OBJECTIVE: Acute laryngeal injury (ALgI) is an identified complication of prolonged intubation. Its evolution into mature stenosis and factors affecting decannulation are unclear. This retrospective review aims to characterize the incidence and characteristics of ALgI development and decannulation.
METHODS: Retrospective study of post-intubated patients with a tracheostomy seen for screening evaluation at a single long-term acute care hospital (LTACH) from 2019 to 2022.
RESULTS: Patients were followed for an average of 115 days after extubation. Forty-nine of 119 adult patients had ALgI. Those with ALgI were more likely female (61% vs. 35.7%, p = 0.006) with higher body mass index (BMI; 32.9 vs. 28.1, p = 0.03) and lower height (166 vs. 171.1 cm, p = 0.01). Decannulation rates in patients with ALgI were 69.4% compared to 84.3% in patients without ALgI (p = 0.053). Patients with ALgI were scoped more quickly post-extubation (28.8 vs. 36.6 days, p = 0.04), but time to decannulation did not differ (66.6 vs. 81.2 days, p = 0.74). Lower CCI (4.03 vs 6.93) and lack of tobacco use (41.2% vs 73.3%) were associated with successful decannulation (p = 0.038, p = 0.0008). Patients with ALgI treated conservatively (observation or medical management) were decannulated up to 71 days post-extubation. Further decannulations only occurred with surgical intervention.
CONCLUSIONS: Female gender, higher BMI, and shorter height are associated with ALgI among patients undergoing a LTACH screening evaluation. CCI and tobacco have a negative association with decannulation success. Among the ALgI cohort, no patient treated conservatively was decannulated after 71 days.
METHODS: 4 Laryngoscope, 2024.

Acute laryngeal dyspnea is a life-threatening emergency often attributed to laryngeal tumors or inflammatory edema in adults. Primary laryngeal lymphomas are especially infrequent. As an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL), mantle cell lymphoma (MCL) cases are particularly complex.  Herein, we present a case of laryngotracheal stenosis secondary to primary MCL. A comprehensive assessment, including in-office flexible laryngoscopy, revealed distinct findings within the supraglottis and subglottis. In the supraglottis, a submucosal lesion with well-defined, rounded edges was observed, while the subglottis exhibited a friable tumor occupying approximately 90% of the airway. This necessitated immediate intervention, leading to microlaryngoscopy, biopsy, and open tracheostomy. Due to the rarity of primary laryngeal lymphomas, they present a significant diagnostic challenge. Timely diagnosis is crucial to enable tailored therapeutic strategies and improved patient outcomes. This case highlights the importance of considering lymphomatous etiologies in the management of laryngotracheal stenosis and emphasizes the need for a multidisciplinary approach to optimize patient care.

BACKGROUND: Benign laryngotracheal stenosis is widely managed with minimally invasive endoscopic interventions, such as laser incision or excision scar, and dilation. However, various endoscopic treatments are significantly associated with a high recurrence rate. Local auxiliary measures, including inhalation of steroids, injection of steroids, and local topical application of mitomycin C, have been studied in order to increase the success rate.
OBJECTIVE: To compare the efficacy of endoscopic treatments with and without local adjuncts in patients with benign laryngotracheal stenosis, and analyze their clinical outcomes, recurrence, and complications.
METHODS: In the meta-analysis, databases including PubMed, EMBASE, OVID, and Web of Science were searched for papers comparing the outcomes of adjunct therapy with non-adjunct therapy in patients with laryngotracheal stenosis. The duplicate publications, reviews, comments or letters, conference abstracts, and case reports were excluded. The random effect model was used for assessing the pooled risk estimates.
RESULTS: Eight studies (1204 cases) referring to two prospective randomized controlled studies, two prospective cohort studies, and four retrospective cohort studies were ultimately included in the meta-analysis. Three delivery modes of adjuncts were identified, including intralesion steroid injection (n = 2), inhaled steroid (n = 2), and topical application of mitomycin C (n = 4). The decreased risk estimates of recurrence rate were detected in patients receiving endoscopic treatments with steroid injection or inhaled steroid, compared with endoscopic interventions alone (P < 0.05). Additionally, patients undergoing adjunct therapies had lower risk estimates of recurrence, compared to those receiving endoscopic procedures alone (P < 0.05), based on the subgroup of prospective cohort studies, subglottis, Mayer-Cotton scale of I-II degree, and stenosis length of < 3 cm. The high heterogeneity of the pooling risk estimates perhaps was due to factors of auxiliary drug, clinical characteristics of patients, and methodology. No discernible difference in the incidence of complication was identified.
CONCLUSIONS: Local application of steroids to minimally invasive interventions appear to reduce the recurrence rate of laryngotracheal stenosis. Various adjuncts available, including steroids and mitomycin C, appear to be safe and associated with a low risk estimate of adjuncts-specific complication rate. High quality multi-center randomized controlled studies are needed, with sufficient periods for follow-up and subjective and objective outcome indicators, to properly evaluate the efficacy, safety, and cost-effectiveness of adjuvant drugs.

OBJECTIVE: Patients with laryngotracheal stenosis (LTS) often have dysphagia after laryngotracheal reconstruction with T-tube insertion, which affects the quality of life. The purpose of this study is to observe the effect of swallowing rehabilitation therapy on the improvement of quality of life in patients of otolaryngology-head and neck surgery with dysphagia undergoing T-tube implantation treatment through longitudinal study.
METHODS: Thirty-eight patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation were recruited. All patients received swallowing rehabilitation therapy. The assessment of swallowing function was performed using the 10-item Eating Assessment Tool (EAT-10), the 30 mL water swallow test (WST), and flexible endoscopic evaluation of swallow (FEES).
RESULTS: After swallowing rehabilitation therapy, timing of swallowing, grade of dysphagia, performance on FEES and 30 mL WST, and EAT-10 score all improved. Thirty-eight patients successfully transitioned to oral feeding and were able to remove their nasogastric tubes without experiencing any complications, including aspiration pneumonia.
CONCLUSIONS: For patients with LTS who experienced dysphagia after laryngotracheal reconstruction and T-tube implantation, swallowing rehabilitation therapy could improve swallowing function of the patients, so as to reduce the potential harm caused by the pain and complications of surgery experienced by patients.

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OBJECTIVE: To investigate the role of periostin (POSTN) and the transforming growth factor β (TGF-β) pathway in the formation of laryngotracheal stenosis (LTS) scar fibrosis and to explore the specific signaling mechanism of POSTN-regulated TGF-β pathway in tracheal fibroblasts.
METHODS: Bioinformatics analysis was performed on scar data sets from the GEO database to preliminarily analyze the involvement of POSTN and TGF-β pathways in fibrosis diseases. Expression of POSTN and TGF-β pathway-related molecules was analyzed in LTS scar tissue at the mRNA and protein levels. The effect of POSTN on the biological behavior of tracheal fibroblasts was studied using plasmid DNA overexpression and siRNA silencing techniques to regulate POSTN expression and observe the activation of TGF-β1 and the regulation of cell proliferation and migration via the TGF-β/RHOA pathway.
RESULTS: The bioinformatics analysis revealed that POSTN and the TGF-β pathway are significantly involved in fibrosis diseases. High expression of POSTN and TGF-β/RHOA pathway-related molecules (TGFβ1, RHOA, CTGF, and COL1) was observed in LTS tissue at both mRNA and protein levels. In tracheal fibroblasts, overexpression or silencing of POSTN led to the activation of TGF-β1 and regulation of cell proliferation and migration through the TGF-β/RHOA pathway.
CONCLUSIONS: POSTN is a key molecule in scar formation in LTS, and it regulates the TGF-β/RHOA pathway to mediate the formation of cicatricial LTS by acting on TGF-β1. This study provides insights into the molecular mechanisms underlying LTS and suggests potential therapeutic targets for the treatment of this condition.
METHODS: NA Laryngoscope, 134:4078-4087, 2024.

OBJECTIVE: Animal models for laryngotracheal stenosis (LTS) are critical to understand underlying mechanisms and study new therapies. Current animal models for LTS are limited by small airway sizes compared to human. The objective of this study was to develop and validate a novel, large animal ovine model for LTS.
METHODS: Sheep underwent either bleomycin-coated polypropylene brush injury to the subglottis (n = 6) or airway stent placement (n = 2) via suspension microlaryngoscopy. Laryngotracheal complexes were harvested 4 weeks following injury or stent placement. For the airway injury group, biopsies (n = 3 at each site) were collected of tracheal scar and distal normal regions, and analyzed for fibrotic gene expression. Lamina propria (LP) thickness was compared between injured and normal areas of trachea.
RESULTS: No mortality occurred in sheep undergoing airway injury or stent placement. There was no migration of tracheal stents. After protocol optimization, LP thickness was significantly increased in injured trachea (Sheep #3: 529.0 vs. 850.8 um; Sheep #4: 933.0 vs. 1693.2 um; Sheep #5: 743.7 vs. 1378.4 um; Sheep #6: 305.7 vs. 2257.6 um). A significant 62-fold, 20-fold, 16-fold, 16-fold, and 9-fold change of COL1, COL3, COL5, FN1, and TGFB1 was observed in injured scar specimen relative to unaffected airway, respectively.
CONCLUSIONS: An ovine LTS model produces histologic and transcriptional changes consistent with fibrosis seen in human LTS. Airway stent placement in this model is safe and feasible. This large airway model is a reliable and reproducible method to assess the efficacy of novel LTS therapies prior to clinical translation.
METHODS: N/A Laryngoscope, 2024.

OBJECTIVE: Occurrence of post-intubation laryngotracheal stenosis (LTS) with respect to COVID-19 status.
METHODS: Retrospective cross-sectional inpatient database.
METHODS: Eleven Midwest academic and community hospitals, United States.
METHODS: Adults, mechanically ventilated, from January 2020 to August 2022, who were subsequently readmitted within 6 months with a new diagnosis of LTS.
METHODS: None.
RESULTS: Six thousand eight hundred fifty-one COVID-19 negative and 1316 COVID-19 positive patients were intubated and had similar distribution by age (median 63.77 vs. 63.16 yr old), sex (male, 60.8%; n = 4173 vs. 60%; n = 789), endotracheal tube size (≥ 7.5, 75.8%; n = 5192 vs. 75.5%; n = 994), and comorbidities. The ICU length of stay (median [interquartile range (IQR)], 7.23 d [2.13-16.67 d] vs. 3.95 d [1.91-8.88 d]) and mechanical ventilation days (median [IQR], 5.57 d [1.01-14.18 d] vs. 1.37 d [0.35-4.72 d]) were longer in the COVID-19 positive group. The occurrence of LTS was double in the COVID-19 positive group (12.7%, n = 168 vs. 6.4%, n = 440; p < 0.001) and was most commonly diagnosed within 60 days of intubation. In multivariate analysis, the risk of LTS increased by 2% with each additional ICU day (hazard ratio [HR], 1.02; 95% CI, 1.02-1.03; p < 0.001), by 3% with each additional day of ventilation (HR, 1.03; 95% CI, 1.02-1.04; p < 0.001), and by 52% for each additional reintubation (HR, 1.52; 95% CI, 1.36-1.71; p < 0.001). We observed no significant association COVID-19 status and risk of LTS.
CONCLUSIONS: The occurrence of post-intubation LTS was double in a COVID-19 positive cohort, with higher risk with increasing number of days intubated, days in the ICU and especially with the number of reintubations. COVID-19 status was not an independent risk factor for LTS.

OBJECTIVE: Surgical treatment for airway stenosis necessitates personalized techniques based on the stenosis location and length, leading to favourable surgical outcomes. However, there is limited literature on functional outcomes following laryngotracheal surgery with an adequate number of patients.
METHODS: We conducted a retrospective analysis of patients who underwent laryngotracheal surgery at the Department of Thoracic Surgery, Medical University of Vienna, from January 2017 to June 2021. The study included standardized functional assessments before and after surgery, encompassing spirometry, voice measurements, swallowing evaluation and subjective patient perception.
RESULTS: The study comprised 45 patients with an average age of 51.9 ± 15.9 years, of whom 89% were female, with idiopathic being the most common aetiology (67%). Procedures included standard cricotracheal resection in 11%, cricotracheal resection with dorsal mucosal flap in 49%, cricotracheal resection with dorsal mucosal flap and lateral cricoplasty in 24% and single-stage laryngotracheal reconstruction in 16%. There were no in-hospital mortalities or restenosis cases during the mean follow-up period of 20.8 ± 13.2 months. Swallowing function remained intact in all patients. Voice evaluations showed a decrease in fundamental vocal pitch [203 (81-290) Hz vs 150 (73-364) Hz, P < 0.001] and dynamic voice range (23.5 ± 5.8 semitones vs 17.8 ± 6.7 semitones, P < 0.001). However, no differences in voice volume were observed (60.0 ± 4.1 dB vs 60.2 ± 4.8 dB, P = 0.788). The overall predicted voice profile changed from R0B0H0 to R1B0H1.
CONCLUSIONS: Laryngotracheal surgery proves effective in fully restoring breathing capacity while preserving vocal function. Even in cases of high-grade and complex airway stenosis necessitating laryngotracheal reconstruction, favourable functional outcomes can be achieved.

OBJECTIVE: To present a comprehensive flow cytometry panel for idiopathic subglottic stenosis (iSGS).
METHODS: Controlled ex vivo cohort study.
METHODS: 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.
CONCLUSIONS: 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.