tacrolimus and Tracheal-Stenosis

Acquired laryngotracheal stenosis is a challenging problem for otolaryngologists. Several studies suggest tacrolimus may inhibit post-transplant airway stenosis that occurs with coronary drug-eluting stents. The objective of the present study was to determine whether tacrolimus modulates wound healing of the airway mucosa and prevents laryngotracheal stenosis in an acute injury animal model.. Basic science.. The laryngotracheal mucosa of rats was scraped with a nylon brush through the tracheostoma. Tacrolimus (0.2 mg/kg or 1.0 mg/kg) was systemically administered intramuscularly for 5 days. Nine days after scraping, the pathological changes and the degree of stenosis were assessed by hematoxylin and eosin staining or by immunohistochemical staining for nuclear factor of activated T cell and interleukin 2.. Lumen stenosis resulted from hyperplasia of the airway epithelium and a thickened submucosal layer with extensive fibrosis, angiogenesis, and collagen deposition. There was a significant preventive effect on airway stenosis at the tracheal and cricoid levels in the low-dose (0.2 mg/kg) tacrolimus-treated animals, compared to the untreated animals (P < .05). This effect was insignificant with treatment by high-dose tacrolimus (1.0 mg/kg). Immunohistochemistry showed that, after tacrolimus treatment, the expressions of nuclear factor of activated T cell and interleukin 2 were downregulated in submucosal fibroblasts, neovascular cells, and glandular cells.. This study suggests that low-dose systemic tacrolimus has a preventive effect on laryngotracheal stenosis by inhibiting the activation of immune cells in the injured airway mucosa via the calcineurin/nuclear factor of activated T cell/interleukin 2 pathway.. NA.

Topics: Animals; Calcineurin Inhibitors; Disease Models, Animal; Laryngostenosis; Larynx; Male; Rats; Rats, Sprague-Dawley; Tacrolimus; Trachea; Tracheal Stenosis

The use of self-expanding metallic airway stents has been extended in recent years in inoperable patients with malignant and benign airway diseases. The risk of granulation tissue formation in the stent is a major concern. The objective of the present study was to determine whether immunosuppression modulates granulation tissue formation in airway stents, as seen in coronary stents.. The study included 19 patients with benign airway obstructions and 11 recipients of lung transplants with anastomotic obstructions who were receiving immunosuppression therapy.. The degree of in-stent granulation tissue formation was evaluated (score range, 0-3) every 3 months for 2 years.. Granulation tissue formation was significantly lower in the transplant recipients than in the nontransplant patients at 3 months (score 0.7 vs. 1.6, P = .031), 15 months (score 0 vs. 1.1, P = .026), and 18 months (score 0 vs. 1.8, P = .020). During the 2 years of follow-up, the transplant recipients underwent significantly fewer laser resections and brachytherapy treatments for in-stent granulation.. The immunosuppression given to lung transplant recipients may have an inhibitory effect on granulation tissue formation in metallic airway stents. Further studies are needed to evaluate the effect of systemic therapy or coated stents with drugs such as sirolimus.

Topics: Adult; Aged; Airway Obstruction; Bronchoscopy; Dyspnea; Female; Granulation Tissue; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Lung Transplantation; Male; Methylprednisolone; Middle Aged; Stents; Surgical Wound Dehiscence; Tacrolimus; Tracheal Stenosis