BRONCHIOLAR BASEMENT-MEMBRANE CHANGES AND BRONCHIOLITIS OBLITERANS INLUNG ALLOGRAFTS STUDY

Lung transplantation is an accepted mode of therapy for selected patie nts with end-stage lung disease. Their long-term survival is mainly li mited by chronic rejection, i.e., bronchiolitis obliterans (BO), which represents a fibrosing inflammatory process of the terminal and respi ratory bronchioles, leading to progressive small airway obstruction, T o evaluate its development, and associated irreversible allograft dysf unction, we retrospectively studied the histological and clinical data from nine patients who developed BO, and nine matched control patient s. A total of 152 serial transbronchial biopsies (87 from patients wit h BO; 65 from the control group) were studied using immunohistochemica l stains, with antibodies to laminin, desmin, fibronectin, collagen IV , collagen III, and vimentin. The staining with anti-collagen IV antib ody was the most productive and in eight of the nine patients with BO demonstrated early focal bronchiolar basement membrane damage, manifes ted by thickening and subsequent splitting and duplication. This was s een in association with the second episode and onward of clinically si gnificant episodes of acute cellular rejection which occurred 7 to 12 months posttransplant. The larger airways were unaffected. The histolo gical onset of BO exhibited varying degrees of obstruction of the bron chioles with no detectable basement membrane staining. The control pat ients failed to demonstrate these findings, The other immunohistochemi cal 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 lun g allograft recipients who have multiple episodes of clinically signif icant acute cellular rejection and later develop BO.