Impact of Procedural Variation in Endoscopic Dilation for Idiopathic Subglottic Stenosis.

OBJECTIVES: 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. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Comparative Treatment Outcomes for Idiopathic Subglottic Stenosis: 5-Year Update.

The North American Airway Collaborative (NoAAC) previously published a 3-year multi-institutional prospective cohort study showing variation in treatment effectiveness between 3 primary surgical techniques for idiopathic subglottic stenosis (iSGS). In this report, we update these findings to include 5 years of data evaluating treatment effectiveness. Patients in the NoAAC cohort were re-enrolled for 2 additional years and followed using the prespecified published protocol. Consistent with prior data, prospective observation of 487 iSGS patients for 5 years showed treatment effectiveness differed by modality. Cricotracheal resection maintained the lowest rate of recurrent operation (5%), followed by endoscopic resection with adjuvant medical therapy (30%) and endoscopic dilation (50%). These data support the initial observations and continue to provide value to providers and patients navigating longitudinal decision-making. Level of evidence: 2-prospective cohort study.

Impact of Serial Intralesional Steroid Injections on Idiopathic Subglottic Stenosis.

OBJECTIVES: Serial intralesional steroid injection (SILSI) has been increasingly used to treat idiopathic subglottic stenosis (iSGS). Prior studies have shown effectiveness, but not in all patients. This multi-institutional study evaluates the effect of SILSI on time to recurrent operation, peak expiratory flow (PEF), and dyspnea. METHODS: Post-hoc secondary analysis of the North American Airway Collaborative data were performed to evaluate the outcomes of iSGS patients undergoing and not undergoing SILSI. The primary outcome was time to recurrent operation, evaluated using Kaplan-Meier curves and Cox regression analysis. Secondary outcomes were change in PEF and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score. Within patients undergoing SILSI, demographics, time from last procedure, and PEF at initiation of SILSI were evaluated to determine the effect on recurrence. RESULTS: Two hundred and ninety patients were included, 238 undergoing endoscopic dilation alone and 52 undergoing dilation and SILSI. No differences in baseline characteristics were observed. There was no difference in time to recurrence (hazard ratio: 0.64; p = 0.183). There were no differences in PEF or CCQ across the 2.5-year study period. Among 52 patients undergoing SILSI, PEF at the time of starting SILSI did not affect recurrence (χ2  = 0.09, p = 0.77). CONCLUSION: Patients undergoing and not undergoing SILSI had similar times to recurrence, PEF, and CCQ. Factors predicting recurrence among patients undergoing SILSI were not identified. These results support a randomized controlled trial with a uniform SILSI protocol to quantify the effects of SILSI on objective and subjective outcomes and help determine which iSGS patients benefit most. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2255-2263, 2023.

Modeling Recurrence in Idiopathic Subglottic Stenosis With Mobile Peak Expiratory Flow.

OBJECTIVES/HYPOTHESIS: We sought to establish normative peak expiratory flow (PEF) data for patients with idiopathic subglottic stenosis (iSGS), evaluate whether immediate changes in PEF after a procedure predict long-term treatment response, and test if a decline in longitudinal PEF is associated with disease recurrence. STUDY DESIGN: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS. METHODS: iSGS patients consented and enrolled in the North American Airway Collaborative (NoAAC) iSGS1000 cohort recorded PEF data on a mobile smartphone app. Cox regression tested the associations between the magnitude of postoperative PEF improvement and longitudinal 90-day PEF decline with the risk of disease recurrence. RESULTS: Within the NoAAC iSGS1000 cohort, 810 patients participated in a 3-year prospective study comparing surgical treatment efficacy and 385 had appropriate PEF measurements and follow-up data. Of those patients, 42% (161/385) required at least one operation during study follow-up. The mean PEF preceding operative intervention was 241 L/min (95% confidence interval [CI]: 120-380) corresponding to a predicted PEF of 52%. The mean increase in PEF following a procedure was 111 L/min (95% CI: 96-125 L/min). Interestingly, the magnitude of immediate PEF improvement was not predictive of disease recurrence (hazard ratio [HR] for 100 L/min increase = 0.90, 95% CI: 0.60-1.00). However, recurrence was associated with the magnitude of PEF decline over 90 days (30% vs. 10% decline, HR = 2.2, 95% CI: 1.5-3.0). CONCLUSIONS: We provide normative PEF data on a large iSGS patient cohort. The degree of PEF improvement immediately after surgery was not associated with a longer procedure-free interval. However, a 30% decline in PEF over 90 days was associated with elevated risk of disease recurrence. LEVEL OF EVIDENCE: 2 Laryngoscope, 131:E2841-E2848, 2021.

Impact of Adjuvant Medical Therapies on Surgical Outcomes in Idiopathic Subglottic Stenosis.

OBJECTIVES/HYPOTHESIS: Adjuvant medications including proton pump inhibitors (PPI), antibiotics (trimethoprim/sulfamethoxazole [TMP-SMX]), and inhaled corticosteroids (ICS) may be prescribed for patients with idiopathic subglottic stenosis (iSGS). We describe medication use with endoscopic dilation (ED) or endoscopic resection with medical treatment (ERMT) and evaluate impact on outcomes. STUDY DESIGN: International, prospective, 3-year multicenter cohort study of 810 patients with untreated, newly diagnosed, or previously treated iSGS. METHODS: Post hoc secondary analysis of prospectively collected North American Airway Collaborative data on outcomes linked with adjuvant medication utilization. Primary outcome was time to recurrent operation, evaluated using Kaplan-Meier curves and Cox regression analysis. Secondary outcomes of change in peak expiratory flow (PEF) and clinical chronic obstructive pulmonary disease questionnaire (CCQ) score over 12 months were compared. RESULTS: Sixty-one of 129 patients undergoing ED received PPI (47%), and 10/143 patients undergoing ED received ICS (7%). TMP-SMX was used by 87/115 patients (76%) undergoing EMRT. PPI use in the ED group did not affect time to recurrence (hazard ratio [HR] = 1.00, 95% confidence interval [CI]: 0.53-1.88; P = .99) or 12-month change in PEF (L/min) (median [interquartile range], 12.0 [10.7-12.2] vs. 8.7 [-5.1 to 24.9]; P = .59), but was associated with 12-month change in CCQ (-0.05 [-0.97 to 0.75] vs. -0.50 [-1.60 to 0.20]; P = .04). ICS did not affect outcome measures. TMP-SMX use in ERMT did not affect time to recurrence (HR = 0.842, 95% CI: 0.2345-3.023; P = .79), PEF at 12 months (75 [68-89] vs. 81 [68-89]; P = .92), or 12-month change in CCQ (0.20 [-1.05 to 0.47] vs. -0.30 [-1.00 to 0.10]; P = .45). CONCLUSION: There is no standard practice for prescribing adjuvant medications. These data do not support that adjuvant medications prolong time to recurrence or increase PEF. Patients with iSGS and gastroesophageal reflux disease may experience some symptom benefit with PPI. LEVEL OF EVIDENCE: 3 Laryngoscope, 131:E2880-E2886, 2021.

Association of Social Determinants of Health with Time to Diagnosis and Treatment Outcomes in Idiopathic Subglottic Stenosis.

OBJECTIVES: To examine whether social determinants of health (SDH) factors are associated with time to diagnosis, treatment selection, and time to recurrent surgical intervention in idiopathic subglottic stenosis (iSGS) patients. METHODS: Adult patients with diagnosed iSGS were recruited prospectively (2015-2017) via clinical providers as part of the North American Airway Collaborative (NoAAC) and via an online iSGS support community on Facebook. Patient-specific SDH factors included highest educational attainment (self-reported), median household income (matched from home zip code via U.S. Census data), and number of close friends (self-reported) as a measure of social support. Main outcomes of interest were time to disease diagnosis (years from symptom onset), treatment selection (endoscopic dilation [ED] vs cricotracheal resection [CTR] vs endoscopic resection with adjuvant medical therapy [ERMT]), and time to recurrent surgical intervention (number of days from initial surgical procedure) as a surrogate for disease recurrence. RESULTS: The total 810 participants were 98.5% female, 97.2% Caucasian, and had a median age of 50 years (IQR, 43-58). The cohort had a median household income of $62 307 (IQR, $50 345-$79 773), a median of 7 close friends (IQR, 4-10), and 64.7% of patients completed college or graduate school. Education, income, and number of friends were not associated with time to diagnosis via multivariable linear regression modeling. Univariable multinominal logistic regression demonstrated an association between education and income for selecting ED versus ERMT, but no associations were noted for CTR. No associations were noted for time to recurrent surgical procedure via Kaplan Meier modeling and Cox proportional hazards regression. CONCLUSIONS: Patient education, income, and social support were not associated with time to diagnosis or time to disease recurrence. This suggests additional patient, procedure, or disease-specific factors contribute to the observed variations in iSGS surgical outcomes.