elastin and Bronchiolitis-Obliterans

Refractory lung function decline in association with recurrent pulmonary exacerbations is a common, yet poorly explained finding in cystic fibrosis (CF). To investigate the histopathologic mechanisms of pulmonary deterioration during adolescence and early adulthood, we reviewed clinically-indicated lung biopsy specimens obtained during a period of persistent decline.. To determine if peribronchiolar remodeling is prominent in lung biopsy specimens obtained in adolescents with CF refractory to conventional therapy.. All computed tomography scans demonstrated a mix of bronchiectasis and hyperinflation that was variable across lung regions and within patients. Lung biopsy revealed significant peribronchiolar remodeling, particularly in patients with more advanced disease, with near complete obliteration of the peribronchiolar lumen (constrictive bronchiolitis). Myofibroblast differentiation (a TGF-β-dependent process) was prominent in specimens with significant airway remodeling.. Constrictive bronchiolitis is widely present in the lung tissue of adolescents with CF with advanced disease and may contribute to impaired lung function that is refractory to conventional therapy (antibiotics, antiinflammatories, and mucolytics). TGF-β-dependent myofibroblast differentiation is prominent in areas of active fibrogenesis and may foster small airway remodeling in CF lung disease.

Topics: Adolescent; Airway Remodeling; Bronchiolitis Obliterans; Case-Control Studies; Child; Cystic Fibrosis; Disease Progression; Elastin; Female; Fibrosis; Humans; Lung; Male; Myofibroblasts; Spirometry; Tomography, X-Ray Computed; Transforming Growth Factor beta; Young Adult

This study presents four patients who underwent bone marrow transplantation and subsequently developed pleuroparenchymal fibroelastosis, hitherto reported as an idiopathic condition. All presented clinically with pneumothorax and subpleural fibrosis on high-resolution computed tomography. In addition to the expected obliterative bronchiolitis, histopathology showed coexistent subpleural changes, and the relationship of pathology in multiple anatomic compartments in post bone marrow transplantation pulmonary disease is discussed.

Topics: Adolescent; Adult; Autopsy; Bone Marrow Transplantation; Bronchiolitis Obliterans; Elastin; Fatal Outcome; Female; Glucocorticoids; Humans; Lung; Male; Middle Aged; Pleural Diseases; Pneumonectomy; Pneumothorax; Pulmonary Fibrosis; Recurrence; Thoracic Surgery, Video-Assisted; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

Constrictive bronchiolitis obliterans is a fibrotic disease of small airways characterized by progressive obliteration of the airway lumen, with resulting obstructive pulmonary physiology. While previous work has demonstrated the collagenous nature of the constrictive fibrotic lesions, elastin expression in the disease has been poorly characterized. Elastin is a critical component of the pulmonary extracellular matrix, and is responsible for the reversible deformability characteristic of the alveoli, pulmonary blood vessels, and airways. Elastin is a long-lived protein with virtually no active protein production occurring after lung development is completed during early childhood. We report a novel case of cryptogenic bronchiolitis obliterans in which elastin gene expression is actively upregulated in affected airways, and accompanied by myofibroblast hyperplasia and disorganized elastic fiber deposition. In addition, deposition of new elastic fibers by myofibroblasts is noted in the alveoli surrounding the affected bronchioles.

Topics: Bronchiolitis Obliterans; Elastin; Gene Expression; Humans; Male; Middle Aged; United States; Up-Regulation