Bronchiolitis obliterans/BO

The most common CTD throughout the world is rheumatoid arthritis (RA). Thoracic manifestations of RA are numerous (Table 1) including forms of ILD. The thoracic disease manifestations independent of ILD include pleural effusions, bronchiolitis obliterans (BO) without an organizing pneumonia, rheumatoid nodules, upper airway obstruction, and acute rheumatoid pneumonitis. 

Bronchiolitis obliterans (BO) with intraluminal polyps is characterized by the presence of buds or polyps of granulation tissue projecting or completely filling the lumens of membranous and/or respiratory bronchioles. These polyps can have a myxoid or pale staining matrix (rich in acid mucopolysaccharides) in which elongated myofibroblasts and inflammatory cells are embedded or they can be richer in collagen fibers. 

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.

Abbreviations BOS, bronchiolitis obliterans syndrome FEVi, forced expiratory volume in one second FEF, forced expiratory flow. 

Figure 3 CT of the chest in a patient with BO showing diffuse areas of parenchymal hypoattenuation, proximal bronchiectasis, and subsegmental bronchial dilatation Abbreviation BO, bronchiolitis obliterans CT, computed tomography. Source Adapted from Ref. 5.

Table 5.1.4. Timeline of complications following lung transplantation that may require intensive care unit treatment (from Lau et al. 2004). (BOS Bronchiolitis obliterans syndrome, CMV cytomegalovirus, GI gastrointestinal)...

---