiopulmonary Bypass in Lung Transplantation D.D. Odell, J. D’Cunha, N. Shigemura, A. Shiose, J.D., Luketich, J.K. Bhama, C. Bermudez. Cardiothoracic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA. Purpose: Extracorporeal membrane oxygenation (ECMO) may be used for intraoperative support as an alternative to cardiopulmonary bypass (CPB) during lung transplantation. We sought to evaluate its efficacy. Methods and Materials: We reviewed lung transplants with intraoperative support (CPB or ECMO) from 8/09-11/12. Patients were stratified into groups by type of support. Postoperative ECMO utilization, graft and overall survival were compared along with blood product utilization and complications. For comparisons, a 2:1 propensity matched cohort of CPB:ECMO was analyzed. Results: 169 patients underwent lung transplantation with mechanical support during the study period (17 ECMO and 152 CPB). Demographic were similar in both groups with higher mean Lung Allocation Score (LAS; 83 vs 56) in the ECMO group. Patients transplanted on ECMO in the overall groups were extubated earlier (0.8 vs 4.8 days; p¼0.11) and had significantly decreased rates of respiratory failure post transplantation (29% vs 6%; p¼0.04) with similar trends in the propensity matched cohort. There were no differences in postoperative ECMO utilization between groups. A trend toward improved overall survival was seen with ECMO at 1 year (100% vs 77%) and 3 years (100% vs 66%; p¼0.13). Graft survival was significantly improved in the ECMO group (p¼0.05). Conclusions: Intraoperative ECMO support for primary lung transplantation is comparable to CPB and is associated with earlier
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The Journal of Heart and Lung Transplantation, Vol 32, No 4S, April 2013
extubation, significant reduction in respiratory complications, a trend toward lower transfusion requirement and improved overall survival. Graft survival was significantly improved with the use of ECMO. F1 Further longitudinal data is necessary. 444 Role of HLA-G Expression as a Predictive Marker of a Low Risk of Bronchiolitis Obliterans Syndrome in Lung Transplant Recipients: A 3-Year Prospective Study 1,2 G. Thabut,1 I. Krawice,2 E. Carosella,2 N. Rouas-Freiss.2 O. Brugiere, 1 ˆ Service de Pneumologie B et Transplantation Pulmonaire. Hopital CEA, Bichat, Paris, France; 2Laboratoire d’Hemato-Immunologie, ˆ Hopital Saint-Louis, Paris, France. Purpose: In lung Tx, the graft expression of the tolerogenic HLA-G molecule has been shown to be associated to a stable clinical condition observed at the date of tissue sampling. To evaluate the role of HLA-G as a predictive marker of graft tolerance, we planned a 3-year prospective study in a LTx recipients cohort to analyze if early expression HLA-G is associated to short and long-term functional stability of the graft, that is, a lower incidence of acute rejection (AR) or bronchiolitis obliterans syndrome (BOS). Methods and Materials: 41 LTx recipients were included and followed up 3 years post-LTx. Expression of HLA-G was analyzed by immunohistochemistry in the graft tissues from TBBx and dosage of soluble HLAG (sHLA-G) in plasma was performed by ELISA both at 3 and 12 months post-Tx in stable patients. Patients were classified first as those with or without histological detection of HLA-G in the graft at 3 and/or 12 months (hHLA-Gþ or - patients) and second as those with or without trough level sHLA-G 4 25 ng/ml at 3 and/or 12 months (sHLA-G þ or - patients). Freedom from BOS (by log-rank test) and an AR score were compared between both hHLA-G þ or - and sHLA-G þ or – patients. Results: Freedom from BOS at 3 year post-LTx was significantly higher for hHLA-G þ patients (n ¼ 21) compared to hHLA-G - patients (n ¼ 20) (p o 0.05, Figure 1) but did not differ for sHLA-G þ and sHLA-G – patients. No difference was observed for an ARS between hHLA-G þ or – patients and between sHLA-G þ and sHLA-G- patients (p ¼ ns). In addition, median through levels of sHLA-G was higher in hHLA-G þ patients compared to to hHLA-G – ones (p ¼ 0.02). Conclusions: Expression of HLA-G in the graft of stable LTx recipients seems predictive of a lower risk of BOS in long-term follow-up. An isolated dosage of sHLA-G seems of no clinical value as a predictive marker. 445 IgG Immunologic Monitoring To Identify Lung Recipients at Risk of Oportunistic Infections: Prospective Multicenter Study E. Sarmiento,1 J. Cifrian,2 R. Laporta,3 P. Ussetti,3 C. Bravo,4 S. Lopez,4 P. Morales,5 A. de Pablos,6 M. Jaramillo,1 J. Navarro,1 J. Rodriguez-Molina,1 J. Carbone.1 1Hospital General Universitario de Valdecilla, Gregorio Maran˜on, Madrid, Spain; 2Hospital Marques Santander, Spain; 3Hospital Universitario Puerta de Hierro, Madrid, Spain; 4Hospital Vall de Hebron, Barcelona, Spain; 5Hospital La Fe, Valencia, Spain; 6Hospital Universitario Doce de Octubre, Madrid, Spain. Purpose: Infection is a leading cause of morbidity and mortality in the first year following lung transplantation. However, reliable markers performed at fixed times before and after transplantation to detect patients at risk for developing these complications are lacking. The purpose of this study is to define the kinetics of humoral immunity parameters, and to evaluate the usefulness of assessment of these parameters in the identification of recipients at risk of developing severe infections after transplantation. Methods and Materials: We prospectively analyzed 97 adult lung recipients from May 2009 to May 2011 performed at 5 centers in Spain. Immunological studies were performed before transplantation and at 7 and 30 days after transplantation. The protocol included total immunoglobulin levels (IgG, IgM, IgA, nephelometry), complement factors (C3 and C4, nephelometry) and specific antibody titers to
pneumococcal polysaccharides (anti-PPS, ELISA, IgG: 23 serotypes), and to cytomegalovirus (ELISA, IgG). Clinical follow-up was performed over a 6-month period. Definition of outcomes: A. Opportunistic infections (including fungal and CMV that required IV antimicrobial therapy: Prevalence 21,6%). B. Bacterial infection that required IV antimicrobial therapy (Prevalence 58.8%). Statistics: Logistic regression analysis. Results: IgG, IgA, C3 and anti-PPS were significantly lower at day 7 as compared with the baseline study. At day 30 IgG, IgA and anti-PPS remained significantly lower. Immunological risk factors for opportunistic infections were: Pre-transplant IgGo1100 mg/dl (OR 4.95, CI95% 1.13-21.70, p¼0.038), day 7 IgGo600 mg/dL (OR 4.62; CI 95%: 1.06-20.13, p¼0.04), day 30 IgG o698 mg/dL (median value) (OR 5.44; CI 95%: 1.14-25.95, p¼0.033). Risk factors for bacterial infection: Pre-transplant C4o36 mg/dL (OR 4.90; CI 95%: 1.39-17.30, p¼0.013). Conclusions: Protocolized early immunologic monitoring of IgG is useful to identify lung recipients who are at risk of oportunistic infection. These patients deserve a more careful follow-up. 446 A Phase One, Open Label, Multi-Dose Study To Evaluate the Safety, Tolerability, and Biologic Effects of Three Doses of IW001 in Patients with Idiopathic Pulmonary Fibrosis (IPF) K. Rothhaar,1 T. Chew,1 S. Frye,1 M. Klemsz,1,2 W. Lange,1 D.S. Wilkes.1,2 1ImmuneWorks, Indianapolis, IN; 2Indiana University School of Medicine, Indianapolis, IN. Purpose: IW001, an oral solution of Type V collagen (col(V)), is a therapeutic agent in clinical development for IPF by ImmuneWorks. ImmuneWorks scientists believe that lung injury might result in the exposure of a normally hidden protein to the immune system, such as col(V). The immune system may recognize this sequestered protein as foreign, initiating an autoimmune cascade, resulting in an attack on the lung. As the autoimmune response expands, a fibrotic response would follow in an attempt to heal the lung. Lung transplantation is the only viable treatment that has shown survival benefit for IPF patients but the survival benefit is still complicated by significant early mortality rates, especially within the first year. High incidence of col(V) autoreactivity was found with IPF patients and associated with a higher incidence of PGD. Pre-clinical studies showed that col(V)induced immune tolerance abrogated acute rejection in a rat lung transplant model. Methods and Materials: ImmuneWorks conducted an open label, multicenter, Phase I clinical trial in IPF patients who tested positive for anti-col(V) antibodies. Study was designed to evaluate the safety, tolerability, and biological/clinical effects of a three doses (0.1mg, 0.5mg, 1.0mg) of IW001, when administered once daily orally for 24 weeks. Results: About 40% of IPF patients screened for this study tested positive for anti-Col(V) IgG. A total of 30 IPF patients were enrolled in one of three IW001 dose treatment groups. Absolute changes in %FVC pred from baseline to week 24 were determined and showed a trend toward the stabilization of the lung function with IW001 doses at both 0.5mg and 1.0mg/day. Additional biomarkers will be discussed. Conclusions: Our phase I results have demonstrated that IW001 is safe and well tolerated with no unexpected adverse events. IW001 may lead to a possible stabilization of lung function, underscoring the potential of col(V)-induced tolerance to be an effective therapeutic strategy in IPF. 447 Predicting Lung Transplant Waitlist Survival with the Lung Allocation Score in British Columbia, Canada A. Hirji,1 J. Yee,2 M. Sadatsafavi,3 L.G. Singer,4 R.D. Levy.1 1 Respiratory Division, Department of Medicine and British Columbia Transplant, University of British Columbia, Vancouver, BC, Canada; 2 Department of Thoracic Surgery, University of British Columbia, Vancouver, BC, Canada; 3Faculty of Medicine, University of British