Objective Laryngotracheal stenosis is largely considered a structural entity, defined on anatomic terms (i.e. percent stenosis, distance from vocal folds, overall length). This has significant implications for identifying at-risk populations, devising systems-based preventive strategies, and promoting patient-centered treatment. The present study was undertaken to test the hypothesis that LTS is heterogeneous in regard to etiology, natural history, and clinical outcome. Study Design Retrospective cohort study of consecutive adult tracheal stenosis patients from 1998–2013. Methods Subjects diagnosed with laryngotracheal stenosis (ICD-9: 478.74, 519.19) between January 1, 1998 and January 1, 2013 were identified. Patient characteristics (age, gender, race, follow-up duration), and comorbidities were extracted. Records were reviewed for etiology of stenosis, treatment approach, and surgical dates. Stenosis morphology was derived from intraoperative measurements. The presence of tracheostomy at last follow-up was recorded. Results 150 patients met inclusion criteria. 54.7% had an iatrogenic etiology followed by idiopathic (18.5%), autoimmune (18.5%), and traumatic (8%). Tracheostomy dependence differed based on etiology (p<0.001). Significantly more patients with iatrogenic (66%) and autoimmune (54%) etiologies remained tracheostomy dependent compared to traumatic (33%) or idiopathic (0%) groups. On multivariate regression analysis, each additional point on Charlson Comorbidity Index was associated with a 67% increased odds of tracheostomy dependence (OR 1.67, 95% CI 1.04 – 2.69; p=0.04). Conclusions Laryngotracheal stenosis is not a homogeneous clinical entity. It has multiple distinct etiologies that demonstrate disparate rates of long-term tracheostomy dependence. Understanding the mechanism of injury and contribution of comorbid illnesses is critical to systems-based preventive strategies and patient-centered treatment.

Objectives/Hypothesis: Idiopathic subglottic stenosis (iSGS) is a rare and potentially life-threatening disease marked by recurrent and progressive airway obstruction frequently requiring repeated surgery to stabilize the airway. Unknown etiology and low disease prevalence have limited the ability to characterize the natural history of iSGS and resulted in variability in surgical management. It is uncertain how this variation relates to clinical outcomes. Study Design: Medical record abstraction. Methods: Utilizing an international, multi-institutional collaborative, we collected retrospective data on patient characteristics, treatment, and clinical outcomes. We investigated variation between and within open and endoscopic treatment approaches and assessed therapeutic outcomes; specifically, disease recurrence and need for tracheostomy at last follow-up. Results: Strikingly, 479 iSGS patients across 10 participating centers were nearly exclusively female (98%, 95% confidence interval [CI], 96.1–99.6), Caucasian (95%, 95% CI, 92.2–98.8), and otherwise healthy (mean age-adjusted Charlson Comorbidity Index 1.5; 95% CI, 1.44–1.69). The patients presented at a mean age of 50 years (95% CI, 48.8–51.1). A total of 80.2% were managed endoscopically, whereas 19.8% underwent open reconstruction. Endoscopic surgery had a significantly higher rate of disease recurrence than the open approach (chi2 = 4.09, P = 0.043). Tracheostomy was avoided in 97% of patients irrespective of surgical approach (95% CI, 94.5–99.8). Interestingly, there were outliers in rates of disease recurrence between centers using similar treatment approaches. Conclusion: Idiopathic subglottic stenosis patients are surprisingly homogeneous. The heterogeneity of treatment approaches and the observed outliers in disease recurrence rates between centers raises the potential for improved clinical outcomes through a detailed understanding of the processes of care.

IMPORTANCE Surgical treatment comparisons in rare diseases are difficult secondary to the geographic distribution of patients. Fortunately, emerging technologies offer promise to reduce these barriers for research. OBJECTIVE To prospectively compare the outcomes of the 3 most common surgical approaches for idiopathic subglottic stenosis (iSGS), a rare airway disease. DESIGN, SETTING, AND PARTICIPANTS In this international, prospective, 3-year multicenter cohort study, 810 patients with untreated, newly diagnosed, or previously treated iSGS were enrolled after undergoing a surgical procedure (endoscopic dilation [ED], endoscopic resection with adjuvant medical therapy [ERMT], or cricotracheal resection [CTR]). Patients were recruited from clinician practices in the North American Airway Collaborative and an online iSGS community on Facebook. MAIN OUTCOMES AND MEASURES The primary end point was days from initial surgical procedure to recurrent surgical procedure. Secondary end points included quality of life using the Clinical COPD (chronic obstructive pulmonary disease) Questionnaire (CCQ), Voice Handicap Index-10 (VHI-10), Eating Assessment Test-10 (EAT-10), the 12-Item Short-Form Version 2 (SF-12v2), and postoperative complications. RESULTS Of 810 patients in this cohort, 798 (98.5%) were female and 787 (97.2%) were white, with a median age of 50 years (interquartile range, 43-58 years). Index surgical procedures were ED (n = 603; 74.4%), ERMT (n = 121; 14.9%), and CTR (n = 86; 10.6%). Overall, 185 patients (22.8%) had a recurrent surgical procedure during the 3-year study, but recurrence differed by modality (CTR, 1 patient [1.2%]; ERMT, 15 [12.4%]; and ED, 169 [28.0%]). Weighted, propensity score-matched, Cox proportional hazards regression models showed ED was inferior to ERMT (hazard ratio [HR], 3.16; 95% CI, 1.8-5.5). Among successfully treated patients without recurrence, those treated with CTR had the best CCQ (0.75 points) and SF-12v2 (54 points) scores and worst VHI-10 score (13 points) 360 days after enrollment as well as the greatest perioperative risk. CONCLUSIONS AND RELEVANCE In this cohort study of 810 patients with iSGS, endoscopic dilation, the most popular surgical approach for iSGS, was associated with a higher recurrence rate compared with other procedures. Cricotracheal resection offered the most durable results but showed the greatest perioperative risk and the worst long-term voice outcomes. Endoscopic resection with medical therapy was associated with better disease control compared with ED and had minimal association with vocal function. These results may be used to inform individual patient treatment decision-making.

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.

Rationale Idiopathic subglottic stenosis (iSGS) is a rare and devastating extrathoracic obstruction involving the lower laryngeal and upper tracheal airway. It arises without known antecedent injury or associated disease process. Persistent mucosal inflammation and a localized fibrotic response are hallmarks of the disease. Despite the initial clinical description of iSGS more than 40 year ago, there have been no substantive investigations into the pathogenesis of this enigmatic and progressive airway obstruction. Objectives In these studies, we present the initial characterization of the molecular pathogenesis underlying the fibrosing phenotype of iSGS. Methods Utilizing 20 human iSGS and healthy control specimens we applied histologic, immunohistochemical, molecular and immunologic techniques. Main Results We demonstrate significant activation of the canonical IL-23/IL-17A pathway in the tracheal mucosa of iSGS patients, as well as identify γδ T cells as the primary cellular source of IL-17A. Conclusions Our results suggest that aberrant mucosal immune activation is a component in of the pathogenesis of iSGS. Most critically, our work offers new targets for future therapeutic intervention. Level of Evidence NA