Presentation and diagnostic evaluation of non-life-threatening and nonmalignant subglottic and tracheal stenosis in adults

INTRODUCTION — Subglottic stenosis and tracheal stenosis (TS) are broad terms that describe a stricture or narrowing of the subglottic and tracheal lumen, respectively. Subglottic stenosis and TS can be due to a diverse group of malignant or nonmalignant conditions and can cause significant morbidity and mortality.

This review will focus on the presentation and evaluation of non-life-threatening stenosis from the subglottis to the main carina caused by nonmalignant disorders in adults. Management of stenosis due to nonmalignant etiologies, including tracheomalacia, and management of central airway obstruction due to malignant etiologies are discussed separately. (See "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults" and "Tracheomalacia in adults: Clinical features and diagnostic evaluation" and "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults".)

ANATOMY, TERMINOLOGY, AND SCOPE

Normal anatomy and tracheal dimensions

●Trachea – The trachea extends from the subglottic region of the larynx through to the bifurcation of the right and left mainstem bronchi (figure 1 and figure 2).

●Subglottis – The subglottis is a region of the larynx directly above the trachea that contains no cartilage rings and connects the trachea with the vocal cords.

●Glottis – The glottis is the part of the larynx that contains the vocal cords.

●Supraglottis – The supraglottis is the region of the larynx above the glottis that connects with the tongue.

The length and diameter of the trachea is roughly proportional to the size of the individual. The adult trachea averages 11.8 cm in length (range 10 to 13 cm). Males generally have a trachea of larger diameter than females (approximately 2.3 cm coronally and 1.8 cm sagittally in males; 2.0 cm coronally and 1.4 cm sagittally in females). The shape of the adult trachea varies, most being nearly circular, others ovoid, or less commonly, triangular.

There are typically 18 to 22 cartilaginous rings within the trachea (two rings per cm, each approximately 4 mm in height) [1]. Tracheal rings encircle the trachea anteriorly and laterally while the posterior trachea lacks cartilage. The only complete cartilaginous ring in the normal airway is the cricoid cartilage, which is the narrowest point in the upper airway just below the glottis.

Terminology — For clarity, we use the following terms:

●Laryngeal and laryngotracheal stenosis – Laryngeal stenosis involves the larynx only while laryngotracheal stenosis describes abnormal narrowing of the airway involving both the larynx and trachea. The latter may include the supraglottic region of the larynx (ie, above the vocal cords including the epiglottis), the glottic region of the larynx (ie, at the level of the vocal cords), and the subglottic region of the larynx (ie, below the vocal cords) that connects to the trachea (figure 2).

●Tracheal stenosis – TS is an abnormal narrowing of the tracheal lumen below the lower limits of normal. Normal tracheal anatomy and dimensions are discussed separately. (See 'Normal anatomy and tracheal dimensions' above.)

●Tracheobronchial and bronchial stenosis – Tracheobronchial stenosis is abnormal narrowing that involves the trachea and the bronchus while bronchial stenosis involves the bronchus only (figure 1).

Scope of topic — For the purposes of this review, we will focus on the diagnostic evaluation of nonmalignant stenosis of the subglottis and trachea to the level of the main carina. We will not be discussing glottic or supraglottic stenosis or tracheal narrowing due to tracheomalacia or impacted mucus or thrombus. (See "Tracheomalacia in adults: Clinical features and diagnostic evaluation".)

The evaluation of bronchial stenosis will not be discussed, but the etiologies and principles of evaluation are somewhat similar to those that affect the subglottis and trachea. Management may be similar if the stenosis is proximal, but unlike TS, many distal bronchial lesions cannot be treated with local bronchoscopic therapy. (See "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults".)

CLINICAL FEATURES OF STENOSIS — The symptoms of subglottic stenosis and TS are variable depending on the etiology, the time course of stenosis onset, and the degree of airway narrowing.

●Manifestations of stenosis – Patients with TS present similarly to those with other forms of central airway obstruction. This ranges from no symptoms to dyspnea, wheeze, stridor, cough, sputum, and hemoptysis. Other symptoms that may suggest laryngeal involvement include dysphonia, dysphagia, odynophagia, tenderness of the throat, pain on coughing or speaking, and difficulty clearing secretions.

The absence of symptoms usually indicates mild obstruction (eg, stenosis found incidentally during intubation or on imaging) while the presence of symptoms usually indicates moderate to severe airflow limitation (eg, when tracheal lumen is <8 mm in diameter or >50 percent luminal narrowing).

Patients are frequently misdiagnosed as having asthma or chronic obstructive pulmonary disease and often treated as such without improvement.

These symptoms are discussed in greater detail separately. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Clinical presentation'.)

●Manifestations of the underlying disorder – Patients may also have signs and symptoms due to an underlying disorder, which is important when trying to distinguish the etiology of the stenosis (table 1). Further details are provided below. (See 'Evaluating the etiology' below.)

INITIAL DIAGNOSTIC TESTING — In most patients with suspected non-life-threatening, nonmalignant subglottic stenosis or TS, we perform chest and neck computed tomography (CT), using a dedicated airway protocol. We also perform pulmonary function testing (PFT), if feasible; flow volume loops (FVLs) are particularly useful.

Patients with life-threating airway stenosis should have their airway stabilized first before undergoing imaging and PFTs. Further details regarding evaluation and management of life-threating stenosis are provided separately. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Life-threatening central airway obstruction'.)

Imaging — CT is our preferred modality when subglottic stenosis or TS is suspected.

Chest radiograph — While the chest radiograph may provide clues to the presence of subglottic stenosis or TS, it is limited in the diagnosis of TS (image 1 and image 2). Narrowing of the tracheal air column can be difficult to appreciate in the subglottic area as the air column typically narrows in this region on standard chest radiography. Depending on the location of the stenosis, the lateral film may offer significant information above the standard posteroanterior or anteroposterior view. The chest radiograph may also provide clues to the underlying etiology. (See 'Evaluating the etiology' below.)

Neck and chest computed tomography — For patients in whom subglottic stenosis or TS is suspected, many centers also have 'airway protocol' imaging that can generate internal (ie, virtual bronchoscopic) and external images of the airway. We perform volumetric neck and chest CT with cross-sectional, multiplanar and three-dimensional reconstructions, before bronchoscopic assessment. The thinner the slice thickness the better the resolution of the CT image and the ability to optimally assess the severity and extent of TS. We routinely reformat the images of the CT of the trachea using a slice thickness of 1 mm and increments of 1 mm. While the sensitivity and specificity of CT have not been formally studied, in our experience, CT is a sensitive tool for the detection of stenosis and even mild cases are rarely missed.

CT imaging provides detailed assessment of the location, length, shape, and severity of the stenosis (image 1 and image 3) and also provides a baseline for following treatment response. (See "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults".)

CT may also provide clues as to the etiology of the stenosis. (See 'Evaluating the etiology' below.)

Other — Other advanced diagnostic imaging techniques have been used in conjunction with bronchoscopy including radial probe endobronchial ultrasound and optical coherence tomography [2]. While these technologies can provide in depth imaging of the airway mucosa and underlying soft tissue and cartilaginous layers, they are not widely available and thus not routinely used for assessment of tracheobronchial stenosis.

Magnetic resonance imaging is not typically used diagnostically but may be used for treatment planning. (See "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults".)

Pulmonary function tests — In patients with suspected subglottic stenosis or TS, we perform PFTs with FVL tracings. FVL is the better tool since spirometry does not clearly correlate with stenosis severity.

PFT findings vary. While in some patients PFTs are normal (eg, mild or asymptomatic disease), others have a nonspecific reduction in spirometric volumes or evidence on the FVL to support subglottic or tracheal obstruction.

Further detailed description of what may be appreciated on PFTs in patients with subglottic stenosis or TS is provided separately. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Pulmonary function tests' and "Flow-volume loops".)

Laboratory — There are no specific laboratory findings associated with subglottic stenosis or TS. However, the patient may have laboratory evidence of an underlying disorder. (See 'Evaluating the etiology' below.)

BRONCHOSCOPIC EVALUATION

Direct visualization — In most patients with suspected subglottic stenosis or TS, we perform visual inspection of the laryngotracheobronchial tree, typically with bronchoscopy. Direct visualization is the gold standard for confirming and characterizing the presence of airway obstruction and also aids in discerning its underlying etiology (image 4 and image 5 and image 6). Noteworthy, is that initial diagnostic bronchoscopy may be combined with therapeutic bronchoscopy (eg, balloon dilation), particularly if severe stenosis is suspected and confirmed. (See "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults".)

●For those with suspected laryngotracheal or tracheobronchial stenosis, we perform bronchoscopy, typically flexible bronchoscopy. However, rigid bronchoscopy may be needed in cases of severe central airway stenosis for emergent procedures with a critically narrowed airway. Bronchoscopy also has the advantage of detecting additional stenoses at distal regions of the tracheobronchial tree. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Airway management' and "Flexible bronchoscopy in adults: Overview".)

●For those in whom supraglottic or glottic involvement (figure 2) is suspected, most ear, nose, and throat specialists perform video laryngoscopy. However, bronchoscopy may be needed in addition to laryngoscopy if visualization of the lower respiratory tract is needed. Supraglottic and glottic stenosis is beyond the scope of this review and will not be discussed.

Initial bronchoscopy (or laryngoscopy) may be performed with moderate sedation or general anesthesia depending on the degree of the stenosis, understanding that in patients with severe stenosis, critical central airway obstruction can be precipitated by the procedure. As such, these procedures are best performed by teams equipped to manage complex airways. (See "Approach to the difficult airway in adults for emergency medicine and critical care" and "Management of the difficult airway for general anesthesia in adults" and "Airway management in the adult with direct airway trauma for emergency medicine and critical care".)

Decision to biopsy or culture sampling — Not every patient requires a biopsy or samples for culture (eg, patients with tracheal narrowing due to thermal injury, vascular ring, or extrinsic compression from a goiter), but some do require one. In general, we obtain tissue when a tissue diagnosis is essential or needs exclusion (eg, sarcoidosis, cancer). Patients with suspected infectious etiologies should have bronchial washes sent for routine bacterial, fungal, and mycobacterial culture. To assist in deciding whether a biopsy or sampling for culture is needed during the procedure, prior to bronchoscopy we rereview the history, examination, and CT findings to generate a provisional diagnosis for the underlying etiology. (See 'Evaluating the etiology' below.)

While forceps biopsy is usually sufficient for the diagnosis of visible endobronchial lesions, endobronchial ultrasound-guided biopsy may be indicated for the diagnosis of extrinsic masses (eg, lymphadenopathy or tumors) causing compression of the airway. Since most cases are trauma-related, routine biopsy has a low yield, but in those with a specific suspected pathologic etiology, biopsy may have a higher yield (eg, sarcoidosis). In general, despite biopsy, in most cases it shows nonspecific inflammation. (See "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Bronchoscopy' and "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Bronchoscopic evaluation'.)

DIAGNOSIS AND CHARACTERIZATION OF STENOSIS

Diagnosis — The diagnosis of subglottic stenosis or TS is typically suggested by CT and confirmed by direct visualization of the stenotic lesion(s) by bronchoscopy or laryngoscopy. (See 'Neck and chest computed tomography' above and 'Laboratory' above and 'Bronchoscopic evaluation' above.)

Characterization — Characterization of the stenotic lesion facilitates both the diagnosis of a possible underlying etiology and therapeutic decision-making. (See 'Evaluating the etiology' below and "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults".)

There are several approaches to describing and classifying benign stenoses of the subglottis and trachea (table 2) [3-8]. We suggest that both bronchoscopy and CT be used for full characterization using the following descriptors:

●An indication of whether the stenosis is simple or complex (eg, isolated short-segment lesion versus long multilevel lesion)

●Location

●Approximate length

●Relation to other structures (eg, distance from vocal cords, cricoid cartilage, and main carina)

●Degree of obstruction (mostly done by gestalt [relative to the size of the bronchoscope or other instruments, such as balloon diameter] or by CT)

●Mucosal appearance (eg, ulcerated, smooth, irregular)

EVALUATING THE ETIOLOGY — Most of the etiologies associated with nonmalignant subglottic stenosis or TS are distinguished from each other by a combination of history and examination, laboratory and imaging findings, direct visualization on bronchoscopy, and/or tissue biopsy and microbiologic culture (table 1). (See 'Specific etiologies' below.)

Re-review history, examination, and imaging — Once the diagnosis of subglottic stenosis or TS has been made, the focus of the evaluation is on determining the etiology. For some patients, the etiology may be apparent (eg, smoke inhalation, recent extubation, known underlying inflammatory disorder) (see 'Patients with obvious etiologies' below). While for others, the etiology may be unclear. (See 'Patients with more subtle findings' below.)

●History – We inquire about a past history of intubation or tracheostomy, radiation, history of blunt or direct trauma to the chest, history of inhalation injury or thermal injury or therapy (eg, electrocautery), and known diagnoses that may increase the risk of TS (eg, sarcoidosis, connective tissue disorder [CTD], old foreign body aspiration, gastroesophageal reflux). We also inquire about systemic symptoms that might suggest a vasculitis or CTD (eg, joint pain, fever, ear, nose and throat symptoms, renal symptoms, asthma, rashes, change in bowel habit). We also ask about a history of old tuberculous or fungal disease as well as travel to or previous residency in areas endemic for such infections. We take a medication history that may support infectious tracheitis in states of immunosuppression. Although Mendelian inheritance has not been described, we also enquire about other family relatives that may have had stenosis since some cases of idiopathic subglottic stenosis have described a familial preponderance [9,10]. Patients with a history of lung transplantation are more likely to have bronchial stenosis than TS.

●Examination – On examination we look for evidence of fever, arthritis, rash (eg, flexural papillomas, pemphigoid), scars (eg, to suggest an old tracheostomy), mucosal ulcers, radiation marks (to suggest upper tracheal fibrosis), tenderness over the cricoid cartilage (to detect cricoarytenoid joint disease in rheumatoid arthritis [RA]), an enlarged thyroid or lymph nodes, and deformities of the auricular or nasal cartilage.

●Supportive data – In some cases, imaging, laboratory, and bronchoscopy findings help narrow the differential to suggest certain diagnoses. As examples:

•Long segment narrowing is more likely to be found in patients with relapsing polychondritis and tracheobronchopathia osteochondroplastica (TPO) (image 7 and image 8 and image 9) while short segment narrowing is more likely in patients with stenosis due to intubation or tracheostomy (image 1), amyloidosis, inflammatory disorders, and thermal injury. (See "Radiology of the trachea", section on 'Tracheal narrowing'.)

•Imaging findings of an underlying disorder may support that disorder as a potential etiology. Bilateral hilar lymphadenopathy may suggest sarcoidosis, inflammatory nodules or parenchymal fibrosis may support inflammatory or vascular disorders, mediastinal fibrosis or hepatosplenic calcification may suggest old Histoplasma infection, or cavities may suggest tuberculous or fungal disease. Classic findings of mediastinal fibrosis, broncholiths, radiation scarring, and vascular rings may be evident on CT to support these etiologies as the cause of the stenosis.

•Basic laboratories may support the presence of an underlying disorder, such as acute infection (eg, elevated white cell count with left shift may suggest bacterial tracheitis), or an underlying inflammatory disorder (eg, markedly elevated erythrocyte sedimentation rate or c-reactive protein). These laboratories may prompt further diagnostic testing, such as serology for a connective tissue disorder.

•Most findings on bronchoscopy are nonspecific but may confirm the clinical suspicion for a select etiology (eg, erythematous airways may suggest thermal or infectious etiologies, papules may suggest papillomatosis, calcium deposits may support broncholiths or TPO, foreign body may be evident).

A provisional diagnosis may be possible at this point (see 'Patients with obvious etiologies' below). However, in some patients, tissue biopsy and/or culture of tissue or washings are needed to confirm the etiologic diagnosis and rule out more serious pathologies (usually malignancy), so that appropriate therapy can be administered (see 'Patients with more subtle findings' below). Some patients may have no etiology. (See 'Idiopathic subglottic stenosis' below.)

Patients with obvious etiologies — For many patients, the etiology may be obvious. As examples:

●Patients with TS who have been recently extubated or decannulated. (See 'Traumatic' below.)

●Patients with recent direct, blunt, chemical, or thermal trauma. (See 'Traumatic' below.)

●Patients with classic CT findings of TPO (particularly males). (See 'Tracheobronchopathia osteochondroplastica' below.)

In such scenarios, biopsy is not typically necessary to establish the etiologic diagnosis unless another etiology is suspected or needs exclusion (eg, malignancy, sarcoidosis).

Patients with more subtle findings — For some patients with subglottic stenosis or TS, the etiology may be less readily apparent and require clinical judgement, microbiologic, or pathologic analysis before a diagnosis can be rendered. As examples:

●Some patients may have a more remote history of trauma or inhalation injury and symptoms only come to light when another issue arises (eg, pneumonia, pulmonary edema, stenosis ulceration or trauma during intubation). (See 'Traumatic' below.)

●Some patients may have inflammatory tracheitis as the initial presentation of an unknown underlying disease (eg, granulomatosis with polyangiitis [GPA]). These patients may or may not have additional clues in their presentation, such as chronic onset of symptoms, rash, joint pain, laboratory evidence of renal disease or inflammation (eg, elevated erythrocyte sedimentation rate, c-reactive protein), or radiologic evidence of lung or mediastinal involvement (eg, bilateral hilar lymphadenopathy to suggest sarcoidosis). In such cases, we perform tissue biopsy to look for specific etiologies, although biopsy material often shows nonspecific inflammation only. (See 'Inflammatory/systemic conditions' below.)

●Patients with or without a known infectious disorder may present with infectious tracheitis. Such patients may have acute onset symptoms and fever, have risk factors for or laboratory evidence of infection, have generalized thickening of the tracheal wall of CT and friable mucosa or pseudomembranes on bronchoscopy. However, culture of tracheal washings and, in most cases, tissue biopsy are generally needed to distinguish these etiologies. This is particularly important when tuberculous (TB) is suspected or needs to be excluded. (See 'Inflammatory/systemic conditions' below and 'Infectious' below and 'Pseudomembranous tracheobronchitis' below.)

●Subglottic stenosis or TS in a patient with no obvious or known underlying disorder may be idiopathic (eg, a woman with subglottic stenosis). However, several etiologies need to be excluded by tissue biopsy and serology before labeling the stenosis as idiopathic. (See 'Idiopathic subglottic stenosis' below.)

Specific etiologies — There are several specific etiologies that can cause subglottic and tracheal stenoses. These causes and important clinical, CT, and bronchoscopic or laryngoscopic findings are described in the table (table 1).

Traumatic — Trauma-related subglottic stenosis or TS may be classified as internal, external, or inhalational.

●Internal trauma - Subglottic stenosis or TS can be due to the following:

•Postintubation tracheal stenosis (PITS) and posttracheostomy stenosis (PTTS) – PITS and PTTS are the most common forms of stenosis in adults and are most often due to pressure induced necrosis from the endotracheal or tracheostomy cuff or tube (image 1) [11]. However, the incidence is decreasing due to the increased use of more compliant cuffs [12-15] and routine maintenance of cuff pressures below 30 mmHg [16]. Further discussion of cuff maintenance, PITS and PTTS are provided separately. (See "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients", section on 'Maintain optimal cuff pressure' and "Complications of the endotracheal tube following initial placement: Prevention and management in adult intensive care unit patients", section on 'Laryngotracheal stenosis' and "Tracheostomy: Postoperative care, maintenance, and complications in adults", section on 'Tracheal and stoma stenosis'.)

•Healing from tracheal laceration – Tracheal laceration can occur from mechanical injury such as that occurring during intubation or tracheostomy tube placement, but this type of injury rarely results in stenosis.

Although stenosis at the anastomotic site post-lung transplantation is the most common airway complication following lung transplantation, it is almost always bronchial stenosis; TS is rare except in the setting of heart-lung transplant or lung transplant with bronchial artery revascularization. Further details are provided separately. (See "Airway complications after lung transplantation", section on 'Bronchial stenosis'.)

●External trauma – Subglottic stenosis or TS can be due to blunt trauma (direct or indirect compression, strangulation, shearing from sudden flexion, extension or deceleration injuries) or penetrating trauma (eg, stab or gunshot wounds). Presentation is typically acute (eg, airway hematoma). These types of traumatic injuries may be associated with high mortality if not intervened upon in an expedited fashion. However, healing from such injuries may result in chronic symptoms from the development of fibrotic scar.

Evaluation and management of airway trauma are beyond the scope of this review and are discussed separately. (See "Identification and management of tracheobronchial injuries due to blunt or penetrating trauma" and "Airway management in the adult with direct airway trauma for emergency medicine and critical care".)

●Inhalation and thermal injury – Inhalation injuries that can cause stenosis include the following:

•Airway exposure to thermal injury (eg, hot gases, steam, particulate matter in smoke [17], thermal ablation [18]) or chemical injury (eg, aldehydes, ammonia, sulfur mustard gas, hydrochloric acid, and particulate matter [19]) may induce an acute exaggerated necrotizing process with or without pseudomembrane formation, causing severe tracheobronchitis with airway narrowing. Inhalation injury can also arise with the ingestion of caustic substances that injure the epiglottis and vocal cords or when there is an abnormal communication between the trachea and upper esophagus (eg, fistula or severe necrosis). (See "Caustic esophageal injury in adults" and "Inhalation injury from heat, smoke, or chemical irritants".)

The intensity of the damage varies depending on the degree and the type of exposure. Initially acute tracheobronchial inflammation results in mucosal edema and sloughing, which can cause significant airway narrowing. If there is destruction of the basal cell layer, granulation tissue formation, cicatrization, and fibrotic stenosis may follow as a late complication. Another late complication includes the formation of bronchial polyposis, generally two to six months after the acute injury, and can further lead to airway obstruction as well as hemoptysis [20,21].

•Subacute or chronic airway stenosis can also be a complication of airway foreign body aspiration (FBA). Aspiration in pill form of iron tablets, aspirin, alendronate, nortriptyline, pomegranate supplements, and potassium chloride are more likely than other aspirated foreign bodies to cause severe airway inflammation and ulceration that leads to stenosis [22-24]. While stenosis is most likely to occur in the mainstem or distal bronchi than trachea, stenosis of the subglottis has been reported in rare cases [24]. Clinical features and management of FBA are provided separately. (See "Airway foreign bodies in adults".)

Inflammatory/systemic conditions

●Vasculitides – Microscopic polyangiitis (MPA) and GPA (formerly Wegener granulomatosis) are systemic inflammatory disorders that can affect the upper respiratory tract and cause stenosis in some patients [25,26]. Stenosis can occur as the initial or only presentation of the disorder or in association with systemic disease (image 10). Clinical features and diagnosis of MPA and GPA are provided separately. (See "Granulomatosis with polyangiitis and microscopic polyangiitis: Respiratory tract involvement", section on 'Tracheobronchial disease' and "Granulomatosis with polyangiitis and microscopic polyangiitis: Respiratory tract involvement", section on 'Diagnosis'.)

Although eosinophilic GPA (EGPA; formerly Churg-Strauss) has lung manifestations, EGPA rarely involves the laryngotracheal space to cause stenosis [27,28]. Clinical features and diagnosis of EGPA are provided separately. (See "Clinical features and diagnosis of eosinophilic granulomatosis with polyangiitis (Churg-Strauss)".)

Pulmonary involvement including bronchial stenosis is rare in Behçet syndrome [29]. (See "Clinical manifestations and diagnosis of Behçet syndrome".)

●Rheumatoid arthritis – In patients with RA, the majority of upper airway stenoses are caused by subluxation of cartilage and/or superimposed airway edema due to cricoarytenoid arthritis [30,31]. Care is warranted performing bronchoscopy if cervical spine instability is an issue; airway management by an expert is prudent. (See "Clinical manifestations of rheumatoid arthritis", section on 'Cricoarytenoid joint' and "Overview of pleuropulmonary diseases associated with rheumatoid arthritis", section on 'Upper airway obstruction'.)

Less commonly, rheumatoid nodules can affect the vocal cords or recurrent laryngeal nerve, leading to vocal cord dysfunction/paralysis. (See "Inducible laryngeal obstruction (paradoxical vocal fold motion)".)

Rare case reports describe laryngotracheal stenosis from amyloidosis due to long standing RA. (See "Causes and diagnosis of AA amyloidosis and relation to rheumatic diseases", section on 'Rheumatoid arthritis'.)

●Sarcoidosis – Significant tracheal obstruction in sarcoidosis is very uncommon. Airway obstruction can result from massive enlargement of mediastinal and hilar lymph nodes causing extrinsic compression and distortion of the trachea or from granulomatous inflammation within the walls of the trachea, bronchi, and larynx (supraglottis more than the subglottis), or rarely from vocal cord or tracheostomy stomal involvement [32-38]. Sarcoidosis can be associated with multiple stenotic sites [39]. Clinical features and diagnosis of sarcoidosis are provided separately. (See "Overview of extrapulmonary manifestations of sarcoidosis", section on 'Upper respiratory tract' and "Clinical manifestations and diagnosis of sarcoidosis".)

●Relapsing polychondritis – Relapsing polychondritis is an immune-mediated condition associated with inflammation in cartilaginous structures including those of the upper airway that can range from mild anterior stenosis to severe, complex, multifocal laryngotracheobronchial stenosis (image 11), which is associated with a high mortality [26,40-44]. Clinical features and diagnosis are provided separately. (See "Clinical manifestations of relapsing polychondritis", section on 'Large airway involvement' and "Diagnostic evaluation of relapsing polychondritis".)

●Inflammatory bowel disease – While inflammatory bowel disease (IBD) is associated with inflammation of the subglottis, trachea, bronchi, and bronchioles, stenosis is an uncommon finding [45]. The pathophysiologic mechanism of IBD airway involvement remains unclear. Biopsies of involved areas have shown extensive lymphoplasmacytic inflammation [46,47]. (See "Pulmonary complications of inflammatory bowel disease", section on 'Airway involvement' and "Clinical manifestations, diagnosis, and prognosis of ulcerative colitis in adults", section on 'Diagnosis'.)

●Immunoglobulin G4-related disease – Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated fibroinflammatory condition capable of affecting multiple organs [48,49]. Sclerosing mediastinitis, mediastinal adenopathy, or hilar adenopathy have been described in patients with IgG4-RD and may lead to airway narrowing from lymph node enlargement or mediastinal fibrosis with airway entrapment [50,51]. However, tracheobronchial stenosis has also been described in cases without lymph node enlargement (image 12) [52,53]. Clinical features and diagnosis of IgG4-RD are provided separately. (See "Clinical manifestations and diagnosis of IgG4-related disease", section on 'Clinical features'.)

●Systemic lupus erythematosus – Subglottic stenosis or TS as a direct manifestation of patients with systemic lupus erythematosus (SLE), is rare with only a few reports, mainly occurring in the subglottic region [54]. Histopathology generally shows inflammation with variable vasculitic features and occasional necrosis. Clinical features and diagnosis of SLE are provided separately. (See "Pulmonary manifestations of systemic lupus erythematosus in adults" and "Clinical manifestations and diagnosis of systemic lupus erythematosus in adults".)

Infectious

●Tuberculosis – Worldwide, TB is one of the most common causes of TS.

TB lesions are more likely to be observed in the main and upper bronchi, but the lower trachea is involved in 5 percent of patients and the larynx is involved in less than 1 percent (the latter may be more common in smokers) [55,56]. As TB heals, cicatricial stenosis may occur, despite adequate treatment [57]. Typically, fibrosis results in circumferential and submucosal involvement, leaving the airway extremely narrowed. TS can also occur from extrinsic compression or invasion by infected lymph nodes.

Further details regarding clinical manifestations and diagnosis of endobronchial TB are provided separately. (See "Pulmonary tuberculosis: Clinical manifestations and complications", section on 'Endobronchial tuberculosis' and "Diagnosis of pulmonary tuberculosis in adults".)

●Fungal – Tracheobronchitis is typically a rare presentation of fungal infection but has been described with numerous fungal species, most commonly Aspergillus and Histoplasma but also Coccidioides, Zygomycetes, Candida, and Cryptococcus [58].

•In patients with Aspergillus, stenosis may be due to tracheal narrowing from active infection (direct infection of the trachea with or without the development of pseudomembranes or mucus plugs) or from fibrosis due to old healed infection [59,60]. (See "Epidemiology and clinical manifestations of invasive aspergillosis", section on 'Tracheobronchitis' and "Diagnosis of invasive aspergillosis".)

•In patients with Histoplasma, stenosis can also be due to the same mechanisms but more commonly is due to airway compression from involved lymph nodes, fibrosing mediastinitis (as a later manifestation of Histoplasma infection), or rarely broncholithiasis [58,61,62]. Clinical features and diagnosis of Histoplasma and fibrosing mediastinitis are provided separately (See "Diagnosis and treatment of pulmonary histoplasmosis", section on 'Diagnosis' and "Mediastinal granuloma and fibrosing mediastinitis" and "Pathogenesis and clinical features of pulmonary histoplasmosis", section on 'Broncholithiasis' and "Diagnosis and treatment of pulmonary histoplasmosis".)

●Viral – While airway stenosis is a rare manifestation of viral infection, Herpes simplex virus (HSV), and less commonly, cytomegalovirus (CMV), and respiratory syncytial virus (RSV) have been reported to cause airway narrowing with endobronchial abnormalities, including pseudomembranous tracheitis [63-65]. Severe infection may heal with scar resulting in a fibrotic lesion.

Recurrent respiratory papillomatosis (RRP) is a condition that is more commonly encountered in childhood, where benign tumors (papillomas) develop or spread in the tracheobronchial tree. Most commonly, RRP is caused by human papillomavirus (HPV) types 6 and 11, however, other subtypes can be implicated [66]. Suspected cases should be biopsied and cultured to identify HPV and its subtypes and to exclude or confirm malignant conversion. (See "Common causes of hoarseness in children", section on 'Papillomatosis'.)

●Bacterial – Bacterial stenosis is also unusual but can occur with organisms including Corynebacterium species, Staphylococcus aureus, Mycoplasma pneumoniae, Haemophilus influenza, and Chlamydia pneumoniae. Those at risk include patients who are intubated or undergo tracheostomy or tracheal surgery.

Pseudomembranous tracheobronchitis — Pseudomembranous tracheobronchitis is a condition where inflammatory material is admixed with fibrin deposit in a layering fashion along the airway wall (image 4). Depending on the degree of pseudomembrane formation, the tracheobronchial tree can be narrowed or obstructed entirely.

Numerous infectious and noninfectious etiologies have been described in association with pseudomembrane formation. Organisms including Corynebacterium, Mycobacterium, Staphylococcus aureus, Mycoplasma, Haemophilus, Aspergillus, CMV, HSV, and RSV have been associated with production of pseudomembranes [67-73]. Noninfectious etiologies include pressure-induced pseudomembrane formation from GPA, endotracheal intubation [74,75] or from chemical or inhalational injury. (See 'Traumatic' above.)

Tracheobronchopathia osteochondroplastica — TPO is a benign disorder of unclear etiology where submucosal nodules containing cartilaginous, osseous, and mineralized acellular protein protrude into the airway lumen [76]. TPO classically affects the lower two-thirds of the trachea and rarely the proximal portions of the primary bronchi but spares the posterior tracheal wall [77]. There is a male predominance. Severe stenosis is, however, unusual and it frequently presents as an incidental radiological finding with long segment narrowing (image 9). Although the diagnosis can be made radiologically, we typically perform bronchoscopy to confirm the classic sparing of the posterior wall and biopsy to exclude other serious pathologies. Histologically, it is characterized by osseous and cartilaginous submucosal nodules connected to tracheal cartilage. (See "Radiology of the trachea", section on 'Tracheobronchopathia osteochondroplastica'.)

Nonmalignant tumors — Several nonmalignant tumors can cause tracheal lumen narrowing without necessarily being associated with circumferential stenosis. This includes obstruction due to hamartoma, lipoma, hemangioma, leiomyoma, schwannomas (image 2), and fibroepithelial polyposis.

Depending upon the etiology, the presentation varies and may also include hemoptysis if the lesion is highly vascular (eg, hemangioma) or ulcerated. CT may reveal a tracheal mass, and bronchoscopy findings vary depending on the etiology. Some tumors may be pedunculated while others have a broad base.

Pathologic biopsy is generally needed. However, bronchoscopic biopsy of highly vascular lesions is not recommended without appropriate surgical or interventional pulmonary back-up; due to the high risk of bleeding, many experts refer these patients for surgical removal without a biopsy to ensure it is not malignant carcinoid.

Other

●Tracheobronchial amyloidosis – Primary tracheobronchial amyloidosis (TBA; ie, occurring in the absence of systemic amyloidosis) is a rare cause of airway stenosis (image 13). While TBA can involve all parts of the trachea, the subglottic larynx is the most common region involved. It does not typically progress to systemic disease. Airway involvement in secondary amyloidosis is even rarer. Clinical features and diagnosis of tracheobronchial amyloidosis are provided separately. (See "Pleuropulmonary manifestations of amyloidosis", section on 'Tracheobronchial amyloidosis'.)

●Pemphigoid – Mucus membrane pemphigoid more commonly affects the larynx and mouth than lower respiratory tract, which is rare, but when it occurs it may be life-threatening [78]. Bullous lesions are unusual, but ulcerative stenosis may be seen in the inflammatory phase and scarring is common later on as the disease remits and relapses over time. CT findings are nonspecific, and bronchoscopically, mucosa appears friable with active erosions eventually developing significant scarring. Clinical features and diagnosis of pemphigoid are provided separately. (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Mucosal features' and "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid", section on 'Diagnosis'.)

●Radiation – Laryngotracheal and bronchial stenosis is a rare complication of radiation therapy (RT), occurring months to years after RT [79-81]. Perichondritis and chondronecrosis of the trachea and bronchi can lead to tissue necrosis following RT with subsequent scarring, fibrosis, and ultimately stenosis [82]. The larynx, cricoid cartilage, and upper trachea are more commonly involved; however, rarely, distal tracheal and bronchial involvement can be seen, depending on the original irradiation field [79,83]. Clinical features and diagnosis of radiation-induced lung injury are provided separately. (See "Radiation-induced lung injury", section on 'Diagnostic evaluation'.)

Although proton beam therapy has the potential to decrease unintended radiation doses to surrounding normal organs, case reports of laryngotracheal stenosis have been published [84].

●Extrinsic compression – Extrinsic compression from nonmalignant etiologies in the mediastinum can cause TS (eg, thyroid or lymph node enlargement).

●Fibrosing mediastinitis – Fibrosing mediastinitis (also known as sclerosing mediastinitis or mediastinal fibrosis) is characterized by an excessive fibrotic reaction in the mediastinum leading to progressive narrowing of mediastinal structures, resulting in airway entrapment (trachea and bronchi). While histoplasma is the most common etiology, fibrosing mediastinitis has several other etiologies. Clinical features and diagnosis of fibrosing mediastinitis are provided separately (See "Mediastinal granuloma and fibrosing mediastinitis", section on 'Fibrosing mediastinitis'.)

●Broncholithiasis – Broncholithiasis (ie, bronchial stones) is a condition defined by the presence of calcified or ossified material within the tracheobronchial lumen (image 14) [85]. Examples include calcified lymph nodes that erode into the tracheal lumen or calcified tracheal granulomas that detach from the tracheal wall, such as that associated with histoplasmosis. Broncholiths rarely cause tracheal obstruction and are more likely to affect mainstem or lobar bronchi.

Although the pathogenesis is unknown, broncholiths occurs as a result of chronic inflammation from an inciting initial event often years prior, most commonly TB or Histoplasma infection, or any other infections or focal injury.

Patients are generally older and may have cough, hemoptysis, and/or wheeze due to bronchial irritation or even expectorate the broncholith itself (clinically known as lithoptysis) [86]. The calcified lesion (a bronchial stone) may be appreciated within the lumen on chest CT and bronchoscopy and can result in distal obstructive atelectasis or pneumonia, even bronchiectasis or cavitation. A mobile broncholith may change position on imaging or bronchoscopy. Bronchoscopy may also reveal fistulization, which is a complication of broncholithiasis. Bronchoscopy may also identify whether the stone is attached to the airway wall or freely mobile as well as identify other smaller, similar lesions in the airway.

Histopathology shows laminated necrosis and extensive calcium deposits. Occasionally, the offending microorganism may be seen.

Conditions that are associated with pulmonary calcification are described separately. (See "Calcification and ossification of the lungs".)

●Congenital – Causes of congenital subglottic stenosis or TS include tracheal webs or rings, vascular rings (eg, double aortic arch can cause extrinsic compression) [87], and laryngoceles [88]. Because these are developmental in nature, they typically manifest early in life rather than during adulthood. (See "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula" and "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula", section on 'Congenital tracheal stenosis'.)

Idiopathic subglottic stenosis — Stenosis located in the subglottis may be idiopathic. However, idiopathic subglottic stenosis (ISGS), also known as idiopathic laryngotracheal stenosis, is a rare inflammatory disease of unknown etiology that appears to be somewhat unique. Idiopathic stenosis isolated to the trachea without subglottic involvement is rare.

●Clinical presentation – Features that are common in ISGS include the following:

•ISGS has an almost complete female preponderance, affecting patients in the third to sixth decades of life with a median age of 47 years in the largest study describing this disease [89].

•ISGS is an inflammatory disease that is recurrent, typically every three to four months in severe cases, and every one to three years in less severe cases, but not necessarily progressive.

•ISGS is characterized on CT and bronchoscopy by a short segment (eg, 1 to 3 cm in length) and circumferential stenotic lesion, typically located at and/or above the level of the cricoid cartilage with or without associated tracheal involvement (including both stenosis or tracheomalacia) [90]. Mucosal inflammation can extend proximally almost to the glottis in more severe cases.

•Histology in ISGS generally shows dense keloid-like fibrosis with epithelial squamous metaplasia and in some cases sparing of cartilage.

●Diagnostic evaluation – Common etiologies of subglottic stenosis include trauma, GPA, SLE, sarcoidosis, and FBA (table 1). Thus, for stenosis to be considered idiopathic, we use existing data to confidently rule out these etiologies. These data are typically derived from the clinical history and examination, imaging (chest and neck CT), biopsy, and microbiologic studies (tissue and tracheal washings), all of which are generally performed during the evaluation process.

We also additionally perform serologic testing for antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme (ACE) level, rheumatoid factor, and antinuclear antibody. Additional evaluation may include testing for IgG4-RD (IgG subclasses and immunoglobulin E levels, serum complement levels, and blood plasma blast concentrations). On mucosal biopsy specimens of the lesion, we also perform staining for amyloidosis or micro-organisms. However, in the absence of clinical suspicion for an underlying disorder, the value of extensive testing is unknown. (See 'Initial diagnostic testing' above and 'Bronchoscopic evaluation' above.)

●Pathogenesis – Several pathogenetic mechanisms for ISGS have been proposed. In particular, gastroesophageal reflux disease (also known as laryngopharyngeal reflux) has been implicated as a contributing or modulating factor in the development of ISGS [91-95]. As an example, one retrospective study found that 46 percent of patients had notable reflux, the majority being in the upright position and despite proton pump inhibitor therapy [95]. The female predilection suggests a possible hormonal mechanism that is supported by an imbalance between estrogen and progesterone receptors expressed in stenotic lesions [96]. A genetic/familial preponderance has also been suggested [9,10].

SUMMARY AND RECOMMENDATIONS

●Definition and scope – Airway stenosis, which is a narrowing of the airway lumen, can occur at the level of the larynx, trachea, or bronchus (figure 2). Stenosis can be caused by a variety of benign and malignant conditions. For this review, we will focus our discussion on subglottic and tracheal stenosis (TS) (ie, from the subglottis to the main carina) that is benign in nature and non-life-threatening. (See 'Anatomy, terminology, and scope' above.)

●Clinical manifestations – While patients with mild stenosis may be asymptomatic, patients with moderate or severe stenosis may complain of dyspnea, wheeze, stridor, cough, sputum, and hemoptysis. Symptoms that suggest laryngeal involvement include dysphonia, dysphagia, odynophagia, tenderness of the throat, pain on coughing or speaking and difficulty clearing secretions. Patients may also have signs and symptoms due to an underlying disorder. (See 'Clinical features of stenosis' above and "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Clinical presentation'.)

●Diagnostic testing – In most patients with suspected subglottic stenosis or TS, we perform the following:

•Computed tomography (CT) – We perform volumetric neck and chest CT with cross-sectional, multiplanar and three-dimensional reconstruction, which provides detailed imaging of the airway, chest and neck. CT is a sensitive tool for the detection of stenosis and provides detailed assessment of the location, length, shape, and severity of the lesion (image 1 and image 3). (See 'Imaging' above and "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Imaging'.)

•Pulmonary function testing with flow volume loop (FVL) tracings – FVL tracings are more helpful than spirometry. (See 'Pulmonary function tests' above and "Clinical presentation, diagnostic evaluation, and management of malignant central airway obstruction in adults", section on 'Pulmonary function tests'.)

•Bronchoscopic diagnosis – Visual inspection of the laryngotracheobronchial tree with bronchoscopy confirms and additionally characterizes the presence of stenosis and also aids in discerning its underlying etiology (image 4 and image 5 and image 6). In general, we biopsy the stenosis when a tissue diagnosis is essential or needs exclusion (eg, sarcoidosis, cancer) and obtain cultures in those in whom an infectious etiology is suspected. In some cases, diagnostic and therapeutic bronchoscopy are combined. (See 'Bronchoscopic evaluation' above and "Management of non-life-threatening, nonmalignant subglottic and tracheal stenosis in adults", section on 'Initial therapy: Bronchoscopy' and 'Diagnosis' above.)

•Characterization – Both bronchoscopy and CT are used for full characterization (table 2). (See 'Characterization' above.)

●Evaluating the etiology – Most of the etiologies associated with nonmalignant subglottic stenosis or TS are distinguished from each other by a combination of history and examination, laboratory and imaging findings, direct visualization on bronchoscopy, and/or tissue biopsy and microbiologic culture. (See 'Re-review history, examination, and imaging' above.)

•Narrowing the differential – While some etiologies are obvious, others may need additional testing (eg, antineutrophil cytoplasmic antibodies, ACE level, rheumatoid factor, and antinuclear antibody, immunoglobulin (eg, IgG subclasses, IgE), serum complement levels and tissue staining for amyloidosis or micro-organisms). (See 'Patients with obvious etiologies' above and 'Patients with more subtle findings' above.)

•Specific etiologies – The most common etiology that we encounter is postintubation or posttracheostomy stenosis while tuberculosis is likely the most common etiology encountered worldwide. Others include inhalation- and trauma-related stenosis, inflammatory conditions including the vasculitides (eg, microscopic polyangiitis and granulomatosis with polyangiitis), sarcoidosis, and relapsing polychondritis, infections, and several other conditions listed on the table (table 1). (See 'Specific etiologies' above.)

•Idiopathic subglottic stenosis (ISGS) – ISGS affects females in their third to sixth decade in life and is characterized by recurrent circumferential, short-segment stenosis, and keloid-like fibrosis. (See 'Idiopathic subglottic stenosis' above.)