Question

Immunosuppressive therapy in lung transplantation.

Hint:

The main challenge in immunosuppressive therapy is balancing the prevention of rejection with minimizing side effects such as infections and cancer. Close monitoring is essential.

Answer 1

Immunosuppressive therapy is critical in lung transplantation to prevent rejection of the transplanted lung. It involves the use of drugs that suppress the recipient's immune system to reduce the risk of immune-mediated graft rejection. However, these drugs also increase the risk of infection and malignancy.
Step 1: Purpose of Immunosuppressive Therapy:
- Preventing Acute Rejection: The primary goal is to prevent acute rejection episodes, which are caused by the immune system attacking the transplanted lung as foreign tissue.
- Long-term Graft Survival: Immunosuppressive therapy helps maintain the function of the transplanted lung over the long term and prevents chronic rejection (bronchiolitis obliterans syndrome).
Step 2: Common Immunosuppressive Drugs:
- Corticosteroids: These are used initially to control rejection and inflammation. However, long-term use can lead to side effects such as osteoporosis, diabetes, and infections.
- Calcineurin Inhibitors (Tacrolimus, Cyclosporine): These drugs inhibit T-cell activation and are the cornerstone of immunosuppressive therapy. They are essential for both acute and chronic rejection prevention.
- Antimetabolites (Mycophenolate Mofetil, Azathioprine): These drugs inhibit the proliferation of T-cells and B-cells, reducing immune system activation. They are often used in conjunction with calcineurin inhibitors.
- mTOR Inhibitors (Sirolimus, Everolimus): These are used to inhibit T-cell proliferation and provide an alternative for patients who cannot tolerate calcineurin inhibitors.
Step 3: Monitoring and Adjusting Immunosuppressive Therapy:
Immunosuppressive drug levels must be closely monitored to balance the risk of rejection with the risk of infection. Regular blood tests are used to adjust the dosages to ensure optimal therapeutic levels. The aim is to minimize toxicity while preventing rejection.
Step 4: Side Effects and Risks:
- Infections: Immunosuppressive therapy increases the risk of bacterial, viral, and fungal infections. Prophylactic antimicrobials are often used during the early post-transplant period.
- Cancer: Chronic immunosuppression increases the risk of malignancies, particularly skin cancers, lymphoma, and Kaposi's sarcoma. Regular screening and sun protection are recommended.
- Renal and Hepatic Toxicity: Some immunosuppressive drugs can cause kidney or liver damage, and renal function needs to be monitored.