Study objectives: Acquired tracheal and subglottic stenosis frequently leads to severe airway narrowing, which requires repeated interventions, such as dilatation, laser resection, stent implantation, or surgery. To get a more detailed insight into the pathogenesis of this condition, we investigated the expression of profibrotic cytokines and the proliferation of the airway wall in benign human airway stenoses.
Methods: Specimens from patients with subglottic and tracheal stenosis and stent-related stenoses were obtained (n = 20) for reverse transcription (RT) polymerase chain reaction (PCR) analysis and immunohistochemistry testing.
Results: Transforming growth factor (TGF)-β1 messenger RNA expression was significantly increased in biopsy specimens from stent-related stenoses compared to nonstenotic control sections. In contrast, TGF-β3 and interleukin-1β showed no such differences in messenger RNA expression. Immunohistochemistry revealed a strong matrix-associated, subepithelial expression of TGF-β1 in tracheal stenosis. Proliferating Ki-67-positive cells were mainly localized in the basal epithelial layer. Only 2 of 16 patients with tracheal stenoses and 3 of 4 patients with stent-related stenoses showed a weak expression of Ki-67-positive cells in the subepithelium. Furthermore, TGF-β1 dose-dependently enhanced the proliferation of human lung fibroblasts in vitro, even in the presence of mitomycin-C.
Conclusion: While a weak subepithelial proliferation occurs in stent-related stenoses, the dominant factor in late stages of untreated tracheal stenoses seems to be the high-level expression of TGF-β1 and the deposition of extracellular matrix.