Chronic Lung Transplant Rejection

Epidemiology

-Peak incidence: 16-20 months post-transplant (but may occur as early as 3 months and as late as years later)
-Incidence: 35-50% (early literature, prior to current immunosuppressives, cited incidence as high as 60%)
-Risk factors for chronic rejection:
1) Severe, recurrent, or persistent acute rejection (most strongly linked risk factor): see above
2) CMV infection (possible)
3) Bacterial pneumonia (possible)
4) Lymphocytic bronchiolitis (possible)
5) Organizing pneumonia (possible)

-Maintenance immunosuppression with tacrolimus vs CSA: demonstrated no difference in episodes of acute rejection but a decreased incidence of chronic rejection (Ann Thor Surg 1995; 60: 580)/ prolonged survival with tacrolimus (J Thor Cardiovasc Surg 1995; 109: 49)

Diagnosis

PFT’s: obstruction (occasionally also restriction)
-Bronchiolitis obliterans syndrome (BOS) staging (with or without histologic confirmation):
1) Stage 0: no significant BO with FEV1 >80% of baseline
2) Stage 1: mild BO with FEV1 66-80% of baseline
3) Stage 2: moderate BO with FEV1 51-65% of baseline
4) Stage 3: severe BO with FEV1 50% of baseline
FOB:
-BAL:
-TBB: pathology is consistent with bronchiolitis obliterans/ also useful to rule out infection
–Sensitivity for chronic rejection ranges from 5-100% in studies
OLB:

CXR/Chest CT patterns: usually unchanged from baseline
HRCT: may reveal peripheral bronchiectasis/ patchy consolidation/ decreased peripheral vascular markings
-Expiratory air trapping is a sensitive and accurate predictor of brocnhiolitis obliterans in this patient population

Clinical

Cough/dyspnea: may mimic a URI

Treatment

Solumedrol pulse: as above

Antithymocyte globulin/ antilymphocyte globulin/ OKT3:
Tacrolimus: inhibits IL-2 gene expression with suppression of T-cell activation and proliferation

Mycophenolate mofetil: inhibition of purine synthesis (similar to azathioprine)

Methotrexate:

Total lymphoid radiation:

Photophoresis:

Aerosolized CSA:

Prognosis

Chronic rejection is the major cause of late morbidity and mortality post-transplant
Typically poor responsiveness to therapy (best responses usually are represented by stabilization of pulmonary function deterioration)