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JAMA Otolaryngology-- Head & Neck... Nov 2017Laryngotracheal stenosis (LTS) is a fibroproliferative disorder of the glottis, subglottis, and trachea. In models of fibrosis from other organ systems, the CD4+ T-cell...
IMPORTANCE
Laryngotracheal stenosis (LTS) is a fibroproliferative disorder of the glottis, subglottis, and trachea. In models of fibrosis from other organ systems, the CD4+ T-cell response has been shown to regulate extracellular matrix deposition. Specifically, helper T cell 2 (TH2) promotes fibrosis, whereas TH1 and associated cytokines have been shown to be antifibrotic. However, this antifibrotic effect of the TH1 response has not been demonstrated in LTS.
OBJECTIVE
To determine whether the TH1 cytokine interferon-γ inhibits the function of LTS-derived fibroblasts in vitro.
DESIGN, SETTING, AND PARTICIPANTS
This in vitro controlled study included 6 patients with iatrogenic LTS undergoing routine surgical subglottic and tracheal dilation at a single institution. Fibroblasts were isolated from biopsy specimens of laryngotracheal scar and normal-appearing trachea. The presence of fibroblasts was confirmed by an immunohistochemical analysis. Laryngotracheal stenosis-derived fibroblasts were treated with interferon-γ and compared with untreated controls (2 sets of untreated, LTS-derived fibroblasts [media did not contain interferon-γ]) and normal airway fibroblasts (fibroblasts isolated from normal trachea). Data were collected from August 2015 through June 2016.
INTERVENTIONS
Treatment with interferon-γ, 10 ng/mL.
MAIN OUTCOMES AND MEASURES
Cellular proliferation, fibrosis gene expression (using quantitative reverse transcription polymerase chain reaction analysis), soluble collagen, and cellular histologic features were assessed.
RESULTS
Among the 6 patients (6 women; mean [SD] age, 38.3 [17.2] years), LTS-derived fibroblast proliferation was reduced in patients who received interferon-γ treatment compared with untreated controls on days 3 (mean difference, -6515 cells; 95% CI, -10 630 to -2600 cells) to 6 (mean difference, -47 521 cells; 95% CI, -81 285 to -13 757 cells). Interferon-γ treatment reduced collagen types I and III gene expression by 86% and 68%, respectively, and resulted in lower total collagen production (10.94 vs 14.89 μg/mL). In addition, interferon-γ treatment resulted in a 32% reduction in expression of transforming growth factor β in LTS-derived fibroblasts.
CONCLUSIONS AND RELEVANCE
Interferon-γ reduced proliferation, soluble collagen production, and collagen expression in LTS-derived fibroblasts while also reducing the expression of the profibrotic cytokine transforming growth factor β. These findings suggest that therapeutics aimed at increasing interferon-γ and the TH1 response could attenuate LTS.
Topics: Cell Proliferation; Collagen; Fibroblasts; Humans; In Vitro Techniques; Interferon-gamma; Laryngostenosis; Reverse Transcriptase Polymerase Chain Reaction; Tracheal Stenosis; Transforming Growth Factor beta
PubMed: 28715559
DOI: 10.1001/jamaoto.2017.0977 -
Annals of Anatomy = Anatomischer... Nov 2016Surfactant proteins (SPs) originally identified in lung tissue are important players in the innate immune system. Beyond this, they contribute to stability and rheology...
PURPOSE
Surfactant proteins (SPs) originally identified in lung tissue are important players in the innate immune system. Beyond this, they contribute to stability and rheology of gaseous or aqueous interphases. In the present study, we determined the expression and presence of SPs (A, B, C and D) in different areas of the human larynx.
METHODS
mRNA expression of SP-A, -B, -C and -D was analyzed by means of RT-PCR in healthy samples of epiglottis, vocal and vestibular folds, subglottis and trachea. Distribution and localization of all four SPs were analyzed by Western blot and immunohistochemistry in healthy human tissue samples.
RESULTS
All four SPs were detected at the mRNA- and protein level in the human larynx as well as by means of immunohistochemistry in the different tissue samples of the human larynx.
CONCLUSION
The results reveal that all four SPs are produced with different expression patterns within the human larynx. Based on the known functions, our results suggest that SPs might be involved in maintaining mucus rheology and subsequently they could be essential components for proper phonation. Moreover, the proteins seem to play a role in immune defense of the larynx.
Topics: Cadaver; Female; Humans; Larynx; Male; Organ Specificity; Pulmonary Surfactant-Associated Proteins; Tissue Distribution
PubMed: 27328406
DOI: 10.1016/j.aanat.2016.05.010 -
Thoracic Surgery Clinics May 2018Optimal management of tracheal stenosis depends on identifying causative factors. Risk factors include high tracheostomy, cricothyroidotomy, prolonged intubation, and... (Review)
Review
Optimal management of tracheal stenosis depends on identifying causative factors. Risk factors include high tracheostomy, cricothyroidotomy, prolonged intubation, and proximal migration of an endotracheal tube cuff. Management ranges from conservative observation to endoscopic procedures or open surgical resections. The goal of surgical repair is an adequate airway, decannulation, and normal laryngeal function. For early stage disease, management of refractory conditions is via endoscopic procedures. An understanding of the respiratory function of the glottis and subglottis is essential when an optimum functional reconstruction of the glottic/subglottic area is considered. In this article we discuss different airway assessments and surgical management techniques.
Topics: Constriction, Pathologic; Costal Cartilage; Cricoid Cartilage; Glottis; Humans; Intubation, Intratracheal; Laryngostenosis; Larynx; Retrospective Studies; Ribs; Trachea; Tracheal Stenosis; Tracheostomy; Transplantation, Autologous; Treatment Outcome
PubMed: 29627053
DOI: 10.1016/j.thorsurg.2018.01.013 -
BMJ Case Reports Apr 2023Tracheobronchopathia osteochondroplastica (TO) is a rare condition affecting the lumen of the tracheobronchial tree. It is characterised by the presence of multiple...
Tracheobronchopathia osteochondroplastica (TO) is a rare condition affecting the lumen of the tracheobronchial tree. It is characterised by the presence of multiple osseous and cartilaginous nodules with posterior wall sparing. While it is a benign condition, it can cause narrowing of the tracheal lumen and subglottis to varying degrees. Approximately 400 cases have been reported worldwide, with an incidence of 0.3% in autopsies and between 1 in 125 and 1 in 5000 on bronchoscopy. As most patients are asymptomatic, this may contribute to underdiagnoses and relative low incidence. Severity of the condition is often unrelated to patient symptomatology. We present a patient with one of the most severe cases of TO seen at our institution. Despite being asymptomatic, significant tracheal and bronchial narrowing was found incidentally on laryngobronchoscopy.
Topics: Humans; Tracheal Diseases; Bronchoscopy; Trachea; Osteochondrodysplasias
PubMed: 37055074
DOI: 10.1136/bcr-2022-249976 -
International Journal of Pediatric... Nov 2020Granular cell tumors of the larynx are exceedingly rare in the pediatric population. The purpose of this review is to further characterize features of these tumors and... (Review)
Review
OBJECTIVE
Granular cell tumors of the larynx are exceedingly rare in the pediatric population. The purpose of this review is to further characterize features of these tumors and trends in their management.
METHODS
A search of the PubMed, Ovid Medline and Cochrane Collaboration databases was undertaken using the terms: pediatric, child, laryngeal, larynx, granular cell tumor, granular cell myoblastoma, benign mass.
RESULTS
A total of 38 children with laryngeal granular cell tumor were identified. Their ages ranged from 4 to 16 years. The most common presenting symptom was dysphonia. Five patients were previously treated for asthma. Within the laryngeal subsites, 49% presented with subglottic tumors, while 43% were found at the level of the glottis. Subglottic tumors were found anteriorly 42% of the time and posteriorly 53% of the time. Multifocal disease was present in four patients. Around half of patients were treated by cold steel excision and/or CO laser, 31% through laryngofissure, and two required laryngectomy. There were four documented cases of recurrence ranging from 4 months to 3 years after treatment.
CONCLUSIONS
Laryngeal granular cell tumor during childhood occurs most commonly in the subglottis. Posterior laryngeal tumors were more frequent than anterior tumors. Patients should be carefully evaluated for multifocal disease. Long-term surveillance for recurrence is recommended.
Topics: Adolescent; Child; Child, Preschool; Glottis; Granular Cell Tumor; Humans; Laryngeal Neoplasms; Larynx; Neoplasm Recurrence, Local
PubMed: 32705988
DOI: 10.1016/j.ijporl.2020.110193 -
European Archives of... Dec 2022To investigate epidemiological, clinical and oncological outcomes of young patients with laryngeal cancer (LC).
OBJECTIVE
To investigate epidemiological, clinical and oncological outcomes of young patients with laryngeal cancer (LC).
METHODS
PubMed, Scopus and Cochrane Library were searched by three researchers for studies investigating epidemiological, clinical and oncological outcomes of patients with age < 40 years old and LC. The following outcomes were investigated with PRISMA criteria: age; ethnicity; gender; tobacco/alcohol habits; anatomical, pathological, therapeutic and survival features. Authors performed a bias analysis of papers and provided recommendations for future studies.
RESULTS
Seventeen papers published between 1982 and 2021 met our inclusion criteria, accounting for 928 patients with age < 40 years (female/male ratio: 2:5). There were on average 54.2 and 45.8% of smokers and drinkers. The tumor location mainly consisted of glottis (70.1%), supraglottis (27.7%) and subglottis (2.2%). Radiation therapy was the main therapeutic strategy used in young adults with LC. The 2-year overall survival ranged from 50 to 100% and depended on tumor stage, treatment, and cohort features. Four studies reported better overall survival in young compared with old adults, while there were no significant differences in three studies. There was an important heterogeneity between studies regarding the inclusion/exclusion criteria, epidemiological, clinical, pathological and treatment.
CONCLUSION
It was suggested that young patients with LC had lower proportion of smokers and drinkers and better overall survival compared with older but both data of the current literature and heterogeneity between studies limit us to draw definitive conclusions.
Topics: Young Adult; Humans; Male; Female; Adult; Laryngeal Neoplasms; Carcinoma, Squamous Cell; Glottis; Larynx; Cohort Studies
PubMed: 35652941
DOI: 10.1007/s00405-022-07466-9 -
Laryngoscope Investigative... Dec 2022The primary aim of this study was to identify expression of TRPV3 and TRPV4 chemoreceptors across perinatal and adult stages using a murine model with direct comparisons...
OBJECTIVE
The primary aim of this study was to identify expression of TRPV3 and TRPV4 chemoreceptors across perinatal and adult stages using a murine model with direct comparisons to human laryngeal mucosa. Our secondary aim was to establish novel cell expression patterns of mechanoreceptors PIEZO1 and PIEZO2 in human tissue samples.
STUDY DESIGN
In vivo
METHODS
We harvested murine laryngeal tissue to localize and describe TRPV3/4 endogenous protein expression patterns via immunofluorescence analyses across two developmental (E16.5, P0) and adult (6 weeks) timepoints. Additionally, we obtained a 60-year-old female larynx including the proximal trachea and esophagus to investigate TRPV3/4 and PIEZO1/2 protein expression patterns via immunofluorescence analyses for comparison to murine adult tissue.
RESULTS
Murine TRPV3/4 expression was noted at E16.5 with epithelial cell colocalization to supraglottic regions of the arytenoids, aryepiglottic folds and epiglottis through to birth (P0), extending to the adult timepoint. Human TRPV3/4 protein expression was most evident to epithelium of the arytenoid region, with additional expression of TRPV3 and TRPV4 to proximal esophageal and tracheal epithelium, respectively. Human PIEZO1 expression was selective to differentiated, stratified squamous epithelia of the true vocal fold and esophagus, while PIEZO2 expression exhibited selectivity for intermediate and respiratory epithelia of the false vocal fold, ventricles, subglottis, arytenoid, and trachea.
CONCLUSION
Results exhibited expression of TRPV3/4 chemoreceptors in utero, suggesting their importance during fetal/neonatal stages. TRPV3/4 and PIEZO1/2 were noted to adult murine and human laryngeal epithelium. Data indicates conservation of chemosensory receptors across species given similar regional expression in both the murine and human larynx.
PubMed: 36544955
DOI: 10.1002/lio2.968 -
Journal of Speech, Language, and... Feb 2022Voluntary cough dysfunction is highly prevalent across multiple patient populations. Voluntary cough has been utilized as a screening tool for swallowing safety deficits...
PURPOSE
Voluntary cough dysfunction is highly prevalent across multiple patient populations. Voluntary cough has been utilized as a screening tool for swallowing safety deficits and as a target for compensatory and exercise-based dysphagia management. However, it remains unclear whether voluntary cough dysfunction is associated with the ability to effectively clear the airway.
METHOD
Individuals with neurodegenerative disorders performed same-day voluntary cough testing and flexible endoscopic evaluations of swallowing (FEES). Participants who were cued to cough after exhibiting penetration to the vocal folds and/or aspiration with thin liquids during FEES met inclusion criteria. One-hundred and twenty-three trials were blinded, and the amount of residue before and after a cued cough on FEES was measured with a visual analog scale. Linear and binomial mixed-effects models examined the relationship between cough airflow during voluntary cough testing and the proportion of residue expelled.
RESULTS
Peak expiratory flow rate ( = .004) and cough expired volume from the entire epoch ( = .029) were significantly associated with the proportion of aspiration expelled from the subglottis. Peak expiratory flow rate values of 3.00 L/s, 3.50 L/s, and 5.30 L/s provided high predicted probabilities that ≥ 25%, ≥ 50%, and ≥ 80% aspirate was expelled. Accounting for depth of aspiration significantly improved model fit ( < .001).
CONCLUSIONS
These findings suggest that voluntary cough airflow is associated with cough effectiveness to clear aspiration from the subglottis, although aspiration amount and depth may play an important role in this relationship. These findings provide further support for the clinical utility of voluntary cough in the management of dysphagia.
Topics: Cough; Deglutition; Deglutition Disorders; Humans; Neurodegenerative Diseases; Peak Expiratory Flow Rate
PubMed: 34936376
DOI: 10.1044/2021_JSLHR-21-00308 -
OTO Open 2021To analyze specific intralaryngeal findings associated with granulomatosis with polyangiitis (GPA).
OBJECTIVE
To analyze specific intralaryngeal findings associated with granulomatosis with polyangiitis (GPA).
STUDY DESIGN
Retrospective chart review.
SETTING
Tertiary referral center.
METHODS
A retrospective chart review was performed on all patients diagnosed with GPA who were evaluated at the laryngology division of Massachusetts Eye and Ear Infirmary between January 2006 and September 2019.
RESULTS
Forty-four patients (14 male, 30 female) were evaluated for laryngeal pathology. The mean age at onset was 48 years. Nine patients (21%) were identified with only vocal fold disease, 11 (25%) with subglottic disease, and 8 (18%) with disease at the glottis and subglottis (transglottic). The remaining 16 patients (36%) had a normal airway upon examination although they presented with laryngeal symptoms. Patients with glottic disease had statistically significantly lower voice-related quality of life scores than patients with isolated subglottic stenosis.
CONCLUSIONS
Although laryngeal manifestations of GPA is often described as a subglottic disease presenting with respiratory symptoms, subsite analysis show that only 25% of patients had subglottic disease alone, with similar rates of glottic disease alone. Laryngeal subsites have different epithelial mucosa, function, and physiology, and understanding the specific sites of involvement will determine symptoms and enable better analysis of the underlying mechanisms of disease. Glottic disease is associated with a reduction in vocal fold motion and voice changes. Subglottic involvement presents more frequently with airway symptoms. Further research is necessary to better define the specific regions of laryngeal involvement in patients diagnosed with GPA.
PubMed: 34396029
DOI: 10.1177/2473974X211036394 -
Otolaryngologia Polska = the Polish... Dec 2017The diagnostic and therapeutic recommendations have been changing over the years to improve treatment outcomes and quality of life of Head and Neck Cancer (HNC) patients. (Review)
Review
INTRODUCTION
The diagnostic and therapeutic recommendations have been changing over the years to improve treatment outcomes and quality of life of Head and Neck Cancer (HNC) patients.
AIM
The aim of this study was to present currently recommended Head and Neck Cancer treatment guidelines based on the literature review with particular emphasis on novel approaches the NCCN algorithms.
MATERIAL AND METHODS
The review of literature covering articles published in the last five years and pointing out essential changes in HNC treatment regarding evidence based medicine. The study focused on the analysis of novel approaches for the particular primaries, the implementation of biological therapies and personalized cancer therapies.
RESULTS
Updates in the oncological NCCN guidelines for all ENT primaries except major salivary glands and subglottis are based on knowledge derived from the basic sciences, clinical trials and the best evidence available currently. The latest recommendations emphasize value of biological therapies use.
Topics: Adult; Aged; Aged, 80 and over; Evidence-Based Medicine; Female; Head and Neck Neoplasms; Humans; Male; Medical Oncology; Middle Aged; Practice Guidelines as Topic; Quality of Life
PubMed: 29327681
DOI: 10.5604/01.3001.0010.7193