Obliterative bronchiolitis rejection

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Barlow, C.W. Moon, M.R. Green, G.R. Gamberg, P. Theodore, J. Reitz, B.A. Robbins, R.C. Rabbit antilymphocyte globulin versus OKT3 induction therapy after heart-lung and lung transplantation effect on survival, rejection, infection, and obliterative bronchiolitis. Transplant Int. 2001, 14, 234-239. 

Figure 2 (A). Typical FEVi evolution in a patient with late acute BOS. After a very stable period of several years, there is a documented acute rejection episode (arrow), with some improvement of the FEVi after classical treatment, however, quickly followed by a very rapid decline in the FEVi, indicative of fBOS. (B). Natural evolution of FEVi in a patient with slowly progressing BOS and biopsy-proven OB. During the last months of evolution, there appears to be a spontaneous arrest in the FEVi decline. This is compatible with the NRAD phenotype, left untreated and leading to pure OB at the end. (C). Another patient with BOS, who has a spontaneous arrest of the FEVi decline, with a plateau, reached after several months of evolution. Abbreviations. FEVi, forced expiratory volume in one second BOS, bronchiolitis obliterans syndrome fBOS, fibrotic BOS OB, obliterative bronchiolitis NRAD, neutrophilic reversible allograft dysfunction.

Figure 4 Possible pathophysiologic events involving innate and adaptive immunity, leading to BOS/OB. Repeat milder stimuli to the respiratory epithelium (such as for instance GER, colonization, etc.) may lead to stimulation of innate immunity ending up in neutrophilic airway inflammation, which may be reversible upon treatment with azithromycin. However, if left untreated, chronic neutrophilic inflammation and increased oxidative stress may further stimulate fibroblast activation, epithelial to mesenchymal transition, with migration of (myo)fibroblasts, leading to fibrosis of the airway wall and fibrotic plugs in the airways, typically for OB. A more severe epithelial injury (as for instance in acute rejection and CMV infection) may directiy lead to fibroblast activation and OB in a short time period, without any neutrophils being present in the airways. Abbreviations BOS, bronchiolitis obliterans syndrome OB, obliterative bronchiolitis GER, gastroesophageal reflux CMV, c) tomegalovirus.

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