Garrett, C. Gaelyn

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

Objective: To examine the distribution of clinic and operative pathology in a tertiary care laryngology practice. Methods: Probability density and cumulative distribution analyses (Pareto analysis) was used to rank order laryngeal conditions seen in an outpatient tertiary care laryngology practice and those requiring surgical intervention during a 3-year period. Results: Among 3783 new clinic consultations and 1380 operative procedures, voice disorders were the most common primary diagnostic category seen in clinic (n = 3223), followed by airway (n = 374) and swallowing (n = 186) disorders. Within the voice strata, the most common primary ICD-9 code used was dysphonia (41%), followed by unilateral vocal fold paralysis (UVFP) (9%) and cough (7%). Among new voice patients, 45% were found to have a structural abnormality. The most common surgical indications were laryngotracheal stenosis (37%), followed by recurrent respiratory papillomatosis (18%) and UVFP (17%). Conclusions: Nearly 55% of patients presenting to a tertiary referral laryngology practice did not have an identifiable structural abnormality in the larynx on direct or indirect examination. The distribution of ICD-9 codes requiring surgical intervention was disparate from that seen in clinic. Application of the Pareto principle may improve resource allocation in laryngology, but these initial results require confirmation across multiple institutions.

Objectives/HypothesisIdiopathic subglottic stenosis (iSGS) is an unexplained obstruction involving the lower laryngeal and upper tracheal airway. Persistent mucosal inflammation is a hallmark of the disease. Epithelial microbiota dysbiosis is found in other chronic inflammatory mucosal diseases; however, the relationship between tracheal microbiota composition and iSGS is unknown.Given the critical role for host defense at mucosal barriers, we analyzed tissue specimens from iSGS patients for the presence of microbial pathogens.MethodsUtilizing 30 human iSGS, 20 intubation‐related tracheal stenosis (iLTS), and 20 healthy control specimens, we applied molecular, immunohistochemical, electron microscopic, immunologic, and Sanger‐sequencing techniques.ResultsWith unbiased culture‐independent nucleic acid, protein, and immunologic approaches, we demonstrate that Mycobacterium species are uniquely associated with iSGS. Phylogenetic analysis of the mycobacterial virulence factor rpoB suggests that, rather than Mycobacterium tuberculosis, a variant member of the Mycobacterium tuberculosis complex or a closely related novel mycobacterium is present in iSGS specimens.ConclusionThese studies identify a novel pathogenic role for established large airway bacteria and provide new targets for future therapeutic intervention.Level of EvidenceNA Laryngoscope, 127:179–185, 2017

Objectives/HypothesisIdiopathic 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. In these studies, we present the initial characterization of the molecular pathogenesis underlying the fibrosing phenotype of iSGS.MethodsUtilizing 20 human iSGS and healthy control specimens, we applied histologic, immunohistochemical, molecular, and immunologic techniques.ResultsWe 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.ConclusionOur 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 EvidenceNA Laryngoscope, 126:E356–E361, 2016

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 (chi 2 = 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. Level of Evidence 4. Laryngoscope , 126:1390–1396, 2016