Evaluation and Comparison of Treatment with Polymerised Collagen or Pirfenidone as Stand-Alone Therapy on the Production of Profibrotic Factors in Tracheal Stenosis and Tracheal Anastomosis Scarring After Resection

Polymerised type I collagen (polymerised collagen) and pirfenidone (PFD) reduce fibrosis. However, their use as pharmacological monotherapy for tracheal stenosis (TS) has not been evaluated. This study aimed to evaluate the effects of polymerised collagen or PFD, used either as monotherapy for TS, or in combination with tracheal resection (TRE) on the development of restenosis (RTS), apoptotic body (AB) formation, production of profibrotic proteins, ITGβ1 expression and metalloproteinase (MMP) expression in a rat model of TS. Eighty Wistar rats underwent TS. Forty received monotherapy (treatment A) with: saline solution (SS), mitomycin C (MMC), polymerised collagen, or PFD. The other forty received TRE combined with the pharmacological treatment (treatment B). They were clinically evaluated. Four weeks after treatment, AB formation, ITGβ1, TGF-β, profibrotic proteins, and MMPs expression were assessed in TS tissue and post-TRE tissue. Our findings showed that treatment A with polymerised collagen or PFD did not reverse TS but halted its progression, reduced the expression of profibrotic proteins, ITGβ1 and MMP-9, and increased AB and MMP-1. Treatment B promoted normal tracheal healing and prevented RTS. We conclude that the use of polymerised collagen or PFD as monotherapy does not reverse TS. However, they halt disease progression by modulating the production of profibrotic factors. In combination with TRE, these agents promote favourable tracheal healing and prevent RTS.