Tracheal Stenosis Research Articles

Role of Adjuvant Mitomycin C in The Endoscopic Treatment of Laryngotracheal Stenosis (Meta-Analytic Study)

Abstract Background Laryngotracheal stenosis is a life-threatening restriction in pulmonary ventilation. It is an umbrella term, including luminal compromise at the level of the larynx, subglottis, or trachea. Etiology of laryngotracheal stenosis is multifactorial. In adults and adolescents it is mostly acquired, where in children it may be acquired or congenital. Acquired laryngotracheal stenosis can result from previous intubation or tracheostomy, systemic disease, trauma, infection, or idiopathic causes. Historically, infectious etiology was common. Currently, laryngotracheal stenosis most frequently results from prolonged intubation or trauma from intubation itself. Objective To evaluate the effectiveness of topical Mitomycin C as an adjuvant treatment with the endoscopic management of laryngotreacheal stenosis. Patients and Methods The total number of patients in all the included studies was 454, 379 patients in MMC group and 75 patients in non-MMC group. Results This meta-analysis study showed that resolution (success) rate in MMC group was (68.7%) and there was a significant increase in resolution (success) rate in MMC compared to non- MMC group (p = 0.011) with the odds of being 5 times higher in MMC group (OR = 5.04). The Complications rate in MMC using patients was (4%). The result of this meta-analysis study showed that Mitomycin C is an effective and safe adjuvant in the endoscopic treatment of laryngotracheal stenosis. However, this study included limitations. We recommend the need of more high quality prospective randomized controlled trials, two armed studies and further studies in the future to achieve stronger results. Conclusion We suggest that that Mitomycin C is an effective and safe adjuvant in the endoscopic treatment of laryngotracheal stenosis. However, this study included limitations. We recommend the need of more high quality prospective randomized controlled trials, two armed studies and further studies in the future to achieve stronger results.

Montgomery Tracheal Tube - A Boon with a Challenge

Crico-tracheal resection and anastomosis are commonly used operative techniques in managing crico-tracheal stenosis grade III-IV. The Montgomery T-tube is used both as a tracheal stent and tracheostomy. Still, it poses various challenges to anaesthesiologists, like loss of anaesthetic gases through the open proximal end of the vertical limb and lack of standard anaesthesia circuit connectors. Here we present a case of 27 years old male with a history of gunshot injury to the neck three years ago with right vocal cord palsy with subglottic tracheal stenosis grade IV posted for microlaryngobronchoscopy (MLB) with crico-tracheal resection and anastomosis with Montgomery tracheal tube insertion. In this case, we used LMA proseal, which not only enabled us to stop the anaesthetic gas loss via the proximal vertical limb of the T-tube but also aided in checking airway patency and proper positioning of the T-tube via flexible bronchoscope through it.

Tracheal Stenosis Detected During Endotracheal Intubation in a Patient With Down Syndrome

We report a case in which tracheal stenosis was discovered during endotracheal intubation. A 19-year-old woman with Down syndrome was scheduled to undergo treatment of multiple dental caries under intubated general anesthesia. During the first general anesthetic, we felt some resistance while advancing the endotracheal tube through the trachea. Prior to a second general anesthetic 2 years later, we performed 3-dimensional computed tomography to evaluate the tracheal stenosis and devised a strategy that established an airway without advancing the endotracheal tube over the stenotic lesion. Careful attention is required when performing endotracheal intubation because patients with Down syndrome sometimes have tracheal stenosis.

Endoscopic recannulation of long-segment, grade IV suprastomal tracheal stenosis: An operative technique

BackgroundLong-segment, grade IV suprastomal tracheal stenosis is rare and difficult to treat (Carpenter et al., 2022 [1]). Patients with grade IV stenosis have significant quality of life impairments since they are tracheostomy dependent and aphonic. Open airway surgery is often needed to improve tracheal patency, restore the patient's voice, and progress towards decannulation (Abouyared et al., 2017 [2]). However, not all patients are candidates for upfront open surgery (Abouyared et al., 2017; Shamji, 2018 [2,3]). Therefore, it is important to develop and refine endoscopic interventions to improve quality of life for these patients. MethodsWe describe a step-by-step endoscopic approach to the recannulation of long-segment, grade IV suprastomal tracheal stenosis. Briefly, our approach utilizes dual (proximal & distal) visualization of the stenosis prior to passing a 25 gauge needle through the stenosis to identify the proper trajectory for recannulation. Then a 16 gauge needle is passed in the same manner, and a wire is placed through the needle and into the distal airway. Once the airway is recannulated, the initial pinpoint opening is gradually widened in Seldinger fashion over the wire with Savary dilators followed by balloon dilation. Finally, a suprastomal L-stent (modified Montgomery T-Tube) is placed to reduce the risk of restenosis (Edwards et al., 2023 [4]). Case discussionA 39-year-old woman with a past medical history significant for poorly controlled type I diabetes mellitus and polysubstance abuse presented with tracheostomy dependence and aphonia. She was diagnosed with a long-segment, grade IV suprastomal tracheal stenosis and initially underwent endoscopic recannulation. This intervention restored her voice and allowed for optimization of her medical conditions before open airway surgery. ConclusionMost patients experience a significant improvement in their quality of life as their voice is typically restored following this procedure. Additionally, individuals who eventually require open airway surgery gain additional time for medical optimization. In our experience, this procedure represents a safe and effective means of extending the utility of traditional endoscopic airway interventions for the management of patients with grade IV stenosis.

Swallowing rehabilitation of patients undergoing T‐tube implantation for the treatment of laryngotracheal stenosis

Swallowing rehabilitation of patients undergoing T‐tube implantation for the treatment of laryngotracheal stenosis

Endoscopic treatment of benign tracheal stenosis: a single-centre study.

Benign tracheal stenosis is relatively rare but remains a significant chronic disease due to its drastic symptoms including dyspnoea and inspiratory stridor, and consequent negative effect on quality of life. Traditionally, the surgical approach by resection of the stenotic tracheal segment has been the therapy of choice. However, endoscopic techniques have arisen and may offer a safe and less invasive alternative. The aim of the retrospective study was to evaluate procedure-related safety and outcome of endoscopic treatment of benign tracheal stenosis at a single centre. The study included all patients at our institution who between 2013 and 2022 had received endoscopic treatment of benign tracheal stenosis by rigid tracheoscopy, radial incision by electric papillotomy needle and dilation (endoscopic tracheoplasty) followed by triamcinolone acetonide as a local submucosal injection and additionally, from 2020, budesonide inhalation. A total of 22 patients were treated in a total of 38 interventions, each resulting in immediate improvement of symptoms. There were no peri-interventional complications or mortality. Of the 38 interventions, 11 received no triamcinolone acetonide administration, resulting in a 54.5% recurrence rate after an average of 21.1 (±18.0) months, while 27 had local triamcinolone acetonide, with a 37% recurrence rate. Since 2020, we additionally initiated post-interventional budesonide inhalation as recurrence prophylaxis for newly admitted patients and patients with recurrences(n = 8), of whom only one (12.5%) has to date experienced a recurrence. Our results indicate that endoscopic tracheoplasty offers a safe and successful, minimally invasive alternative to open surgery for patients with benign tracheal stenosis. We recommend local administration of triamcinolone into the mucosa as an additional treatment to decrease the risk of recurrence. However, given the uncontrolled study design and low sample size, safety and effectiveness cannot be conclusively demonstrated. Nonetheless, our findings suggest promising avenues for further investigation. Further studies on the additional benefit of inhaled corticosteroids are warranted.

Identifying Molecular Pathophysiology and Potential Therapeutic Options in Iatrogenic Tracheal Stenosis.

While most patients with iatrogenic tracheal stenosis (ITS) respond to endoscopic ablative procedures, approximately 15% experience a recalcitrant, recurring disease course that is resistant to conventional management. We aimed to explore genetic profiles of patients with recalcitrant ITS to understand underlying pathophysiology and identify novel therapeutic options. We collected 11 samples of granulation tissue from patients with ITS and performed RNA sequencing. We identified the top 10 most highly up- and down-regulated genes and cellular processes that these genes corresponded to. For the most highly dysregulated genes, we identified potential therapeutic options that favorably regulate their expression. The dysregulations in gene expression corresponded to hyperkeratinization (upregulation of genes involved in keratin production and keratinocyte differentiation) and cellular proliferation (downregulation of cell cycle regulating and pro-apoptotic genes). Genes involved in retinoic acid (RA) metabolism and signaling were dysregulated in a pattern suggesting local cellular RA deficiency. Consequently, RA also emerged as the most promising potential therapeutic option for ITS, as it favorably regulated seven of the ten most highly dysregulated genes. This is the first study to characterize the role of hyperkeratinization and dysregulations in RA metabolism and signaling in the disease pathophysiology. Given the ability of RA to favorably regulate key genes involved in ITS, future studies must explore its efficacy as a potential therapeutic option for patients with recalcitrant ITS.

Approaching Saber-Sheath Trachea in a Patient with Bilateral Vocal Cord Abductor Palsy and Post Tracheostomy Tracheal Stenosis.

Human trachea has variable shapes and the most common are circular and oval-shaped. Other shapes are rare to find and usually related to some diseases. Such as the Saber-sheath shaped trachea, which was commonly attributed to patients with chronic obstructive pulmonary disease (COPD). This case is about a patient who was detected to have dual pathology, bilateral vocal cord abductor palsy, and post-tracheostomy complicated with tracheal stenosis for 40 years. Symptoms worsened in the last three years until he was admitted to the ward. However, upon managing this case with multilevel airway obstruction, we have found out that this patient who did not have COPD, has a Saber-sheath trachea shape. This finding may indicate that the shape is not limited to a certain disease only.

Is tracheal stenosis more common and developed earlier in intubated pregnant patients?

Is tracheal stenosis more common and developed earlier in intubated pregnant patients?

Dose-Escalated Radiotherapy for Primary Tracheobronchial Adenoid Cystic Carcinoma.

Primary tracheobronchial adenoid cystic carcinoma (ACC) is a rare malignancy, so the optimal radiotherapy (RT) dose remains unestablished. We aimed to evaluate the effectiveness of dose-escalated RT for primary tracheobronchial ACC. We retrospectively reviewed 48 patients who had undergone definitive or postoperative RT. Patients classified into the low- and high-dose groups received RT doses <70.0 and ≥70.0 Gy in EQD2, respectively. The primary endpoint was freedom from local progression (FFLP) and overall survival (OS). Throughout the follow-up period, seven patients (14.6%) experienced local progression, while 31 (64.6%) exhibited distant metastasis, most commonly in the lungs. In total, the 5-year FFLP and OS rates were 85.7 and 84.7%, respectively. Multivariate analysis revealed that regional lymph node metastasis at diagnosis and receipt of definitive RT were associated with poorer OS. In the subgroup analysis, the definitive RT group had a 5-year FFLP rate of 33.3 and 78.2% in the low- and high-dose groups (p = 0.065), whereas 5-year OS rates were 66.7 and 79.0%, respectively (p = 0.022). Four patients (8.3%) experienced Grade 3 toxicity with tracheal or main bronchus stenosis. Dose-escalated RT with conventional fractionation may be effective in patients with tracheobronchial ACC, especially for a definitive aim.

Impact of preoperative respiratory distress on outcomes of slide tracheoplasty.

Children with congenital tracheal stenosis born in the developing world face a high risk of mortality due to limited access to proper treatment. Patients who required preoperative respiratory support were suspected to have poor survival after slide tracheoplasty; however, this was not clearly demonstrated in the previous studies. This study aims to investigate the impact of preoperative respiratory conditions on outcomes of slide tracheoplasty. From 2016 to 2022, children who underwent slide tracheoplasty were retrospectively reviewed. Patients with respiratory distress requiring emergency operations (group A) were compared with patients in stable condition who were scheduled for surgery (group B). Perioperative results revealed that group A (n = 43) had a longer bypass time (P < 0.001), operation time (P = 0.01), postoperative ventilation time (P < 0.001) and length of intensive care unit stay (P = 0.00125) than group B (n = 60). The early mortality rate was 7.8%, and the actuarial 5-year survival rate was 85.3%. The cumulative incidence test revealed that group A was highly significant for overall mortality [sudistribution (SHR) 4.5; 95% confidence interval (CI) 1.23-16.4; P = 0.023]. Risk factors for overall mortality were prolonged postoperative ventilation time (hazard ratio 3.86; 95% CI 1.20-12.48; P = 0.024), bronchial stenosis (hazard ratio 5.77; 95% CI 1.72-19.31; P = 0.004), and preoperative tracheal mucositis (hazard ratio 5.67; 95% CI 1.51-21.31; P = 0.01). Four patients needed reintervention during a follow-up of 28.4 months (interquartile range 15.3-47.3). Preoperative respiratory distress negatively affected the outcomes of patients who required slide tracheoplasty. Therefore, early detection of congenital tracheal stenosis and aggressive slide tracheoplasty are crucial and obligatory to enhance long-term survival in this lethal congenital airway disease.

Automated xeno-free chondrogenic differentiation from human embryonic stem cells: Enhancing efficiency and ensuring high-quality mass production

IntroductionRepairing damaged cartilage poses significant challenges, particularly in cases of congenital cartilage defects such as microtia or congenital tracheal stenosis, or as a consequence of traumatic injury, as the regenerative potential of cartilage is inherently limited. Stem cell therapy and tissue engineering offer promising approaches to overcome these limitations in cartilage healing. However, the challenge lies in the size of cartilage-containing organs, which necessitates a large quantity of cells to fill the damaged areas. Therefore, pluripotent stem cells that can proliferate indefinitely are highly desirable as a cell source. This study aims to delineate the differentiation conditions for cartilage derived from human embryonic stem cells (ESCs) and to develop an automated cell culture system to facilitate mass production for therapeutic applications. MethodsCartilage cell sheets were derived from human ESCs (SEES2, clinical trial-compatible line) by forming embryoid bodies (EBs) with either conventional manual culture or a benchtop multi-pipetter and an automated medium exchange integrated cell incubator, using xeno-free media. Cell sheets were implanted into the subcutaneous tissue of immunodeficient NOG mice to obtain cartilage tissue. The properties of cartilage tissues were examined by histological staining and quantitative PCR analysis. ResultsWe have optimized an efficient xeno-free system for cartilage production with the conventional culture method and successfully transitioned to an automated system. Differentiated cartilage was histologically uniform with cartilage-specific elasticity and strength. The cartilage tissues were stained by Alcian blue, safranin O, and toluidine blue, and quantitative PCR showed an increase in differentiation markers such as ACAN, COL2A1, and Vimentin. Automation significantly enhanced the efficiency of human ESC-derived chondrocyte differentiation. The number of constituent cells within EBs and the seeding density of EBs were identified as key factors influencing chondrogenic differentiation efficiency. By automating the process of chondrogenic differentiation, we achieved scalable production of chondrocytes. ConclusionsBy integrating the differentiation protocol with an automated cell culture system, there is potential to produce cartilage of sufficient size for clinical applications in humans. The resulting cartilage tissue holds promise for clinical use in repairing organs such as the trachea, joints, ears, and nose.

POSTN Regulates Fibroblast Proliferation and Migration in Laryngotracheal Stenosis Through the TGF-β/RHOA Pathway.

To investigate the role of periostin (POSTN) and the transforming growth factor β (TGF-β) pathway in the formation of laryngotracheal stenosis (LTS) scar fibrosis and to explore the specific signaling mechanism of POSTN-regulated TGF-β pathway in tracheal fibroblasts. Bioinformatics analysis was performed on scar data sets from the GEO database to preliminarily analyze the involvement of POSTN and TGF-β pathways in fibrosis diseases. Expression of POSTN and TGF-β pathway-related molecules was analyzed in LTS scar tissue at the mRNA and protein levels. The effect of POSTN on the biological behavior of tracheal fibroblasts was studied using plasmid DNA overexpression and siRNA silencing techniques to regulate POSTN expression and observe the activation of TGF-β1 and the regulation of cell proliferation and migration via the TGF-β/RHOA pathway. The bioinformatics analysis revealed that POSTN and the TGF-β pathway are significantly involved in fibrosis diseases. High expression of POSTN and TGF-β/RHOA pathway-related molecules (TGFβ1, RHOA, CTGF, and COL1) was observed in LTS tissue at both mRNA and protein levels. In tracheal fibroblasts, overexpression or silencing of POSTN led to the activation of TGF-β1 and regulation of cell proliferation and migration through the TGF-β/RHOA pathway. POSTN is a key molecule in scar formation in LTS, and it regulates the TGF-β/RHOA pathway to mediate the formation of cicatricial LTS by acting on TGF-β1. This study provides insights into the molecular mechanisms underlying LTS and suggests potential therapeutic targets for the treatment of this condition. NA Laryngoscope, 134:4078-4087, 2024.

DYNAMIC CHANGES IN HISTOLOGICAL AND MORPHOMETRIC INDICATORS OF THE LUNGS IN SEXUALLY IMMATURE RATS DURING SIMULATION OF PARTIAL TRACHEAL STENOSIS

Introduction. The morphological features of the respiratory system in laryngomalacia remain insufficiently understood, particularly regarding structural, cytological, and functional alterations. The aim of this study is to investigate the morphological characteristics of the respiratory compartment in the lungs of sexually immature rats, conduct a morphometric assessment of lung tissue density, analyze the dynamics of erythrocyte mass and collagen accumulation, and identify correlations between these parameters. Materials and Methods: The study involved sexually immature male Wistar rats aged 25-28 days and weighing 40-55 g. Partial tracheal stenosis was induced in experimental animals using a developed method, restricting the tracheal lumen by 20-25%. The stenosis was maintained for 7 and 21 days in different groups. In one group, tracheal stenosis was relieved after 7 days by removing the compressive ligature. Histological, histochemical, and morphometric methods were employed to study changes in lung tissue. Results. Pathological changes in lung tissue during hypoxia were characterized by an increase in the number of different types of cells and erythrocyte mass, especially on the 21st day of the experiment and the removal of ligatures from the trachea in experimental animals. Disturbances in the microcirculation of the lung acini were manifested by a sharp increase in blood filling of the microvessels and expansion of their lumen. In this case, the process of erythrocyte penetration into the lumen of the alveoli was sometimes noted. The results of histochemical detection of collagen indicate that in the lung tissue of experimental animals there is no activation of fibrogenetic processes, which would be accompanied by a simultaneous increase in the specific density of collagen. Indicators characterizing the lung tissue (number of cells, their specific density) made it possible to evaluate the corresponding correlations. At the same time, they were not associated with the level of collagen or erythrocyte density in the studied loci of the respiratory system of experimental sexually immature rats. A significant increase in the specific density of erythrocyte mass in lung tissue did not depend on the duration of the experiment. Removal of the ligature and restoration of the tracheal lumen did not significantly affect the restoration of alveolar acini and the spectrum of identified cells. In addition, an increase in the specific density of lung tissue was observed. Conclusion. The findings of this study contribute to deeper understanding of lung damage in children with laryngomalacia and associated respiratory system ventilation impairment. The observed reactive changes in lung connective tissue and collagen synthesis during hypoxia do not necessarily indicate the development of respiratory system fibrosis. However, longer exposure to hypoxic conditions may increase the risk of fibrosis in children.

Gene expression profiles in COVID-19-associated tracheal stenosis indicate persistent anti-viral response and dysregulated retinol metabolism

IntroductionCoronavirus disease 2019 (COVID-19)-associated tracheal stenosis (COATS) may occur as a result of prolonged intubation during COVID-19 infection. We aimed to investigate patterns of gene expression in the tracheal granulation tissue of patients with COATS, leverage gene expression data to identify dysregulated cellular pathways and processes, and discuss potential therapeutic options based on the identified gene expression profiles.MethodsAdult patients (age ≥ 18 years) presenting to clinics for management of severe, recalcitrant COATS were included in this study. RNA sequencing and differential gene expression analysis was performed with transcriptomic data for normal tracheal tissue being used as a control. The top ten most highly upregulated and downregulated genes were identified. For each of these pathologically dysregulated genes, we identified key cellular pathways and processes they are involved in using Gene Ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) applied via Database for Annotation, Visualization, and Integrated Discovery (DAVID).ResultsTwo women, aged 36 years and 37 years, were included. The profile of dysregulated genes indicated a cellular response consistent with viral infection (CXCL11, PI15, CCL8, DEFB103A, IFI6, ACOD1, and DEFB4A) and hyperproliferation/hypergranulation (MMP3, CASP14 and HAS1), while downregulated pathways included retinol metabolism (ALDH1A2, RBP1, RBP4, CRABP1 and CRABP2).ConclusionGene expression changes consistent with persistent viral infection and dysregulated retinol metabolism may promote tracheal hypergranulation and hyperproliferation leading to COATS. Given the presence of existing literature highlighting retinoic acid’s ability to favorably regulate these genes, improve cell-cell adhesion, and decrease overall disease severity in COVID-19, future studies must evaluate its utility for adjunctive management of COATS in animal models and clinical settings.

Stents for the treatment of laryngotracheal stenosis: review and proposal of a 3D-printed solution

Laryngotracheal stenosis is the leading indication for tracheostomy in children. Correction of stenosis and removal of the tracheostomy is a multi-stage process, and laryngeal stents are sometimes necessary to maintain the patency of the endolaryngeal lumen. Several laryngeal stents are commercially available, with varying designs, materials, and costs. The present study will give an overview of these devices. After a review of the literature and considering the expertise of our team, we conclude that computed tomography imaging and 3D printing technology can be used to make custom laryngeal molds designed to meet the individual needs of each patient.

Biodegradable tracheal stents: our ten-year experience with adult patients

BackgroundBiodegradable (BD) stents made from polydioxanone have been used only in human airways. These stents combine the advantages of classical tracheal stents, and fewer side effects are expected due to their biocompatibility and their time-limited presence in airways. However, new clinical consequences have arisen. Here, the authors share their experiences with BD stents for tracheal indications, focusing on their safety and efficacy.MethodsThis was a retrospective review of a collected database of adult patients who underwent implantation of biodegradable tracheal stents between September 2013 and December 2022 at the Department of Respiratory Medicine of the 1st Faculty of Medicine in Prague and Thomayer University Hospital. The indications included functionally significant nonmalignant tracheal stenosis and tracheomalacia. Self-expandable, biodegradable, polydioxanone tracheal stents manufactured by ELLA-CS Ltd. (Hradec Kralove, Czech Republic) were implanted during rigid bronchoscopy under general anaesthesia. All patients were followed up in the department and were provided with the necessary care. The main efficacy and safety parameters and relationships were analysed using descriptive statistics and Fisher´s exact, Wilcoxon and Kruskal‒Wallis tests.ResultsA total of 65 stents were implanted in 47 adult patients. During the first two months after implantation, when adequate function was expected, the stent was found to be effective in 26 out of 39 patients who completed this period (66.7%). The clinical effectiveness reached 89.7%, as early restenoses were mostly mild and necessitated treatment in only 4 patients. The frequencies of significant mucostasis, migration and granulation tissue growth were 2.6%, 7.5% and 23.1%, respectively, during this period. Thirty-four participants completed the half-year follow-up period after the first or second stent insertion, and some were followed up beyond this period. Poor control of symptoms, the development of restenosis and the need for interventions were characteristic of this period as the stents degraded. Twenty-two patients who experienced remodelling or stabilization of the tracheal lumen achieved a stent-free state. Seven patients underwent subsequent surgical treatment.ConclusionsBD stents are safe and provide adequate tracheal support until they begin to degrade. The use of BD stents necessitates close monitoring of patients and accurate treatment of possible restenosis.Trial registrationBased on project NT14146 – Biodegradable stents in the management of the large airways (2013–2015, MZ0/NT), registered on May 1, 2013, in the Research and Development and Innovation Information System of the Czech Republic and at ClinicalTrials.gov (reg. no. NCT02620319, December 2, 2015).

An Ovine Model Yields Histology and Gene Expression Changes Consistent with Laryngotracheal Stenosis.

Animal models for laryngotracheal stenosis (LTS) are critical to understand underlying mechanisms and study new therapies. Current animal models for LTS are limited by small airway sizes compared to human. The objective of this study was to develop and validate a novel, large animal ovine model for LTS. Sheep underwent either bleomycin-coated polypropylene brush injury to the subglottis (n = 6) or airway stent placement (n = 2) via suspension microlaryngoscopy. Laryngotracheal complexes were harvested 4 weeks following injury or stent placement. For the airway injury group, biopsies (n = 3 at each site) were collected of tracheal scar and distal normal regions, and analyzed for fibrotic gene expression. Lamina propria (LP) thickness was compared between injured and normal areas of trachea. No mortality occurred in sheep undergoing airway injury or stent placement. There was no migration of tracheal stents. After protocol optimization, LP thickness was significantly increased in injured trachea (Sheep #3: 529.0 vs. 850.8 um; Sheep #4: 933.0 vs. 1693.2 um; Sheep #5: 743.7 vs. 1378.4 um; Sheep #6: 305.7 vs. 2257.6 um). A significant 62-fold, 20-fold, 16-fold, 16-fold, and 9-fold change of COL1, COL3, COL5, FN1, and TGFB1 was observed in injured scar specimen relative to unaffected airway, respectively. An ovine LTS model produces histologic and transcriptional changes consistent with fibrosis seen in human LTS. Airway stent placement in this model is safe and feasible. This large airway model is a reliable and reproducible method to assess the efficacy of novel LTS therapies prior to clinical translation. N/A Laryngoscope, 134:4239-4245, 2024.

Further experience with polydioxanone airway stents in children

AbstractIntroductionThe aims of this study were to update our experience with biodegradable polydioxanone (PDO) airway stents in children, focusing on effectiveness and safety, and to analyze the factors involved in the different outcomes observed.Materials and MethodsRetrospective study of patients managed with PDO stents from 2012 to 2023. Variables collected: demographics, comorbidities, indication, clinical baseline, stent size, location, complications, clinical outcome, and time of follow‐up. Statistical analyses were performed to detect the eventual contribution of variables in the different outcomes observed.ResultsFifty‐four PDO stents were placed in 26 patients (median age, 4 months). All showed severe symptoms of central airway obstruction due to tracheomalacia in nine patients, bronchomalacia five, tracheobronchomalacia 10, and tracheal stenosis two. Stent placement was uneventful in every case: 29 stents in the trachea and 25 in the main bronchi. 53.8% of patients needed successive stenting, and all exhibited comorbidities. Complete clinical resolution was observed in eight cases (30.7%), partial improvement in 13 (50%), unchanged in 4 (15.3%), and worsened in one. Age had a significant positive impact on outcome (6 vs. 3 months; p = 0.024). Additionally, smaller stents were associated with a better outcome (20 vs. 26 mm; p = 0.044). Granulation tissue was the most frequent complication (34.6%). Five patients (19.2%) died due to severe comorbidities, follow‐up was complete in survivors (median, 58 months).ConclusionsPDO stents are safe and effective when dealing with severe tracheobronchial obstruction. Stent‐related granulation tissue continues to be a relevant matter of concern. This issue, together with increased degradation times, deserves further research.

Involvement of PD-1+CD4+ T cells in the development of traumatic tracheal stenosis by regulating the IL-17/STAT3 pathway

Studies have highlighted an upregulation of PD-1 expression in CD4+ T cells, which accelerates lung fibrosis by activating the IL-17/STAT3 pathway, leading to IL-17A and TGF-β1 secretion. However, the relation with traumatic tracheal stenosis (TS) remains unexplored. Our analysis found significant increases in PD-1+CD4+ T cells, IL-17A, and TGF-β1 in the TS patients (n = 10). The cellular model used CD4+ T cells co-cultured with bronchial fibroblasts while the animal model used a nylon brush to scrape the damaged tracheal mucosa. Interventions with PD-1 and STAT3 inhibitors both in vitro (n = 5) and in vivo (n = 6) showed decreased expression of TGF-β1 and IL-17A in CD4+ T cells, decreased collagen I synthesis in vitro, and reduced tractal fibrosis in vivo. Furthermore, PD-1's modulation of the STAT3 was evident. This research unveils PD-1+CD4+ T cells' role in TS, thus suggesting a novel immunotherapeutic strategy to counteract tracheal fibrosis.