tacrolimus and Bronchitis

The optimal maintenance immunosuppressive regimen after lung transplantation is uncertain.. We conducted a randomized controlled trial of tacrolimus versus cyclosporine in combination with azathioprine and prednisone after lung transplantation. Ninety adults were randomized to tacrolimus (n = 44) or cyclosporine (n = 46). The primary end point was a composite of a cumulative acute rejection A score of 3 or higher, a cumulative lymphocytic bronchitis B score of 4 or higher, or the onset of bronchiolitis obliterans syndrome (BOS) stage 0-p.. Recipients randomized to cyclosporine were significantly more likely to develop the primary end point than those randomized to tacrolimus. During the study period, the primary end point developed in 39 of 46 cyclosporine subjects compared with 24 of 44 tacrolimus subjects (p = 0.002); acute rejection or lymphocytic bronchitis end points developed in 29 of 46 cyclosporine subjects compared with 18 of 44 tacrolimus subjects (p = 0.036). Furthermore, BOS stage 0-p was more likely to develop in the cyclosporine group than in the tacrolimus group, but this was not statistically significant (log-rank p = 0.1). In addition, there was a trend to a higher incidence of diabetes among those in the tacrolimus group, but there was no significant difference in graft survival or the total number of infections, or in the incidence of hypertension, chronic kidney disease, or cancer between the 2 groups.. Tacrolimus is associated with a lower burden of acute rejection and lymphocytic bronchitis and a trend to a greater freedom from BOS stage 0-p than cyclosporine after lung transplantation.

Topics: Adult; Azathioprine; Bronchiolitis Obliterans; Bronchitis; Cyclosporine; Diabetes Mellitus; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Lung Transplantation; Male; Middle Aged; Postoperative Care; Tacrolimus

Immunosuppressive regimens for lung transplantation frequently fail to prevent rejection and are toxic. Alemtuzumab was used as induction to investigate whether oral immunosuppression could be reduced. From November 2006 to March 2008, 20 consecutive lung transplant patients received alemtuzumab induction, with reduced maintenance immunosuppression; tacrolimus (target level 10 ng/ml), mycophenolate mofetil (MMF) 250 mg bid and prednisone 7.5 mg. Twenty control cases transplanted before 2006 were treated with standard immunosuppression; tacrolimus (target level 10 ng/ml), MMF 750 mg bid and prednisone 15 mg qd. End-points included patient and graft survival, acute rejection (AR) and infection rate. There were no significant differences in six-month and 12-month survival (alemtuzumab 90% vs. controls 95%, P=0.52 and 76% vs. 95%, respectively, P=0.19). AR events were similar (alemtuzumab 2/16 vs. controls 5/20, P=0.43) - as were - bacteria positive bronchoalveolar lavage (BAL) cultures (alemtuzumab 4.9+/-7.3 per patient per year vs. controls 2.7+/-3.3, P=0.26) and viral or fungal infections (alemtuzumab 0.4+/-1.4 per patient per year vs. controls 0.1+/-0.3, P=0.87; alemtuzumab 3.9+/-6.6 vs. controls 2.3+/-1.9, P=0.57, respectively). Alemtuzumab induction and reduced immunosuppression appears to offer comparable early survival, rejection and infection rates to high-dose standard immunosuppression.

Topics: Administration, Oral; Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Bronchitis; Drug Therapy, Combination; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Kaplan-Meier Estimate; Length of Stay; Lung Transplantation; Male; Middle Aged; Mycophenolic Acid; Mycoses; Prednisone; Respiratory Function Tests; Retrospective Studies; Risk Assessment; Tacrolimus; Time Factors; Treatment Outcome; Virus Diseases

Guinea-pigs sensitized by a subcutaneous injection of ovalbumin in Al(OH)3 and boosted 2 weeks later exhibit marked bronchial hyperresponsiveness to various agonists and intense bronchial wall infiltration by CD4+ T-lymphocytes and eosinophils. We have compared the effect of FK506, a novel immunosuppressive agent, on the mucosal infiltration by T-cells and eosinophils with the well established drugs, nedocromil sodium and dexamethasone. Sensitized Hartley guinea-pigs were treated subcutaneously for 5 days with FK506 (100 micrograms.kg-1 daily), nedocromil sodium (30 micrograms.kg-1 daily), or dexamethasone (200 micrograms.kg-1 daily). On the day of the experiment, i.e. one week after the booster injection of antigen, the animals were killed, the lungs dissected, frozen and cryostat sections stained by immunohistochemical methods using monoclonal antibodies specific for total T-lymphocytes, CD4+ and CD8+ T-cells. Cyanide-resistant eosinophil peroxidase activity was used to stain the eosinophils. Sections were coded and positive cells enumerated in the lamina propria and adventitia of the bronchi. Sensitized and antigen-stimulated vehicle-treated guinea-pigs showed marked infiltration of the bronchial wall by CD4+ T-lymphocytes and eosinophils compared with sensitized, non-antigen stimulated animals. As compared to vehicle, FK506 or dexamethasone abolished the T-cell/eosinophil invasion in the bronchial wall, whereas nedocromil sodium was ineffective in protecting the lungs from T-lymphocyte or eosinophil infiltration. We conclude that both FK506 and dexamethasone are effective in curtailing bronchial inflammation in allergic guinea-pigs, whereas nedocromil sodium did not resolve the inflammation associated with T-lymphocytes or eosinophils.

Topics: Animals; Anti-Inflammatory Agents; Antigens; Bronchi; Bronchitis; Dexamethasone; Eosinophil Peroxidase; Eosinophils; Guinea Pigs; Immunization; Inflammation; Lung; Male; Mucous Membrane; Nedocromil; Ovalbumin; Peroxidases; Respiratory Hypersensitivity; T-Lymphocytes; Tacrolimus