111: Medical Management of Lung Transplant Patients

Introduction

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.

Immunosuppression

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 of acute rejection is 40% to 50% in the first posttransplant year, and 50% of patients will have developed chronic rejection by the fifth posttransplant year.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. Approximately 50% of lung transplant programs utilize some form of induction therapy.¹ 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 and equine polyclonal antithymocyte globulins (thymoglobulin and ATGAM, respectively), murine monoclonal anti-CD3 antibody (OKT3), and interluekin-2 (IL-2) receptor antagonists. Antithymocyte globulin and OKT3 act on the entire T-cell population. IL-2 receptor antibodies (e.g., basiliximab) 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 flu-like 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 of the induction agents increase the risk of infection. In one 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 OKT3.²

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. Intravenous (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 dose to reduce the risk of infection, ...