[Application of acellular dermal matrix in prevention of laryngeal stenosis in glottic carcinoma].

Objective:To investigate the effect of acellular dermal matrix in preventing laryngeal stenosis in glottic carcinoma patients. Methods:Fifty-five patients with glottic carcinoma（T2, T3） from February 2018 to December 2022 were divided into experimental group（28 cases） and control group（27 cases） according to their wishes. Acellular dermal matrix was placed in the operation cavity in the experimental group after laryngofission, while control group 12 cases were sutured by pulling the upper and lower edges, 15 cases were repaired with sternohyoid muscle fascia flap. Results:In the experimental group, 1 case had laryngeal stenosis caused by laryngeal mucosa swelling after operation, and extubated successfully after symptomatic treatment. In the control group, 7 cases had laryngeal stenosis after operation, of which 3 cases were caused by granulation tissue hyperplasia in laryngeal cavity, and extubated after symptomatic treatment. 2 cases extubated after operation suffered from progressive dyspnea during radiotherapy, and underwent tracheotomy again, extubation successful after treatment. 2 cases caused by laryngeal mucosa swelling, after symptomatic treatment, one case was successfully extubated, and one case had long-term intubation. The laryngeal stenosis rate of the experimental group was 3.6%（1/28） , which was lower than control group 25.9%（7/27）, and the therapeutic effect of the experimental group was significantly better than control group （χ²=5.526, P=0.019）. Conclusion:Implanting acellular dermal matrix in the operation cavity of glottic carcinoma can reduce the occurrence of laryngeal stenosis and have satisfactory preventive effect on laryngeal stenosis.

[Balloon dilation as an alternative to tracheotomy for acquired subglottic stenosis in children of the first year of life]. / Ballonnaya dilatatsiya kak al'ternativa trakheotomii pri priobretennom podskladkovom rubtsovom stenoze u detei pervogo goda zhizni.

OBJECTIVE: To study the efficacy and safety of balloon dilation as the first choice method in the treatment of children of the first year of life with acquired subglottic stenosis. MATERIAL AND METHODS: A retrospective analysis of the treatment of 25 patients aged 27 days to 11 months of life (average age 5.3±3.76 months) with subglottic stenosis caused by prolonged intubation, in whom balloon dilation was the first method of treatment. Grade III Cotton-Myer stenosis was preoperatively detected in 22 children, the remaining 3 had grade II stenosis. RESULTS: The success rate of balloon dilation was 100%; tracheotomy was not required in any case, the absence of stenosis during a follow-up examination in the catamnesis was recorded in 14 (56%) children, the remaining 11 (44%) had grade 0-I stenosis and did not cause respiratory disorders. In 1 child (1.5 years old), a subglottic cyst was removed after balloon dilation. One dilation was required in 18 (72%) children, two - in 5 (20%), three and four - respectively for 1 patient. If additional intervention was necessary, the operation was repeated 10 days - 3 months after the previous one. There were no postoperative complications. CONCLUSION: Balloon dilation is a highly effective and safe alternative to traditional surgical interventions for acquired subglottic stenosis in children of the first year of life and can be recommended as a method of first choice.

Open airway surgery for post-COVID laryngotracheal stenosis.

INTRODUCTION: This study reports our experience with open reconstructive surgery in patients with laryngotracheal stenosis (LTS) following prolonged intubation and/or tracheostomy in the context of COVID-19. METHODS: All patients underwent a preoperative endoscopic airway assessment. Posterior glottic lesions were graded according to the Bogdasarian classification, subglottic-tracheal lesions according to the Cotton-Myers classification and postoperative complications reported by the Clavien-Dindo classification. We report postoperative outcomes and functional results in this patient subset. RESULTS: We include 14 patients diagnosed to have post COVID LTS, one female and 13 males. This group was compared with a control group, diagnosed with LTS following prolonged intubation. In the COVID group, mean age of patients at the time of the airway surgery was 52.1 ± 16.8 years (range: 13.7-76.3). More than half the patients were multi-morbid with hypertension and obesity being the most common conditions. Eleven patients had multi-site stenoses. Open surgical interventions performed were tracheal resection and anastomosis, laryngotracheal reconstruction and extended cricotracheal resection, and postoperative complications were seen in 12 (85.6%) patients. 70% patients with pre-existing tracheostomy were decannulated. Oral swallowing was not tolerated in one-fifth of the patients and a significant number of them have poor voice quality. CONCLUSION: Post-COVID pandemic, airway surgeons are seeing an increased number of patients with complex LTS, and we report significant postoperative complications in this patient subset. Decannulation rates, voice and swallowing results are poor in patients with glottic involvement as compared to isolated tracheal stenosis.

Surgery for tracheal and laryngotracheal stenosis: a historical case series.

OBJECTIVES: Benign (laryngo-)tracheal stenosis is a relatively rare pathology and its surgical treatment is performed only at few specialized centres. This study aims to investigate outcomes after (laryngo-)tracheal resection-anastomosis, to explore potential risk factors for postoperative complications and to assess whether, over a 33-year period, there were major changes in surgical indications, techniques or outcomes. METHODS: Retrospective, single-centre review of all consecutive patients who underwent tracheal or laryngo-tracheal resection/anastomosis for benign pathologies from 1990 to 2023. RESULTS: Overall, 211 patients underwent tracheal (149 patients, 70.6%) and laryngo-tracheal (62 patients, 29.4%) resection-anastomosis. Of these, 195 patients (93.8%) were affected by iatrogenic stenosis, while 13 (6.2%) suffered from idiopathic stenosis. The median length of stenosis was 25 mm (interquartile range 1-3, 20-30). The overall morbidity rate was 27.5%, while major morbidity occurred in 10.5% of cases. One patient (0.5%) died in the postoperative period. Glottic oedema (17 patients, 8.1%), granulations (12 patients, 5.7%) and restenosis (10 patients, 4.7%) were the main complications. The only independent risk factor for postoperative complications was the length of the resected airway (P = 0.019). In the latest half of the study period, an older median age was observed, and no patient with idiopathic tracheal stenosis underwent surgery. Postoperative outcomes were comparable between surgical eras. CONCLUSIONS: Surgical treatment of (laryngo-)tracheal stenosis is challenging and should be performed by specialized centres. In our experience, morbidity and mortality rates were satisfactory, and in most cases, patients could breathe without tracheostomy. The length of the stenosis was the most significant risk factor for postoperative complications.

The voice and swallowing profile of adults with laryngotracheal stenosis before and after reconstructive surgery: A prospective, descriptive observational study.

OBJECTIVES: Airway reconstruction for laryngo tracheal stenosis (LTS) improves dyspnoea. There is little evidence relating to impact upon voice and swallowing. We explored voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. DESIGN: Outcome measures were collected pre-reconstructive surgery, two-weeks post-surgery and up to 4-6 months post-surgery. SETTING: Tertiary referral centre. PARTICIPANTS: With ethical approval, twenty consecutive adult (≥18 years) LTS patients undergoing airway reconstruction were prospectively recruited. MAIN OUTCOME MEASURES: These included physiological values (maximum phonation time (MPT) and fundamental frequency; penetration aspiration score, residue score), clinician-reported (GRBAS, functional oral intake score, 100ml Water Swallow Test) and patient-reported outcomes (Voice Handicap Index-10, Reflux Symptoms Index, Eating Assessment Tool, Dysphagia Handicap Index). RESULTS: The observational study identified patient-reported and clinician-reported voice and swallow difficulties pre- and post-surgery; median and interquartile range are reported at each time point: Voice Handicap Index-10 23 (8-31); 20.5 (9-33.5), 24.5 (12.5-29); Dysphagia Handicap Index 9 (0-37); 13 (7-44); 15 (4-34); GRBAS grade 1(1-2); 2 (1-2.5); 2(1-2); 100ml Water Swallow Test volume score 16.7 (11.1-20); 14.3 (12.5-16.7); 16.7 (14.3-20.0); 100ml Water Swallow Test capacity score 16.3 ± 9.0; 11.0 ± 4.1; 12.5 ± 2.6. CONCLUSIONS: We present the first prospective data on voice and swallowing outcomes in adults with LTS before and after reconstructive surgery. The variability of the outcomes was higher than expected but importantly, for many the voice and swallow outcomes were not within normal limits before surgery. The clinical value of the study demonstrates the need for individual assessment and management of LTS patients' voice and swallowing.

Familial congenital laryngotracheal stenosis: A systematic review.

BACKGROUND: Congenital laryngotracheal stenosis (CLS) is a rare cause of stridor among newborns. Evidence has shown that several family members can be affected by CLS. Knowledge of the pathophysiology of familial congenital laryngotracheal stenosis (FCLS) will enable more effective therapeutic strategies. OBJECTIVE: To determine the clinical course and outcome of familial congenital laryngotracheal stenosis (FCLS). METHODS: A literature search was conducted over a period of one month (September 2023) by searching several databases to identify studies published from inception to 31st August 2023. RESULTS: Of 256 papers identified, five articles met the inclusion criteria. A total of 17 patients with slight female predominance (59 %) were identified. Familial congenital tracheal stenosis was reported in female twins (100 %). A variety of clinical presentations were listed. An endoscopic airway study was performed on all patients. 64.8 % of the included children were managed surgically. Genetic studies performed on 41 % of children could not locate genetic abnormalities. CONCLUSION: Consanguinity, twin births, and female gender could be predisposing factors for FCLS, although the quality of evidence is low due to the rarity of the condition.

Utilizing a Functional Lumen Imaging Probe for Evaluation of the Pediatric Airway, A Pilot Study.

OBJECTIVES: Accurate and reproducible measurements of the pediatric airway are critical for diagnostic evaluation and management of subglottic and tracheal stenosis. The endoluminal functional lumen imaging probe (EndoFLIP) is a catheter-based imaging probe which utilizes impedance planimetry to calculate luminal parameters, including cross-sectional area and compliance. Herein, we demonstrate the feasibility of this system for multidimensional evaluation of the pediatric airway. METHODS: 3D-printed pediatric laryngotracheal models were created based on computed tomography scans, then artificially deformed to simulate both circumferential and posterior subglottic stenosis. Two observers made six measurements of the minimum cross-sectional area (MCSA) and length of stenosis of each model with EndoFLIP. Agreement between observer measurements and model dimensions was evaluated using Lin's concordance correlation coefficient; inter-observer reliability was assessed using intraclass correlation. RESULTS: Four models were created: two without pathology (MCSA: 132.4, 44.3 mm2 ) and two with subglottic stenosis (MCSA: 28.7, 59.7 mm2 , stenotic length 27.8, 24.4 mm). Observer measurements of MCSA and length of stenosis demonstrated high concordance with the models (r = 0.99, 0.95, p < 0.001) with a mean error of 4.5% and 18.2% respectively. There was a low coefficient of variation (0.6%-2.8%) for measurements, indicating high precision. Interrater reliability was high for both MCSA and stenotic length (ICC: 0.99, 0.98). CONCLUSIONS: The EndoFLIP system allows for accurate and reproducible measurements of cross-sectional area and stenotic length in pediatric airway models. This method may provide further advantages in the evaluation of airway distensibility, as well as measurements of asymmetric airway pathology. LEVEL OF EVIDENCE: NA Laryngoscope, 134:108-112, 2024.

Pediatric Airway Balloon Dilation: Urge for Safety Redesign.

Airway balloons are widely used by otolaryngologists to treat laryngotracheal stenosis. We review an adverse event and interventions that may prevent similar occurrences. There are no other reports of similar incidents in the Food and Drug Administration Manufacturer and User Facility Device Experience. We implore Acclarent to redesign their airway balloon device to prevent accidental airway irrigation.

Single stage pediatric airway reconstruction in solid organ transplant recipients.

OBJECTIVES: To describe results of single stage laryngotracheal reconstruction (ssLTR) in patients with solid organ transplants and to discuss modifications which need to be considered in this subset of patients pre-operatively, intra-operatively and post-operatively. STUDY DESIGN: We performed a retrospective case series review of children undergoing single stage laryngotracheal reconstruction in the context of prior solid organ transplant. SETTING: A tertiary care academic setting. METHODS: Pediatric cases undergoing Laryngotracheal reconstruction over a 3-year period. Demographic data including age, sex, presenting symptoms, operative details. RESULTS: Two cases of ssLTR in solid organ transplant patients were found, one each with renal and cardiac transplants respectively. Both patients successfully underwent ssLTR for Grade 2 subglottic stenosis. The care of these patients was multidisciplinary and required alterations in their preoperative prophylactic antibiotics. While they did not require changes to the LTR post-operative sedation protocol, their immunosuppressant doses and target ranges were lowered. Special care was taken to avoid nephrotoxic and cardiotoxic medications throughout their hospital stay. CONCLUSIONS: Although traditionally considered for double stage laryngotracheal reconstruction, single stage laryngotracheal reconstruction is a viable option in patients with solid organ transplant. These patients require a multidisciplinary approach and pharmacological protocol alterations pre-, intra-, and post-operatively.

Mucosal Microbiome Disruption in Acute Laryngeal Injury Following Intubation.

The objective of this study was to characterize mucosal microbial shifts in patients with acute laryngeal injury (ALgI) after intubation. This cross-sectional study included 20 patients with ALgI who underwent early endoscopic intervention with tissue culture, 20 patients with idiopathic subglottic stenosis (iSGS) who underwent tissue culture during the routine endoscopic intervention, and 3 control patients who underwent mucosal swab culture. 70% of the ALgI patients had a positive culture compared to 5% of the iSGS patients and none of the controls. The most identified microbes isolated from ALgI patients included Staphylococcus species in 30% and Streptococcus species in 25%. The high rate of pathologic bacterial infiltration into postintubation laryngeal wounds supports efforts to reduce bacterial colonization of endotracheal tubes and highlights the role of culture-directed antibiotic therapy as a part of early intervention to improve outcomes for patients with ALgI.

Decision-Making in the Treatment of Idiopathic Subglottic Stenosis: A Survey of Laryngologists.

OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a rare condition involving the subglottic larynx and upper trachea, commonly affecting Caucasian females between 30 and 50 years of age. Despite its homogeneous presentation, clinical management for iSGS is yet to be standardized, leading to variability in outcomes between predominant interventions. In recognition of the heterogenicity in iSGS treatment and the need to improve patient outcomes, this study aimed to survey laryngologists to understand the factors influencing clinical decision-making and the incorporation of new treatment modalities for iSGS. METHODS: An online survey was sent to 145 academic laryngologists. The survey assessed respondents' professional backgrounds, experience treating iSGS, treatment algorithms, and how various patient factors affect management. RESULTS: Of the 87 (60%) laryngologists who responded to the survey, the most common clinical assessments were tracheoscopy/bronchoscopy (96.8%) and pulmonary function tests (43.6%). Endoscopic dilation (ED) was the most common primary treatment offered (97.5%): 28.7% of surveyed laryngologists offer SISI as a primary treatment, and 74.7% perform SISI as a planned postoperative treatment. The most common SISI protocol was repeated injections every 4-6 weeks for a series of 1-3 total injections. Notably, 9.2% perform the Maddern procedure. Routine algorithms of care involving surgery were most often based on prior experience and prior patient outcomes (75.9%) and conversations with colleagues (64.4%). Only 31% report using the same protocol learned during their fellowship training. CONCLUSION: This survey highlights significant variation in the management of patients with iSGS. Understanding the factors that influence decision-making may lead to potential standardization in heterogeneous treatment approaches and may improve clinical outcomes. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:865-872, 2024.

Association between Estrogen Exposure and Idiopathic Subglottic Stenosis.

OBJECTIVE: Idiopathic subglottic stenosis (iSGS) is a rare, recurrent, fibroinflammatory disease affecting the larynx and proximal trachea. Given it occurs primarily in adult females, estrogen is speculated to play a central pathophysiological role. This study aimed to evaluate relationships between estrogen exposure, disease progression, and recurrence. METHODS: North American Airway Collaborative (NoAAC) data of adults with iSGS obstructive airway lesions, who underwent index endoscopic airway dilation, were used to identify associations between estrogen exposure, disease characteristics, and time to recurrence (TTR), and interventions were analyzed using Kruskal-Wallis test and Pearson coefficient. Cox proportional hazards regression models compared hazard ratios by estrogen exposure. Kaplan-Meier curves were plotted for TTR based on menopausal status. RESULTS: In all, 533 females had complete estrogen data (33% premenopausal, 17% perimenopausal, 50% postmenopausal). Median estrogen exposure was 28 years. Overall, there was no dose-response relationship between estrogen exposure and disease recurrence. Premenopausal patients had significantly shorter time from symptom manifestation to diagnosis (1.17 vs. 1.42 years perimenopausal vs. 2.08 years postmenopausal, p < 0.001), shorter time from diagnosis to index endoscopic airway dilation (1.90 vs. 2.50 vs. 3.76 years, p = 0.005), and higher number of procedures (1.73 vs. 1.20 vs. 1.08 procedures, p < 0.001). CONCLUSIONS: We demonstrate premenopausal patients may have a more aggressive disease variant than their peri- and postmenopausal counterparts. However, it is unclear as to whether this is related to reduced estrogen in the peri- and postmenopausal states or the age-related physiology of wound healing and inflammation, regardless of estrogen. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:825-830, 2024.

Murine Model of Airway Fibrosis has Anatomic, Physiologic, and Molecular Congruency to Human iSGS.

OBJECTIVE: To narrow knowledge gaps in the pathophysiology of idiopathic subglottic stenosis (iSGS) through comparison of a murine subglottic stenosis model with iSGS. STUDY DESIGN: In vivo animal study. SETTING: Academic institution. METHODS: Murine samples/measurements were obtained from mice that underwent chemomechanical injury with a wire brush and bleomycin. Human samples/measurements were obtained from iSGS patients. Anatomic, physiologic, and epithelial molecular data were collected using histology, human peak expiratory flow (PEF) and murine airway conductance, gene expression analysis with quantitative polymerase chain reaction, and protein analysis with quantitative immunohistochemistry. RESULTS: Anatomic patterns of scars at the subglottis and proximal trachea seen in the murine model are similar to iSGS patients. Subglottic stenosis (SGS) mice had a decrease (P = .0194) in airway conductance compared to healthy controls, similar to a decrease (P = .0001) in predilation PEF versus postdilation in iSGS patients. There was decreased epithelial gene expression of E-cadherin (ECAD) (P < 0.01), occludin (OCLN) (P < .01), and cytokeratin-5 (CK5) (P < .05) and protein expression of ECAD (H/M: P < .001), OCLN (H: P < 0.05, M: P < .001), and CK5 (H: P < .001, M: P < .01) in murine SGS and iSGS versus controls. CONCLUSION: The murine SGS model shows anatomic, physiologic, and molecular congruency with human iSGS, making it a reasonable model to investigate iSGS. The molecular similarities in epithelial barrier dysfunction suggest it may best be suited to explore epithelial mechanisms of iSGS and therapies directed at epithelial reconstitution. This model provides a foundation to collect data that will improve understanding of iSGS, and, ultimately, translate into more accurate animal models for future use.

Surgical Management of Airway Stenosis During Pregnancy: A Scoping Review.

OBJECTIVE: There are several options for surgical management of subglottic stenosis, including endoscopic and open procedures. However, treatment algorithms, outcomes, and anesthetic management of subglottic stenosis during pregnancy are not well described. DATA SOURCES: MEDLINE, EMBASE, and the Cochrane databases. REVIEW METHODS: A scoping review of management of subglottic stenosis during pregnancy was performed, and then reported in compliance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria consisted of those with subglottic or tracheal stenosis aged greater than 18 years, those in whom management was performed during pregnancy, and those who reported delivery related outcomes. RESULTS: After systematic review and detailed search of 330 identified articles, 15 articles met inclusion criteria and were included in the final analysis. All studies were case reports or case series (level 4 evidence). This study identified 27 patients. The median age was 29 and the median gestational age at intervention was 28 weeks. Left lateral positioning and fetal heart rate monitoring were used in nearly every case. The most common intervention performed was endoscopic balloon dilation. In many cases, jet ventilation or transnasal humidified rapid insufflation ventilatory exchange was satisfactory for maintenance of the airway. Three women ultimately required tracheostomy prior to labor and delivery. There was no fetal death or complications reported in these studies, and all but one woman proceeded to deliver at term. CONCLUSION: Endoscopic balloon dilation during pregnancy is safe and effective, resulting in optimized respiratory outcomes for the mother and safe delivery of the fetus. The third trimester appears to be safe for airway intervention. Laryngoscope, 134:1014-1022, 2024.

Surgical Outcomes by Early Airway Endoscopy Findings after Pediatric Staged Laryngotracheoplasty.

OBJECTIVES: To determine how initial postoperative airway endoscopy findings after stent removal predict successful decannulation in children undergoing double-staged laryngotracheoplasty (dsLTP). Secondary objectives assessed timing of decannulation and number of endoscopic interventions needed after dsLTP. METHODS: A case series with chart review included children who underwent dsLTP at a tertiary children's hospital between 2008 and 2021. Rates of decannulation, time to decannulation, and number of interventions after dsLTP were recorded for children with high- or low-grade stenosis at the first bronchoscopy after stent removal. RESULTS: Of the 65 children who were included, 88% had high-grade stenosis and 98% had a preoperative tracheostomy. Successful decannulation happened in 74% of the children, and 44% of the children were decannulated within 12 months of surgery. For children with low-grade stenosis at the first endoscopy after stent removal, 84% were successfully decannulated compared with 36% of the children with high-grade stenosis (p = 0.001). After dsLTP, children with high-grade stenosis required 7.5 interventions (SD: 3.3) compared with 4.0 interventions (SD: 3.0) for children with low-grade stenosis (p < 0.001). Decannulated children with high-grade stenosis necessitated more endoscopic procedures (7.0 vs. 3.7, p = 0.02). Time to decannulation was similar between children with high- and low-grade early postoperative stenosis (21.9 vs. 17.8 months, p = 0.63). CONCLUSIONS: Higher grade stenosis identified on the first airway endoscopy after suprastomal stent removal is correlated with lower decannulation rates and more postoperative endoscopic interventions. Although time to decannulation was not impacted by early stenosis grade, surgeons might utilize these early airway findings to counsel families and prognosticate possible surgical success. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:963-967, 2024.

Predictors of Clinical Outcomes in Adult Laryngotracheal Stenosis.

OBJECTIVES: Sequelae of laryngotracheal stenosis (LTS) can be devastating, often necessitating tracheostomy. This study aims to describe the characteristics and outcomes of patients with LTS and identify risk factors for long-term tracheostomy dependence stratified by etiology. METHODS: A retrospective chart review was performed on 215 patients diagnosed with LTS from 09/01/2011 to 12/31/2020. Patients were grouped based on the cause of LTS. Patient factors were compared to evaluate risk factors for long-term tracheostomy dependence. RESULTS: Of the 215 patients, 129 (60%) were classified as iatrogenic, 41 (19%) idiopathic, 10 (4.7%) cancer treatment, 18 (8.3%) autoimmune, and 17 (8%) patients unknown. Idiopathic patients were significantly less likely to be tracheostomy-dependent compared with iatrogenic patients (p < 0.001) and cancer patients (p < 0.05). The mortality rate did not significantly differ among the categories (p = 0.1078). Significant improvement was seen after treatment, as the median percent of stenosis at presentation was 52.5%, and the median percent of stenosis at the most recent visit was 10% (p < 0.001). The autoimmune group received the most steroid injections (mean = 6.56; SD = 11.96). The idiopathic group had the longest surgery-free interval (mean = 30.8 months; SD = 27.7). CONCLUSION: Iatrogenic and cancer patients were more likely to be tracheostomy-dependent. There was a significant improvement in percent and length of stenosis after treatment, with the idiopathic group having the longest surgery-free interval. Mortality risk did not differ among the different etiologies of LTS. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:257-263, 2024.

Idiopathic Subglottic Stenosis Is Associated With More Frequent and Abnormal Squamous Metaplasia.

OBJECTIVES: Gain insights into the pathophysiology of idiopathic subglottic stenosis (iSGS) by investigating differences in transcriptome of subglottic mucosal tissue between patients with iSGS and controls, and between tracheal and subglottic tissue within patients. METHODS: RNA sequencing was conducted on biopsied mucosal samples collected from subglottic and tracheal (in-patient control) regions in iSGS patients, and from subglottis in controls. The gene expression differences were validated on a protein level by (1) staining the tissue samples obtained from a second cohort of patients and controls; and (2) in vitro functional assays using primary subglottic epithelial cells from both iSGS patients and healthy donors. RESULTS: We found 7 upregulated genes in the subglottic region of iSGS patients relative to both the tracheal mucosa and subglottic region of controls. A gene ontology enrichment analysis found that the epithelial cell differentiation and cornification pathways are significant, involving specifically 3 of the genes: involucrin (IVL), small proline rich protein 1B (SPRR1B), and keratin 16 (KRT16). Involvement of these pathways suggests squamous metaplasia of the epithelium. Histological analyses of epithelium in subglottic mucosal biopsies revealed squamous metaplasia in 41% of the samples from iSGS patients and in 25% from controls. Immunohistochemical evaluation of the samples presented with squamous epithelium revealed increased expression of the protein encoded by SPRR1B, hyperproliferative basal cells, shedding of apical layers, and accompanying lesions in iSGS compared to CTRL. Cultured primary subglottic epithelial cells from iSGS patients had higher proliferation rates compared to healthy donors and squamous metaplastic differentiation formed thinner epithelia with increased expression proteins encoded by INV, SPRR1B, and KRT16, suggesting intrinsic dysfunction of basal cells in iSGS. CONCLUSIONS: Abnormal squamous differentiation of epithelial cells may contribute to the pathogenesis of iSGS. Patients having metaplastic epithelial phenotype may be sensitive to drugs that reverse it to a normal phenotype.

Navigating Pathways to Diagnosis in Idiopathic Subglottic Stenosis: A Qualitative Study.

OBJECTIVE: Idiopathic subglottic stenosis is a rare disease, and time to diagnosis is often prolonged. In the United States, some estimate it takes an average of 9 years for patients with similar rare disease to be diagnosed. Patient experience during this period is termed the diagnostic odyssey. The aim of this study is to use qualitative methods grounded in behavioral-ecological conceptual frameworks to identify drivers of diagnostic odyssey length that can help inform efforts to improve health care for iSGS patients. METHODS: Qualitative study using semi-structured interviews. Setting consisted of participants who were recruited from those enrolled in a large, prospective multicenter trial. We use directed content analysis to analyze qualitative semi-structured interviews with iSGS patients focusing on their pathways to diagnosis. RESULTS: Overall, 30 patients with iSGS underwent semi-structured interviews. The patient-reported median time to diagnosis was 21 months. On average, the participants visited four different health care providers. Specialists were most likely to make an appropriate referral to otolaryngology that ended in diagnosis. However, when primary care providers referred to otolaryngology, patients experienced a shorter diagnostic odyssey. The most important behavioral-ecological factors in accelerating diagnosis were strong social support for the patient and providers' willingness to refer. CONCLUSION: Several factors affected time to diagnosis for iSGS patients. Patient social capital was a catalyst in decreasing time to diagnosis. Patient-reported medical paternalism and gatekeeping limited specialty care referrals extended diagnostic odysseys. Additional research is needed to understand the effect of patient-provider and provider-provider relationships on time to diagnosis for patients with iSGS. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:815-824, 2024.

Comparison of Hemodynamics in Jet Ventilation vs. Intermittent Apnea for Airway Stenosis Surgery.

OBJECTIVE: The objective of this study is to assess the impact of two different ventilation techniques, jet ventilation and apneic anesthesia with intermittent ventilation (AAIV), on patient hemodynamics and operative time during endoscopic laryngotracheal stenosis surgery. METHODS: Retrospective chart review of patients who underwent airway dilation for laryngotracheal stenosis by a single surgeon at a single institution from October 1, 2000 through January 2, 2020. Logistic regression, Mann-Whitney U tests and chi square analysis were used to determine statistical significance. RESULTS: A total of 157 patients, 43 (27.4%) male and 114 (72.6%) female, and 605 total encounters were included for analysis. There were no significant differences in hemodynamic outcomes when comparing the AAIV and jet ventilation groups. Specifically, there was no significant difference in either peak end-tidal CO2 or nadir O2 saturation between the AAIV and jet ventilation groups (p = 0.4016) and (p = 0.1357), respectively. The patients in the AAIV group had a significantly higher median BMI 32.93 (27.40-39.40) compared with 28.80 (24.1-32.65) (p = 0.0001). Although not necessarily clinically significant, patients with higher BMI had lower median O2 nadirs (97.8%) than non-obese patients (99.2%) (p < 0.0001). The median total procedure time was equivalent when comparing the two ventilation techniques. CONCLUSION: AAIV is a safe method of ventilation for patients undergoing endoscopic laryngotracheal stenosis surgery with no significant differences in patient hemodynamics or procedure time when compared with jet ventilation. AAIV was the preferred method of ventilation for obese patients undergoing endoscopic laryngotracheal stenosis surgery. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1343-1348, 2024.

A Pilot Study of Decellularized Cartilage for Laryngotracheal Reconstruction in a Neonatal Pig Model.

OBJECTIVE: Severe subglottic stenosis develops as a response to intubation in 1% of the >200,000 neonatal intensive care unit infants per year and may require laryngotracheal reconstruction (LTR) with autologous hyaline cartilage. Although effective, LTR is limited by comorbidities, severity of stenosis, and graft integration. In children, there is a significant incidence of restenosis requiring revision surgery. Tissue engineering has been proposed to develop alterative grafting options to improve outcomes and eliminate donor-site morbidity. Our objective is to engineer a decellularized, channel-laden xenogeneic cartilage graft, that we deployed in a proof-of-concept, neonatal porcine LTR model. METHODS: Meniscal porcine cartilage was freeze-thawed and washed with pepsin/elastase to decellularize and create microchannels. A 6 × 10-mm decellularized cartilage graft was then implanted in 4 infant pigs in an anterior cricoid split. Airway patency and host response were monitored endoscopically until sacrifice at 12 weeks, when the construct phenotype, cricoid expansion, mechanics, and histomorphometry were evaluated. RESULTS: The selective digestion of meniscal components yielded decellularized cartilage with cell-size channels. After LTR with decellularized meniscus, neonatal pigs were monitored via periodic endoscopy observing re-epithelization, integration, and neocartilage formation. At 12 weeks, the graft appeared integrated and exhibited airway expansion of 4 mm in micro-CT and endoscopy. Micro-CT revealed a larger lumen compared with age-matched controls. Finally, histology showed significant neocartilage formation. CONCLUSION: Our neonatal porcine LTR model with a decellularized cartilage graft is a novel approach to tissue engineered pediatric LTR. This pilot study sets the stage for "off-the-shelf" graft procurement and future optimization of MEND for LTR. LEVEL OF EVIDENCE: NA Laryngoscope, 134:807-814, 2024.