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In addition to representing a significant surgical challenge, successful medical management of the lung transplant patient is a very complex issue. The protocol for medical management has evolved over time. The focus of care in this patient population is fourfold: immunosuppression, graft rejection, complications arising from infection, and other medical complications.

To attenuate graft injury owing to immunologic rejection, all lung transplant patients require lifelong systemic immunosuppression. The morbidity associated with mandatory immunosuppression is a key to the complexity of medical care for this patient group.

Induction Therapy

The risk for acute rejection of transplanted lungs begins in the first days and weeks of the postoperative period.1 To ameliorate this risk, clinicians have adopted an early and aggressive postoperative immunosuppression strategy using prophylactic T-cell depletion, commonly referred to as induction therapy. One small randomized study found that the incidence of acute rejection was 23% in the group treated with induction therapy compared with 55% in the controls.2 In addition to mitigating the incidence of acute rejection, induction therapy also has the advantage of delaying the use of the traditional immunosuppressants (i.e., calcineurin inhibitors) in the immediate postoperative period when the nephrotoxicity induced by these medications is potentially more harmful to the patient.

The standard choices for induction include rabbit or equine polyclonal antithymocyte globulin (Thymoglobulin and ATGAM, respectively) and murine monoclonal anti-CD3 antibody (OKT3). All these agents act on the entire T-cell population. Additionally, recently there has been increased interest in interleukin 2 (IL-2) receptor antibodies (e.g., daclizumab and basiliximab) that target the IL-2 receptor alpha chain, which is found selectively on activated T cells. Both antithymocyte globulin and OKT3 work by depleting the number of circulating lymphocytes, resulting in a predictable lymphopenia. Both antibodies are also associated with thrombocytopenia and flulike illness with fever and chills. A more dramatic release of cytokines (i.e., tumor necrosis factor, IL-2, and γ-interferon) with subsequent cardiovascular collapse has been described with the use of OKT3. All the induction agents increase the risk of infection. In the only study comparing the three main agents, there was no difference in episodes of acute rejection, episodes of bronchiolitis obliterans syndrome (BOS), or survival at 2 years, although there was a statistically significant risk of increased infection with OKT3.3

Maintenance Therapy

Long-term immunosuppression is a core component of medical care. Most lung transplant patients are maintained on a three-medication regimen consisting of an oral corticosteroid, a calcineurin inhibitor (i.e., cyclosporine or tacrolimus), and a purine synthesis inhibitor [i.e., azathioprine or mycophenolate mofetil (MMF)].

Most clinicians initiate corticosteroids in the early postoperative period. IV dosing of moderate to high levels of drug is administered during the first week, and patients are thereafter transitioned to oral glucocorticoids, traditionally prednisone. Although lung transplant patients are maintained on glucocorticoids for the long term, attempts are made to minimize the ...

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