Postinfectious bronchiolitis obliterans in children: lessons from bronchiolitis obliterans after lung transplantation and hematopoietic stem cell transplantation

Abstract

Postinfectious bronchiolitis obliterans (PIBO) is an irreversible obstructive lung disease characterized by subepithelial inflammation and fibrotic narrowing of the bronchioles after lower respiratory tract infection during childhood, especially early childhood. Although diagnosis of PIBO should be confirmed by histopathology, it is generally based on history and clinical findings. Irreversible airway obstruction is demonstrated by decreased forced expiratory volume in 1 second with an absent bronchodilator response, and by mosaic perfusion, air trapping, and/or bronchiectasis on computed tomography images. However, lung function tests using spirometry are not feasible in young children, and most cases of PIBO develop during early childhood. Further studies focused on obtaining serial measurements of lung function in infants and toddlers with a risk of bronchiolitis obliterans (BO) after lower respiratory tract infection are therefore needed. Although an optimal treatment for PIBO has not been established, corticosteroids have been used to target the inflammatory component. Other treatment modalities for BO after lung transplantation or hematopoietic stem cell transplantation have been studied in clinical trials, and the results can be extrapolated for the treatment of PIBO. Lung transplantation remains the final option for children with PIBO who have progressed to end-stage lung disease.

Keywords: Bronchiolitis obliterans; Child; Fibrosis; Inflammation; Post-infectious.

Fig. 1. Pathogenesis of postinfectious bronchiolitis obliterans. (1) Epithelial injury is induced by lower respiratory tract infection with microorganisms such as virus or mycoplasma. (2) Epithelial cells release interleukin (IL) 8 and other proinflammatory mediators, which recruit neutrophils and other inflammatory cells to the small airway. (3) Matrix metalloproteinase (MMP) and profibrotic cytokines and mediators are released from those cells, resulting in matrix degradation, collagen deposition, fibroblast proliferation, and ultimately, peribronchial fibrosis. (4) CD8+ T cells play a predominant role in epithelial injury and chronic inflammation after viral infection. (5) Th17 cells are involved in tissue remodeling, and IL-17 induces IL-8 secretion, which is related to airway neutrophilia.