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Objective: To evaluate the impact of age on disease recurrence in idiopathic subglottic stenosis (iSGS) patients. Methods: This was a retrospective chart review of iSGS patients treated with laser wedge excision. Patients did not have prior surgery. Survival rates free of recurrence were estimated using the Kaplan–Meier methods, and associations were evaluated using Cox Proportional Hazards models. Results: Eighty‐five female patients were included in the study. Most patients (68%) were postmenopausal, had first period at or before 13 years of age, had at least one full‐term pregnancy (82%), were not undergoing hormone replacement therapy (93%), were not using hormonal birth control (88%), and were either partially or completely compliant with triple therapy regime (80%). There was a statistically significant average reduction in risk of recurrence of 5% for every additional year of age (p < 0.0001). When compared to patients older than 65 years of age, patients less than 35 were nearly 10 times more likely to recur (p = 0.002), and patients 55–65 and 45–55 years of age were 8 and 5 times more likely to recur, respectively (p = 0.003 and 0.009). Additionally, females on birth control showed decreased risk of recurrence of 74% compared with their counterparts (p = 0.04). Conclusion: This is the first study to demonstrate an inverse relationship between age and disease recurrence in patients with iSGS following surgery. Using age as a surrogate for menopausal status, these results suggest that increased age and/or birth control provide a protective effect through decreased recurrence rates, possibly mediated by decreased estrogen levels. Level of Evidence: 4 Laryngoscope, 135:198–205, 2025 [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of methotrexate and rituximab therapy on highly recurrent idiopathic subglottic stenosis (iSGS) patients with a negative antineutrophil cytoplasmic antibody titer cANCA(−). Methods: This was a retrospective cohort study of highly recurrent iSGS patients who recurred within 1 year or less and were treated with methotrexate (MTX), and rituximab (RTX), or a combination of both at different time points (MTX/RTX). Average surgical durations before and after drug treatment were summarized, and the differences were calculated. Results: A total of 21 female patients with median age of 62 years were included. Fifteen patients were treated with MTX, three were treated with RTX, and five treated with both. Patients treated with immunosuppressants showed a trend toward longer intervals between operations (mean pre‐drug interval: 338; mean post‐drug interval: 697 days) (p‐value = 0.25). Three patients did not recur following drug initiation with median follow‐up of 1265 days. All three treatment groups demonstrated a trend toward increased post‐drug recurrence intervals (MTX: 444 days, RTX: 374 days, MTX/RTX: 55 days), that was not statistically significant. Patients with prior dilations demonstrated longer post‐drug recurrence intervals (mean pre‐drug interval: 341 days, mean post‐drug interval 978 days) (p‐value = 0.17). Four patients in the cohort with the highest recurring disease improved from mean 129 days between operations to 509 days with drug therapy. The most common drug side effect was nausea (16%). Conclusion: MTX and RTX may be treatment options for some highly recurrent iSGS patients. Initial results are variable and demonstrate a need for further research on drug candidacy. Level of Evidence: 3 Laryngoscope, 135:168–175, 2025 [ABSTRACT FROM AUTHOR]

Objective: To compare the incidence of glottic stenosis in idiopathic subglottic stenosis (iSGS) patients with no prior surgical intervention to those with a history of endoscopic dilation and characterize the incidence of glottic involvement, changes in scar length, and progression of scar toward glottis following laser wedge excision (LWE). Methods: A retrospective review of iSGS patients who underwent LWE between 2002 and 2021 was performed. Patients without prior airway surgery were labeled LWE primary (LWEP) and operative findings for LWEP patients were reviewed for glottic involvement, scar length (DL), and distance from the glottis to superior‐most aspect of scar (DGS). Rates (in mm/procedure) of DΔL, reflecting an increase in length, and D−ΔGS, reflecting proximal migration, were calculated by dividing DΔL and D−ΔGS by the number of LWE procedures. Results: 213 iSGS patients underwent LWE, with 132 being LWEP patients. LWEP had a lower incidence of baseline glottic involvement (n = 6, 4.5%) than LWE secondary (LWES; n = 6, 7.5%). Four new cases of glottic involvement were noted in LWEP patients following LWE, with only one being clinically significant resulting in permanently decreased vocal fold mobility. With each procedure, scar length increased by 1.0 mm and DGS decreased by 0.7 mm, reflecting a migration or decrease in DGS of 9.5% with each procedure with respect to initial DGS. Overall rates of glottic stenosis following operations were similar between LWEP and LWES cohorts, 7.6% and 7.5% respectively. Conclusion: There appears to be a low risk of glottic involvement resulting from the LWE procedure in iSGS patients. Level of Evidence: 4 Laryngoscope, 133:875–882, 2023 [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Idiopathic subglottic stenosis (iSGS) is an unexplained obstruction involving the lower laryngeal and upper tracheal airway. Persistent mucosal inflammation is a hallmark of the disease. Epithelial microbiota dysbiosis is found in other chronic inflammatory mucosal diseases; however, the relationship between tracheal microbiota composition and iSGS is unknown. Given the critical role for host defense at mucosal barriers, we analyzed tissue specimens from iSGS patients for the presence of microbial pathogens.Methods: Utilizing 30 human iSGS, 20 intubation-related tracheal stenosis (iLTS), and 20 healthy control specimens, we applied molecular, immunohistochemical, electron microscopic, immunologic, and Sanger-sequencing techniques.Results: With unbiased culture-independent nucleic acid, protein, and immunologic approaches, we demonstrate that Mycobacterium species are uniquely associated with iSGS. Phylogenetic analysis of the mycobacterial virulence factor rpoB suggests that, rather than Mycobacterium tuberculosis, a variant member of the Mycobacterium tuberculosis complex or a closely related novel mycobacterium is present in iSGS specimens.Conclusion: These studies identify a novel pathogenic role for established large airway bacteria and provide new targets for future therapeutic intervention.Level Of Evidence: NA Laryngoscope, 127:179-185, 2017. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Idiopathic subglottic stenosis (iSGS) is a rare and devastating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. It arises without known antecedent injury or associated disease process. Persistent mucosal inflammation and a localized fibrotic response are hallmarks of the disease. Despite the initial clinical description of iSGS more than 40 year ago, there have been no substantive investigations into the pathogenesis of this enigmatic and progressive airway obstruction. In these studies, we present the initial characterization of the molecular pathogenesis underlying the fibrosing phenotype of iSGS.Methods: Utilizing 20 human iSGS and healthy control specimens, we applied histologic, immunohistochemical, molecular, and immunologic techniques.Results: We demonstrate significant activation of the canonical IL-23/IL-17A pathway in the tracheal mucosa of iSGS patients, as well as identify γδ T cells as the primary cellular source of IL-17A.Conclusion: Our results suggest that aberrant mucosal immune activation is a component in of the pathogenesis of iSGS. Most critically, our work offers new targets for future therapeutic intervention.Level Of Evidence: NA Laryngoscope, 126:E356-E361, 2016. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Idiopathic subglottic stenosis (iSGS) is a rare and potentially life-threatening disease marked by recurrent and progressive airway obstruction frequently requiring repeated surgery to stabilize the airway. Unknown etiology and low disease prevalence have limited the ability to characterize the natural history of iSGS and resulted in variability in surgical management. It is uncertain how this variation relates to clinical outcomes.Study Design: Medical record abstraction.Methods: Utilizing an international, multi-institutional collaborative, we collected retrospective data on patient characteristics, treatment, and clinical outcomes. We investigated variation between and within open and endoscopic treatment approaches and assessed therapeutic outcomes; specifically, disease recurrence and need for tracheostomy at last follow-up.Results: Strikingly, 479 iSGS patients across 10 participating centers were nearly exclusively female (98%, 95% confidence interval [CI], 96.1-99.6), Caucasian (95%, 95% CI, 92.2-98.8), and otherwise healthy (mean age-adjusted Charlson Comorbidity Index 1.5; 95% CI, 1.44-1.69). The patients presented at a mean age of 50 years (95% CI, 48.8-51.1). A total of 80.2% were managed endoscopically, whereas 19.8% underwent open reconstruction. Endoscopic surgery had a significantly higher rate of disease recurrence than the open approach (chi(2) = 4.09, P = 0.043). Tracheostomy was avoided in 97% of patients irrespective of surgical approach (95% CI, 94.5-99.8). Interestingly, there were outliers in rates of disease recurrence between centers using similar treatment approaches.Conclusion: Idiopathic subglottic stenosis patients are surprisingly homogeneous. The heterogeneity of treatment approaches and the observed outliers in disease recurrence rates between centers raises the potential for improved clinical outcomes through a detailed understanding of the processes of care.Level Of Evidence: 4. Laryngoscope, 126:1390-1396, 2016. [ABSTRACT FROM AUTHOR]

Objectives/Hypothesis Idiopathic subglottic stenosis (ISS) is a rare type of airway stenosis of unclear etiology. Open resection, while effective, remains a complex surgery and requires a hospital stay. Endoscopic management is often preferred but has historically been associated with a high recurrence rate. We aimed to analyze our experience, consisting of a standardized endoscopic approach combined with an empiric medical treatment. Study Design Retrospective cohort study. Methods All patients with ISS managed with standardized endoscopic treatment at our institution between 1987 and 2012 were identified, and their electronic medical records were reviewed. The treatment consisted of CO2 laser resection without dilatation and local infiltration with steroids and application of mitomycin C. Patients were also treated with antireflux medications, inhaled corticosteroids, and occasionally trimethoprim-sulfamethoxazole. The influence of medical management on annual recurrence rate was analyzed using negative binomial logistic regression. Results A total of 110 patients treated with standardized endoscopic management were included in our analysis. The procedure was well tolerated by all patients without complications. Recurrences were observed in approximately 60% of patients at 5 years. There was a trend suggesting an association between aggressive medical treatment and a reduction in the rate of recurrence/person/year (relative risk = 0.52, P = 0.051). Conclusion A standardized endoscopic management of ISS consisting of CO2 laser vaporization of the fibrotic scar appears effective in symptom control, with 40% of patients not requiring retreatment in the follow-up period, and with recurrence noted in a majority of patients. Aggressive medical treatment may have a role, but further prospective studies are required to confirm these findings. Level of Evidence 4. Laryngoscope, 124:498-503, 2014 [ABSTRACT FROM AUTHOR]