Posterior Glottic Injury Following Prolonged Intubation in COVID-19 Patients.

OBJECTIVE: The objective of this study was to characterize the risk factors for posterior glottic injury (PGI) in patients with coronavirus disease 2019 (COVID-19) who underwent prolonged intubation. STUDY DESIGN: This was a case-control study designed to assess the risk factors associated with development of PGI in COVID-19 patients who underwent prolonged intubation. SETTING: This single-center study was conducted at a tertiary care academic hospital in a metropolitan area. METHODS: We retrospectively reviewed patients who underwent prolonged intubation (≥7 days) for COVID-19 and compared those with PGI to those without. Patient demographics, comorbidities, and intubation characteristics were compared. Factors associated with PGI development among COVID-19 patients were assessed using multivariate regression. RESULTS: We identified 56 patients who presented with PGI following prolonged intubation for COVID-19 and 60 control patients who underwent prolonged intubation for COVID-19 but did not develop PGI. On univariate analyses, the number of reintubations due to failed extubation efforts was significantly associated with development of PGI (odds ratio [OR], 2.9; 95% CI, 1.4-6.2). On multivariate analyses, patients with cardiovascular disease (OR, 3.3; 95% CI, 1.2-9.0); non-COVID-19 respiratory illnesses, which included obstructive sleep apnea and asthma (OR, 5.9; 95% CI, 2.0-17.8); and diabetes mellitus (OR, 11.6; 95% CI, 3.7-36.6) were more likely to develop PGI. CONCLUSION: Our results represent the largest case-control study investigating risk factors for PGI in the setting of prolonged intubation specific to COVID-19. Our study suggests a significant role of comorbidities associated with poor wound healing with development of PGI.

Characterization of Fibroblasts in Iatrogenic Laryngotracheal Stenosis and Type II Diabetes Mellitus.

OBJECTIVES: Iatrogenic laryngotracheal stenosis (iLTS) is the pathological narrowing of the glottis, subglottis, and/or trachea due to scar tissue. Patients with type 2 diabetes mellitus (T2DM) are over 8 times more likely to develop iLTS and represent 26% to 53% of all iLTS patients. In this investigation, we compared iLTS scar-derived fibroblasts in patients with and without T2DM. STUDY DESIGN: Controlled ex vivo study. METHODS: iLTS scar fibroblasts were isolated and cultured from subglottic scar biopsies in iLTS patients diagnosed with or without type 2 diabetes (non-T2DM). Fibroblast proliferation, fibrosis-related gene expression, and metabolic utilization of oxidative phosphorylation (OXPHOS) and glycolysis were assessed. Contractility was measured using a collagen-based assay. Metabolically targeted drugs (metformin, phenformin, amobarbital) were tested, and changes in fibrosis-related gene expression, collagen protein, and contractility were evaluated. RESULTS: Compared to non-T2DM, T2DM iLTS scar fibroblasts had increased α-smooth muscle actin (αSMA) expression (8.2× increased, P = .020), increased contractility (mean 71.4 ± 4.3% vs. 51.7 ± 16% Δ area × 90 minute-1 , P = .016), and reduced proliferation (1.9× reduction at 5 days, P < .01). Collagen 1 (COL1) protein was significantly higher in the T2DM group (mean 2.06 ± 0.19 vs. 0.74 ±.44 COL1/total protein [pg/µg], P = .036). T2DM iLTS scar fibroblasts had increased measures of OXPHOS, including basal respiration (mean 86.7 vs. 31.5 pmol/minute/10 µg protein, P = .016) and adenosine triphosphate (ATP) generation (mean 97.5 vs. 25.7 pmol/minute/10 µg protein, P = .047) compared to non-T2DM fibroblasts. Amobarbital reduced cellular contractility; decreased collagen protein; and decreased expression of αSMA, COL1, and fibronectin. Metformin and phenformin did not significantly affect fibrosis-related gene expression. CONCLUSION: T2DM iLTS scar fibroblasts demonstrate a myofibroblast phenotype and greater contractility compared to non-T2DM. Their bioenergetic preference for OXPHOS drives their increased contractility, which is selectively targeted by amobarbital. LEVEL OF EVIDENCE: NA Laryngoscope, 131:1570-1577, 2021.

Postoperative sore throat and subglottic injury after McGrath® MAC videolaryngoscopic intubation with versus without a stylet in patients with a high Mallampati score: a randomized controlled trial.

BACKGROUND: A tracheal tube stylet can be used to assist successful tracheal intubation, especially during videolaryngoscopic intubation because videolaryngoscopes with a Macintosh-type blade such as McGrath® MAC videolaryngoscope have more acute angle than conventional Macintosh laryngoscope. However, the use of a stylet during tracheal intubation can raise concerns about stylet-induced postoperative airway complications, such as sore throat, subglottic injury, and hoarseness. In this study, we compared the incidence of postoperative airway complications after McGrath® MAC videolaryngoscopic intubation with versus without a stylet in patients with a high Mallampati score. METHODS: In 104 patients with Mallampati score III or IV and who were scheduled for lumbar or thoracic spine surgery, McGrath® MAC videolaryngoscopic intubation was performed either with a stylet (group S, n = 52) or without a stylet (group N, n = 52). The primary outcome measure was the incidences of sore throat evaluated at 1 and 24 h postoperatively. Secondary outcome measures were the incidences of subglottic injury and postoperative hoarseness. RESULTS: The incidence of CL grade III in group S and N was 3.8 and 5.8%, respectively. No patient showed CL grade IV. The incidences of sore throat at 1 (26.9 vs 19.2%, P = 0.485) and 24 h (17.3 vs 13.5%, P = 0.786, respectively) postoperatively were not significantly different between the group S and N. However, the incidence of subglottic injury was significantly higher in the group S, compared with the group N (65.4 vs 42.3%, P = 0.030). The incidence of postoperative hoarseness did not differ significantly between the two groups. CONCLUSIONS: The use of a stylet during McGrath® MAC videolaryngoscopic intubation did not have a significant impact on the incidence of postoperative sore throat in patients with a high Mallampati score. Avoiding the use of a stylet during intubation with McGrath® MAC videolaryngoscope may reduce the incidence of subglottic injury in such patients. TRIAL REGISTRATION: Clinical Research Information Service (identifier: KCT0002427 , date of registration: June 12, 2017).

Demographic and Symptomatic Features of Voice Disorders and Their Potential Application in Classification Using Machine Learning Algorithms.

BACKGROUND: Studies have used questionnaires of dysphonic symptoms to screen voice disorders. This study investigated whether the differential presentation of demographic and symptomatic features can be applied to computerized classification. METHODS: We recruited 100 patients with glottic neoplasm, 508 with phonotraumatic lesions, and 153 with unilateral vocal palsy. Statistical analyses revealed significantly different distributions of demographic and symptomatic variables. Machine learning algorithms, including decision tree, linear discriminant analysis, K-nearest neighbors, support vector machine, and artificial neural network, were applied to classify voice disorders. RESULTS: The results showed that demographic features were more effective for detecting neoplastic and phonotraumatic lesions, whereas symptoms were useful for detecting vocal palsy. When combining demographic and symptomatic variables, the artificial neural network achieved the highest accuracy of 83 ± 1.58%, whereas the accuracy achieved by other algorithms ranged from 74 to 82.6%. Decision tree analyses revealed that sex, age, smoking status, sudden onset of dysphonia, and 10-item voice handicap index scores were significant characteristics for classification. CONCLUSION: This study demonstrated a significant difference in demographic and symptomatic features between glottic neoplasm, phonotraumatic lesions, and vocal palsy. These features may facilitate automatic classification of voice disorders through machine learning algorithms.

Transcricothyroid Endoscopic Subglottic Surgery for Posterior Glottic Stenosis: A Case Report.

Posterior glottic stenosis (PGS) is a rare but life-threatening condition mostly caused by damage to the interarytenoid mucosa by an endotracheal tube. In surgical treatment of PGS, airway patency is prioritized, and the laryngeal functions involved in swallowing and phonation are considerably sacrificed. In the majority of cases, lateralization of a vocal fold or partial excision of a vocal fold and arytenoid cartilage results in glottal closure insufficiency and deterioration of phonatory function. We present the first report of transcricothyroid endoscopic subglottic surgery to treat a 46-year-old man with PGS who was intubated for 10 days. Postoperative hypofunction was not observed in the aerodynamic examination and acoustic analysis, and phonatory function has been maintained within normal limits.

Conservative management of laryngeal dog bite.

BACKGROUND AND AIMS: Dog bites represent an important public health issue, causing injuries from trivial to fatal. The true incidence is unknown due to the lack of national and local reporting system. School children, mostly male, are more commonly affected with the majority of injuries occurring in the head and neck area, followed by the limbs and trunk. METHODS: The conservative management of a 6-year-old girl who sustained a fracture of her laryngeal structure from an attack by her neighbours' dog is described. Only a 1 cm visible puncture wound in the midline of her neck with air escaping through the wound was seen at presentation. RESULTS: Ten days were spent in hospital including the first four in intubated Paediatric Intensive Care Unit. Initial microlaryngoscopy and bronchoscopy (MLB) showed a swelling in the right anterior subglottis not reducible by manipulation. She was re-intubated with progressively larger naso-tracheal tube until the fracture was fully reduced on her 3rd MLB. Three months post-injury, there is no evidence of airway narrowing. CONCLUSION: The literature advocates early surgical management of laryngeal trauma including dog bites. Conservative management of laryngeal fracture from a dog bite is feasible and associated with a good outcome and no long-term sequela.

Subglottic injury: a clinically relevant animal model.

OBJECTIVES/HYPOTHESIS: To develop a clinically aligned, reproducible model for subglottic injury. STUDY DESIGN: Prospective randomized control pilot study. METHODS: Juvenile (3-month-old) New Zealand White rabbits underwent intubation with a 3-cm length of an endotracheal tube that was chosen so that there would be no air leak below 20 cm of water. This tube was one or two sizes above the appropriate tube for the animal. It was held in situ with a suture placed at the trachea and secured over a button in the neck for a period of 1 week. Animals were sacrificed 1 week postextubation, and larynges were harvested. A range of histological techniques and gross morphology were utilized to examine the injury caused at the level of the subglottis. Unintubated animals constituted controlled specimens. RESULTS: Intubated animals demonstrated considerable histopathology including evidence of ulceration, inflammation, granulation tissue, perichondritis, and chondritis when compared with control animals. Morphometric analysis demonstrated a significant increase in lamina propria thickness (P = .0013), mucosal thickness (P ≤ .0001), and in goblet cell areal density (P = .014). Analysis of mucin types found a significant decrease in acidic (P = .0001) mucin coinciding with a significant increase in mixed mucin types (P = .0013). CONCLUSIONS: Our model provides a reliable and reproducible technique for acute/subacute injury to the subglottis secondary to intubation, which is consistent with previous histological findings of early changes associated with acquired subglottic stenosis (SGS). Future uses of this model could include the examination of current adjunctive therapies and their effects on limiting progression to SGS.

Management and prevention of endotracheal intubation injury in neonates.

PURPOSE OF REVIEW: To summarize the diagnosis, pathology, and management of glottic, subglottic, and tracheal injuries secondary to endotracheal intubation in neonates. RECENT FINDINGS: Published reports of intubation-related injuries include laryngeal stenosis, subglottic stenosis (SGS), tracheal rupture, subglottic cysts, and pharyngoesophageal perforation. Such injuries are multifactorial, with risk factors including patient size and weight, use of cuffed versus uncuffed endotracheal tubes, and fragility of the mucosa. In addition, the skill and awareness of the person performing the intubation may also influence risk of intubation-related injuries. Studies on fetal cricoid anatomy demonstrate differences in the configuration of cricoids lumen between premature infants and the adult larynx. Most recently reported airway injuries due to intubation have history of prematurity as a common risk factor, with increasing incidence associated with decreasing gestational age and weight. Prematurity and prolonged intubations remain the top risk factors for development of subglottic cysts. Management of above-mentioned complications includes endoscopy versus open laryngotracheoplasty for SGS, using balloon or traditional dilatation or augmentation with cartilage grafts, respectively; bridging injured area with endotracheal tube versus open resection and primary closure for tracheal rupture; and use of laser or cold techniques for removal of cysts. SUMMARY: Although intubation-related injuries may occur in anyone, neonates are at increased risk due to their small airway lumen and cricoids cartilage morphology. Endoscopic and open reconstructive techniques increase treatment options to treat glottic and SGS.

A prospective randomized trial comparing supraglottic airways for flexible bronchoscopy in children.

OBJECTIVE: A prospective randomized, controlled trial was conducted comparing supraglottic airways (SGA) for flexible bronchoscopy in 100 children. BACKGROUND: Pediatric flexible bronchoscopy is commonly performed using a SGA as both a ventilation device and a conduit for flexible bronchoscopy. We observed that some disposable SGAs were associated with increased resistance to bronchoscope manipulation compared to the LMA Classic (cLMA). METHODS: We compared the cLMA to the Ambu Aura Once, Portex Soft Seal, Boss Systems disposable silicone laryngeal mask, and LMA Unique. We recorded the subjective resistance of the bronchoscope manipulation within the SGA by linear analog score and measured the time to insert the bronchoscope from the proximal end of the SGA to the right upper lobe. We also scored the view of the larynx through the bronchoscope and measured SGA cuff pressures. RESULTS: Resistance to bronchoscope manipulation during pediatric flexible bronchoscopy was higher using polyvinyl chloride (PVC) disposable SGAs (Ambu, Unique, and Portex) than the silicone re-usable cLMA (P < 0.0001). The Unique and Ambu laryngeal masks were clinically inferior to the cLMA at all levels of the airway (P < 0.0001). The Portex Soft Seal was not different above the larynx but was significantly statistically inferior at (P < 0.04) and below the larynx (P < 0.006) and inferior overall (P < 0.007). Boss Systems single-use laryngeal mask was as effective as the cLMA. CONCLUSION: In this trial, PVC single-use laryngeal masks were inferior to the silicone cLMA and Boss Systems laryngeal masks for flexible bronchoscopy in children.

[Laryngeal and pharyngeal actinomycosis]. / Aktinomykose im Bereich von Pharynx und Larynx.

Cervicofacial actinomycosis is an uncommon infection and in most cases odontogenic in origin. Pharyngeal and/or laryngeal lesions, usually occurring secondary to mucosal trauma, are very rare and may mimic a malignant tumor. In such cases, which represent less than 1% of all cases, the differential diagnosis with upper aerodigestive tract malignancy remains challenging. We report a case of actinomycosis in a 56-year-old male patient who presented with an extensive, centrally necrotic mass in the oropharynx, hypopharynx and larynx region suspected to be a tumor. The lesion was diagnosed 6 months following accidental ingestion of an ear of corn and ultimately proved to be cervicofacial actinomycosis. The clinical and pathological features and current aspects of the diagnosis and treatment of cervicofacial actinomycosis are discussed.

Posterior glottic stenosis with a calcified interarytenoid scar band: CT and laryngoscopic correlation.

A 52-year-old man with burn injuries and prolonged intubation developed PGS with hoarseness, dyspnea, and bilateral vocal cord immobility. On CT, a calcified interarytenoid scar band was identified, corresponding to an interarytenoid scar on laryngoscopy. Endoscopic laser lysis of the calcified scar band relieved the symptoms. We present laryngoscopic and CT findings of PGS with interarytenoid calcification along with the postlysis findings. The classification, clinical findings, imaging, and management of PGS are reviewed.

Acute and chronic changes in the subglottis induced by graded carbon dioxide laser injury in the rabbit airway.

OBJECTIVE: To investigate the repair process following carbon dioxide laser injury to the upper airway mucosa (UAM) during the development of chronic subglottic stenosis (SGS). DESIGN: Animals were assigned to either sham control (cricothyroidotomy only) or injured (cricothyroidotomy and posterior subglottic laser) groups using various carbon dioxide laser exposures (8, 12, and 16 W) for 4 seconds. SUBJECTS: Twenty-four New Zealand white rabbits. INTERVENTIONS: The subglottis was approached via cricothyroidotomy. Sham control airways were immediately closed, whereas injured airways were subjected to graded carbon dioxide laser exposures prior to closure. Airways were endoscopically monitored preoperatively, postoperatively, and on postoperative days 7, 14, 28, 42, 56, 70, and 84. Animals were killed at 14 and 84 days. Subglottic tissue was harvested for histologic evaluation (reepithelialization, extracellular matrix, vascularity, and inflammation). MAIN OUTCOME MEASURES: Endoscopic visualization and histologic analysis. RESULTS: (1) Increases in UAM thickness (up to 5 times the thickness of normal mucosa) were observed but were limited primarily to the lamina propria. The mucosal epithelium regenerated without chronic changes. Focal areas of cartilage repair were encountered acutely after injury and to a greater extent in the chronic phases of repair. (2) Acutely, the thickened lamina propria comprised poorly organized extracellular matrix components and demonstrated increases in blood vessel size and number. (3) Histologic changes present in the acute phase only partially resolved in progression to chronic SGS. Chronic SGS was characterized by thick collagen fiber bundles extending into the remodeled subglottic cartilage. CONCLUSIONS: The carbon dioxide laser induces acute changes to lamina propria architecture and vascularity that persist chronically. Elucidating responsible signaling pathways may facilitate the development of therapeutic agents to prevent or reduce the formation of SGS.

Graded carbon dioxide laser-induced subglottic injury in the rabbit model.

OBJECTIVE: To conduct an endoscopic and histologic analysis of the subglottic effects of various carbon dioxide laser-induced injuries in the rabbit model. DESIGN: Animals were assigned to either a control (cricothyroidotomy only) group or 4 (cricothyroidotomy and posterior subglottic laser) groups that were injured using varying systematically controlled carbon dioxide laser power exposures (5 W, 8 W, and 12 W), with durations of 2 or 4 seconds, and surface area exposures (25% or 40%). SUBJECTS: Twenty-seven New Zealand white rabbits. INTERVENTIONS: The subglottis was approached via cricothyroidotomy. Control airways were immediately closed, while injured airways were subjected to graded carbon dioxide laser exposures prior to closure. Airways were endoscopically monitored preoperatively, immediately postoperatively, and on postoperative days 1, 7, 14, and 21, after which the animals were humanely killed and subglottic tissue harvested for histological evaluation. RESULTS: Clinical observation revealed no significantly obstructive (acute) stenosis during the duration of the study. Endoscopic visualization revealed the formation of posterior subglottic scarring. Histological analysis of the mucosa revealed that use of carbon dioxide laser resulted in a statistically significant (unpaired, 2-tailed t test, P<.05) proportional thickening of the lamina propria layer, without significant changes in the epithelial and cartilaginous layers. In addition, mucosal blood vessel size increased proportional to the power of the laser delivered to the area (P<.05). CONCLUSIONS: Carbon dioxide laser-induced injury to the subglottis caused localized scarring, lamina propria thickening, and increased vascularity, which resolved with time and was not associated with significant airway obstruction. This model describes a systematic, controlled, and reproducible method of investigating subglottic injury.

Elucidating the role of interleukin 1beta and prostaglandin E2 in upper airway mucosal wound healing.

OBJECTIVES: To determine whether (1) inflammatory mediators IL-1beta (interleukin 1beta) and prostaglandin E2 (PGE2) in mucosal secretions correlate with subglottic mucosal injury; and (2) mucosal fibroblasts contribute to PGE2 production during mucosal healing. DESIGN: The subglottic mucosa in rabbits was wounded by means of varied carbon dioxide laser power and duration. Subglottic fibroblasts were exposed to IL-1beta and assayed for production of PGE2. SUBJECTS: Thirty-eight New Zealand white rabbits were used. Fibroblasts from normal and pathologic human subglottic tissues were grown in culture. INTERVENTIONS: Subglottic injury was established in 29 rabbits, and 9 rabbits were sham-wounded. Subglottic mucosal secretions were collected at baseline and days 1, 3, 7, 14, and 21 postoperatively and assayed for IL-1beta and PGE2 by enzyme-linked immunosorbent assay. Tissue was analyzed using quantitative polymerase chain reaction. Fibroblast cultures were exposed to IL-1beta and analyzed for PGE2 and its synthetic enzymes. RESULTS: Subglottic injury was associated with increased levels of IL-1beta and PGE2 in secretions. More extensive mucosal injury resulted in higher PGE2 levels at earlier times. Levels of IL-1beta were maximal after lesser damage. Expression of IL-beta and cyclo-oxygenase 2 was elevated after mucosal injury. Fibroblast treatment with IL-1beta resulted in translocation of nuclear factor kappaB, up-regulation of PGE2 synthetic enzymes, and increased production of endogenous PGE2. CONCLUSIONS: Mucosal injury is associated with up-regulation of inflammatory genes and parallel increases in secretion levels of IL-1beta and PGE2, key mediators of inflammation and healing. Subglottic mucosal fibroblasts are a potential source of inflammatory mediators after injury or other trauma.

Subglottic wound healing in a new rabbit model of acquired subglottic stenosis.

OBJECTIVES: It is difficult to develop models of subglottic stenosis in small animals that ensure reliable stenosis. We therefore sought to establish a new animal model of subglottic stenosis in rabbits and observe subglottic wound healing. METHODS: Using a diode laser under endoscopic visualization after anterior tracheal incision, we induced full-thickness injury to the subglottis in 60 rabbits: 20 on the anterior 120 degrees, 20 on the posterior 120 degrees, and 20 circumferentially. The animals were painlessly sacrificed 2 or 4 weeks later, and their gross and histologic findings were compared with those of each other and with those of 16 age-matched nonwounded controls. RESULTS: Of the 60 animals, 22 died, primarily of acute airway obstruction and mostly in the circumferential group. All of the injured rabbits showed subglottic stenosis compared with controls, ranging from 12% to 56% reduction in cross-sectional area in the 120 degrees injured groups and from 32% to 82% reduction in the 360 degrees injured group. The significant narrowing of the subglottic lumina resulted in substantial early mortality in the circumferential group. Histologic examination showed mucosal ulceration, inflammation, and formation of granulation tissues during the acute phase after wounding, and collapse of the injured cartilage and submucosal thickening and fibrosis at later times. CONCLUSIONS: Subglottic healing and stenosis depend on the extent of cartilaginous injury. This model may be useful for developing methods to treat subglottic stenosis.