Motz, Kevin M

ObjectivesIdiopathic subglottic stenosis (iSGS) is an inflammatory process leading to fibrosis and narrowing of the laryngotracheal airway. There is variability in patient response to surgical intervention, but the mechanisms underlying this variability are unknown. In this pilot study, we measure expression of candidate targets at the mucosal surface of the subglottis in iSGS patients. We aim to identify putative biomarkers for iSGS that provide insights into the molecular basis of disease progression, yield a gene signature for the disease, and/or predict a response to therapy.Study DesignIn vitro comparative study of human cells.MethodsLevels of candidate transcripts and proteins were measured in healthy and stenotic laryngotracheal tissue specimens taken from the mucosal surface in 16 iSGS patients undergoing endoscopic balloon dilation. Pre‐ and post‐operative pulmonary function test and patient reported voice and breathing outcomes were also assessed. Unsupervised clustering was used to define patient subgroups based on expression profile.ResultsPulmonary function and voice and breathing outcome metrics demonstrated significant post‐operative improvement. Transcript levels of αSMA, CCL2, COL1A1, COL3A1, FN1, IFNG, and TGFB1 and protein levels of CCL2, IFNG, and IL‐6 were significantly upregulated in stenotic as compared to healthy tissues. Marked heterogeneity was observed in the patterns of expression of candidate markers across individuals and tissue types. Patient subgroups defined by expression profile did not show a statistically significant difference in dilation interval.ConclusionPro‐inflammatory and pro‐fibrotic pathways are significantly upregulated along the mucosal surface of stenotic laryngotracheal tissues, and CCL2 and IFNG merit further investigation as potential iSGS biomarkers.Level of Evidence4 Laryngoscope, 131:342–349, 2021

The laryngotracheal region resides at the intersection between the heavily studied nasal cavity and lungs; however, examination of the microbiome in chronic inflammatory conditions of the subglottis and trachea remains scarce. To date, studies have focused on the microbiota of the vocal folds, or the glottis, for laryngeal carcinoma, as well as healthy larynges, benign vocal fold lesions, and larynges exposed to smoking and refluxate. In this study, we seek to examine the structure and composition of the microbial community in adult laryngotracheal stenosis of various etiologies. Due to the heterogeneity among the underlying pathogenesis mechanisms and clinical outcomes seen in laryngotracheal stenosis disease, we hypothesized that different microbial profiles will be detected among various stenosis etiology types. Understanding differences in the microbiota for subglottic stenosis subtypes may shed light upon etiology-specific biomarker identification and offer novel insights into management approaches for this debilitating disease.

ObjectiveLaryngotracheal stenosis (LTS) is resource‐intensive disease. The cost‐effectiveness of LTS treatments has not been adequately explored. We aimed to conduct a cost‐effectiveness analysis comparing open reconstruction (cricotracheal/tracheal resection [CTR/TR]) with endoscopic dilation in the treatment of LTS.Study DesignRetrospective cohort.SettingTertiary referral center (2013‐2017).Subjects and MethodsThirty‐four LTS patients were recruited. Annual costs were derived from the Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University. Cost‐effectiveness analysis compared CTR/TR versus endoscopic dilation at a willingness‐to‐pay threshold of $50,000 per quality‐adjusted life year (QALY) over 5‐ and 10‐year time horizons. The incremental cost‐effectiveness ratio (ICER) was calculated with deterministic analysis and tested for sensitivity with univariate and probabilistic sensitivity analysis.ResultsMean LTS costs were $4080.09 (SE, $569.29) annually for related health care visits. The major risk factor for increased cost was etiology of stenosis. As compared with idiopathic patients, patients with intubation‐related stenosis had significantly higher annual costs ($5286.56 vs $2873.62, P =. 03). The cost of CTR/TR was $8583.91 (SE, $2263.22). Over a 5‐year time horizon, CTR/TR gained $896 per QALY over serial dilations and was cost‐effective. Over a 10‐year time horizon, CTR/TR dominated dilations with a lower cost and higher QALY.ConclusionThe cost of treatment for LTS is significant. Patients with intubation‐related stenosis have significantly higher annual costs than do idiopathic patients. CTR/TR contributes significantly to cost in LTS but is cost‐effective versus endoscopic dilations for appropriately selected patients over a 5‐ and 10‐year horizon.