Bronchiolitis Obliterans Syndrome Complicating Lung or Heart-Lung Transplantation

John A. Belperio, MD; Kathleen Lake, PharmD; Henry Tazelaar, MD; Michael P. Keane, MD; Robert M. Strieter, MD; Joseph P. Lynch, III, MD


Semin Respir Crit Care Med. 2003;24(5) 

In This Article

Histology of Allograft Rejection

Acute rejection (AR) occurs in > 85% of LTRs to some degree.[1,21,22] The histopathology of AR ( Table 1 ) is characterized by dense infiltration with CD8(+) lymphocytes; this infiltrate may be localized to the perivascular regions or may involve the bronchial and bronchiolar epithelium and submucosa to produce a lymphocytic bronchitis/bronchiolitis (LBB).[1,21,23] Extension into the alveolar interstitium and alveolar spaces may cause parenchymal injury.[24] Although LBB may be observed concomitantly with AR,[23,24] LBB is often a precursor to BOS,[5,25,26] particularly at later time points posttransplant.[27]

BO, a manifestation of chronic rejection, is a cicatricial process affecting the small airways of the lung allograft. It is hypothesized that the initial process is a peribronchiolar lymphocytic infiltration in the submucosa of the airways that invades/disrupts the basement membrane and injures epithelial cells (ECs).[5,11,12,13] EC necrosis, elicitation of nonspecific inflammatory mediators, and cytokines recruit neutrophils, fibroblasts (FBs), and myofibroblasts. This is followed by fibroproliferation with increased numbers of mesenchymal cells, extracellular matrix (ECM) deposition, and granulation tissue formation within/around the lumen of the allograft airway[12,13] (Figs. 1 and 2). Ultimately, smooth muscle cells, myofibroblasts, and mature collagen obliterate the airways ("vanishing airways disease").[7,12,13]

Chronic airway rejection [International Society of Heart and Lung Transplantation (ISHLT)]. Bronchiole with lumen filled by a combination of granulation tissue and chronic inflammatory cells. An arrow highlights the smooth muscle. Normally, the bronchiolar epithelium lies immediately adlumenal. In this case, the lumen is completely obliterated. Hematoxylin-eosin, high power.

Chronic airway rejection [International Society of Heart and Lung Transplantation (ISHLT)]. Bronchiolar lumen (*), which is severely compromised by dense connective tissue (**) that lies between the epithelium and the elastic lamina (arrows). The adjacent artery and its lumen (***) are normal. Verhoeff von Gieson, high power.


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