No abstract

Conversion from cyclosporine to tacrolimus after lung transplantation is associated with reversal of recurrent-ongoing rejection. Conversion for bronchiolitis obliterans syndrome allows short-term stabilization of lung function in most patients.

Bronchiolitis obliterans syndrome (BOS) is a severe complication after lung transplantation (LTX).In a retrospective cohort study 12 stable healthy recipients (non-BOS) and eight patients with BOS were enrolled after LTX and matrix metalloproteinases (MMP)-9, TIMP-1 and cell characteristics in bronchoalveolar lavage (BAL) samples (n5145) were analysed. BALs from patients with BOS were further divided according to whether they were obtained before (pre-BOS) or after manifestation of BOS (BOS group).The MMP-9/TIMP-1 ratio was significantly increased in the BOS group compared with non-BOS or pre-BOS; furthermore, the ratio was negatively correlated with forced expiratory volume in one second. In zymography, the active form of MMP-9 was detected predominantly in the BOS group. In addition, zymography showed the banding pattern of neutrophil-derived MMP-9, indicating that polymorphonuclear neutrophils (PMNs) were the main source of MMP-9. According to that, MMP-9 was significantly correlated with the number of PMN. In immunocytochemistry, MMP-9 was also associated predominantly with PMN. This is the first study to evaluate the expression of matrix metalloproteinase-9 and tissue inhibitors of metalloproteinases-1 over time during manifestation of a fibroproliferative lung disease in patients. It demonstrates development of bronchiolitis obliterans syndrome after lung transplantation is associated with an imbalance of matrix metalloproteinases-9/tissue inhibitors of metalloproteinase-1 ratio.

Background: Cytomegalovirus (CMV) is known as a common pathogen causing infections after lung transplantation. Rapid diagnosis of CMV infection is important for the initiation of a specific treatment. Objective: Evaluation of methods for the rapid diagnosis of CMV pneumonitis. Methods: The detection rates of CMV DNA in bronchoalveolar lavage (BAL) and bronchial brushes by polymerase chain reaction (PCR), of viral antigens (p52 and IE1) in BAL and of pp65 antigen in peripheral blood leukocytes were compared to the clinical status after lung transplantation. In 28 patients, 105 BAL, 96 blood samples and 14 brushes were analyzed. Results: In 6 patients, a total of eight episodes of CMV pneumonitis occurred. Five of the 6 with positive CMV antigens in BAL (p52 or IE1) showed signs of CMV pneumonitis. All episodes of CMV pneumonitis were detected by the PCR of BAL cells. Fourteen samples positive for CMV pp65 antigen in blood were negative in BAL PCR. In these cases, no clinical signs of pulmonary CMV infection occurred. Overall sensitivity, specificity, and positive and negative predictive values for the detection of CMV pneumonitis by PCR of BAL cells were 100, 98.9, 88.9 and 100%, respectively. In brush samples, PCR did not provide additional information to the results of the PCR of BAL cells. Conclusions: PCR of DNA from BAL cells is suitable for reliable and rapid detection of CMV pneumonitis.

Soluble HLA (sHLA) antigens were measured in a panel of 50 renal and 50 cardiac graft recipients by a quantitative ELISA over periods ranging between 2 months and 3 years. 72% of the renal patients and 68% of the cardiac graft patients experienced episodes of acute rejection during the observation period. sHLA were elevated to over 2-5 times the normal levels up to 10 days before histological evidence of rejection. This duration was for each individual patient very variable. Cytomegalovirus (CMV) infections did not appear to elevate sHLA levels. Donor-specific HLA-A2 was measured in only 1 cardiac recipient. 15% of the sera obtained from cardiac patients had cytotoxic anti-HLA antibodies, when tested against a panel of 50 test cells. After thermal inactivation at 56 degrees C, 42.5% of the sera became positive against at least 10% of the test cells. This finding suggests thermal dissociation of immune complexed anti-HLA antibodies. sHLA measurement and careful monitoring of serum for the presence of cytotoxic anti-HLA antibodies in graft patients are useful techniques which could help predict the long-term fate of an allograft.