Antibody-mediated rejection (AMR) is a recognized cause of allograft dysfunction in lung transplant recipients. Unlike AMR in other solid-organ transplant recipients, there are no standardized diagnostic criteria or an agreed-upon definition. Hence, a working group was created by the International Society for Heart and Lung Transplantation with the aim of determining criteria for pulmonary AMR and establishing a definition. Diagnostic criteria and a working consensus definition were established. Key diagnostic criteria include the presence of antibodies directed toward donor human leukocyte antigens and characteristic lung histology with or without evidence of complement 4d within the graft. Exclusion of other causes of allograft dysfunction increases confidence in the diagnosis but is not essential. Pulmonary AMR may be clinical (allograft dysfunction which can be asymptomatic) or sub-clinical (normal allograft function). This consensus definition will have clinical, therapeutic and research implications.

Severity of lymphocytic bronchiolitis is associated with increased risk of BOS and death after lung transplantation independent of acute vascular rejection.

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The clinical significance of minimal acute rejection (grade A1) 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 A1 histology at a mean postoperative day of 229 +/- 340. Sixty four of 255 surveillance A1 lesions progressed to high-grade acute rejection by 3 months of follow-up, whereas 40 developed new lymphocytic bronchiolitis. Twenty-four A1 biopsies were symptomatic, with only two cases progressing to high-grade rejection after steroid therapy. Seventy-eight of 184 patients experienced multiple (> or = 2) A1 biopsies in the first 12 months after transplant. Bronchiolitis obliterans syndrome developed in 68% of patients with multiple A1 lesions at a mean of 599 +/- 435 days, compared with 43% of patients with one or less A1 lesions at a mean of 819 +/- 526 (p = 0.022). Eighteen patients experienced multiple A1 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 A1 transbronchial lung biopsies, the conventional treatment of observation only is now challenged even in patients who are asymptomatic. Patients who experience multiple A1 lesions develop an earlier onset of obliterative bronchiolitis and may warrant alternative immunosuppressive strategies.