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Table 12.6. Working formulation for classification and grading of pulmonary rejection

A. Acute rejection

0. Grade 0-no significant abnormality

1. Grade 1-minimal acute rejection

2. Grade 2-mild acute rejection

3. Grade 3-moderate acute rejection

4. Severe acute rejection

B. Airway damage without scarring

1. Lymphocytic bronchitis

2. Lymphocytic bronchiolitis

C. Chronic airway rejection

1. Bronchiolitis obliterans, subtotal a. active b. inactive

2. Bronchiolitis obliterans a. active b. inactive

D. Chronic vascular rejection

E. Vasculitis previously stable baseline), and pulmonary infiltrates may develop on chest roentgenograms (in particular a peri-hilar or basal haziness)- The main differential diagnosis in the early post-operative period includes acute rejection, bacterial sepsis, and pulmonary edema (resulting either from reperfusion injury or fluid overload). Later in the post-transplant period, a similar constellation of clinical features may be noted, but the chest x-ray is often not abnormal.

The main concern during these later episodes of decline in graft function is making the distinction between acute rejection and CMV infection, which generally cannot be made without a biopsy.50 In the past, antirejection therapy was given based upon clinical findings alone, allowing the diagnosis of acute rejection to be made in retrospect if there was an improvement in the clinical picture. Currently, an aggressive approach for documenting acute rejection with FOB and TBLB is used. The TBLB specimens allow histologic detection of the presence and grade of acute rejection, cytomegalic inclusions, and OB. The key histologic finding in acute lung allograft rejection is that of perivascular mononuclear cell infiltrates. A working formulation has been developed and is shown in Table 12.6.53 Bronchoalveolar lavage is done concomitant to TBLB but is useful mainly in identifying the presence of infection.

Acute rejection can be effectively controlled in most patients. Trulock has summarized the approach to treatment of acute lung transplant rejection and is similar to that followed by most lung transplant programs.49 The basic components include:

1. High dose corticosteroids. This is usually given in the form of an intravenous bolus of methylprednisolone, 500-1000 mg daily for 3 days. Most patients respond to the first course of methylprednisolone.

2. An increase in the maintenance prednisone dose to 1mg/kg/day, then tapering back to the previous dose over 2 to 3 weeks.

This approach has been found to be most useful in treating severe acute rejection episodes, especially if the oral prednisone dose has been drastically diminished or discontinued.

3. Persistent rejection despite the previous intervention is distinctly unusual but requires cytolytic therapy. Options include the use of OKT3 monoclonal antibody (5 mg/day for 10 to 14 days), or anti-thymocyte globulin (ATGAM, 10-20 mg/kg/day for 10 to 14 days) or rescue use of tacrolimus.42-43

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