Interstitial pneumonitis after lung or heart-lung transplantation in very young recipients

The Journal of Heart and Lung Transplantation Volume 20, Number 2 post-transplant to diagnosis of DR was 361.2 days (range 21⫺1672). There were 78 episodes of acute rejection, 29 in 13 DR patients (2.2 episodes/patient), and 49 in 21 NR patients (2.3 episodes/patient). ISHLT grades in 38 biopsies were A1 (9), A2 (19), A3 (8), lymphocytic bronchiolitis (1), acute rejection ⫹ cytomegalovirus (1). Multiple, often recurrent infections caused by a wide spectrum of organisms occurred in 13 DR patients (81.3%) and in 24 NR patients (82.8%). Nine patients (3 DR, 6 NR) developed obliterative bronchiolitis, causing death in 5 patients (1 DR, 4 NR). Fifteen patients (33.3%) died, 4 (25%) of 16 with DR and 11 (37.9%) of 29 with NR. In 1 DR patient death was due to sarcoidosis in the graft and the native lung. Mean time to death after tx for DR was 1483 days (64⫺3280) and for NR was 1128 days (32⫺2547). Mean time to death after DR was 1227 days (33-3155). Our findings of DR in 16 (35.5%) of 45 patients surviving ⬎ 30 days after tx is probably conservative given the limitations of our study. Although the frequency of acute rejection and infections is similar in both groups, DR may confer a slight survival advantage due to better control of subclinical rejection which warrants further study. 18 INTERSTITIAL PNEUMONITIS AFTER LUNG OR HEARTLUNG TRANSPLANTATION IN VERY YOUNG RECIPIENTS T.M. Hoffman, N.D. Bridges, P.A. Russo, T.L. Spray, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA Histologic examination of lung tissue obtained in the setting of acute, early graft failure (AEGF) frequently reveals diffuse alveolar damage or evidence of viral infection. In this report, we describe the clinical and pathological characteristics of a group of patients with a previously undescribed interstitial pneumonitis seen in association with AEGF. Methods: Among 45 pediatric lung or heart-lung transplant procedures performed between 10/94 and 9/00, there were 13 (29%) episodes of acute, early lung graft failure. The histologic and clinical findings in 5 patients, in whom the etiology of AEGF was unclear, were reviewed. Results: The patients ranged in age at the time of transplantation from 2.4 to 18.4 months (median 5.7 months). Indications for lung transplantation included surfactant B deficiency (1), chronic pneumonitis of infancy (1), and primary pulmonary hypertension (1). The indication for heart-lung transplantation was complex congenital heart disease with pulmonary hypertension in 2 patients. AEGF occurred within 2 weeks of transplant in all patients. Evaluation for viral and fungal infection was negative in all. Consistent histologic findings at open lung biopsy in all 5 patients included widening of the interstitium with a predominantly chronic inflammatory infiltrate and filling of the alveolar air spaces with macrophages. No patient had histologic evidence of an eosinophilic infiltrate, bronchiolitis obliterans, or acute cellular rejection. In one patient, the interstitial pneumonitis was preceded by acute necrotizing pneumonia. Three of 5 patients survived; one underwent repeat lung transplant, and in 2, the process resolved after therapy with ibuprofen. Conclusions: Pulmonary graft dysfunction early after lung or heart-lung transplantation in young patients may be associated with this previously undescribed interstitial pneumonitis, without evidence for rejection, viral infection, or allergic reaction. Antiinflammatory agents may prove to be of benefit in the recovery of these patients.

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19 NONIMMUNOLOGIC REJECTION OF THE HEART C.A. Labarrere, Clarian Health Partners, Inc., Indianapolis, IN, USA Incompatibility between recipient immune cells and donor cells can cause rejection of solid organ transplants. Recently the importance of the microvasculature for transplant survival has been revealed. Evidence indicates that organ transplants fail, not because of cellular rejection, but from loss of donor vessels within the allograft. We asked whether increasing numbers of nonimmunologic changes in the microvasculature such as depletion of vascular antithrombin and arteriolar tissue plasminogen activator and presence of arterial endothelial intercellular adhesion molecule-1 (ICAM-1) and microvascular fibrin, as well as increased levels of soluble ICAM-1 and detectable serum levels of cardiac troponin I, augment the risk of developing coronary artery disease (CAD) and graft failure. We followed up 141 heart transplant recipients 44.9 ⫹/- 2.5 months after transplantation. CAD was evaluated angiographically. Microvascular antithrombin, tissue plasminogen activator, ICAM-1, and fibrin were evaluated immunohistochemically in serial biopsies obtained during the first 3 months after transplantation. Serum soluble ICAM-1 and cardiac troponin I were studied using an enzymelinked immunosorbent assay. After adjusting for potentially confounding variables, we found that the risk of CAD increases 2.0 times (95% confidence intervals [CI]: 1.6-2.6; p⬍0.001) and the risk of failure increases 1.9 times (95% CI: 1.3-2.8; p⬍0.001) with each additional nonimmunologic risk factor. The absence of nonimmunologic risk factors soon after transplantation was associated with a 24-month period free of CAD. Each of these changes, and not cellular rejection, was independently associated with the development of transplant CAD and failure. The greater the number of nonimmunologic risk factors present within the first 3 months after transplantation, the greater the association with increasing development of CAD and failure. We propose that a prothrombogenic microvasculature during the peritransplant period, and not cellular rejection, may cause chronic rejection of the cardiac allograft and subsequent failure. 20 ANTI-THYMOCYTE GLOBULIN TREATMENT IS ASSOCIATED WITH COMPLEMENT DEPOSITION IN EARLY CARDIAC TRANSPLANT BIOPSIES W.M. Baldwin1, L.P. Armstrong2, M.D. Samaniego1, S. Rahimi1, E.K. Kasper3, J.V. Conte1, E.R. Rodriguez1, R.H. Hruban1, 1Johns Hopkins University, Baltimore, MD; 2University of Virginia, Charlottesville, VA, USA Polyclonal and monoclonal antibodies (Ab) to human lymphocytes have been reported to activate complement systemically. Because polyclonal anti-thymocyte globulin can contain antibodies with reactivity to endothelial cells, we investigated whether treatment with this reagent caused complement deposition in cardiac transplants. Frozen tissue was available from the first endomyocardial biopsy of 72 patients, who were transplanted between April, 1995 and May, 2000. In 8 of these patients horse anti-thymocyte globulin (ATGAM; Pharmacia & Upjohn, Kalamazoo, MI) was substituted for cyclosporin A (CsA) in the first month after transplantation; 4 other patients received OKT3. All of the biopsies were stained for C4d as evidence of activation of the classical pathway of complement. In addition, biopsies from the 12 patients treated