Anticytomegalovirus CD4+ T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV.

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A survey of patients with laryngotracheal stenosis on future clinical trial design.

BACKGROUND/AIMS: Laryngotracheal stenosis is a rare but devastating proximal airway fibrosis that restricts a patient's ability to breathe. Treatment is primarily surgical and to date, there has never been a multi-institutional, randomized, prospective, and interventional clinical trial for a medical therapy to treat laryngotracheal stenosis. Therefore, we aimed to obtain patient feedback to guide successful trial design, recruitment, retention, and for identifying potential barriers to study participation. METHODS: Over 1000 members of an international laryngotracheal stenosis online support community (the Living with Idiopathic Subglottic Stenosis Facebook group) were sent two questionnaires for a proposed interventional double-blinded, randomized, placebo-controlled clinical trial. RESULTS: A total of 317 and 558 participants responded to the first and second surveys, respectively. The majority of participants (77%) were willing to consider enrollment, regardless of having a 50% chance of receiving placebo versus treatment (78%). The majority (84%) of participants were willing to travel 200 miles to participate for up to six in-person visits over 50 days. Specific side effects, including anemia/thrombocytopenia (72%) or risk of infection (69.3%) had the greatest impact on clinical trial participation with other side effects (peripheral edema (53%), oral ulcers (51%), and gastrointestinal side effects (41%)) having less impact. CONCLUSION: Patients with laryngotracheal stenosis possess nuanced insight into their disease and treatment options. As a group, they are extremely motivated for better therapies. Future laryngotracheal stenosis clinical trials should focus on providing excellent side effect -related education and utilizing feedback from online advocacy groups to optimize recruitment and retention.

Incidence and Outcomes of Acute Laryngeal Injury After Prolonged Mechanical Ventilation.

OBJECTIVES: Upper airway injury is a recognized complication of prolonged endotracheal intubation, yet little attention has been paid to the consequences of laryngeal injury and functional impact. The purpose of our study was to prospectively define the incidence of acute laryngeal injury and investigate the impact of injury on breathing and voice outcomes. DESIGN: Prospective cohort study. SETTING: Tertiary referral critical care center. PATIENTS: Consecutive adult patients intubated greater than 12 hours in the medical ICU from August 2017 to May 2018 who underwent laryngoscopy within 36 hours of extubation. INTERVENTIONS: Laryngoscopy following endotracheal intubation. MEASUREMENTS AND MAIN RESULTS: One hundred consecutive patients (62% male; median age, 58.5 yr) underwent endoscopic examination after extubation. Acute laryngeal injury (i.e., mucosal ulceration or granulation tissue in the larynx) was present in 57 patients (57%). Patients with laryngeal injury had significantly worse patient-reported breathing (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 1.05; interquartile range, 0.48-2.10) and vocal symptoms (Voice Handicap Index-10: median, 2; interquartile range, 0-6) compared with patients without injury (Clinical Chronic Obstructive Pulmonary Disease Questionnaire: median, 0.20; interquartile range, 0-0.80; p < 0.001; and Voice Handicap Index-10: median, 0; interquartile range, 0-1; p = 0.005). Multivariable logistic regression independently associated diabetes, body habitus, and endotracheal tube size greater than 7.0 with the development of laryngeal injury. CONCLUSIONS: Acute laryngeal injury occurs in more than half of patients who receive mechanical ventilation and is associated with significantly worse breathing and voicing 10 weeks after extubation. An endotracheal tube greater than size 7.0, diabetes, and larger body habitus may predispose to injury. Our results suggest that acute laryngeal injury impacts functional recovery from critical illness.

Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis.

OBJECTIVES: To describe tracheobronchial disease in patients with granulomatosis with polyangiitis (GPA) and evaluate the utility of dynamic expiratory CT to detect large-airway disease. METHODS: Demographic and clinical features associated with the presence of subglottic stenosis (SGS) or endobronchial involvement were assessed in a multicentre, observational cohort of patients with GPA. A subset of patients with GPA from a single-centre cohort underwent dynamic chest CT to evaluate the airways. RESULTS: Among 962 patients with GPA, SGS and endobronchial disease were identified in 95 (10%) and 59 (6%) patients, respectively. Patients with SGS were more likely to be female (72% vs 53%, P < 0.01), younger at time of diagnosis (36 vs 49 years, P < 0.01), and have saddle-nose deformities (28% vs 10%, P < 0.01), but were less likely to have renal involvement (39% vs 62%, P < 0.01). Patients with endobronchial disease were more likely to be PR3-ANCA positive (85% vs 66%, P < 0.01), with more ENT involvement (97% vs 77%, P < 0.01) and less renal involvement (42% vs 62%, P < 0.01). Disease activity in patients with large-airway disease was commonly isolated to the subglottis/upper airway (57%) or bronchi (32%). Seven of 23 patients screened by dynamic chest CT had large-airway pathology, including four patients with chronic, unexplained cough, discovered to have tracheobronchomalacia. CONCLUSION: SGS and endobronchial disease occur in 10% and 6% of patients with GPA, respectively, and may occur without disease activity in other organs. Dynamic expiratory chest CT is a potential non-invasive screening test for large-airway involvement in GPA.

Predictors of Posterior Glottic Stenosis: A Multi-Institutional Case-Control Study.

OBJECTIVE: To assess intrinsic and extrinsic risk factors in the development of posterior glottic stenosis (PGS) in intubated patients. METHODS: Patients diagnosed with PGS between September 2012 and May 2014 at 3 tertiary care university hospitals were included. Patient demographics, comorbidities, duration of intubation, endotracheal tube (ETT) size, and indication for intubation were recorded. Patients with PGS were compared to control patients represented by patients intubated in intensive care units (ICU). RESULTS: Thirty-six PGS patients were identified. After exclusion, 28 PGS patients (14 male, 14 female) and 112 (65 male, 47 female) controls were studied. Multivariate analysis demonstrated ischemia (P < .05), diabetes (P < .01), and length of intubation (P < .01) were significant risk factors for the development of PGS. Fourteen of 14 (100%) males were intubated with a size 8 or larger ETT compared to 47 of 65 (72.3%) male controls (P < .05). Posterior glottic stenosis (P < .01), length of intubation (P < .001), and obstructive sleep apnea (P < .05) were significant risk factors for tracheostomy. CONCLUSION: Duration of intubation, ischemia, diabetes mellitus, and large ETT size (8 or greater) in males were significant risk factors for the development of PGS. Reducing the use of size 8 ETTs and earlier planned tracheostomy in high-risk patients may reduce the incidence of PGS and improve ICU safety.

Removal of Metal Tracheal Stent: A Difficult Foreign Body.

INTRODUCTION: With its introduction in 1986, the use of metal tracheal stents gained favor due to relative ease of deployment and reduced risk of stent migration and mucus plugging. However, adverse events associated with metal stenting led the FDA to publish a recommendation against its use for benign airway stenosis in 2005. We present a case which illustrates the difficulty in removal of a metal stent from the airway. CASE REPORT: Our patient is a 47-year-old woman with a history of postintubation tracheal stenosis. She underwent multiple interventions with Thoracic Surgery at an outside facility, including stenting with an Ultraflex expandable metal stent. Her course was complicated by recurrent intraluminal granulation tissue, which led to placement of additional metal stents, as well as a tracheostomy due to obstructive proximal granulation tissue. On presentation at our institution, removal of the stents was recommended due to recurrent tracheitis and proximity of stent fragments to the innominate artery on CT imaging. She underwent direct microlaryngoscopy and bronchoscopy, and stent fragments were removed using a hemostat through the trach stoma. Postoperative imaging has confirmed retained stent fragments, and additional procedures have been required for further removal. DISCUSSION/CONCLUSION: Removal of metal stents from the trachea is challenging for several reasons. Neoepithelization of respiratory mucosa makes identification of fragments difficult. Furthermore, growth of granulation tissue through the metal lattice framework, as well as the stents' tendency to fracture, complicates extraction. This case illustrates the dangers of metal stenting for benign airway stenosis. Laryngoscope, 2024.

A Single Center Description of Adult and Pediatric Endoscopic Posterior Costal Cartilage Grafting.

OBJECTIVE: Posterior glottis impairment alters breathing, voicing, and swallowing. Bilateral vocal fold movement impairment (BVFMI) occurs when the vocal cords are fixed/remain midline. Studies inadequately assessed endoscopic posterior costal cartilage grafting (enPCCG) for BVFMI across broad ages. We aim to assess decannulation and prosthesis free airway in children and adults who have undergone enPCCG. STUDY DESIGN: Retrospective cohort. SETTING: Referral center. METHODS: This study included adults and children who received enPCCG for BVFMI (2010-2018) and were followed for 35 months on average. The main outcome was successful decannulation of patients, or airway improvement in those without tracheostomy. Data on comorbidities, surgical complications, and interventions following surgery were collected. RESULTS: Ten children and 11 adults underwent enPCCG for BVFMI. Eighty-one percent of patients had a tracheostomy at surgery; adults were more likely to have a tracheostomy at surgery (P = 0.035), and to undergo double-staged procedure (P = 0.035) and stent (P = 0.008). Average stent duration was 29.7 days. Overall decannulation rate was 76% (90% for children; 70% for adults). Children were more likely to receive postoperative intensive care unit care (P = 0.004). Adults had mean 4.4 post-enPCCG interventions per patient compared to children's mean 3.91 interventions. The most common interventions were steroid injection (17.6%) and balloon dilation (16%). Preliminary analysis suggests postoperative dysphonia was reported in 66.7% of patients; postoperative dysphagia was rare. CONCLUSION: EnPCCG was more successful at achieving decannulation in children. Adults required additional interventions. A double-staged operation with prolonged stenting is recommended for adult patients. A majority of patients were decannulated at last follow-up.

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.

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.

A Comprehensive Flow Cytometry Panel for Analysis of Idiopathic Subglottic Stenosis.

OBJECTIVE: To present a comprehensive flow cytometry panel for idiopathic subglottic stenosis (iSGS). STUDY DESIGN: Controlled ex vivo cohort study. SETTING: 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. CONCLUSION: 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.

#OtoTwitter: The Top 75 Twitter Influencers in Otolaryngology and Association With Academic Impact.

OBJECTIVES: Social media has enabled discussion of relevant topics within otolaryngology. With increasing academic discourse occurring on virtual platforms, it is important to examine who is influencing these discussions. This study thus aims to: (1) identify the top Twitter influencers in otolaryngology and (2) assess the relationship between Twitter influence and academic impact. STUDY DESIGN: Cross-sectional analysis. SETTING: Twitter. METHODS: The Right Relevance program was used to identify and rank the top 75 Twitter influencers, excluding organizations, according to the search terms "otolaryngology," "head and neck surgery," "ear nose throat," "rhinology," "head and neck," "laryngology," "facial plastics," and "otology." Demographic data and h-index were collected for each influencer. Correlational analyzes were performed to assess the relationships between Twitter rank and geographic location, sex, subspecialty, and h-index. RESULTS: The majority of the top 75 influencers were otolaryngologists (87%), female (68%), and located in the United States (61%). General otolaryngology (n = 20, 31%) was more well-represented than any individual subspecialty including facial plastics (n = 10, 15%), rhinology (n = 10, 15%), and neurotology (n = 9, 14%). There was a significant relationship between Twitter rank and h-index (Spearman ρ value of -0.32; 95% confidence interval: -0.51 to -0.01; P = .006). Twitter rank was not significantly correlated with subspecialty, sex, or geographic location (P > .05). CONCLUSION: The majority of Twitter influencers within otolaryngology were otolaryngologists, female, and located in the United States. Social media influence is positively associated with academic impact among otolaryngologists.

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, 134:3260-3266, 2024.

Current Practices in Voice Data Collection and Limitations to Voice AI Research: A National Survey.

INTRODUCTION: Accuracy and validity of voice AI algorithms rely on substantial quality voice data. Although commensurable amounts of voice data are captured daily in voice centers across North America, there is no standardized protocol for acoustic data management, which limits the usability of these datasets for voice artificial intelligence (AI) research. OBJECTIVE: The aim was to capture current practices of voice data collection, storage, analysis, and perceived limitations to collaborative voice research. METHODS: A 30-question online survey was developed with expert guidance from the voicecollab.ai members, an international collaborative of voice AI researchers. The survey was disseminated via REDCap to an estimated 200 practitioners at North American voice centers. Survey questions assessed respondents' current practices in terms of acoustic data collection, storage, and retrieval as well as limitations to collaborative voice research. RESULTS: Seventy-two respondents completed the survey of which 81.7% were laryngologists and 18.3% were speech language pathologists (SLPs). Eighteen percent of respondents reported seeing 40%-60% and 55% reported seeing >60 patients with voice disorders weekly (conservative estimate of over 4000 patients/week). Only 28% of respondents reported utilizing standardized protocols for collection and storage of acoustic data. Although, 87% of respondents conduct voice research, only 38% of respondents report doing so on a multi-institutional level. Perceived limitations to conducting collaborative voice research include lack of standardized methodology for collection (30%) and lack of human resources to prepare and label voice data adequately (55%). CONCLUSION: To conduct large-scale multi-institutional voice research with AI, there is a pertinent need for standardization of acoustic data management, as well as an infrastructure for secure and efficient data sharing. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1333-1339, 2024.

Characterizing the T Cell Repertoire in the Proximal Airway in Health and Disease.

OBJECTIVES: Recent translational scientific efforts in subglottic stenosis (SGS) support a disease model where epithelial alterations facilitate microbiome displacement, dysregulated immune activation, and localized fibrosis. Given the observed immune cell infiltrate in SGS, we sought to test the hypothesis that SGS cases possessed a low diversity (highly clonal) adaptive immune response when compared with healthy controls. METHODS: Single cell RNA sequencing (scRNA-seq) of subglottic mucosal scar in iSGS (n = 24), iLTS (n = 8), and healthy controls (n = 7) was performed. T cell receptor (TCR) sequences were extracted, analyzed, and used to construct repertoire structure, compare diversity, interrogate overlap, and define antigenic targets using the Immunarch bioinformatics pipeline. RESULTS: The proximal airway mucosa in health and disease are equally diverse via Hill framework quantitation (iSGS vs. iLTS vs. Control, p > 0.05). Repertoires do not significantly overlap between individuals (Morisita <0.02). Among iSGS patients, clonality of the TCR repertoire is driven by CD8+ T cells, and iSGS patients possess numerous TCRs targeting viral and intercellular pathogens. High frequency clonotypes do not map to known targets in public datasets. CONCLUSION: SGS cases do not possess a lower diversity adaptive immune infiltrate when compared with healthy controls. Interestingly, the TCR repertoire in both health and disease contains a restricted number of high frequency clonotypes that do not significantly overlap between individuals. The target of the high frequency clonotypes in health and disease remain unresolved. LEVEL OF EVIDENCE: NA Laryngoscope, 134:1757-1764, 2024.

Similarity Network Analysis of the Adaptive Immune Response in the Proximal Airway.

OBJECTIVES: Recent immunologic study of the adaptive immune repertoire in the subglottic airway demonstrated high-frequency T cell clones that do not overlap between individuals. However, the anatomic distribution and antigenic target of the T cell repertoire in the proximal airway mucosa remain unresolved. METHODS: Single-cell RNA sequencing of matched scar and unaffected mucosa from idiopathic subglottic stenosis patients (iSGS, n = 32) was performed and compared with airway mucosa from healthy controls (n = 10). T cell receptor (TCR) sequences were interrogated via similarity network analysis to explore antigenic targets using the published algorithm: Grouping of Lymphocyte Interactions by Paratope Hotspots (GLIPH2). RESULTS: The mucosal T cell repertoire in healthy control airways consisted of highly expressed T cell clones conserved across anatomic subsites (trachea, bronchi, bronchioles, and lung). In iSGS, high-frequency clones were equally represented in both scar and adjacent non-scar tissue. Significant differences in repertoire structure between iSGS scar and unaffected mucosa was observed, driven by unique low-frequency clones. GLIPH2 results suggest low-frequency clones share targets between multiple iSGS patients. CONCLUSION: Healthy airway mucosa has a highly conserved T cell repertoire across multiple anatomic subsites. Similarly, iSGS patients have highly expressed T cell clones present in both scar and unaffected mucosa. iSGS airway scar possesses an abundance of less highly expanded clones with predicted antigen targets shared between patients. Interrogation of these shared motifs suggests abundant adaptive immunity to viral targets in iSGS airway scar. These results provide insight into disease pathogenesis and illuminate new treatment strategies in iSGS. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3245-3252, 2024.