Quantitative Assessment of the Immune Microenvironment in Patients With Iatrogenic Laryngotracheal Stenosis.

OBJECTIVE: Iatrogenic laryngotracheal stenosis (iLTS) is characterized by fibroinflammatory narrowing of the upper airway and is most commonly caused by intubation injury. Evidence suggests a key role for CD4 T cells in its pathogenesis. The objective of this study is to validate emerging multiplex immunofluorescence (mIF) technology for use in the larynx and trachea while quantitatively characterizing the immune cell infiltrate in iLTS. In addition to analyzing previously unstudied immune cell subsets, this study aims to validate previously observed elevations in the immune checkpoint PD-1 and its ligand PD-L1 while exploring their spatial and cellular distributions in the iLTS microenvironment. STUDY DESIGN: Controlled ex vivo cohort study. SETTING: Tertiary care center. METHODS: mIF staining was performed with formalin-fixed, paraffin-embedded slides from 10 patients with iLTS who underwent cricotracheal resection and 10 control specimens derived from rapid autopsy for CD4, CD8, CD20, FoxP3, PD-1, PD-L1, and cytokeratin. RESULTS: There was greater infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, FoxP3+CD4+ Tregs, and FoxP3+CD8+ early effector T cells in the submucosa of iLTS specimens as compared with controls (P < .05 for all). PD-1 was primarily expressed on T cells and PD-L1 predominantly on CD4+ cells and "other" cells. CONCLUSION: This study leverages the power of mIF to quantify the iLTS immune infiltrate in greater detail. It confirms the highly inflammatory nature of iLTS, with CD4+ cells dominating the immune cell infiltrate; it further characterizes the cellular and spatial distribution of PD-1 and PD-L1; and it identifies novel immunologic targets in iLTS.

Health Care Costs and Cost-effectiveness in Laryngotracheal Stenosis.

OBJECTIVE: Laryngotracheal 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 DESIGN: Retrospective cohort. SETTING: Tertiary referral center (2013-2017). SUBJECTS AND METHODS: Thirty-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. RESULTS: Mean 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. CONCLUSION: The 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.

A Case Series of the Probability Density and Cumulative Distribution of Laryngeal Disease in a Tertiary Care Voice Center.

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.