533: Risk Factors for Death in High LAS Patients after Lung Transplantation

The Journal of Heart and Lung Transplantation Volume 27, Number 2S

Abstracts

intend to validate this set prospectively to assess the diagnostic and predictive value. The identity of the self antigens that the 13 autoantibodies bind to elucidates the nature of the immunological response resulting in BOS. 531 Longitudinal Analysis of Exhaled Breath Condensate Biomarkers after Lung Transplantation A. Krishnan,1 S. Chow,2 P.S. Thomas,2 A.R. Glanville,1 D.H. Yates,1 1 Thoracic Medicine and Lung Transplantation, St.Vincents Hospital, Sydney, NSW, Australia; 2Thoracic Medicine, University of New South Wales, Sydney, NSW, Australia Purpose: Improved outcomes post lung transplantation (LTx) depend on close surveillance for rejection and infections. Exhaled breath condensate (EBC) collection is a novel, non-invasive method of sampling the airway. Several markers of inflammation and oxidative imbalance are measurable in EBC and may be early markers of graft dysfunction. We have previously reported significant differences between various post LTx diagnoses in a cross sectional study. This study aimed to investigate the utility of longitudinal exhaled breath biomarker measurements in the follow-up of LTx patients. Methods and Materials: We studied 68 LTx patients prospectively, at 6 monthly intervals and analysed 148 samples. EBC was collected using a refrigerator circuit (Ecoscreen V1.1, Jaeger, Germany). Between-group comparisons done using ANOVA. Results: Table 1: Values expressed as mean (SEM) Conclusions: This is the first study of longitudinal EBC biomarker measurements in LTx patients. Patients with BOS have a significant increase in markers of oxidative stress and neutrophilic inflammation as well as low pH. There is also evidence of marked oxidative stress in ACR and viral infections. EBC biomarker analysis is an easily repeatable test which has the potential to delineate both the processes and time course of complications after lung transplantation. Further studies are required to validate its use in clinical practice.

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Methods and Materials: From January 2005 to July 2007, 185 sequential bilateral lung transplants were performed in our center.Of these,148(80%) had complete donor information required for the retrospective donor score calculation: age, smoking history, chest x-ray, secretions on bronchoscopy and ABGs.Logistic regression relating the score to various post-transplant outcomes such as PaO2/FiO2⬎24h after transplantation, length of intubation (log-transf.) and ICU stay were used in order to study the predictive value of the score. Results: The median and IQR donor score in the lungs used for transplantation were 4(1.7-6.2) in 2005, 4(2.7-6) in 2006 and 5(3-7) in 2007.The number of donors at each donor score is shown in Fig.1.In univariate analyses the score was not significantly correlated with post-transplant PaO2/FiO2(Fig.2).There was also no significant correlation between the score and recipient length of intubation (r2⫽0.019 p⫽0.23) or ICU stay (r2⫽0.018 p⫽0.2). Conclusions: The proposed scoring system based solely on donor clinical variables did not predict early recipient outcomes in our center.

Table 1 Biomarker

Viral 6 weeks p value infection post (nⴝ11)

Biomarker

BOS 0 BOS>1

p value

pH

5.8 (0.35) 6.2 (0.56) 0.04

NOx (␮M)

0.002

Iso (pg/ml)

729.2 (185.1) ACR (n⫽9) 29.91 (9.14)

0.05

Iso (pg/ml)

p value

LTB4

27.82 (7.5) 531.6 (158.6) 584.2 (188.1)

Biomarker H2O2 (pg/ml)

323.1 (64.3) 6 weeks post 21.89 (14.3)

58.79 (6.5) 2091.1 (613.7) 1068.2 (125.1)

0.008 0.02

0.009

NOx: nitrogen oxides, Iso: isoprostane, LTB4: leukotriene B4, H2O2: Hydrogen peroxide

532 Donor Scoring Does Not Predict Early Outcome M. Cypel,1 E. Yildirim,1 C. Boasquevisque,1 M. Anraku,1 V.T. Sales,1 D.E. Rodrigues,1 C. Payne,1 A. Pierre,1 M. de Perrot,1 S. Keshavjee,1 T.K. Waddell,1 1Thoracic Surgery, Toronto Lung Transplant Group, University of Toronto, Toronto, ON, Canada Purpose: A donor lung scoring system might prove useful to improve decision making in donor selection and for data comparison among different centers.A new donor lung score using 5 traditional clinical donor variables was recently reported to correlate with early results after transplantation.We aimed to determine whether this specific score predicted early recipient outcomes in our center.

533 Risk Factors for Death in High LAS Patients after Lung Transplantation C.A. Merlo,1 J.B. Orens,1 J.V. Conte,2 A.S. Shah,2 1Division of Pulmonary and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD; 2Cardiac Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD

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Abstracts

Purpose: The Lung Allocation Score (LAS) has changed organ allocation in lung transplantation (LTx) in the U.S. Recent evidence suggests that patients with an LAS ⬎ 44 are at increased risk of death after LTx. The purpose of the study was to examine clinical predictors of death in high LAS patients after lung transplantation. Methods and Materials: All patients undergoing lung transplantaion reported to UNOS during the period May 1, 2005 through January 1, 2007 were included in the study. Patient characteristics, anthropometrics, and clinical characteristics were collected. High LAS was defined as having an LAS ⬎ 44. In the high LAS group, a time-to-event analysis for risk of death after transplantation was performed. Cox proportional hazards models were constructed to identify risk factors for death after adjusting for potential confounders. Results: There were 2,427 patients who underwent LTx during the study period. Of these, 530 patients were in the high LAS group. The mean follow-up time for the high LAS group was 142.4 days. The average age was 51.5⫾14.1 and 40.6% were females. The majority of patients in the high LAS group were transplanted for IPF (51.3%) and CF (14.2%), while patients with COPD (3.4%) and pulmonary arterial hypertension (0.9%) were only a small portion of the group. For the high LAS group, the 30-day, 60-day, 90-day, and 365-day survival were 93%, 86%, 82%, and 69% respectively. In the high LAS group, there was no significant effect of diagnosis on short term survival. Likewise, age, sex, BMI, FVC, creatinine, diabetes, oxygen requirement, and 6-MWT distance had no significant effect on mortality. There was a trend towards decreased survival among patients on mechanical ventilation (HR: 1.45; 95% CI: 0.83-2.55), but this did not reach statistical significance. Conclusions: The current study examined all high LAS LTx patients reported to UNOS from 2005-2007. No single risk factor had a significant influence on survival. Importantly, the LAS independently identifies a high risk cohort, regardless of diagnosis.

534 Eliminating Local for Some or All Lung Candidates Would Reduce Deaths in Nearly All Geographic Regions in the US S. Murray,1 J. Moore,2 A.M. Rodgers,2 T.H. Shearon,1 D.B. Dyke,1 R.M. Merion,1 1SRTR, University of Michigan, Ann Arbor, MI; 2 SRTR, Arbor Research, Ann Arbor, MI Purpose: Lung transplantation (TX) candidates in the US are prioritized by a Lung Allocation Score (LAS) offered to the local OPO then Zone A, B and C geographic areas. This study explored whether enhanced patient access to organs would lead to fewer deaths. Methods and Materials: The Thoracic Simulated Allocation Model (TSAM) compared outcomes of (1) current lung allocation (2) shared allocation to Zone A for all candidates and (3) shared allocation to Zone A (⬍500 miles) for patients with LAS ⱖ 40. TSAM input for lung waitlist candidates included waitlist and organ arrivals, LAS and removal data, and probability models for organ placement and post-TX survival. Post-TX survival was estimated from multivariate Cox models with significant patient and donor characteristics. Results: Compared to current rules, simulating shared allocation to Zone A resulted in 33 fewer total deaths, while restricting sharing to those with LAS ⱖ 40 resulted in 30 fewer deaths (2% of current total deaths). Decreased mortality was seen primarily among waitlisted patients. Reduced total deaths were seen in nearly all regions, see table. Average distance traveled per organ increased from 219 miles (current) to 240 miles (LAS ⱖ 40) to 274 miles (no local). Conclusions: Complete or partial removal of local prioritization would reduce overall deaths in patients with end-stage lung disease.

The Journal of Heart and Lung Transplantation February 2008

535 Post-Mortem and Ex-Vivo Nitric Oxide (NO) Ventilation Reduces Ischemia-Reperfusion Injury (IRI) in Rat Lungs Transplanted from Non-Heart-Beating Donors (NHBDs) B. Dong,1 T. Egan,1 1Division of Cardiothoracic Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC Purpose: Lung retrieval from NHBDs may solve the donor shortage but is limited by warm ischemic time. Ex-vivo perfusion and ventilation of lungs retrieved from NHBDs allows functional assessment and treatment of lungs. We sought to determine if ventilation of NHBD lungs with NO during warm ischemia, ex-vivo perfusion, and perioperatively might reduce IRI and improve oxygenation post–transplant in a clinically relevant model. Methods and Materials: One hour after death, Sprague-Dawley rats were ventilated for another hour with 60% O2 alone (Control) or 40 ppm NO in 60% O2 (n ⫽ 6 per group). Then lungs were flushed with 20 ml cold Perfadex, stored cold for one hour, warmed to 37oC in an ex-vivo circuit perfused with Steen solution. At 37 oC, lungs were ventilated for 15 minutes with alveolar gas with or without NO, then perfusion-cooled to 20oC, flushed with cold Perfadex and stored cold (2.2 – 3 hours). The wet/dry weight ratio (W/D) of the donor right lung (DRL) was measured. The left lung (Graft) was transplanted using a modified cuff technique. Recipients were ventilated with 60% O2 with or without NO. After one hour of reperfusion, arterial blood gases from the left pulmonary vein (LPV) and the aorta, W/D of both graft lungs and native right lungs (NRL) were measured. Results: W/D increased in the circuit but reduced after transplant. NO-ventilation was associated with significantly reduced W/D and better oxygenation (See Table). Conclusions: Administration of NO facilitated transplantation of lungs from NHBDs by reducing IRI and improving oxygenation. W/D ratio

PaO2/FiO2

Group

DRL

Control NOventilate p value

8.08⫾0.6 6.55⫾0.27 4.95⫾0.08 245.0⫾21.6 309.4⫾18.6 6.26⫾0.28 5.77⫾0.37 4.97⫾0.09 464.4⫾43.4 446.9⫾48.4 0.021

Graft

0.114

NRL

0.819

LPV

0.001

Aorta

0.024

Mean⫾SEM

536 Despite Decreasing Wait Times for Lung Transplantation, Lung Allocation Score Continues to Increase M.J. Russo,1,2 D. Sternberg,1 K.N. Hong,2 A.J. Moskowitz,2 A.C. Gelijns,2 D.J. Lederer,3 J. Wilt,3 F. D’Ovidio,1 S.M. Kawut,3