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The table shows the SP-A2 genotype frequency. Donor lungs with SP-A2 allele 1A1 had greater freedom from BOS. Genotype 1A0-1A had significantly shorter time to BOS. 1A0-1A donor lungs had lower mRNA levels prior to implantation and higher ratio of acute rejection diagnosis per valuable lung-bx post-Tx.

The Journal of Heart and Lung Transplantation February 2006

sation precedes BOS development by many months and may contribute to the airway damage seen in BOS. Strategies aimed at disrupting PA colonisation may offer additional protection from BOS development.

Conclusions: Donor lung SP-A2 gene polymorphism is associated with post transplant BOS development: presence of allele 1A1 seems to be protective; while allele1A may promote BOS. The observed donor lung genetic differences, via innate immunity may predetermine the post-Tx clinical outcome. 111 COLONIZATION OF LUNG TRANSPLANT RECIPIENTS WITH PSEUDOMONAS AERUGINOSA AND THE DEVELOPMENT OF BRONCHIOLITIS OBLITERANS SYNDROME P. Botha,1 L. Archer,1 R.L. Anderson,1 J. Lordan,2 J.H. Dark,1 P.A. Corris,2 F.K. Gould,1 A. Fisher,2 1Department of Cardiopulmonary Transplantation, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, United Kingdom; 2Immunobiology and Transplantation Research Group, University of Newcastle upon Tyne, Newcastle upon Tyne, Tyne and Wear, United Kingdom

WHICH FACTORS PREDICT THE BENEFICIAL EFFECT OF AZITHROMYCIN IN PATIENTS WITH BRONCHIOLITIS OBLITERANS SYNDROME AFTER LUNG TRANSPLANTATION? G.M. Verleden,1,2 L.J. Dupont,1,2 B.M. Vanaudenaerde,1,2 D.E. Van Raemdonck,2,3 1Dept Pulmonary Dis, University Hospital Gasthuisberg, Leuven, Belgium; 2Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium; 3Dept Thor Surg, University Hospital Gasthuisberg, Leuven, Belgium

Airway colonisation with Pseudomonas Aeruginosa (PA) is common in lung recipients with bronchiolitis obliterans syndrome (BOS). Whether PA colonisation occurs secondary to the damaged airway in BOS or plays a role in the aetiology of BOS remains unclear. We investigated the relationship between PA colonisation post transplant and the development of BOS in a retrospective longitudinal study of 155 lung transplants performed between 2000 and 2003. Forty-nine patients (31.6%) were colonized with PA pre-transplant, they did not have a higher incidence of BOS at 2 years compared to those not colonised pre-transplant (20% vs. 14% respectively, p⫽0.153). Recipient colonization with PA posttransplant however, was associated with the earlier development of BOS (23.4% vs. 7.7%, p⫽0.006). In addition, freedom from BOS was significantly less in the 20 recipients with de-novo PA colonisation after transplant compared to those with no PA (Figure 1, Kaplan-Meier Log-rank p⫽0.0206). In 14 (78%) of the recipients with PA and BOS, PA colonisation preceded BOS by a median of 238 days (95% CI 88 –531 days, p⫽0.002, Wilcoxon signed ranks test). We conclude that new PA colonisation in recipients who were culture-negative for PA pre- transplant is associated with a significant increase in BOS development. Furthermore, PA coloni-

Bronchiolitis obliterans syndrome (BOS) remains the most important cause of late mortality after lung transplantation (LTx). Treatment is difficult, although recently azithromycin (azi) has been shown to have a beneficial effect in about 45% of patients. It is not known at the present time which patients have the most chance to benefit from this treatment. Therefore, in this study we investigated the characteristics of patients with BOS before starting treatment with azi and compared these parameters between responders (⬎10% increase in FEV1) and non-responders (no increase in FEV1). Fourteen patients were included, with a mean age of 47(13)y at the time of Ltx. There initial BOS stages were: 0-p (3), 1 (10), 2 (1). After 3 months of azi the mean FEV1 (SD) increased from 2.40 (0.82) to 2.67 (0.85) (p⫽0.014). There were 6 responders (R) and 8 non-responders (NR). The FEV1 in group R increased from 2.11 (0.54)L to 2.75 (0.74)L (p⫽0.016), whereas in the NR group there was no change. The characteristics of both groups at inclusion are summarized in the table. In conclusion: the only significant different parameter discriminating between the R and NR group seems to be the % neutrophils in the BAL fluid. In fact, a BAL neutrophilia of ⬎15% has a positive predictive value of 85% for a significant FEV1 response to azi, whereas a BAL neutrophilia of ⬍15% confers no effect at all (negative predictive value 100%).

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The Journal of Heart and Lung Transplantation Volume 25, Number 2S

Abstracts

Characteristics at Inclusion

Age Sex (M/F) Type of Ltx FK/CyA POD azi start Pre azi FEV1 pre LTx disease BAL Pseudomonas % BAL neutrophilia

Responders (n ⴝ 6)

Non-responders (n ⴝ 8)

p-value

48.8 (15) 4/2 4SS/2SLtx 5/1 438 (493) 2.20 (0.56) L 2E/3F/1CF 2 69.6 (24.3)

46.3 (12.5) 5/3 6SS/1S/1HLTx 8/0 1309 (942) 2.50 (1.03) L 4E/1F/2CF/1PPH 2 9.2 (12.4)

NS NS NS NS 0.06 NS NS NS 0.0013

S, single; SS, sequential single; H, heart-lung; E, emphysema; F, fibrosis, CF, cystic fibrosis; PPH, primary pulmonary hypertension; BAL, broncho-alveolar lavage; POD, postoperative day.

113 COMPARISON OF EXHALED NITRIC OXYDE (ENO) AND HELIUM SLOPE (SHE) FOR THE EARLY DETECTION OF GRAFT DYSFUNCTION AFTER HEART-LUNG (HLT) AND BILATERAL LUNG (BLT) TRANSPLANTATION A. Van Muylem,1 C. Knoop,1 M. Estenne,1 1Chest Service, Erasme University Hospital, Brussels, Belgium The slope of the alveolar plateau for Helium (SHe) measured during a single-breath washout test allows early detection of bronchiolitis obliterans syndrome (BOS) stage 1 after lung transplantation. The aim of this study was to examine the relationship over time between the development of BOS stage 0-p and changes in both eNO and SHe. 59 patients (14 HLT and 45 BLT), of whom 17 developed BOS 0-p, were studied. There were 34 patients who had been transplanted before 09/2000 and were in BOS 0, and 25 patients who were transplanted after 09/2000. Standard pulmonary function tests, eNO (measured at 200ml/s following ERS guidelines), and single-breath washouts were measured on 765 occasions from 09/2000 to 12/2004 (median follow-up 1179 days); only data obtained while patients were free of acute infection and rejection were included in the analysis. The lowest values of eNO and SHe obtained in each of the 17 patients during the BOS 0 period (T1) were compared to values obtained at the end of the BOS 0 period immediately before the change to BOS 0-p (T2), and to values obtained during the BOS 0-p period (T3). Average (SD) values for eNO at T1, T2, and T3 were 4.0 (2.4), 4.5 (1.6), and 8.0 (6.0) ppb; corresponding values for SHe were 1.6 (1.0), 4.0 (3.3), and 5.9 (4.2) %/l. For eNO, the only significant difference was found between T3 and T1 (p ⬍0.001); for SHe, both T2 and T3 were significantly greater than T1 (p ⬍0.001). eNo increased above the 95% confidence interval computed from all values recorded in BOS 0 in 0/17 patients at T2, and 7/17 patients at T3; corresponding values for SHe were 10/17 at T2 and 13/17 at T3. The 7 patients who had an increase in eNO at T3 also had an increase in SHe. We conclude that 1) SHe has a better sensitivity than eNO for the early detection of graft dysfunction; 2) SHe and BOS stage 0-p have complementary roles as early markers of graft dysfunction, and adding eNO does not improve the detection. 114 A NOVEL DIAGNOSTIC MARKER FOR BRONCHIOLITIS OBLITERANS IN LUNG TRANSPLANT RECIPIENTS: SERUM KL6 LEVEL J.N. Walter,1 M. Doan,2 H. Zhang,2 L.L. Fan,2 G.B. Mallory,2 R. Bag,3 O. Elidemir,2 1Pediatrics, Driscoll Children’s Hospital, Corpus Christi, TX; 2Pediatric Pulmonology, Baylor College of Medicine, Houston, TX; 3Medicine, Baylor College of Medicine, Houston, TX

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The single major cause of reduced long-term survival of lung transplant recipients is Bronchiolitis Obliterans (BO). The early diagnosis of BO is very difficult and requires invasive diagnostic tests such as a lung biopsy. The term Bronchiolitis Obliterans Syndrome (BOS) was adopted due to the poor sensitivity of biopsy for diagnosing early BO. Patients are diagnosed with BOS when they have a sustained drop in FEV1 of at least 20% from their post-transplant baseline. By the time the diagnosis is made, most patients have significant and irreversible loss of lung function. There is a need for a simple and accurate diagnostic test for BO in lung transplant recipients. KL-6 is a protein expressed on the surface of pulmonary epithelial cells and has been reported to be elevated in the sera of patients with interstitial lung diseases. We hypothesized that serum levels of KL-6 would be elevated in patients who develop BOS after lung transplantation.We collected single serum samples from 26 lung transplant recipients and 20 healthy controls. The BOS status of the lung transplant recipients was determined based upon routinely collected lung function testing. Of the 26 lung transplant recipients, 8 met the criteria for BOS and 18 did not. The serum KL-6 levels were determined using a sandwich ELISA technique. Mean serum KL-6 concentration ⫾ SD in lung transplant recipients with BOS, without BOS and controls were 688.7 ⫾ 225.8, 321.3 ⫾ 163.9 and 235.2 ⫾ 141.5 U/ml, respectively (p ⬍0.01, for patients with BOS vs. patients without BOS and patients with BOS vs. controls). There was a significant correlation between the decrease in FEV1 from the post-transplant baseline and the serum KL-6 levels (R⫽0.44, p ⬍0.05). Serum KL-6 levels were significantly elevated in lung transplant recipients with BOS when compared with lung transplant recipients without BOS. Our results indicate that serum KL-6 measurement has the potential to serve as a non-invasive diagnostic test for the detection of BO in lung transplant recipients.

115 ROLE OF PROFIBROTIC CYTOKINES IL-17 AND IL-11 IN CHRONIC REJECTION FOLLOWING LUNG TRANSPLANTATION C. Bergeron,1,2 M. Alkerithy,2 T.C. Kotsimbos,3 Q. Hamid,2 1 Medecine, Hotel-Dieu du CHUM, University of Montreal, Montreal, QC, Canada; 2Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada; 3Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Monash University, Melbourne, Australia Background: Bronchiolitis obliterans (BO) is the leading cause of long term mortality and graft loss in lung transplant recipients. BO is thought to be a manifestation of chronic rejection, with extensive inflammation and fibroblast proliferation. IL-11 and IL-17 are novel profibrotic cytokines, stimulating extracellular matrix production, with roles in tissue remodeling and induction of tissue fibrosis. Objectives: To investigate the expression of IL-11 and IL-17 (mRNA and protein) in lung transplant recipient with and with chronicrejection, and to examine their expression as prognostic and predictive markers of chronic lung rejection. Methods: Twenty post lung transplant recipients and ten healthy non smoking subjects underwent transbronchial biopsies and bronchial alveolar lavage. Clinical data of these patients were obtained. Immunohistochemistry was used to examine the pres-