sirolimus and Tracheal-Stenosis

Recent material science advancements are driving tracheal stent innovation. We sought to assess the state of the science regarding materials and preclinical/clinical outcomes for tracheal stents in adults with benign tracheal disease.. A comprehensive literature search in April 2021 identified 556 articles related to tracheal stents. One-hundred and twenty-eight full-text articles were reviewed and 58 were included in the final analysis. Datapoints examined were stent materials, clinical applications and outcomes, and preclinical findings, including emerging technologies.. In the 58 included studies, stent materials were metals (n = 28), polymers (n = 19), coated stents (n = 19), and drug-eluting (n = 5). Metals included nitinol, steel, magnesium alloys, and elgiloy. Studies utilized 10 different polymers, the most popular included polydioxanone, poly-l-lactic acid, poly(d,l-lactide-co-glycolide), and polycaprolactone. Coated stents employed a metal or polymer framework and were coated with polyurethane, silicone, polytetrafluoroethylene, or polyester, with some polymer coatings designed specifically for drug elution. Drug-eluting stents utilized mitomycin C, arsenic trioxide, paclitaxel, rapamycin, and doxycycline. Of the 58 studies, 18 were human and 40 were animal studies (leporine = 21, canine = 9, swine = 4, rat = 3, ovine/feline/murine = 1). Noted complications included granulation tissue and/or stenosis, stent migration, death, infection, and fragmentation.. An increasing diversity of materials and coatings are employed for tracheal stents, growing more pronounced over the past decade. Though most studies are still preclinical, awareness of tracheal stent developments is important in contextualizing novel stent concepts and clinical trials. Laryngoscope, 132:2111-2123, 2022.

Topics: Adult; Alloys; Animals; Arsenic Trioxide; Cats; Dogs; Doxycycline; Humans; Magnesium; Mice; Mitomycin; Paclitaxel; Polydioxanone; Polyesters; Polylactic Acid-Polyglycolic Acid Copolymer; Polymers; Polytetrafluoroethylene; Polyurethanes; Rats; Sheep; Silicones; Sirolimus; Steel; Stents; Swine; Tracheal Stenosis

Laryngotracheal stenosis (LTS) is pathologic fibrotic narrowing of the larynx and trachea characterized by hypermetabolic fibroblasts and CD4+ T cell-mediated inflammation. However, the role of CD4+ T cells in promoting LTS fibrosis is unknown. The mTOR signaling pathways have been shown to regulate the T cell phenotype. Here we investigated the influence of mTOR signaling in CD4+ T cells on LTS pathogenesis. In this study, human LTS specimens revealed a higher population of CD4+ T cells expressing the activated isoform of mTOR. In a murine LTS model, targeting mTOR with systemic sirolimus and a sirolimus-eluting airway stent reduced fibrosis and Th17 cells. Selective deletion of mTOR in CD4+ cells reduced Th17 cells and attenuated fibrosis, demonstrating CD4+ T cells' pathologic role in LTS. Multispectral immunofluorescence of human LTS revealed increased Th17 cells. In vitro, Th17 cells increased collagen-1 production by LTS fibroblasts, which was prevented with sirolimus pretreatment of Th17 cells. Collectively, mTOR signaling drove pathologic CD4+ T cell phenotypes in LTS, and targeting mTOR with sirolimus was effective at treating LTS through inhibition of profibrotic Th17 cells. Finally, sirolimus may be delivered locally with a drug-eluting stent, transforming clinical therapy for LTS.

Topics: Animals; Constriction, Pathologic; Drug-Eluting Stents; Fibrosis; Humans; Laryngostenosis; Mice; Sirolimus; Th17 Cells; TOR Serine-Threonine Kinases; Tracheal Stenosis

Currently, interventional pulmonology has the tools for efficient de-bulking of tracheal stenosis, which can either be the result of cancer tissue or benign tissue growth inside the respiratory tract. There are additionally other situations, such as thracheomalece and fistula formation, which require stent placement for efficient support in the tract wall. These are situations where the placement of a stent is necessary either directly upon diagnosis or after interventional treatment. However, a major adverse effect of stent placement is the formation or reformation of granuloma tissue and the site of the lesion has to be frequently evaluated and treated. In this article we provide insights of novel methods for inhibiting the pathways that are activated or deregulated and subsequently induce granuloma tissue formation. We also present a future 3D model that we are currently constructing in our laboratory from human lung fibroblast (adult) in order to evaluate novel local treatment administrations with sirolimus biodegradable stents, in order to block or prolong the granuloma tissue formation.

Topics: Drug-Eluting Stents; Granulation Tissue; Humans; Models, Biological; Sirolimus; Tracheal Stenosis

The aim of this study was to evaluate the use of balloon-expandable metallic stents in the treatment of children with congenital tracheal stenosis in whom conventional therapy has failed. From 2010 to 2011, balloon-expandable metallic stents were implanted into the trachea of eight infants aged 2-20 months in the paediatric intensive care unit. The infants had severe airway obstruction caused by congenital tracheal stenosis. Tracheal stents were placed after intraluminal balloon dilatation of the tracheal stenosis, inserted with balloon catheters and implanted into the desired position bronchoscopically. The stents were 12 to 29 mm long and 4 mm in diameter. Seven children were relieved of airway obstruction after this procedure. However, a child died due to severe sepsis after the placement of bronchial stents. No granulation tissue developed over the stents in any of the children. Stents have been in place for 1-6 months after insertion without any other complication. Balloon-expandable metallic stents are effective in relieving airway obstruction by congenital tracheal stenosis in children. This technique may provide an important remedy for congenital tracheal stenosis in children.

Topics: Airway Obstruction; Bronchoscopy; Catheterization; China; Drug-Eluting Stents; Humans; Infant; Intensive Care Units, Pediatric; Metals; Prosthesis Design; Sirolimus; Time Factors; Tracheal Stenosis; Treatment Outcome