Pulmonary capillaritis in lung transplant recipients: response to therapy and effect on long-term allograft function

Pulmonary capillaritis in lung transplant recipients: response to therapy and effect on long-term allograft function

S166 Abstracts 367 EXHALED NITRIC OXIDE (eNO) CORRELATES WITH IL-17 IN BRONCHOALVEOLAR LAVAGE FLUID (BALF) DURING ACUTE LUNG REJECTION B.M. Vanauden...

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S166

Abstracts

367 EXHALED NITRIC OXIDE (eNO) CORRELATES WITH IL-17 IN BRONCHOALVEOLAR LAVAGE FLUID (BALF) DURING ACUTE LUNG REJECTION B.M. Vanaudenaerde,1 W.A. Wuyts,1 L.J. Dupont,1 D.E. Van Raemdonck,2 G.M. Verleden,1 1Lab of Pneumology, Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium; 2Dept Thoracic Surg, Lung Transplantation Unit, University Hospital Gasthuisberg, Leuven, Belgium Despite improved immunosuppression, acute lung rejection (AR) still occurs in ⬎50% of the patients during the first year after lung transplantation (Ltx). Since AR is the major risk factor for OB, unraveling its pathophysiology is very important. We recently demonstrated that IL-17 is increased in BALF of patients with acute rejection (AR), compared to those without AR. IL-17 also stimulates smooth muscle cells to release IL-8, the major chemokine involved in OB. NO seems to be involved in the process of AR, at least in human heart and renal transplantation and in experimental animal transplantation. Although eNO is increased during chronic rejection, it remains a matter of discussion whether eNO is also increased during AR of the lung. The present study aimed to measure eNO and to correlate eNO with IL-17 in BALF of LTx patients with AR and to compare these parameters with a nonacute rejection group. 23 Ltx patients were included in the study. Their mean age at transplantation was 45.8 ⫾ 14.2y. They were all clinically stable and underwent bronchoscopy with BAL and TBB, spirometry and eNO measurements before discharge at postoperative day 24 ⫾ 7 (range 12-41 d). Twelve patients proved to have AR (A1-A3), whereas 11 had A0. There were no significant differences in spirometry between the 2 groups. Compared to the non AR patients (group NAR), those with AR (group AR) had a significant increase of IL-17 in their BALF (0.30 ⫾ 0.12 pg/ml versus 0.06 ⫾ 0.02 pg/ml, p ⬍ 0.05). The eNO value was 7.5 ⫾ 2.3 ppb in the AR versus 4.9 ⫾ 0.6 ppb in the NAR, p ⬎ 0.05. For all patients together, there was a significant correlation between IL-17 and eNO (p ⫽ 0.0013); the correlation remained significant in the AR group only (p ⫽ 0.048). In Conclusion: the eNO value is not significantly increased during AR, however, the correlation between IL-17 and eNO suggests a potential role for NO during acute lung rejection. 368 PULMONARY CAPILLARITIS IN LUNG TRANSPLANT RECIPIENTS: RESPONSE TO THERAPY AND EFFECT ON LONGTERM ALLOGRAFT FUNCTION T.L. Astor,1 D. Weill,1 M.R. Zamora,1 1Division of Pulmonary and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, CO Background: Pulmonary capillaritis (PC) has been previously described in lung transplant recipients as a possible histological form of acute allograft rejection. It is characterized by edema, fibrinoid necrosis, neutrophilic infiltration, and red blood cells in the alveolar interstitium and space. The clinical outcomes of pts. presenting with post-transplant PC have not been well described. Methods: We retrospectively reviewed the response to therapy and long term allograft function in 33 cases of PC in LTx recipients. Pre-LTx diagnoses included COPD (n ⫽ 16), alpha-1 ATD (n ⫽ 8), ILD (n ⫽ 5), CF (n ⫽ 3), and PH (n ⫽ 1). Patients presented with a clinical syndrome characterized by dyspnea, hypoxemia, abnormal chest radiographs, and a decrease in FEV1; 20% also had hemoptysis. Transbronchial or open lung biopsy confirmed the diagnosis of PC. For the purpose of analysis patients were divided into three groups based on the time after transplant when PC was diagnosed: (1) 0-4

The Journal of Heart and Lung Transplantation February 2004

weeks; (2) 1-12 months; (3) ⬎12 months. For pts. in Gp1, FEV1 was determined 1 year post-LTx. For Gps2 and 3, FEV1 was determined 1 month prior to and 6 months after the diagnosis of PC. Patients were initially treated with IV steroids, and underwent plasmapharesis in the absence of clinical improvement. Results: Therapy with IV steroids resulted in improvement in 19 cases (59%). A response to plasmapheresis was observed in 8/13 cases (62%) refractory to steroids. 3/5 that did not respond to therapy died within 2 months of diagnosis. 7/9 pts. in Gp1 were alive at 1 year; all 7 attained the expected 1-yr % predicted FEV1 values. There were 16 cases of PC in 12 pts. in Gp2. 10 pts. were alive 6 months after the diagnosis of PC; 2 had a decline in FEV1 ⬎15%. 5/8 pts. in Gp3 were alive 6 months after PC; 1 had a decline in FEV1 ⬎15%. Conclusions: These results suggest that post-LTx PC often does not respond to therapy with IV steroids alone, and may require treatment with plasmapheresis. Although PC may represent a form of severe acute allograft rejection, it does not appear to be associated with a significant long-term decline in allograft function. 369 P-GLYCOPROTEIN AND OUTCOME FOLLOWING LUNG TRANSPLANTATION J.E. Fildes,1 J. Thekkudan,1 R. Guntamadugu,1 A. Owen,2 D. Singh,3 N. Yonan,1 C.T. Leonard,1 1The Transplant Centre, South Manchester University Hospitals NHS Trust, Wythenshawe Hospital, Wythenshawe, Manchester, United Kingdom; 2 Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, United Kingdom; 3North West Lung Research Centre, South Manchester University Hospital Trust, Wythenshawe, Manchester, United Kingdom Introduction: Survival after lung transplantation is ⬍50% at 5 years due to chronic rejection. P-glycoprotein (P-Gp), the membrane bound efflux pump encoded by the multi drug resistance (MDR1) gene may be one reason for poor response to immunosuppression. Over 10 years ago one study suggested an association with rejection in lung transplant recipients. This study set out to test the hypothesis that peripheral blood expression of P-glycoprotein is associated with rejection and nephrotoxicity in lung transplant recipients. Methods: Using a previously described flow cytometric method with directly conjugated monoclonal antibody to P-Gp, we assessed peripheral blood mononuclear cell expression of P-Gp in terms of mean fluorescence intensity in a group of 26 lung transplant recipients. Five of the 26 patients were in the early post-operative phase. We tested for any correlation with clinical course, lung function, difficulty obtaining Cyclosporine A (CsA) levels, renal function and number of acute rejection (AR) episodes. Results: There was a strong correlation between peripheral blood P-Gp expression and concurrent CsA dose (p ⫽ ⬍ 0.01). There was no correlation between P-Gp expression and number of AR episodes, preservation of lung function (%best baseline FEV1 and FEF25-75), chronic rejection grade, serum creatinine or estimated creatinine clearance. In the 5 early post-operative patients higher expression of P-Gp correlated with difficulty achieving adequate CsA levels. Conclusions: High P-gp expression may be helpful in giving early warning of those patients who may have difficulty gaining adequate CsA levels. 370 HLA SENSITIZATION BUT NOT TOLERANCE TO INCOMPATIBLE DONOR ABO ANTIGENS FOLLOWS TISSUE ALLOGRAFT PLACEMENT IN INFANT NORWOOD PATIENTS N.E. Lobach,1 L. Hornberger,1 J.F. Smallhorn,1 A.I. Dipchand,1 N. denHollander,2 G. VanArsdell,1 S.M. Pollock-BarZiv,1 L.J. West,1