Lung allograft loss: naming helps seeing... and vice versa!

The loss of allograft function in the long term (whatever its pattern over time) not only remains the single major cause of death following lung transplantation but has continued largely unabated since the beginning of the modern era in the 1980s [1–3]. As obliterative bronchiolitis (OB) was the most common histopathological finding on biopsy of the failing lung allograft, this feature became the unequivocal manifestation of chronic rejection in the lung allograft [3]. The logistical difficulties of obtaining frequent and numerous sampling biopsies to reliably and easily detect OB, however, led to another leap of faith where a syndromic definition (bronchiolitis obliterans syndrome; BOS) became the “working definition” of chronic rejection in the lung allograft [4]. BOS had both defining features that had to be present (irreversible loss in forced expiratory volume in 1 s (FEV1) as a percentage of the best achieved post-transplant) and exclusionary ones (the irreversible loss in FEV1 was “otherwise unexplained”; e.g. clinically relevant airways infection and aspiration had to be absent) [4, 5]. However, although the concept of BOS greatly increased the ease with which “chronic rejection” could be diagnosed after lung transplant, it also railroaded thinking for many years. In particular, a protocolised definition of chronic rejection through the diagnostic label of BOS hindered thoughts that infection (key non-alloimmune factor)and alloreactivity-associated obliterative bronchiolitis may not necessarily be independent events [6, 7] and that chronic rejection could either have a reversible component or manifest as a restrictive pattern of lung allograft loss [8].