A Retrospective Evaluation of the Treatment Effects of Rituximab in Patients with Progressive and Symptomatic Fibrosing Mediastinitis.

RATIONALE: Fibrosing mediastinitis is an uncommon fibro-inflammatory condition without established or effective medical therapies. Infiltrating B-lymphocytes are commonly present, and progressive fibrosis compromises mediastinal structures including blood vessels and airways resulting in significant morbidity and mortality. OBJECTIVE: To evaluate the benefits and side effects of Rituximab in patients with progressive and symptomatic fibrosing mediastinitis. METHODS: We treated 22 patients (median age 35 years, range: 15-68 years, 45% female) with metabolically active, progressive fibrosing mediastinitis with off-label rituximab. Additionally, patients were put on pneumocystis and antifungal prophylaxis when immunosuppressed with rituximab. Modeling of longitudinal treatment response based on changes in relative lesion volume from baseline was performed retrospectively using functional data analysis; time-to-event modeling was performed to estimate treatment response rates based on a >30% reduction in pre-treatment volume. MEASUREMENTS: The primary end points were lack of disease progression and change in mediastinal lesion volume by CT (evaluated retrospectively). MAIN RESULTS: No patient experienced disease progression after rituximab therapy. Median clinical follow-up was 42 months (range: 7 to 94) and imaging follow-up 21 months (range: 7 to 62). 82% of patients had confirmed histoplasmosis-associated fibrosing mediastinitis. After rituximab treatment a 49.6% (95% CI = [17.5%, 64.4%]) mean estimated decrease in pre-treatment lesion volume was observed at 24 months. The estimated objective treatment response rate was 47.9% (95% CI = [26.7%, 70.3%]). CONCLUSION: This observational study suggests that Rituximab is well tolerated and potentially effective therapy in a cohort of patients with symptomatic and progressive FM.

Methotrexate and Rituximab Use in Highly Recurrent Idiopathic Subglottic Stenosis.

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, 2024.

Age and Menopausal Status in Idiopathic Subglottic Stenosis.

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, 2024.

Custom silicone Y-stents for the management of anastomotic stenosis in lung transplant recipients.

BACKGROUND: Airway stenting may be needed to manage anastomotic complications in lung transplant recipients. Conventional stenting strategies may be inadequate due to anatomic variations between the recipient and donor or involvement of both the anastomosis and lobar bronchi. METHODS: We investigated the efficacy of 3D-designed patient-specific silicone Y-stents in managing this scenario. 9 patients with complex airway stenosis underwent custom stent insertion after either failing traditional management strategies or having anatomy not suitable for conventional stents. CT images were uploaded to stent design software to make a virtual stent model. 3D printing technology was then used to make a mold for the final silicone stent which was implanted via rigid bronchoscopy. Forced expiratory volume in 1 s (FEV1) was measured pre- and post-stent placement. RESULTS: 78 % of patients experienced an increase in their FEV1 after stent insertion, (p = 0.001, 0.02 at 30 and 90 days respectively). Unplanned bronchoscopies primarily occurred due to mucous plugging. 2 patients had sufficient airway remodeling allowing for stent removal. CONCLUSIONS: Personalized 3D-designed Y-stents demonstrate promising results for managing complicated airway stenosis, offering improved lung function and potential long-term benefits for lung transplant recipients.

Symptom-Free Intervals Following Laser Wedge Excision for Recurrent Idiopathic Subglottic Stenosis.

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. STUDY DESIGN: Retrospective review. SETTING: 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). CONCLUSION: 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.

Medical Maintenance Therapy Following Laser Excision in Patients With Granulomatosis With Polyangiitis (GPA)-Associated Subglottic Stenosis.

OBJECTIVE: To report on a series of patients with cANCA/PR3-positive, granulomatosis with polyangiitis (GPA)-associated subglottic stenosis (SGS) and evaluate response to medical maintenance therapy with rituximab versus other immunosuppressants following initial endoscopic laser excision. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary academic center. METHODS: A retrospective chart review of patients with SGS and cANCA/PR3-positive GPA who received immunosuppressive maintenance therapy following endoscopic laser excision at our institution from June 1989 to March 2020 was performed. Data pertaining to patient demographics, clinical features, medications, and endoscopic laser procedures were collected. RESULTS: A total of 27 patients (15 women) with mean age (range) of 40 (19-59) years and mean (range) follow-up of 12.6 years (1.5-28.6) were identified. Sixteen patients (60%) had limited GPA. Six patients (24%) had previously received local intervention with open surgery (n = 1, 4%) or endoscopic techniques (n = 5, 20%). All patients experienced symptom improvement following initial CO2 laser excision at our institution without any procedural complications or adverse events. Following initial laser excision, 15 patients (60%) were treated with rituximab and 10 patients (40%) were treated with nonrituximab immunosuppressive agents. Patients treated with rituximab were less likely to recur (P = 0.040). Limited GPA was associated with an increased incidence of recurrence (P = 0.031). Median time (years) to recurrence (range) was 3.2 (0.3-19.3) and was not significantly associated with treatment or GPA subtype. CONCLUSION: Endoscopic CO2 laser excision is a safe and effective local intervention for GPA-associated SGS. Medical maintenance therapy with rituximab reduces risk of recurrence following initial laser excision relative to treatment with non-rituximab agents.

Shape-Sensing Robotic-Assisted Bronchoscopy versus Computed Tomography-Guided Transthoracic Biopsy for the Evaluation of Subsolid Pulmonary Nodules.

INTRODUCTION: Lung cancer remains the leading cause of cancer death worldwide. Subsolid nodules (SSN), including ground-glass nodules (GGNs) and part-solid nodules (PSNs), are slow-growing but have a higher risk for malignancy. Therefore, timely diagnosis is imperative. Shape-sensing robotic-assisted bronchoscopy (ssRAB) has emerged as reliable diagnostic procedure, but data on SSN and how ssRAB compares to other diagnostic interventions such as CT-guided transthoracic biopsy (CTTB) are scarce. In this study, we compared diagnostic yield of ssRAB versus CTTB for evaluating SSN. METHODS: A retrospective study of consecutive patients who underwent either ssRAB or CTTB for evaluating GGN and PSN with a solid component less than 6 mm from February 2020 to April 2023 at Mayo Clinic Florida and Rochester. Clinicodemographic information, nodule characteristics, diagnostic yield, and complications were compared between ssRAB and CTTB. RESULTS: A total of 66 nodules from 65 patients were evaluated: 37 PSN and 29 GGN. Median size of PSN solid component was 5 mm (IQR: 4.5, 6). Patients were divided into two groups: 27 in the ssRAB group and 38 in the CTTB group. Diagnostic yield was 85.7% for ssRAB and 89.5% for CTTB (p = 0.646). Sensitivity for malignancy was similar between ssRAB and CTTB (86.4% vs. 88.5%; p = 0.828), with no statistical difference. Complications were more frequent in CTTB with no significant difference (8 vs. 2; p = 0.135). CONCLUSION: Diagnostic yield for SSN was similarly high for ssRAB and CTTB, with ssRAB presenting less complications and allowing mediastinal staging within the same procedure.

Efficacy of Robotic Bronchoscopy for Molecular Marker Analysis in Primary Lung Cancer.

BACKGROUND: Molecular testing has become a more frequent necessity in NSCLC management. Using next-generation sequencing, multiple targets for therapy can be identified with small amounts of nuclear material. The authors evaluated the performance of robotic-assisted bronchoscopy in acquiring tissue that meets pre-analytic criteria for PD-L1 immunohistochemistry and/or next-generation sequencing. MATERIALS AND METHODS: Patients with a diagnosis of primary lung cancer identified through robotic bronchoscopy were retrospectively reviewed. Pathology reports were assessed for results of molecular testing and detection of programmed death-ligand 1 (PD-L1). An independent pathologist evaluated each specimen type (smears, cell block, tissue biopsy, and/or touch prep) to determine whether each tissue type would meet pre-analytic criteria for attempting next-generation sequencing and/or PD-L1 immunohistochemistry. RESULTS: Seventy-eight patients with primary lung were reviewed. By independent pathologic assessment of cytological smears, cell block, biopsy, and/or touch preparations, 72% of samples were found to be adequate for molecular and PD-L1 testing. Preanalytic adequacy (%) for next-generation sequencing (NGS) and PD-L1 staining was determined based on specimen type: cytological smear 48.6% for NGS; cell block 14.3% for NGS and 32.9% for PD-L1; biopsy 29.2% for NGS and 62.5% for PD-L1; and touch prep 61.4% for NGS. CONCLUSION: Robotic-assisted bronchoscopy yielded samples that met preanalytic criteria for molecular testing in 72% of cases. These results support the use of robotic-assisted bronchoscopy for both the diagnosis and molecular testing of early-stage lung cancer.

Flexible CO2 Laser in Therapeutic Bronchoscopy: Initial Experiences in a Tertiary Center.

BACKGROUND: CO2 Laser (CO2L) technology deployable through flexible endoscopes now allows for their use throughout the airway, although published data are limited. METHODS: Retrospective analysis of CO2L bronchoscopic procedures, excluding glottic and subglottic interventions. Procedural success was defined as >50% visual reduction in airway obstruction in the area treated or resolution of the procedural indication. RESULTS: Seventy-two procedures were performed on 36 patients. Nonmalignant indications comprised 66%: stent-associated granulation tissue (28%), granulomatosis with polyangiitis lesions (23%), and lung transplant-related granulation tissue (16%) were the most common. Bronchoscopic access was flexible only in 81% and primarily rigid (combined with flexible) in 18%. The site of intervention was the trachea at 19%, the mainstem at 56%, and lobar/segmental airways at 45%. Procedural success was 89%. CO2L was used exclusively in 19%; in 81%, additional techniques were required, most commonly balloon dilation (59%), cryo-debulking (23%), and rigid dilation (16%). Malignant indications had a nonsignificant trend toward requiring adjuvant techniques ( P =0.05). Seventy-six percent of the patients required more than 1 procedure. CO2L exclusive cases had no statistically different needs for subsequent therapeutic bronchoscopies ( P =0.10) or time to reintervention (109 vs. 41 days, P =0.07), and reintervention-free survival was similar ( P =0.10) and difficult to predict. The complication rate attributable to CO2L was 2.7%. CONCLUSION: CO2L is a safe and useful tool when precise cutting and vaporization are desired. Its use in multi-modality approaches has high levels of success in adequately selected lesions, adding an ablative potential to dilation techniques. Vasculitis-associated scars/webs and granulation tissue (including stent-associated) appear to be ideal targets.

Bronchoscopic Lung Volume Reduction: Highlighting the Patient Selection Process.

Patients with advanced emphysema frequently experience severe dyspnea that is inadequately treated with medical therapy alone. Over the past 4 years, we have seen increased usage of bronchoscopic lung volume reduction (BLVR) with endobronchial valves. Success of the procedure is dependent on patient selection because it is not necessarily appropriate for all patients with severe emphysema. (Table 1) The purpose of this review is to highlight the selection process at a single institution. We also discuss the influence of this process on outcomes. Between March 1, 2019, and October 12, 2021, 2402 patients were referred to a dedicated chronic obstructive pulmonary disease clinic at Mayo Clinic - Rochester, whereas 161 patients were subsequently referred for multidisciplinary BLVR review. Of those patients, 53 (32.9%) were selected to receive valves and 35 (21.7%) ultimately underwent the procedure. The main reasons for exclusion included an incompatible quantitative computed tomography analysis (n=37, 34.3%), presence of pulmonary nodule or active malignancy (n=14, 13.0%), or need for completion of pulmonary rehabilitation (n=9, 8.3%). Full or partial (>70%) target lobe collapse was observed in 58.6% of patients who received valves. Those with collapse experienced statistically significant improvements in spirometric measures. Twelve patients experienced a pneumothorax (34.3%), with 10 patients requiring thoracostomy tube placement and prolonged hospitalization (median, 11 days; range, 4-39 days). Nineteen patients required a secondary procedure within the first year. The study highlights how a multidisciplinary approach to the BLVR selection process enables individualization of a complex procedure and enhances the exclusion of inappropriate candidates.

Remotely operated robotic microscopy for rapid diagnosis of bronchoscopic cytology specimens.

BACKGROUND: Obtaining a diagnosis and treating pulmonary malignancies during the same anesthesia requires either an on-site pathologist or a system for remotely evaluating microscopic images. Cytology specimens are challenging to remotely assess given the need to navigate through dispersed and three-dimensional cell clusters. Remote navigation is possible using robotic telepathology, but data are limited on the ease of use of current systems, particularly for pulmonary cytology. METHODS: Air dried modified Wright-Giemsa stained slides from 26 touch preparations of transbronchial biopsies and 27 smears of endobronchial ultrasound guided fine needle aspirations were scored for ease of adequacy assessment and ease of diagnosis on robotic (rmtConnect Microscope) and non-robotic telecytology platforms. Diagnostic classifications were compared between glass slides and the robotic and non-robotic telecytology assessments. RESULTS: Compared to non-robotic telecytology, robotic telecytology had a greater ease of adequacy assessment and non-inferior ease of diagnosis. The median time to diagnosis using robotic telecytology was 85 s (range 28-190 s). Diagnostic categories were concordant for 76% of cases in robotic versus non-robotic telecytology and 78% of cases in robotic telecytology versus glass slide diagnosis. Weighted Cohen's kappa scores for agreement in these comparisons were 0.84 and 0.72, respectively. CONCLUSIONS: Use of a remote-controlled robotic microscope improved the ease of adequacy assessment compared to non-robotic telecytology and enabled strongly concordant diagnoses to be expediently rendered. This study provides evidence that modern robotic telecytology is a feasible and user-friendly method of remotely and potentially intraoperatively rendering adequacy assessments and diagnoses on bronchoscopic cytology specimens.

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.

Accuracy of Preliminary Pathology for Robotic Bronchoscopic Biopsy.

BACKGROUND: Diagnosis and treatment of peripheral pulmonary lesions (PPLs) currently require at least 2 procedures. An all-in-1 approach would require diagnosing malignancy with preliminary cytology results. This study investigated the concordance between preliminary cytology and final pathology results in biopsies of PPLs obtained by shape-sensing robotic-assisted bronchoscopy (ssRAB). METHODS: This study was a retrospective, consecutive, single-arm, single-center study of 110 ssRABs for PPLs. Concordance was defined as agreement between preliminary cytology and final pathology results. Accuracy, sensitivity, specificity, positive and negative predictive values, and safety outcomes were examined. RESULTS: The concordance was 89% for needle biopsies, 85% for forceps biopsies, and 92% overall, with substantial agreement. There was no significant association of concordance with patients' demographics or lesion characteristics. Preliminary cytology resulted in a malignant diagnosis in 70%, a nonmalignant diagnosis in 4%, and a nondiagnostic result in 26%, with accuracy of 86% and sensitivity of 84%. The total complication rate was 3.6%, with a pneumothorax rate of 1.8%. CONCLUSIONS: This study compared the concordance of preliminary pathology results with final pathology results for ssRAB biopsies in PPLs. The results showed that preliminary samples have a high concordance with final pathology results and may enable management of PPLs with a single anesthetic procedure including biopsy, staging, and treatment.

Proximal Scar Progression in Idiopathic Subglottic Stenosis After Wedge Excision: Does it Happen?

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.

Robotic-assisted bronchoscopy versus CT-guided transthoracic biopsy for diagnosis of pulmonary nodules.

BACKGROUND AND OBJECTIVE: Currently, computed tomography-guided transthoracic biopsy (CTTB) is the most accurate diagnostic approach for pulmonary nodules suspected of malignancy. Traditional bronchoscopy has shown suboptimal diagnostic sensitivity, but the emergence of robotic-assisted bronchoscopy (RAB) has the potential to improve diagnostic accuracy, maximize diagnostic yield and complete mediastinal and hilar staging in a single procedure. We aim to assess the efficacy and diagnostic performance of RAB compared to CTTB for diagnosing pulmonary nodules suspected of lung cancer. METHODS: A multicenter retrospective review of consecutive patients who underwent RAB and CTTB for evaluating pulmonary nodules from January 2019 to March 2021 at Mayo Clinic Florida and Mayo Clinic Rochester, United States. Clinical and demographic information, nodule characteristics, outcomes and complications were compared between RAB and CTTB. RESULTS: A total of 225 patients were included: 113 in the RAB group and 112 in the CTTB group. Overall diagnostic yield was 87.6% for RAB and 88.4% for CTTB. For malignant disease, RAB had a sensitivity of 82.1% and a specificity of 100%, CTTB had a sensitivity of 88.5% and a specificity of 100%. Complication rate was significantly higher for CTTB compared to RAB (17% vs. 4.4%; p = 0.002). CONCLUSION: RAB, when available, can be as accurate as CTTB for sampling pulmonary nodules with similar or reduced complications and should be considered as a means for nodule biopsy, particularly when mediastinal staging is also clinically warranted.

Complications following laser wedge excision for idiopathic subglottic stenosis.

OBJECTIVES: Endoscopic laser wedge excision (LWE) is an effective treatment option for idiopathic subglottic stenosis (iSGS); however, data regarding complications following LWE are limited. The aim of the following analysis was to provide a review of frequency and type of complications that occur with LWE in patients with iSGS. STUDY DESIGN: Retrospective review. METHODS: Patients with iSGS undergoing LWE between January 2002 and September 2021 were performed. Demographic data were recorded. Complications were stratified into major and minor categories. The frequency of these complications and the respective treatment for them was analyzed. RESULTS: 212 patients within the study period underwent a total of 573 LWE procedures. All but two patients were female, with a median age of 54 years at time of LWE. Of these patients, 43 (20 %) patients experienced a complication. Of these, only 7 (15 %) of the reported complications were considered major while the rest were minor in nature. Major complications included 3 cases of post-operative hemoptysis, 1 case of tracheitis, and 3 cases of reduced vocal fold hypomobility with concurrent glottic stenosis. Minor complications consisted of 2 cases of tooth fracture and 34 cases of tongue paresthesia post-operatively that was self-limited. There were no mortalities. CONCLUSION: Major complications occur in <5 % of LWE procedures based off the analysis. All major complications were managed without significant long-term morbidity. Minor complications with the LWE are self-limited in nature. Our data supports the LWE as a safe treatment option for iSGS.

RNA Sequencing of Idiopathic Subglottic Stenosis Tissues Uncovers Putative Profibrotic Mechanisms and Identifies a Prognostic Biomarker.

Idiopathic subglottic stenosis (iSGS) is a localized airway disease that almost exclusively affects females. Understanding the molecular mechanisms involved may provide insights leading to therapeutic interventions. Next-generation sequencing was performed on tissue sections from patients with iSGS (n = 22), antineutrophil cytoplasmic antibody-associated vasculitis (AAV; n = 5), and matched controls (n = 9) to explore candidate genes and mechanisms of disease. Gene expression changes were validated, and selected markers were identified by immunofluorescence staining. Epithelial-mesenchymal transition (EMT) and leukocyte extravasation pathways were the biological mechanisms most relevant to iSGS pathogenesis. Alternatively activated macrophages (M2) were abundant in the subepithelium and perisubmucosal glands of the airway in iSGS and AAV. Increased expression of the mesenchymal marker S100A4 and decreased expression of the epithelial marker epithelial cell adhesion molecule (EPCAM) further supported a role for EMT, but to different extents, in iSGS and antineutrophil cytoplasmic antibody-associated subglottic stenosis. In patients with iSGS, high expression of prostate transmembrane protein, androgen induced 1 (PMEPA1), an EMT regulator, was associated with a shorter recurrence interval (25 versus 116 months: hazard ratio = 4.16; P = 0.041; 95% CI, 1.056-15.60). Thus, EMT is a key pathogenetic mechanism of subglottic stenosis in iSGS and AAV. M2 macrophages contribute to the pathogenesis of both diseases, suggesting a shared profibrotic mechanism, and PMEPA1 may be a biomarker for predicting disease recurrence in iSGS.