Association of minimal rejection in lung transplant recipients with obliterative bronchiolitis

The clinical significance of minimal acute rejection (grade A,) in lung transplant recipients is unknown. We prospectively analyzed 1,159 transbronchial lung biopsies in 184 patients. Two hundred seventy-nine biopsies in 128 participants confirmed A, histology at a mean postoperative day of 229 +/- 340. Sixty four of 255 surveillance A, lesions progressed to high-grade acute rejection by 3 months of follow-up, whereas 40 developed new lymphocytic bronchiolitis. Twenty-four A, biopsies were symptomatic, with only two cases progressing to high-grade rejection after steroid therapy. Seventy-eight of 184 patients experienced multiple (greater than or equal to 2) A, biopsies in the first 12 months after transplant. Bronchiolitis obliterans syndrome developed in 68% of patients with multiple A(1) lesions at a mean of 599 +/- 435 days, compared with 43% of patients with one or less A, lesions at a mean of 819 +/- 526 (p = 0.022). Eighteen patients experienced multiple A, biopsies after transplant in the absence of high-grade rejection episodes yet also developed earlier obliterative bronchiolitis (456 +/- 245 days, p = 0.020). We conclude that for A(1) transbronchial lung biopsies, the conventional treatment of observation only is now challenged even in patients who are asymptomatic. Patients who experience multiple A(1) lesions develop an earlier onset of obliterative bronchiolitis and may warrant alternative immunosuppressive strategies.