OBJECTIVE: To identify, group and document the surgical management of idiopathic subglottic stenosis (iSGS) in pregnant women among North American centers with expertise in the treatment of airway stenosis.
BACKGROUND: Idiopathic subglottic stenosis is a rare airway disease that primarily affects women in their third to fifth decade of life. Symptoms of iSGS often worsen during pregnancy and can present as a threat to optimal maternal and fetal health; however there is a lack of evidence addressing the management of iSGS in pregnancy.
METHODS: Cross-Sectional Survey Study.
METHODS: A twenty-four question survey was designed to query the surgical management, ventilation, and perioperative considerations for pregnant patients with iSGS. Twenty-nine North American academic tertiary care centers with airway surgery expertise were identified. A designated surrogate for each center was contacted by email to distribute and obtain results of the survey.
RESULTS: 17 centers responded. Most centers include differences in perioperative assessment such as frequency of consultation with a maternal/fetal medicine specialist. There is occasional use of a tocometer and rarely a non-stress test. Ventilation with intermittent jet ventilation or high-flow nasal cannula is favored. The surgical protocols include positional modifications, with pregnant patients in the left lateral decubitus position. The preferred timing for intervention is in the second or third trimester.
CONCLUSIONS: This is the first national survey describing surgical and perioperative considerations for the pregnant patient with iSGS among centers with airway expertise in the United States and Canada.

UNASSIGNED: To characterize presentation, disease course, and treatment of idiopathic subglottic stenosis (iSGS) in non-Caucasian women and compare this cohort to the predominantly female, Caucasian patient cohorts identified in the literature.
UNASSIGNED: Retrospective review. Results are compared to systematic review of demographics.
UNASSIGNED: Multiple California institutions from 2008 to 2021.
UNASSIGNED: Patients with intubation within 2 years of disease or who met exclusion criteria listed in prior publications were excluded. A systematic review of iSGS patient demographics was also completed for comparison.
UNASSIGNED: Of 421 patients with iSGS, 58 self-identified as non-Caucasian women, with 50 ultimately included. Mean age of onset was 45.1 years old (95% confidence interval [CI], 41.5-48.8), and mean age at diagnosis was 47.2 years (95% CI, 43.6-50.7). Mean Charlson comorbidity index was 1.06 (n = 49, 95% CI, 0.69-1.44). At diagnosis, Cotton-Meyer severity scores (documented in n = 45) were Cotton-Myer (CM) I (28.9%), CM II (40%), and CM III (31.1%). Mean age at first endoscopic surgery was 47.7 (95% CI, 44.2-51.3) years. 64% experienced disease recurrence with a median of 11 months between their first and second surgery. Our systematic review identified 60 studies that reported demographic features in patients with iSGS. 95% of pooled patients were Caucasian, while other demographic features were similar to the current cohort.
UNASSIGNED: The non-Caucasian population, almost 14% of this Californian cohort, does not differ from the majority Caucasian population detailed in contemporary literature. This cohort supports the presence of some racial and ethnic heterogeneity in this disease population.

Idiopathic subglottic stenosis (ISGS) is a rare fibrotic disease of the upper trachea with an unknown pathomechanism. It typically affects adult Caucasian female patients, leading to severe airway constrictions caused by progressive scar formation and inflammation with clinical symptoms of dyspnoea, stridor and potential changes to the voice. Endoscopic treatment frequently leads to recurrence, whereas surgical resection and reconstruction provides excellent long-term functional outcome. This study aimed to identify so far unrecognized pathologic aspects of ISGS using single cell RNA sequencing. Our scRNAseq analysis uncovered the cellular composition of the subglottic scar tissue, including the presence of a pathologic, profibrotic fibroblast subtype and the presence of Schwann cells in a profibrotic state. In addition, a pathology-associated increase of plasma cells was identified. Using extended bioinformatics analyses, we decoded pathology-associated changes of factors of the extracellular matrix. Our data identified ongoing fibrotic processes in ISGS and provide novel insights on the contribution of fibroblasts, Schwann cells and plasma cells to the pathogenesis of ISGS. This knowledge could impact the development of novel approaches for diagnosis and therapy of ISGS.

Intralesional steroid injections are commonly used to treat idiopathic subglottic stenosis and are believed to have minimal systemic effects. This case report presents an immunocompetent 67-year-old woman with idiopathic subglottic stenosis who developed Scedosporium apiospermum infection of the subglottis following in-office steroid injections, suggesting a potential risk for infection associated with this treatment. This highlights the need for further research to understand the impact of intralesional steroid injections on local and systemic immunocompetency to inform treatment protocols for idiopathic subglottic stenosis. Laryngoscope, 2024.

OBJECTIVE: Analyze the duration of symptom-free intervals following laser wedge excision (LWE) for recurrent idiopathic subglottic stenosis (iSGS). Secondary aim includes evaluating the influence of patient-related or disease factors.
METHODS: Retrospective review.
METHODS: Tertiary center.
METHODS: Review of iSGS patients who underwent LWE between 2002 and 2021. LWE patients without prior airway surgery were labeled LWE primary (LWEP) and those with prior history of dilation were labeled LWE secondary (LWES). A conditional frailty repeated events model was used to analyze the median time to recurrence (MTR) for each nth recurrence. Secondary analysis included stratification by use of medical therapy and initial preoperative characteristics of scar (Myer-Cotton grade, distance between the glottis and superior-most aspect of scar, DGS; length of scar, DL).
RESULTS: Two hundred and ten iSGS patients underwent LWE (131 LWEP, 79 LWES). The proportion of patients experiencing at least 1, 3, 6, and 12 recurrences, respectively, was 68.0% (n = 143), 40.7% (n = 85), 20.0% (n = 42), and 5.2% (n = 11). There was exponential time-shortening from the 1st to 12th recurrence (P < .0001). While MTR was 4.1 years after the first LWE, this fell to 2.8, 1.7, 1.0, and 0.7 years for the 2nd, 3rd, 6th, and 12th recurrences. Furthermore, LWEP patients experienced longer MTR than LWES counterparts within the first 6 recurrences (P < .01). There was no significant relationship between intersurgical interval and medication adherence, DL, DGS, or grade for recurrences beyond the first (P = .207, P = .20, P = .43, P = .16).
CONCLUSIONS: Symptom-free intervals in iSGS shorten with each subsequent recurrence and LWE. The difference in MTR between LWEP and LWES groups was significant within the first 6 recurrences with LWEP having longer MTR.
METHODS:

OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
METHODS: N/A Laryngoscope, 2024.

OBJECTIVE: To present a comprehensive flow cytometry panel for idiopathic subglottic stenosis (iSGS).
METHODS: Controlled ex vivo cohort study.
METHODS: Tertiary care academic hospital in a metropolitan area.
METHODS: Flow cytometry and single-cell RNA sequencing were performed on 9 paired normal and scar tissue samples from iSGS patients. Flow cytometry was used to assess the presence of myeloid (CD11b, CD14, CD15, Siglec8), lymphoid (CD3, CD4, CD8, gamma delta [γδ], FOXP3), endothelial (CD31), fibroblast (CD90, SMA), and epithelial (CD326, CK5) markers.
RESULTS: On flow cytometry, iSGS scar is characterized by an increased presence of myeloid, lymphoid, endothelial, and fibroblast cell types, but a decreased presence of epithelial cells. In the myeloid lineage, iSGS scar samples demonstrated increased CD11b+ monocytes (P < .001), Siglec8+ eosinophils (P = .03), and CD14+ monocytes (P = .02). In the lymphoid lineage, iSGS scar demonstrated increased CD3+ T-cells (P < .001), CD4+ helper T-cells (P < .001), γδ+ T-cells (P < .001), and FOXP3+ regulatory T-cells (P = .002). iSGS scar exhibited specific increases in CD90+ (P = .04) and SMA+ (P < .001) fibroblasts but decreased CD326+ (E-cadherin) epithelial cells (P = .01) relative to normal samples.
CONCLUSIONS: We present a comprehensive flow cytometry panel for iSGS. This flow panel may serve as a common platform among airway scientists to elucidate the cellular mechanisms underpinning iSGS and other upper airway pathologies. Scar iSGS samples demonstrate a distinct cellular profile relative to normal iSGS specimens, exhibiting increased fibroblast, endothelial, and inflammatory cell types but decreased epithelium.

OBJECTIVE: A small number of Idiopathic subglottic stenosis (iSGS) patients are treated at institutions across the country. Divergence in operative techniques for endoscopic dilation (ED) of iSGS has been anecdotally recognized but not formally characterized. Additionally, the relationship between procedural variation and clinical outcome has not been studied.
METHODS: Secondary analysis of the NoAAC iSGS1000 cohort investigated variation in procedural techniques and treatment outcomes in patients treated with ED across high-enrolling treatment centers (enrolled >10 patients in PR-02 trial).
RESULTS: Thirteen NoAAC centers each enrolled >10 patients treated with ED for a total of 281 subjects. There was significant variation in procedural details and rate of recurrence among institutions. Hierarchal cluster analysis revealed significant heterogeneity among institutions and clusters in all procedural variables. However, analysis demonstrated a transient delay in disease recurrence in cluster 2 which disappeared with longer longitudinal follow-up. Patient-reported outcome and peak expiratory flow data supported the potential benefit of the technical variation in Cluster 2. Distinct to cluster 2, however, was routine use of adjuvant triple medical therapy (proton pump inhibitor (PPI), antibacterial agent, and steroid inhaler).
CONCLUSIONS: Both outcome and procedural technique vary among centers employing ED to treat iSGS. A transient delay in recurrence was observed among centers that routinely prescribed adjuvant medical therapy (antibiotic, inhaled corticosteroid, and PPI) to iSGS patients after endoscopic dilation, which was further supported by patient-reported data and peak expiratory flow data. Prospective studies are needed to understand the effects of adjuvant medical therapy on recurrence after endoscopic dilation.
METHODS: 4 Laryngoscope, 134:3260-3266, 2024.

UNASSIGNED: Cricotracheal resection (CTR) is considered the standard of care for patients suffering from idiopathic subglottic stenosis (iSGS). Although CTR results in permanent restoration of airway patency, it has a mild to moderate impact on voice quality. Here we propose modifications of the standard CTR technique to make it a voice-preserving procedure.
UNASSIGNED: Five women with iSGS underwent voice-sparing CTR between January 2022 and January 2023. In this procedure, through several technical adaptations, the function of the cricothyroid joint was preserved. Outcomes of these voice-sparing CTRs were compared to outcomes in patients who underwent standard CTR in our institution. All patients underwent full functional preoperative and postoperative workups, including spirometry, voice measurements, patient self-assessment, and fiberoptic endoscopic evaluation of swallowing.
UNASSIGNED: All 5 patients in the study group suffered from iSGS with high-grade Myer-Cotton III° stenosis (100%); 1 patient had previously undergone endoscopic laser resection. Voice evaluation demonstrated a nearly unchanged fundamental pitch (mean preoperative, 191 ± 73.1 Hz; postoperative, 182 ± 64.2 Hz) and dynamic voice range (preoperative, 24.4 semitones; postoperative, 20.4 semitones). This was in contrast to the control group, in which significantly reduced voice quality was observed.
UNASSIGNED: In selected patients suffering from iSGS, excellent functional results can be obtained with voice-sparing CTR.

OBJECTIVE: The aim was to assess changes in physical parameters of subglottic stenosis (SGS) following serial endoscopic surgical intervention.
METHODS: This was a retrospective chart review.
METHODS: A retrospective review of 52 idiopathic subglottic stenosis (iSGS) patients undergoing multiple endoscopic (excision/dilation) procedures between 2014 and 2022 was completed. Parameters including proximal stenosis distance from the vocal process and total stenosis length collected intraoperatively were compared over serial treatments. Differences between patient variables affecting distances from the vocal process and mean stenosis length were statistically analyzed utilizing nonparametric estimators including the Mann Whitney U, Fisher exact, and linear regression models.
RESULTS: For the cohort of iSGS patients (N = 52), the mean age was 55.1 (±15.1). The patients were predominantly female (96.2%) and Caucasian (84.6%). Patients underwent an average of 3.4 (±1.3) endoscopic procedures for long-term treatment of iSGS (range: 1 to 5 procedures). Patients undergoing a total of two (2) total procedures within the data collection window demonstrated a statistically significant decrease in mean stenosis length between the first and second procedures (p = 0.014). Changes in distance of the stenosis from the glottis was not found to be statistically significant (p = 0.833). There was a statistically significant decrease in mean length of stenosis from the 1st to the 2nd procedure by approximately 0.11 cm (p = 0.0003). No additional statistically significant differences in stenosis length or location were detected.
CONCLUSIONS: Serial endoscopic excision/dilation procedures (the mainstay of iSGS surgical management) do not appear to significantly lengthen intraluminal stenosis nor change the distance of the stenosis from the glottis.
METHODS: 4 Laryngoscope, 134:1769-1772, 2024.