Bronchiolar basement membrane changes associated with bronchiolitis obliterans in lung allografts: a retrospective study of serial transbronchial biopsies with immunohistochemistry [corrected].

Lung transplantation is an accepted mode of therapy for selected patients with end-stage lung disease. Their long-term survival is mainly limited by chronic rejection, i.e., bronchiolitis obliterans (BO), which represents a fibrosing inflammatory process of the terminal and respiratory bronchioles, leading to progressive small airway obstruction. To evaluate its development, and associated irreversible allograft dysfunction, we retrospectively studied the histological and clinical data from nine patients who developed BO, and nine matched control patients. A total of 152 serial transbronchial biopsies (87 from patients with BO; 65 from the control group) were studied using immunohistochemical stains, with antibodies to laminin, desmin, fibronectin, collagen IV, collagen III, and vimentin. The staining with anti-collagen IV antibody was the most productive and in eight of the nine patients with BO demonstrated early focal bronchiolar basement membrane damage, manifested by thickening and subsequent splitting and duplication. This was seen in association with the second episode and onward of clinically significant episodes of acute cellular rejection which occurred 7 to 12 months posttransplant. The larger airways were unaffected. The histological onset of BO exhibited varying degrees of obstruction of the bronchioles with no detectable basement membrane staining. The control patients failed to demonstrate these findings. The other immunohistochemical stains used were found to be noncontributory. We conclude that the usage of anti-collagen IV on lung allograft biopsies demonstrates the sequential changes of bronchiolar basement membrane disruption in lung allograft recipients who have multiple episodes of clinically significant acute cellular rejection and later develop BO.