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Importance: Current medical therapies in idiopathic subglottic stenosis (iSGS) are insufficient in preventing the development and progression of scar tissue. An inhibitor of mammalian target of rapamycin, everolimus is an immunosuppressive medication shown to be effective in reducing fibrosis across a variety of fibroproliferative disorders, including preclinical models of iSGS., Objective: To evaluate the effect of oral everolimus on postoperative recurrence of stenosis in iSGS., Design, Setting, and Participants: This open-label, single-arm, phase 1, nonrandomized clinical trial analyzed 7 perimenopausal participants diagnosed with iSGS and followed-up at a tertiary care academic center for 6 months after dilation surgery. The trial was conducted from November 1, 2022, through May 15, 2024., Intervention: Participants took a 1.5-mg daily oral dose of everolimus for 42 days after surgery., Main Outcomes and Measures: The primary outcome measure was safety as determined by adverse events. Secondary outcome measures included change in peak expiratory flow from baseline through 180 days after surgery; change in the luminal area, measured by computed tomographic (CT) scan, from the 14th and the 180th day; and changes in quality-of-life scores., Results: Of the 8 perimenopausal participants, 7 (median age, 50 years [IQR, 45.0-52.5 years]) completed the study. Compared with baseline at all time points, there was an increase in peak expiratory flow. The median difference in liters per minute was 125 (95% CI, 90-270) on day 7 after surgery; 150 (95% CI, 110-290) on day 14; 138 (95% CI, 116-280) on day 28; 160 (95% CI, 100-270) on day 42; 155 (95% CI, 110-270) on day 60; 140 (95% CI, 100-270) on day 90; and 100 (95% CI, 20-240) on day 180. A decrease in the CT luminal area was observed from the day-14 measure to the day-180 measure (median stenosis, 7.2%; IQR, 1.9%-15.4%). During the trial, 1 participant (14.3%) each developed oral ulcers, a urinary tract infection, and a skin infection., Conclusions and Relevance: In this interventional nonrandomized clinical trial of iSGS, adjuvant everolimus was well-tolerated with minor adverse events. Participants sustained postdilation peak expiratory flow for 13 weeks. These results support proceeding to a phase 2 trial to study drug efficacy and a more detailed investigation of adverse effects., Trial Registration: ClinicalTrials.gov Identifier: NCT05153668.

Introduction: Subglottic stenosis, manifested by granulation tissue hyperplasia, is challenging and requires multiple repeated treatments and stent maintenance at times. Corticosteroids prevent severe subglottic stenosis development owing to their antifibrotic and anti-inflammatory properties. Submucosal injection of glucocorticoids, a useful adjuvant therapeutic method, improves the mean interval between endoscopic procedures and reduces airway restenosis risks., Case Presentation: We report a rare case of a man with complex subglottic stenosis who underwent balloon dilatation combined with cryotherapy, stent placement, and adjuvant submucosal triamcinolone injection. The drug was injected efficiently and safely into the submucosal layer under percutaneous ultrasound guidance, and subglottic stenosis was well-controlled at a low cost., Conclusion: POCUS-guided medication injections may be a useful adjuvant medical therapy for subglottic stenosis., (© 2024 S. Karger AG, Basel.)

Purpose: Subglottic stenosis (SGS) is a potentially life-threatening manifestation of granulomatosis with polyangiitis (GPA). Endoscopic dilation is effective, but relapses are frequent and the benefit of systemic immunosuppression in this setting is still controversial. We aimed to investigate the role of immunosuppressive treatment on SGS relapse risk., Methods: This is a retrospective observational study based on review of medical charts among our cohort of patients with GPA., Results: Twenty-one patients with SGS-GPA were identified, with a prevalence of 20% among our entire GPA cohort (n = 105). Compared to patients without SGS, patients with SGS-GPA had an earlier disease onset (mean age 30.2 vs. 47.3 years, p<0.001), and lower BVAS (mean 10.5 vs 13.5; p = 0.018). Five patients didn't receive systemic immunosuppression for SGS and they all (100%) relapsed after the first procedure, while among medical treatment group relapse rate was 44% (p = 0.045). When single treatment regimens are considered, rituximab (RTX) and cyclophosphamide (CYC) yielded a protective role towards the need of subsequent dilation procedure after the first if compared with absence of medical treatment. Patients with SGS and generalized disease, who initially received either a RTX- or a CYC-based induction treatment, and higher cumulative doses of glucocorticoids, showed a delayed median time to SGS relapse (36 vs. 12 months, p = 0.024)., Conclusions: Subglottic stenosis is highly prevalent in patients with GPA and may define a milder systemic disease subset occurring more frequently in younger patients. Systemic immunosuppression provides benefit in preventing recurrence of SGS in GPA patients and regimens based on cyclophosphamide or rituximab might have a non-redundant role in this setting., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest related to the present work., (Copyright © 2023. Published by Elsevier B.V.)

Background: Therapeutic options for managing laryngotracheal stenosis (LTS) are limited. Endoscopy is a minimally invasive approach to treating LTS, but carries a high risk of stenosis recurrence. Mitomycin C (MMC) is often used as an adjunct therapy to delay the time to symptomatic recurrence of LTS. This review synthesizes the current literature on the topic of MMC as an adjunct treatment strategy for LTS., Methods: A focused literature search was carried out from PubMed on June 12, 2022 using the terms "mitomycin c AND stenosis" in all fields with no date limitations. Evidence-based recommendations relevant to the clinical application of MMC as an adjunct therapy for LTS were formulated. Three questions were addressed: 1) efficacy of MMC, 2) single versus multiple application(s) of MMC, and 3) safety of MMC. The evidence rating and recommendation strength were guided by the GRADE system., Results: Twenty-nine studies were reviewed. The efficacy of MMC as an adjunct therapy for LTS varied across studies. Randomized controlled trials have not shown an outcome difference with MMC use, although methodologic flaws including underpowering were noted. A meta-analysis of observational studies with a comparator arm found the unadjusted probability of remaining symptom-free for > 1 year is greater with versus without MMC application (73% vs. 35%). Single versus multiple application(s) of MMC resulted in similar restenosis rates at long-term follow-up. Complications related to MMC use are rarely reported using conventional doses (0.4 mg/mL). Overall, the quality of evidence was low and the recommendation for intervention was weak., Conclusion: The role for MMC as an adjunct therapy in LTS is uncertain. While safe in its application, the efficacy of MMC in reducing stenosis recurrence remains a matter of debate. Large, prospective studies are needed to inform future recommendations., Competing Interests: Disclosure: W.S. grant money for trial from GALA for Rheoplasty study and royalties from UpToDate for authorship. M.S.M. Olympus America: Consulting; Serpex Medical: Medical Advisory Board; UpToDate: Royalties for authorship. The remaining author has no conflict of interest or other disclosures., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The objective of this work was to assess the effect of a single intralesional subglottic steroid injection on fasting blood glucose over 7 days in a cohort of patients with subglottic stenosis., Methods: A prospective cohort study of patients undergoing intralesional steroid injections at a tertiary academic center. Patients had baseline bloodwork performed, including fasting blood glucose (FBG), and hemoglobin A1C levels. Demographic data and risk factors were collected. Fasting capillary glucose (FCG) was measured using a capillary glucometer and performed by patients daily from days 0 to 7 after a single injection of Triamcinolone into the subglottic airway. Data were analyzed using descriptive and comparative statistics., Results: Eleven patients were enrolled, and 10 completed data collection over 7 days. All were female, with a mean age of 52.6 years (SD 17.5). Two patients were diabetic (non-insulin dependent). There was a statistically significant increase in FCG on day 1 post-injection (mean = 122.4 mg/dl compared to 100.7 mg/dl) that normalized for all patients within 24-72 h. The mean increase in FCG was 21.5% (SD 22.5%) of the initial value for the cohort. The diabetic group had statistically significant higher glucose values on day 1 compared to the non-diabetic group (146.5 mg/dl compared to 117.0 mg/dl)., Conclusion: A single subglottic steroid injection appears to cause a transient increase in FCG 1 day post injection, which resolves after 24-72 h and can be more pronounced in diabetic patients., Level of Evidence: 4 Laryngoscope, 133:1590-1594, 2023., (© 2022 The Authors. The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

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.

Objective: To determine the efficacy of office-based intralesional steroid injections (ILSI) as a management therapy for adult subglottic stenosis (SGS)., Data Sources: A systematic review was completed using PubMed and Science Direct for office-based management of SGS due to various etiologies., Review Methods: The primary end point measured was a change in surgery free interval (SFI) between endoscopic procedures due to office-based serial ILSI. The secondary end point was to determine what percentage of patients did not require further operative intervention for SGS maintenance therapy after changing management to office-based serial ILSI., Results: We identified 187 abstracts, 4 of which were included in the analysis. The total number of participants was 55. The mean age was 50.4, and 78.1% were women. The etiologies were as follows: idiopathic (58.2%), postintubation/tracheotomy (29.1%), and autoimmune (12.7%). The SFI was reported in 3 of the 4 studies. The reported mean pre-ILSI SFI was 362.9 days and the post-ILSI SFI was 582.2 days. The secondary outcome was reported in 3 of the 4 studies. Forty-one of the 55 patients (74.5%) did not require further operative intervention during the duration of the study., Conclusion: This review explored office-based ILSI as a potential treatment option for patients with SGS. The limited data presented found ILSI significantly lengthened SFI, potentially reducing surgical burden. In addition, ILSI was found to be safe with few reported side effects.

Objectives/hypothesis: Laryngotracheal stenosis (LTS) is a functionally devastating condition with high respiratory morbidity and mortality. This preliminary study investigates airflow dynamics and stenotic drug delivery in patients with one- and two-level LTS., Study Design: A Computational Modeling Restropective Cohort Study., Methods: Computed tomography scans from seven LTS patients, five with one-level (three subglottic, two tracheal), and two with two-level (glottis + trachea, glottis + subglottis) were used to reconstruct patient-specific three-dimensional upper airway models. Airflow and orally inhaled drug particle transport were simulated using computational fluid dynamics modeling. Drug particle transport was simulated for 1-20 μm particles released into the mouth at velocities of 0 m/s, 1 m/s, 3 m/s, and 10 m/s for metered dose inhaler (MDI) and 0 m/s for dry powder inhaler (DPI) simulations. Airflow resistance and stenotic drug deposition in the patients' airway models were compared., Results: Overall, there was increased airflow resistance at stenotic sites in subjects with two-level versus one-level stenosis (0.136 Pa s/ml vs. 0.069 Pa s/ml averages). Subjects with two-level stenosis had greater particle deposition at sites of stenosis compared to subjects with one-level stenosis (average deposition 2.31% vs. 0.96%). One-level stenosis subjects, as well as one two-level stenosis subject, had the greatest deposition using MDI with a spacer (0 m/s): 2.59% and 4.34%, respectively. The second two-level stenosis subject had the greatest deposition using DPI (3.45%). Maximum deposition across all stenotic subtypes except one-level tracheal stenosis was achieved with particle sizes of 6-10 μm., Conclusions: Our results suggest that patients with two-level LTS may experience a more constricted laryngotracheal airflow profile compared to patients with one-level LTS, which may enhance overall stenotic drug deposition., Level of Evidence: NA Laryngoscope, 133:366-374, 2023., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Background/aims: Laryngotracheal stenosis is a rare but devastating proximal airway fibrosis that restricts a patient's ability to breathe. Treatment is primarily surgical and to date, there has never been a multi-institutional, randomized, prospective, and interventional clinical trial for a medical therapy to treat laryngotracheal stenosis. Therefore, we aimed to obtain patient feedback to guide successful trial design, recruitment, retention, and for identifying potential barriers to study participation., Methods: Over 1000 members of an international laryngotracheal stenosis online support community (the Living with Idiopathic Subglottic Stenosis Facebook group) were sent two questionnaires for a proposed interventional double-blinded, randomized, placebo-controlled clinical trial., Results: A total of 317 and 558 participants responded to the first and second surveys, respectively. The majority of participants (77%) were willing to consider enrollment, regardless of having a 50% chance of receiving placebo versus treatment (78%). The majority (84%) of participants were willing to travel 200 miles to participate for up to six in-person visits over 50 days. Specific side effects, including anemia/thrombocytopenia (72%) or risk of infection (69.3%) had the greatest impact on clinical trial participation with other side effects (peripheral edema (53%), oral ulcers (51%), and gastrointestinal side effects (41%)) having less impact., Conclusion: Patients with laryngotracheal stenosis possess nuanced insight into their disease and treatment options. As a group, they are extremely motivated for better therapies. Future laryngotracheal stenosis clinical trials should focus on providing excellent side effect -related education and utilizing feedback from online advocacy groups to optimize recruitment and retention.

Idiopathic subglottic stenosis (iSGS) is a progressive fibrotic disease characterized by life-threatening airway narrowing. Although the molecular underpinnings are unknown, previous reports showing that subglottic serial intralesional steroid injections (SILSIs) improve clinical outcomes suggest a steroid-sensitive pathway in iSGS. Herein, a prospective study was conducted to determine the changes in profibrotic markers during SILSI to identify steroid-sensitive profibrotic drivers. Seven newly diagnosed patients with iSGS were recruited for SILSI. Subglottic biopsies before and after SILSI treatments were evaluated for histologic and molecular markers by confocal microscopy and RT-qPCR. At baseline, iSGS subglottises contained abundant vimentin-positive/α-smooth muscle actin-negative fibroblasts, intermingled with a matrix of fibronectin and types I and VI collagen. Transforming growth factor (TGF)-β1 was up-regulated primarily in glandular epithelium. Cellular communication network factor 2 (CCN2) was mainly up-regulated in stromal fibroblasts surrounding TGF-β1-positive glandular structures. SILSI improved iSGS by reducing fibroblast infiltration and increasing matrix remodeling. Mechanistically, SILSI counteracted the effects of TGF-β1 by inducing matrix metalloprotease 9 (MMP9) expression while repressing CCN2 expression, without affecting TGFβ1 levels. Treatment of primary iSGS-derived fibroblasts with TGF-β1 recapitulated aspects of the disease in vivo, demonstrating that the induction in CCN2 and repression of MMP9 are caused by changes in histone acetylation induced by TGF-β1. Triamcinolone counteracted the coregulation of these genes by impairing SMAD2/3 binding to promoter regions, and not through histone acetylation. In conclusion, this study shows that SILSI counteracts a dysregulated TGF-β1/CCN2/MMP9 axis involved in iSGS development., (Copyright © 2021 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective/hypothesis: Glutamine inhibition has been demonstrated an antifibrotic effect in iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts in vitro. We hypothesize that broadly active glutamine antagonist, DON will reduce collagen formation and fibrosis-associated gene expression in iLTS mice., Study Design: Prospective controlled animal study., Methods: iLTS in mice were induced by chemomechanical injury of the trachea using a bleomycin-coated wire brush. PBS or DON (1.3 mg/kg) were administered by intraperitoneal injection (i.p.) every other day. Laryngotracheal complexes were harvested at days 7 and 14 after the initiation of DON treatment for the measurement of lamina propria thickness, trichrome stain, immunofluorescence staining of collagen 1, and fibrosis-associated gene expression., Results: The study demonstrated that DON treatment reduced lamina propria thickness (P = .025) and collagen formation in trichrome stain and immunofluorescence staining of collagen 1. In addition, DON decreased fibrosis-associated gene expression in iLTS mice. At day 7, DON inhibited Col1a1 (P < .0001), Col3a1 (P = .0046), Col5a1 (P < .0001), and Tgfβ (P = .023) expression. At day 14, DON reduced Co1a1 (P = .0076) and Tgfβ (P = .023) expression., Conclusions: Broadly active glutamine antagonist, DON, significantly reduces fibrosis in iLTS mice. These results suggest that the concept of glutamine inhibition may be a therapeutic option to reduce fibrosis in the laryngotracheal stenosis., Level of Evidence: N/A Laryngoscope, 131:E2125-E2130, 2021., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Adjuvant management for laryngotracheal stenosis (LTS) may involve inhaled corticosteroids, but metered dose inhalers are designed for pulmonary drug delivery. Comprehensive analyses of drug particle deposition efficiency for orally inhaled corticosteroids in the stenosis of LTS subjects are lacking., Study Design: Descriptive research., Setting: Academic medical center., Methods: Anatomically realistic 3-dimensional reconstructions of the upper airway were created from computed tomography images of 4 LTS subjects-2 subglottic stenosis and 2 tracheal stenosis subjects. Computational fluid dynamics modeling was used to simulate airflow and drug particle transport in each airway. Three inhalation pressures were simulated, 10 Pa, 25 Pa, and 40 Pa. Drug particle transport was simulated for 100 to 950 nanoparticles and 1 to 50 micron-particles. Particles were released into the airway to mimic varying inhaler conditions with and without a spacer chamber., Results: Based on smallest to largest cross-sectional area ratio, the laryngotracheal stenotic segment shrunk by 57% and 47%, respectively, for subglottic stenosis models and by 53% for both tracheal stenosis models. Airflow resistance at the stenotic segment was lower in subglottic stenosis models than in tracheal stenosis models: 0.001 to 0.011 Pa.s/mL vs 0.024 to 0.082 Pa.s/mL. Drug depositions for micron-particles and nanoparticles at stenosis were 0.06% to 2.48% and 0.10% to 2.60% for subglottic stenosis and tracheal stenosis models, respectively. Particle sizes with highest stenotic deposition were 6 to 20 µm for subglottic stenosis models and 1 to 10 µm for tracheal stenosis models., Conclusion: This study suggests that at most, 2.60% of inhaled drug particles deposit at the stenosis. Particle size ranges with highest stenotic deposition may not represent typical sizes emitted by inhalers.

Objectives: Serial intralesional steroid injection (SILSI) is an emerging treatment for idiopathic subglottic stenosis (ISGS), providing improvement in both subjective symptoms and objective airflow parameters. Little is known about how this airway remodeling affects the voice. This project analyzes subjective voice changes after SILSI and correlates these with airflow parameters., Methods: An ISGS database containing voice-related quality of life (V-RQOL) and spirometry (peak expiratory flow percentage [%PEF]) was retrospectively queried. Included were ISGS patients from 2009 to 2019 who had at least one SILSI treatment. Encounters without complete data were excluded. Differences between preprocedure and postprocedure metrics were calculated. Correlations and nonparametric bivariate analysis were performed., Results: Six hundred and seventeen steroid injections were performed in 55 patients, with an average of 3.5 years of follow-up. The average V-RQOL for all patient encounters, both pre- and postprocedure, showed little subjective dysphonia (83.5 of 100, 95% confidence interval [CI] 81.6 to 85.4). Considering SILSI-only treatments, there were 143 encounters with full data; of these, V-RQOL improved in 70 (49.0%), did not change in 40 (28.0%), and worsened in 33 (23.0%). Average V-RQOL improvement for the entire cohort was 1.9 points (95% CI: 0.7 to 3.2), which was small but significant (P = .0003). Across all data, there was a weak but significant correlation between PEF% and V-RQOL (ρ = 0.22, P = .0043)., Conclusion: SILSI was associated with improvement in subjective voice ratings in about half of patients, and the improvement correlated with improved airflow measurements. This research adds to the growing body of data regarding SILSI and suggests that further work on functional changes to the larynx with airway remodeling is imperative., Level of Evidence: 4 Laryngoscope, 131:366-369, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Purpose: To assess the incidence and severity of 12 systemic side effects of serial intralesional steroid injections (SILSI) in patients with idiopathic subglottic stenosis (iSGS)., Methods: This retrospective study included patients with iSGS who underwent SILSI with Triamcinolone 40 mg/dL. After SILSI, the patients were asked to answer 12 questions regarding frequently encountered systemic side effects of steroids. Each answer was rated as mild, moderate, or severe. Descriptive statistics were used to analyze and present the findings., Results: The study included 49 patients (42 female and 7 male) with a mean age of 59.1 years (range 21-83 years). Post-SILSI treatment, 27 (55%) reported experiencing side effects while 22 (45%) patients reported no side effects. The most frequent side effect reported in women of reproductive age (n: 8) was menstrual irregularities (3/8, 37%). Other frequently reported side effects were feeling joyful and sleeping difficulties, each reported by 30% of the patients. All side effects resolved after the completion of SILSI., Conclusions: SILSI can be administered with minimal tolerable side effects. Clinicians should make their patients aware of the most frequent side effects. Special attention should be given to women of reproductive age to inform them of the possibility of menstrual irregularities during SILSI.

Objective : Subglottic stenosis (SGS) is a severe, life-threatening disease found in immune-mediated diseases such as granulomatosis with polyangiitis (GPA) and in rare cases of immunoglobulin G 4 (IgG 4 )-related disease. It can result in persistent airway compromise due to the fibrotic response following inflammation. Standard management involves repeated endoscopic interventions to dilate the airway, and tracheostomy is occasionally required. In addition, immunosuppression remains a cornerstone of therapy aimed at controlling the underlying inflammatory disease; however, cumulative dosing leads to significant adverse effects. We present five cases of predominantly anti-neutrophil cytoplasmic antibody-negative GPA and a case of IgG 4 -related disease with SGS, in whom we evaluated the long-term utility of sirolimus, which has beneficial anti-proliferative and fibrotic effects, in the management of their disease. Method : We conducted a retrospective review of a cohort of patients with SGS at a tertiary vasculitis unit. These patients were treated with sirolimus, in addition to conventional medical and endoscopic treatment. Clinical symptoms, frequency and time to endoscopic intervention pre- and post-treatment, additional rescue therapy, and any adverse effects were recorded and analysed. Results : Six patients were treated with sirolimus and followed for up to 9 years; two discontinued the drug owing to adverse effects, early on. In the remaining four patients, glucocorticoids were withdrawn, and the frequency of endoscopic intervention was reduced. One patient on sirolimus required rituximab therapy for disease flare. Conclusion : Sirolimus may be a therapeutic option for some patients with severe SGS, allowing steroid withdrawal and resulting in a positive adverse effect profile.

Objectives/hypothesis: Glutamine metabolism is a critical energy source for iatrogenic laryngotracheal stenosis (iLTS) scar fibroblasts, and glutaminase (GLS) is an essential enzyme converting glutamine to glutamate. We hypothesize that the GLS-specific inhibitor BPTES will block glutaminolysis and reduce iLTS scar fibroblast proliferation, collagen deposition, and fibroblast metabolism in vitro., Study Design: Test-tube Lab Research., Methods: Immunohistochemistry of a cricotracheal resection (n = 1) and a normal airway specimen (n = 1) were assessed for GLS expression. GLS expression was assessed in brush biopsies of subglottic/tracheal fibrosis and normal airway from patients with iLTS (n = 6). Fibroblasts were isolated and cultured from biopsies of subglottic/tracheal fibrosis (n = 6). Fibroblast were treated with BPTES and BPTES + dimethyl α-ketoglutarate (DMK), an analogue of the downstream product of GLS. Fibroblast proliferation, gene expression, protein production, and metabolism were assessed in all treatment conditions and compared to control., Results: GLS was overexpressed in brush biopsies of iLTS scar specimens (P = .029) compared to normal controls. In vitro, BPTES inhibited iLTS scar fibroblast proliferation (P = .007), collagen I (Col I) (P < .0001), collagen III (P = .004), and α-smooth muscle actin (P = .0025) gene expression and protein production (P = .031). Metabolic analysis demonstrated that BPTES reduced glycolytic reserve (P = .007) but had no effects on mitochondrial oxidative phosphorylation. DMK rescued BPTES inhibition of Col I gene expression (P = .0018) and protein production (P = .021)., Conclusions: GLS is overexpressed in iLTS scar. Blockage of GLS with BPTES significantly inhibits iLTS scar fibroblasts proliferation and function, demonstrating a critical role for GLS in iLTS. Targeting GLS to inhibit glutaminolysis may be a successful strategy to reverse scar formation in the airway., Level of Evidence: NA Laryngoscope, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Shortness of breath and wheezing are common presenting signs for children in the emergency department. In adolescence, it is often due to asthma or lower respiratory tract infections. We present a rare pediatric case of an adolescent with biphasic stridor and progressive exercise-induced shortness of breath who was found to have severe idiopathic subglottic stenosis.

Objectives/hypothesis: Topical mitomycin-C (MMC) application is a commonly accepted adjuvant therapy in the surgical treatment for laryngotracheal stenosis (LTS). However, the efficacy of MMC has not been examined in a prospective, randomized clinical trial in humans. We aimed to examine the efficacy of MMC in the treatment of LTS patients as compared to a placebo-controlled group., Study Design: Prospective, randomized, double-blind, placebo-controlled clinical trial., Methods: Fifteen patients with LTS were enrolled in a 24-month trial and randomized into one of two groups: 1) endoscopic surgical treatment with topical application of MMC or 2) endoscopic surgical treatment with topical application of saline. Postoperatively, patients were evaluated at standardized intervals with a symptom questionnaire and spirometry. Subsequent surgery was performed as needed based on relapse of stenosis on exam and patient-reported symptom severity., Results: The average interval between surgical treatments was 17.9 months in the placebo group and 17.4 months in the MMC group (P = .95). There was no difference in magnitude of peak inspiratory flow (PIF) improvement between groups. The average magnitude of PIF change was 1.3 L/sec and 1.1 L/sec for the placebo and MMC groups, respectively (P = .64). Similarly, there was no difference in magnitude of symptom improvement or duration of symptom improvement between the two groups., Conclusions: This prospective, randomized. double-blind. placebo-controlled trial suggests that the use of MMC as a topical adjuvant therapy has no additional benefit in the endoscopic surgical management of LTS. Further study is needed., Level of Evidence: 1b Laryngoscope, 130:706-711, 2020., (© 2019 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Laryngeal stenosis is challenging for treatment due to uncertain etiology. Primary laryngeal lymphoma as the initial clinical manifestation of laryngeal stenosis has been rarely reported. Primary diffuse large B-cell lymphoma as an underlying etiology has not been reported., Case Report: A 79-year-old male presented with dyspnea, stridor and dysphonia of 6 months' duration. Computed tomography scans and flexible laryngoscopic examination revealed vocal cord mobility with bilaterally limited abduction and a subglottic stenosis up to 50%. The laryngeal mucosa was smooth. Laryngeal biopsy showed atypical lymphoid infiltrates, predominantly large sized B-cells, in the submucosa with crush/cauterized artifacts. The tumor cells were positive for B-lymphocyte antigen CD20, paired-box 5 (PAX5), B-cell lymphoma 2 (BCL2), BCL6 and multiple myeloma oncogene 1 (MUM1). They were negative for CD10, CD30, cyclin D1 (CCND1), SRY-box 11 (SOX11), activin-receptor like kinase 1 (ALK1), CD138 and c-MYC, and negative for kappa/lambda light chain and Epstein-Barr virus-encoded small RNA by in situ hybridization. The pathologic diagnosis was diffuse large B-cell lymphoma. Fluorescent in situ hybridization (FISH) for MYC was negative. Next-generation sequencing using a 175-gene panel was performed and no pathologic mutations were identified. No lymphadenopathy elsewhere was identified. The patient was treated with chemotherapy and was doing well at the 5-month follow-up., Conclusion: To the best of our knowledge, this is the first documented case of primary laryngeal diffuse large B-cell lymphoma presenting as increasing laryngeal stenosis. The rarity, diagnosis and treatment of this entity are discussed., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives/hypothesis: Serial intralesional steroid injection (SILSI) has recently been proposed as an effective scar-modifying therapy for subglottic stenosis (SGS). We aimed to explore the systemic absorption of steroid following SILSI and to characterize the magnitude and chronicity of any effect observed. Specifically, we aimed to show that any effect resolves prior to the next intralesional injection., Study Design: Prospective, observational pilot study., Methods: Patients were injected intralesionally with 40 to 200 mg triamcinolone. Serum cortisol, as well as white cell counts and inflammatory markers were measured at day 0 (baseline), 1, 7, and 28. Salivary cortisol was measured at baseline and for 7 consecutive days following injection., Results: Six patients with idiopathic SGS were recruited. At baseline, serum cortisol measured 284.0 ± 61.4 nmol/L and fell significantly to 15.5 ± 4.3 nmol/L 1 day following triamcinolone injection (P = .03). At day 7, serum steroid levels showed significant recovery to 221.8 ± 78.9 nmol/L (P = .03) and further rose to 279.5 ± 29.9 nmol/L at 28 days (P = .07). Salivary cortisol exhibited a similar pattern with significant recovery by day 6 (P = .04) and suggestion of exponential clearance of triamcinolone systemically. White cell counts were also affected by systemic absorption of exogenous steroid. No significant change in inflammatory markers was observed., Conclusions: Our findings demonstrate systemic absorption of steroid following SILSI, with acute hypothalamic-pituitary-adrenal (HPA) axis suppression. However, normalization of HPA axis function by day 7 suggests that although acute steroid side effects should be discussed with patients, no cumulative systemic steroid side effect would occur with serial injections., Level of Evidence: 2 Laryngoscope, 129:1634-1639, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: The utility of topical mitomycin C (MMC) as an adjuvant treatment in the management of laryngeal and tracheal stenosis has been studied; however, the ideal timing of MMC application has not been fully elucidated. There is a paucity of studies evaluating the timing of MMC application after surgical airway intervention for stenosis. The purpose of this study is to describe a novel technique for MMC application that allows for delayed application in the unsedated, office-based setting, approximately one week following endoscopic airway dilation., Methods: A technique for retrograde transtracheal application of MMC was developed and utilized in 3 tracheostomy-dependent patients with subglottic stenosis and glottic stenosis with bilateral vocal fold immobility. After administration of topical anesthesia, a MMC (0.4 mg/ml) coated pledget was advanced via a transtracheal approach and directed to the area of stenosis in retrograde fashion using endoscopic frontal sinus instruments. Appropriate positioning of the pledget was confirmed via transnasal flexible fiberoptic laryngoscopy., Results: All 3 patients underwent successful in-office retrograde application of MMC onto the area of laryngeal stenosis 7-9 days after their preceding surgery. There were no complications. Two patients achieved decannulation while the third patient's management was interrupted due to cancer treatment., Conclusions: We present a novel and well tolerated technique for delayed in-office application of MMC in tracheostomy-dependent patients with laryngeal stenosis. This approach can facilitate the study of the ideal timing of topical MMC use in airway stenosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was to describe a patient with idiopathic supraglottic stenosis who experienced persistent disease despite multiple office-based and operative interventions, whose disease is now better controlled with scheduled serial office-based steroid injections., Methods: This is a case report and literature review., Results: A 42-year-old female was referred for worsening supraglottic stenosis despite systemic steroids. She underwent awake tracheotomy. A thorough historical, histologic, and laboratory workup did not reveal an etiology to her stenosis. She later underwent endoscopic partial laryngectomy and was able to be decannulated. She underwent a second endoscopic partial laryngectomy two years later for worsening disease and then was managed over the next seven years with intermittent systemic steroids. Over the last year, she has undergone eight office-based steroid injections with improvement in her degree of stenosis and symptom burden., Conclusions: There are only four prior reported cases of idiopathic supraglottic stenosis, none of which has been managed with serial office-based steroid injections. This case report adds to the small body of literature on the management of this rare disease and proposes a new office-based treatment pathway that may help induce regression of stenosis., (Copyright © 2018 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: Long-term intubation of premature infants sometimes induces acquired subglottic stenosis (SGS), causing glottic or supraglottic problems. These kinds of SGS often require tracheostomy and subsequently make decannulation difficult. The aim of our study was to clarify the efficacy of repeated intralesional steroid injections to the stenosis., Methods: Six children with acquired SGS, who were treated with triamcinolone acetonide injections to the subglottic space just below the vocal folds between September 2015 and December 2017 were retrospectively reviewed., Results: The patients' mean age was 4.3 (range 1.3-4.4) years, the mean gestational age at birth was 25 (23-28) weeks, and the mean birth weight was 591 (456-734) g. The degree of SGS was grade II in one patient and III in five patients, with both tracheostoma and glottic or supraglottic abnormalities. They generally underwent ten procedures, every 3-4 weeks. In most cases, the patency of the injected space improved by 25-220%, and the symptoms were relieved. One patient achieved decannulation, and another one underwent laryngotracheal reconstruction and decannulation. Two patients started using a speech cannula. There were no severe complications., Conclusion: Serial intralesional steroid injections are likely to be effective in improving the patency of acquired SGS.

Importance: Endoscopic dilation is the mainstay treatment strategy for subglottic and proximal tracheal stenosis (SGS/PTS). Its major limitation is restenosis requiring repeated surgery. Intralesional steroid injection (ISI) is a promising adjunctive treatment aimed at prolonging the effects of dilation., Objective: To evaluate the association of serial in-office ISI after endoscopic dilation with surgery-free interval (SFI) in adults with SGS/PTS., Design, Setting, and Participants: A retrospective study of adults with SGS/PTS who underwent at least 2 consecutive in-office ISI at the University of Southern California, Keck School of Medicine, over a 3-year period was conducted., Exposure: Serial ISI with triamcinolone 40 mg/mL using topical anesthesia, spaced 3 to 6 weeks apart., Main Outcomes and Measures: Surgery-free interval, number of dilations, need for open airway surgery, decannulation rate, and adverse events. Patients with previous dilations and sufficient follow-up time were included in a comparative analysis of SFI before and after ISI. The Mann-Whitney U test was applied for comparisons., Results: Twenty-four patients met eligibility criteria. Mean (SD) age was 50.1 (15.1) years; 18 (75%) were female. Ten (42%) patients had idiopathic, 8 (33%) had traumatic, and 6 (25%) had rheumatologic-related SGS/PTS. Mean (SD) follow-up time was 32.3 (33.4) months. Patients underwent mean (SD) 4.08 (1.91) injections. Seventeen (71%) patients have not undergone further surgery after ISI. Mean (SD) SFI was 17.8 (12.8) months overall and was 15.7 (10.6) months for idiopathic, 13.8 (9.9) for traumatic, and 26.7 (16.9) for rheumatologic-related SGS/PTS. Twenty-one (88%) patients underwent dilation(s) prior to ISI. Among patients who fulfilled eligibility criteria for comparison of SFI before and after ISI, SFI improved from 10.1 months before, to 22.6 months after ISI (mean difference, 12.5 months; 95% CI, -2.1 to 27.2 months). Three of 6 patients (all with traumatic SGS/PTS) presenting with a tracheotomy were decannulated. No patients required open airway surgery after ISI. There were no adverse events associated with ISI., Conclusions and Relevance: Serial in-office ISI are safe and well-tolerated in adults with SGS/PTS. This technique can reduce the surgical burden on these patients and may obviate the need for future airway intervention.

Objectives/hypothesis: The fibrotic/erythematous appearance of the subglottis in idiopathic subglottic stenosis (iSGS) hints that it might respond to repeated intralesional steroid treatment similar to keloids., Study Design: Retrospective cohort study., Methods: Thirteen iSGS subjects (six treated in-office with serial intralesional steroid injections [SILSI] versus seven treated endoscopically in the operating room [OR] followed by awake SILSI) between October 2011 and April 2017. Forced spirometry was performed before injections and at each follow-up visit (peak expiratory flow [%PEF] and peak inspiratory flow). Steroids were injected via transcricothyroid or transnasal routes. Injections were grouped into rounds of four to six injections separated by 3 to 5 weeks., Results: Thirteen subjects with a mean follow-up of 3 years (3.3 years for SILSI and 2.7 years for OR). Awake-only SILSI subjects had a mean improvement/round of 23.1% %PEF (range, 65.4%-88.6%), whereas the OR-treated subjects had a mean %PEF improvement/round of 25.1% (range, 57.4%-82.5%). Both groups had improved breathing, and the improvements were statistically equal (P = .569). SILSI subjects underwent 5.3 injections/round in 1.3 rounds, whereas OR subjects had 5.9 injections/round over 2.1 rounds. Statistically significant improvement was seen in %PEF for both groups (SILSI P = .007, OR P = .002). Overall, SILSI achieved sustained %PEF above 80% in 83% (5/6) and OR + SILSI 86% (6/7)., Conclusions: SILSI in the awake outpatient setting can improve the airway caliber in iSGS and is equivalent to endoscopic OR treatment. We believe iSGS can be viewed as a chronic scarring/inflammatory condition that can benefit from steroid scar-modification therapy., Level of Evidence: 4. Laryngoscope, 128:610-617, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: We aimed to investigate the prophylactic effect simvastatin of and mitomycin C (MMC) on laryngeal and tracheal stenosis in tracheotomised rats by histopathological evaluation of laryngotracheal segment. Randomized prospective single-blind., Material and Method: Standard vertical tracheotomy was performed on 24 rats. Then the animals were randomly divided into three groups as A, B and C. In group A 0.4 mg/day once daily mitomycin C was injected to the paratracheal region for 14 days. In group B daily 30 mg/kg/day simvastatin was given via gavage to rats for 14 days. In group C 2 cc/day intraperitoneal saline given to rats and the created control group by 14 days follow up. After 10 days, tracheal cannulas were removed. Three weeks later, all animals were euthanized and trachea specimens were harvested. The present study investigates the effects of MMC and Simvastatin on fibrosis, inflammation, stenosis index and tracheal wall thickness in a tracheal injury model., Results: The difference between the groups in terms of degree of inflammation scores was statistically insignificant (P = 0,187). Differences between the groups were found to be insignificant in terms of the preventionof fibrosis (P = 0,993). There was no significant difference between groups in terms of stenosis index (P = 0.645). In terms of wall thickness, control, simvastatin and mitomycin C groups were statistically different (p = 0.038). The difference between post-hoc test results was between Mitomycin C and control groups (p = 0.036). Maximum wall thickness in the MMC group (0,299 mm) was significantly lower compared to the control group (0,382 mm)(P < 0,0001). Maximum wall thickness was statistically lower in the simvastatin (0.324 mm) group compared with the control group (0.382 mm) (P < 0.0001). There was no statistically significant difference between the simvastatin group (0,198 mm) and control group (0,200 mm) with respect to minimum wall thickness (P = 0.982). Minimum wall thickness was significantly lower in the mitomycin-C group (0,160 mm) comparison to the control group (0,200 mm) (P < 0.0001)., Conclusion: It was detected that the simvastatin and MMC is not effective in preventing the tracheal stenosis, inflammation and fibrosis formation., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Management of laryngotracheal stenosis (LTS) remains primarily surgical, with a critical need to identify targets for adjuvant therapy. Laryngotracheal stenosis scar fibroblasts exhibit a profibrotic phenotype with distinct metabolic shifts, including an increased glycolysis/oxidative phosphorylation ratio. This study examines the effects of the glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) on collagen production, gene expression, proliferation, and metabolism of human LTS-derived fibroblasts in vitro., Method: Paired normal and scar-derived fibroblasts isolated from subglottic and proximal tracheal tissue in patients with iatrogenic laryngotracheal stenosis (iLTS) were cultured. Proliferation rate, gene expression, protein production, and cellular metabolism were assessed in two conditions: 1) fibroblast growth medium, and 2) fibroblast growth medium with 1 × 10 -4 M DON., Results: DON treatment reduced cellular proliferation rate (n = 7, P =  0.0150). Expression of genes collagen 1 and collagen 3 both were reduced (n = 7, P =  0.0102, 0.0143, respectively). Soluble collagen production decreased (n = 7, P =  0.0056). As measured by the rate of extracellular acidification, glycolysis and glycolytic capacity decreased (n = 7, P =  0.0082, 0.0003, respectively). adenosine triphosphate (ATP) production and basal respiration decreased (n = 7, P = 0.0045, 0.0258, respectively), determined by measuring the cellular rate of oxygen consumption., Conclusion: The glutamine antagonist DON reverses profibrotic changes by inhibiting both glycolysis and oxidative phosphorylation in iLTS scar fibroblasts. In contrast to untreated iLTS scar fibroblasts, collagen gene expression, protein production, metabolic rate, and proliferation were significantly reduced. These results suggest DON and/or its derivatives as strong candidates for adjuvant therapy in the management of iatrogenic laryngotracheal stenosis. Enzymes involved in glutamine metabolism inhibited by DON offer targets for future investigation., Level of Evidence: NA. Laryngoscope, 128:E59-E67, 2018., (© 2017 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Laryngotracheal stenosis (LTS) is a fibroproliferative disorder of the glottis, subglottis, and trachea. In models of fibrosis from other organ systems, the CD4+ T-cell response has been shown to regulate extracellular matrix deposition. Specifically, helper T cell 2 (TH2) promotes fibrosis, whereas TH1 and associated cytokines have been shown to be antifibrotic. However, this antifibrotic effect of the TH1 response has not been demonstrated in LTS., Objective: To determine whether the TH1 cytokine interferon-γ inhibits the function of LTS-derived fibroblasts in vitro., Design, Setting, and Participants: This in vitro controlled study included 6 patients with iatrogenic LTS undergoing routine surgical subglottic and tracheal dilation at a single institution. Fibroblasts were isolated from biopsy specimens of laryngotracheal scar and normal-appearing trachea. The presence of fibroblasts was confirmed by an immunohistochemical analysis. Laryngotracheal stenosis-derived fibroblasts were treated with interferon-γ and compared with untreated controls (2 sets of untreated, LTS-derived fibroblasts [media did not contain interferon-γ]) and normal airway fibroblasts (fibroblasts isolated from normal trachea). Data were collected from August 2015 through June 2016., Interventions: Treatment with interferon-γ, 10 ng/mL., Main Outcomes and Measures: Cellular proliferation, fibrosis gene expression (using quantitative reverse transcription polymerase chain reaction analysis), soluble collagen, and cellular histologic features were assessed., Results: Among the 6 patients (6 women; mean [SD] age, 38.3 [17.2] years), LTS-derived fibroblast proliferation was reduced in patients who received interferon-γ treatment compared with untreated controls on days 3 (mean difference, -6515 cells; 95% CI, -10 630 to -2600 cells) to 6 (mean difference, -47 521 cells; 95% CI, -81 285 to -13 757 cells). Interferon-γ treatment reduced collagen types I and III gene expression by 86% and 68%, respectively, and resulted in lower total collagen production (10.94 vs 14.89 μg/mL). In addition, interferon-γ treatment resulted in a 32% reduction in expression of transforming growth factor β in LTS-derived fibroblasts., Conclusions and Relevance: Interferon-γ reduced proliferation, soluble collagen production, and collagen expression in LTS-derived fibroblasts while also reducing the expression of the profibrotic cytokine transforming growth factor β. These findings suggest that therapeutics aimed at increasing interferon-γ and the TH1 response could attenuate LTS.

The aim of this study is to evaluate the efficacy of ethosomes encapsulated with 5-fluorouracil (5-FU) in treatment of laryngotracheal stenosis in rabbit models. The 5-FU ethosome was prepared by the thin film hydration method, and the amorphous, size distribution and the encapsulation efficiency was investigated. The tracheal mucosa were scraped about 0.5 cm with a nylon brush to induce the scar in airway grow, then models were divided into three groups: 5-FU ethosome group, 5-FU group and saline group, drug were injected into scar of every group by paracentesis guided under endoscope, respectively. The stenosis states were observed under laryngo fiberscope immediate, 7, 14 and 21 days after administrated. Airway stenosis of 5-FU ethosome group has no significant difference when compared with 5-FU group at 7 days after administration, but 5-FU ethosome significantly reduced the airway stenosis after 21-day administration when compared with 5-FU group again and has no restenosis during the period under observation. The fact that ethosomes encapsulated with 5-FU were effective for laryngotracheal stenosis suggests that it has potential as a new method for ameliorating airway stenosis originating from granulation tissue.

Background: Iatrogenic laryngotracheal stenosis (LTS) continues to be a known complication of indwelling endotracheal tubes (ETTs). It is well established that secondary scar formation caused by inflammation and mucosal injury are the main mechanisms by which stenosis occurs. Additionally, there are reports of bacterial colonization of ETTs and its potential association with tracheal scar formation. We describe 4 cases of patients with history of intubation and/or tracheostomy and presumed LTS that improved with the management of concurrent bacterial laryngotracheitis., Methods: A retrospective case series of 4 subjects initially diagnosed at a tertiary care center with posterior glottic or subglottic stenosis and positive bacterial laryngotracheal cultures was performed., Results: All 4 patients with presumed LTS had culture-proven bacterial growth isolated from the laryngotrachea and were treated with adjunct antibiotics. In the first 3 cases, complete resolution of upper airway obstruction was achieved. The fourth patient had notable improvement in her airway status without the need for additional surgical intervention., Conclusion: This case series suggests that bacterial growth within the airway may play a larger role in adult postintubation airway injury. Those patients presenting with concern for LTS and symptoms suspicious for an ongoing bacterial infection may benefit from adjunct antibiotic therapy., (© The Author(s) 2015.)

Purpose: The purpose of our article was to explore the effect of ethosomes containing 5-fluorouracil (5-FU) with different sizes on laryngotracheal stenosis treatment., Methods: The physical characteristics of ethosomes containing 5-FU were investigated, including size, shape, and entrapment percentage. The effect of ethosomes containing 5-FU was evaluated on the airway stenosis rabbit model. The formation of fibrous/scar tissue was investigated by hematoxylin and eosin (HE) staining, and the permeation depth was observed under fluorescence microscope., Results: The mean sizes of 5-FU ethosomes extruded by D=50 nm and D=100 nm pore were 60±10 nm and 110±13 nm, respectively. The 5-FU entrapment percentage of ethosomes was determined to be 15% (D=60±10 nm) and 32% (D=110±13 nm). After being treated by ethosomes containing 5-FU (D=60±10 nm), the fibroblast and collagenous fiber distributed sparsely in the deep scar tissue. The permeation capability of ethosomes containing 5-FU (D=60 nm) was significantly better than ethosomes (D=110 nm). Besides, the 5-FU ethosomes resulted in less stenosis than 5-FU only., Conclusions: Topical administration of 5-FU ethosomes may be a novel candidate therapy for laryngotracheal stenosis treatment., (© The Author(s) 2015.)

Background/aims: Laryngotracheal stenosis (LTS) is a difficult entity to treat, with many patients requiring multiple procedures. Our study assessed the efficacy of mitomycin C (MMC) application as complimentary treatment of LTS., Methods: We reviewed clinical charts of patients with operative procedures for LTS between January 2005 and May 2013. Patients were grouped according to mitomycin use. Several outcome measures were assessed, including the number of procedures and time between procedures., Results: Seventy-one patients were included in the study (30 MMC, 41 non-MMC). They underwent similar numbers of procedures (2.3 MMC, 2.0 non-MMC, p > 0.05). The average time between procedures was 360 (MMC) and 178 (non-MMC) days (p = 0.015). Multiple treatments with mitomycin increased the duration between procedures (366 vs. 340 days, multiple vs. single application, p > 0.05). Fewer mitomycin patients underwent procedures for respiratory distress than non-MMC patients (6.6 vs. 19.5%, p > 0.05). Mitomycin use increased the duration between procedures in patients treated specifically for subglottic stenosis (375 vs. 186 days, p > 0.05)., Conclusion: Our results and experiences with mitomycin demonstrate it is an effective agent for adjuvant treatment of LTS. Its use lengthens the symptom-free period, with further improvement demonstrated when patients expected to undergo multiple surgeries receive multiple mitomycin treatments., (© 2015 S. Karger AG, Basel.)

Objectives: We aimed to determine the prevalence of symptomatic subglottic laryngotracheal stenosis in patients with granulomatosis with polyangiitis (Wegener's granulomatosis); we also wanted to characterise the clinical outcomes and surgical interventions required, and the relapse rate in our cohort., Methods: We undertook a retrospective clinical review of all granulomatosis with polyangiitis patients with symptomatic subglottic laryngotracheal stenosis attending St Thomas' Hospital, London, United Kingdom., Results: Symptomatic subglottic laryngotracheal stenosis developed in 16 per cent of granulomatosis with polyangiitis patients attending our clinic. The median age of patients at diagnosis was 44 years (range: 34-81 years); 78 per cent of those presenting with subglottic laryngotracheal stenosis were women and 22 per cent were men. All patients were white; 67 per cent of patients were proteinase 3-antineutrophil cytoplasmic antibody-positive and 67 per cent developed relapsing disease requiring repeated surgical intervention. Subglottic laryngotracheal stenosis relapse was not associated with active systemic vasculitis elsewhere., Conclusion: Subglottic laryngotracheal stenosis is an uncommon but significant complication of granulomatosis with polyangiitis. Management of subglottic laryngotracheal stenosis requires a multi-disciplinary approach, with both rheumatological and otolaryngological expertise involved, given the relapsing nature of the disease.

Objectives/hypothesis: To evaluate the endoscopic surgical management of adult subglottic stenosis and describe treatment outcomes., Study Design: Retrospective review., Methods: Ten-year review of adult patients with subglottic stenosis., Results: Ninety-two adults (23 male, 69 female) with subglottic stenosis underwent 247 endoscopic dilations between 2001 and 2010. The mean age was 48 years at time of first surgery. Etiology was GPA (granulomatosis with polyangiitis, formerly Wegener's granulomatosis) (45%), intubation (25%), or idiopathic (33%). Forty-one patients (45%) underwent a single procedure; 51 patients (55%) required multiple surgeries. The average interval for patients requiring a subsequent procedure was 13.7 months. Variations in surgical technique did not show differences in time to next procedure, and the use of mitomycin-C did not result in longer intervals between procedures. No significant complications were encountered after dilation., Conclusions: Subglottic stenosis remains a treatment challenge. Although patients are often symptomatically improved after endoscopic dilation, recurrence rates remain high., (© 2013 The American Laryngological, Rhinological and Otological Society, Inc.)

A patient with severe Behcet's disease (BD) was referred to our clinic because of severe pharyngolaryngeal involvement. This complication developed under treatment of prednisone and etanercept (Enbrel) 25 mg twice a week. A surgical approach was considered, but following three daily doses of Solu-Medrol (500 mg each) and 300 mg infliximab on the fourth day, the patient improved significantly. This is the first case reporting treatment with infliximab in laryngeal involvement of BD. Although some cases may still require surgical intervention, the therapeutic option of anti-TNF agents, specifically anti-TNF antibodies such as infliximab, may decrease the need for the surgical option.

Objective: Using a functional model of airway granulation tissue in subglottic stenosis, we investigated changes in inflammatory markers within granulation tissue in response to intraperitoneal dexamethasone injections. Changes in inflammatory markers will allow us to identify potential targets for immunological therapy., Study Design: Institutional Animal Care and Use Committee-approved animal study., Setting: Philadelphia Veterans Administration Medical Center animal research facility., Subjects and Methods: Laryngotracheal complexes of donor mice underwent direct airway injury and were transplanted into subcutaneous tissue of 19 recipient mice in 2 groups: steroid treated and untreated, with sample sizes of 10 and 9, respectively. The steroid-treated arm received intraperitoneal injection of dexamethasone for 3 weeks. Laryngotracheal complexes were then harvested, and granulation formation was measured. The messenger RNA (mRNA) expression of transforming growth factor (TGF)-β(1) and interleukin (IL)-1 was quantified., Results: At 3 weeks posttransplantation, there were statistically significant differences in observable granulation formation as well as mRNA expression of TGF-β(1) and IL-1β in all groups within the steroid treated arm as compared with the untreated arm., Conclusions: Systemic steroids have been used to prevent formation of granulation tissue and subglottic stenosis. However, the study of the immunologic markers and the corresponding changes with steroid treatment has not been well studied in animal models. Using a previously described novel murine model, we begin to delineate inflammatory markers that can be applied for potential therapeutic targets.