Airway stent insertion can quickly and effectively alleviate airway stenosis and can be used as preoperative transition or palliative treatment for patients with severe airway stenosis. Airway restenosis caused by granulation tissue proliferation after stent insertion is the main complication of bare metal stents [11, 12]. Therefore, airway metal stents, especially bare stents, are mostly used for malignant airway stenosis. For benign airway stenosis, metal bare stent insertion is considered only when there is no other alternative choice . However, metal stents also have many advantages when compared with silicone stents, such bigger ease of insertion with electronic bronchoscope under local anesthesia, larger lumen diameter, less migration, and unaffected ciliary removal function [14–16]. Metal stents continue to evolve in terms of drug elution and structure, with reduced complications.. In this study, rapamycin eluting airway stents were inserted into the Beagle dog tracheal model of airway stenosis, and we concluded that rapamycin-eluting stents could reduce local airway inflammation and inhibit the proliferation of granulation tissue, when compared with bare metal stents.
In earlier studies on airway stents, most of the experimental animal models were of normal airways or of airway stenosis models made by argon plasma burning and coagulation of the airway mucosa. Part of the tracheal cartilage and damaged airway mucosa was then removed by brush. However, in clinical practice, benign airway stenosis is mostly caused by endotracheal intubation or tracheotomy , which is different from these models. Therefore, in order to replicate this clinical scenario to the greatest extent, we referred to the method of making the Beagle dog airway stenosis model by Su Zhuquan , which uses endotracheal intubation and high-pressure cuff to compress the tracheal wall mucosa. This results in local mucosal and cartilage ischemia and necrosis, and repair with granulation and scar tissue that creates airway stenosis. The average modeling time of this experiment was 40.0 ± 12.4 hours, and all tracheal stenosis rates ranged between 40.2% and 63.4%.
Rapamycin is a new immunosuppressant drug that blocks signal transduction through different cytokine receptors. It blocks transition from stage G1 to S in T lymphocytes and other cells, and has intensive anti-proliferation and immunosuppressive effects. In mammals, rapamycin acts on mTOR , which regulates a variety of cells involved in immune response, such as dendritic cells and regulatory T cells (Tregs). In recent years, rapamycin has been increasingly used in settings of immune inflammation. In asthma models, intraperitoneal injection of rapamycin can reduce the concentration of IL-5 in alveolar lavage fluid and inhibit the aggregation of eosinophils, so as to alleviate the symptoms of asthma . In this study, it was reported that the lung inflammation and the Th2 inflammatory factors IL-4, IL-5 and IL-13 in alveolar lavage fluid and nasal lavage fluid decreased significantly after aerosol inhalation of rapamycin. In this study, the degree of tracheal inflammation in the RES group was significantly lower than that in the BMS group, which further proves that rapamycin can locally inhibit airway inflammation.
Rapamycin eluting drug stents have been proven effective in preventing restenosis after coronary stenting [5–7]. At present, there are few studies on rapamycin eluting airway stents. Madhavi Duvvuri  applied rapamycin coated absorbable PLLA-PCL stents to the mouse model of tracheal stenosis. After a period of 6 weeks’ observation, rapamycin coated PLLA-PCL stents significantly reduced the thickness of the lamina propria mucosa around the stents and reduced the amounts of collagen 1, 3 and TGF-β, which suggests that rapamycin eluting stents can reduce granulation tissue proliferation and scar tissue formation around the stent. In our study, the degree of granulation tissue proliferation in the RES group was significantly lower than that in the BMS group and at the end of the 12th week, the airway stenosis rates in the RES group were 15%, 13% and 18% while those in the BMS group were 30%, 95% and 51%, respectively. Under the microscope, the degree of granulation hyperplasia in the RES group was significantly less than that in BMS group.