Laryngotracheal Stenosis

Etiology

Several etiologies are associated with the development of LTS.[1] Recognized causes of laryngeal stenosis include: iatrogenic (ex, complication of endotracheal intubation), autoimmune, infectious, neoplastic, traumatic, and idiopathic. Autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, vasculitis, sarcoidosis, and scleroderma, among others, can cause LTS. Infectious causes include bacterial tracheitis, viral papillomatosis, and tuberculosis. Neoplasms of the larynx or trachea can also cause airway narrowing, with squamous cell carcinoma and adenoma being the most common malignancies in this setting.[2] Direct injury to the trachea by trauma, inhalation burns, or radiation is 1 of the causes of traumatic LTS.[3]

Acute laryngeal injury has been described as a potential component of post-intensive care syndrome.[4] Common post-intubation complications include transient dysphonia, dysphagia, and sore throat for patients undergoing surgery. However, these complications present more markedly in critically ill patients. Endotracheal tubes can cause laryngeal injury through direct compression of the posterior glottic mucosa, which may eventually progress to fibrosis and scarring, resulting in stenosis.

Epidemiology

There is no clear data on the epidemiology of LTS, as it is difficult to regard this disorder as a single entity given the range of causes. Tracheal stenosis may occur in up to 30% of patients with tracheostomies, though many factors can contribute, depending on the patient's comorbidities, the indication for, and duration of, the tracheotomy.[5]

Pathophysiology

The narrowest part of the adult airway is at the subglottic space at the level of the cricoid cartilage, which extends from the inferior part of the vocal cords to the lower part of the cricoid cartilage.[3] This area is only a few centimeters in length but can be commonly injured during endotracheal intubation, as the endotracheal tube makes contact with the posterior aspect of the subglottic space during intubation. Prolonged intubation can also cause LTS when cuff pressure exceeds mucosal capillary perfusion pressure (approximately 35 mmHg), leading to ischemia, ulceration of the posterior mucosa, and subsequent fibrotic strictures.[6] Among patients with underlying autoimmune diseases, granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) is the most commonly associated with LTS, characterized by necrotizing granulomatous inflammation of the upper airways, with vasculitis perpetuating fibrotic changes and stenosis.[7]

History and Physical

Evaluating a patient with suspected LTS includes a detailed history and physical examination. History should include any prior endotracheal intubations and their durations, a history of infection, autoimmune disease, vasculitis, trauma, or surgery, as well as current symptoms. The most common symptoms of LTS, regardless of etiology, include dyspnea, stridor, hoarseness, and cough. In the acute, emergent setting, a physician may not have sufficient time to obtain such detailed information; in such cases, the physical examination becomes crucial. One must be able to identify inspiratory stridor, which is most commonly neck-based and associated with cough and dyspnea. If the patient has extrathoracic stenosis, they may present with hoarseness, inspiratory wheezing, stridor, and nonproductive cough. Intrathoracic stenosis is evident with difficulty in expiration and lying in the recumbent position. There may be reduced ability to clear secretions, as well as wheezing mimicking asthma that does not respond to bronchodilators.[8] Localization of the stenosis is difficult on clinical grounds alone. 

Evaluation

LTS can be evaluated by laryngoscopy or bronchoscopy. The clinician may obtain a computed tomography scan of the neck in severe cases in which the obstruction does not allow for direct laryngoscopy or in patients who have a traumatic injury to the trachea, and in planning for surgical treatment. Computed tomography scans may demonstrate artificial extratracheal stenosis, such as in a massive goiter, owing to the trachea's dependent position during imaging.[2] Performing spirometry on these patients helps establish a baseline and monitor their status over time.[9]

There are 3 classification systems based on anatomic characteristics that are derived from intraoperative findings. The Cotton-Myer classification is based on percent stenosis (1 = <50% obstruction; 2 = 51% to 70% obstruction; 3 = 71% to 99% obstruction; 4 = Complete obstruction). The Lano classification is based on subsite involvement (1 = 1 subsite involvement; 2 = 2 subsite involvement; 3 = 3 subsite involvement, with the subsite meaning the glottis, subglottis, and trachea). The McCaffrey classification is based on the length of stenosis (1 = subglottis or trachea <1 cm; 2 = subglottis >1 cm; 3 = subglottis and trachea >1 cm; 4 = any lesion involving glottis). Percent stenosis is important with regard to prognosis, individualized treatment planning, and risk stratification of tracheostomy dependence. Patients with grade 3 and 4 stenosis in the Cotton-Myer classification were found to be tracheostomy dependent compared to patients with grade 1 and 2. According to the Lano classification, greater subsite involvement was associated with a higher risk of tracheostomy dependence and a higher stage in the McCaffrey classification. In adult LTS, the Lano and McCaffrey classifications are more precise than the Cotton-Myer scale.[1]

Treatment / Management

Overview

The management of LTS is complex, as it may involve multiple procedures and may be associated with restenosis in certain cases. Treatment goals are to maintain airway patency, reduce the number of procedures required, and achieve decannulation in patients with tracheostomy. Unfortunately, there is no standard guideline for the approach to and management of LTS to date. Most treatment modalities have been described in studies across various specialties in the medical literature. Treatment options for LTS include endoscopic dilatation, surgery, stent placement, laser therapy, or immunosuppression to restore airway patency, depending on the underlying etiology and the degree and complexity of stenosis.[10]

Bronchoscopic Approach

Bronchoscopy may be used for mechanical dilation, laser therapy, and stenting to treat LTS. These treatment modalities may have limited use in subglottic stenosis due to anatomical challenges. Dilation or laser treatment is an option for strictures or granulomas; however, these procedures are at risk of recurrence. Stent placement can migrate and cause a larger airway injury. A laser is used cautiously for subglottic stenosis due to the risk of damaging the cricoid cartilage, which is the site of the laryngeal nerves and plays a role in vocal cord function. Several studies have shown that laser therapy and stenting achieve success rates below 20%.[3] Bronchoscopic therapy has been used in cases where the patient is not a surgical candidate to palliate symptoms. 

Endoscopic Mechanical Dilation 

Endoscopically guided dilation is performed using several devices, including gum-tipped bougies, endotracheal tubes, and balloon catheters. It could be performed in the outpatient setting for a selected group of patients. This route yields more favorable voice-preservation outcomes than stenosis less than 2 cm from the vocal folds or stenosis at multiple levels. Endoscopic dilation should be the first-line treatment for simple stenosis, whereas more complex stenoses require an interprofessional approach and possible surgical evaluation. The average patient may be able to remain free of subsequent dilations for approximately 1 year.[11]

Tracheal Stenting

Tracheal stenting is a palliative option for patients with advanced and unresectable cancer-causing airway obstruction. As noted above, stenting is a challenging and high-risk procedure that requires a risk-benefit discussion with the patient. Higher preoperative performance status correlates with better patient outcomes. A Japanese study by Matsuo et al aimed to clarify indications for stent placement, including severe central airway obstruction with dyspnea and flow limitation on a flow-volume curve, a prognosis that is prolonged by stent placement, and intact peripheral airways and lungs.[12]

Preoperative Assessment

Several preoperative assessments may aid prognostication and the selection of a suitable treatment modality. The patient should be screened for methicillin-resistant Staphylococcus aureus (MRSA) colonization at least 2 to 3 weeks before possible surgery, as MRSA colonization may increase the risk of postoperative complications. If patients test positive for MRSA, they should be treated prophylactically with a 3-day course of double-strength trimethoprim-sulfamethoxazole orally and mupirocin intranasally, and with 14 days of intravenous vancomycin postoperatively until all drains have been removed. Before pursuing further treatment, patients should also undergo a swallowing evaluation using a fiberoptic endoscopic evaluation of swallowing or a modified barium swallow study to determine the optimal route for postoperative nutrition. Fiberoptic endoscopic evaluation of swallowing also assesses vocal fold mobility and the extent of the stricture.[13]

Open Surgery

Open surgery is offered in patients with Myer-Cotton grade 3 or 4, loss of cartilage, or stenosis longer than 1 cm. Open surgery is an option in cases with hard tissue and scar tissue greater than 1cm in length. Surgical cases have higher success rates, whereas endoscopic procedures require more repeat interventions. Open surgery may be divided into laryngotracheal resection with reanastomosis or laryngotracheoplasty using native tissue or tissue grafts.[13]

Laryngotracheal resection with reanastomosis 

A systematic review by Lewis et al found that laryngotracheal resection with anastomosis was associated with a lower need for additional surgeries and a higher rate of decannulation than endoscopic procedures. They also found that patients with idiopathic stenosis required less additional surgery compared to patients with LTS due to trauma or intubation.[14](A1)

Laryngotracheoplasty

Laryngotracheoplasty encompasses surgical techniques that employ single- or multistage approaches, using various luminal grafts or tracheal stents.[15] Outcomes are typically favorable, with a high rate of decannulation. They also have low postoperative complications, which include granulation tissue and glottic edema. They may be treated with a short course of dexamethasone for 24 to 48 hours, along with diuresis and elevation of the head of the bed.[16][17](B2)

Montgomery T-Tube 

The Montgomery T-tube is placed through the trachea’s anterior wall distal to the anastomosis. It provides a stable airway for prolonged periods (at least 6 months) until the consideration of decannulation, or permanently in inoperable cases.[2][9][18](B3)

Adjunctive Treatments

Several adjunctive treatment options are currently used for the treatment of LTS. A review of the literature suggests the use of adjunctive treatments such as mitomycin C, steroids, and proton pump inhibitors. 

Mitomycin C

Mitomycin C is a chemotherapeutic agent used topically for 4 minutes after incision. It works as an alkylating agent that inhibits cell division, protein synthesis, and fibroblast proliferation, ultimately decreasing the formation of scar tissue. It has been reported that this may be a therapeutic option for thinner stenoses; however, restenosis may occur at similar rates at 5 years with or without reapplication.[19] (B2)

Steroids

For patients undergoing dilation, local or systemic corticosteroids administered orally have favorable evidence in current data, with greater success noted in stenoses greater than 1 cm.[20][21]

Differential Diagnosis

Some differential diagnoses that must be considered in the evaluation of LTS include the following:

• Angioedema
• Asthma
• Epiglottitis
• Esophageal tumor
• Foreign body aspiration
• Gastroesophageal reflux disease
• Mediastinal mass
• Retrosternal goiter
• Subglottic web
• Tracheomalacia
• Vocal cord dysfunction [22]

Prognosis

Overall prognosis is excellent for patients with idiopathic LTS who undergo definitive surgery. Prognosis in other etiologies is determined by the clinical course of the underlying disease that causes LTS.

Complications

Acute LTS (eg, post-extubation LTS) may result in respiratory arrest if not promptly and correctly identified. In idiopathic LTS, complications include changes in voice, tracheostomy dependence without the ability to decannulate, and the requirement for multiple procedures. Tracheostomy decannulation is a target goal of open surgery. Approximately 63-95% of patients who undergo open surgery are successfully decannulated. However, patients with grade 3 or 4 stenosis (Myer-Cotton scale), diabetes, gastroesophageal reflux disease, and/or body mass index greater than 30 may have higher rates of tracheostomy dependence. 

Additionally, open surgery may be complicated by dysphagia due to injury to the recurrent laryngeal nerves or the use of a stent to maintain airway patency.[9] A prospective study by Bibas et al in the Journal of Thoracic Disease found that quality of life in patients with benign tracheal stenosis (eg, endotracheal intubation, not amenable to surgical treatment) is severely impaired.[23] Health-related quality of life entails the physical and mental welfare of the patient and their family. This study included patients with Montgomery T-tubes, endotracheal silicone stents or tracheostomy, and the ability to fill out a questionnaire. They excluded patients with chronic comorbidities, such as chronic obstructive pulmonary disease, advanced heart failure, and renal failure.