Etiology, mechanism, evaluation and management of non-life-threatening, nonmalignant tracheal stenosis

• Classically present with chronic progressive symptoms after 3 to 6 weeks of removal of endotracheal tube or with failure to wean from tracheostomy tube.
• Nonspecific findings of fibrotic, nonfriable stenosis on CT and bronchoscopy, FVL may be abnormal. Occasionally, lesions are multiple. The injury is typically submucosal but occasionally extends deeper into the cartilage.
• Biopsy not necessary but typically performed to exclude other etiologies.

• Local bronchoscopic techniques including balloon dilation with local thermal ablation; recurrence high especially with dilation alone; thus, patients may need repeat procedures.
• Surgical resection or reconstruction for those who fail local bronchoscopic surgeries or have complex lesions.
• Tracheostomy or T-tube for refractory cases or patients who are not suitable candidates for surgery in whom local therapy has failed or those who need a bridge to surgery.

• Chronic symptoms 2 to 9 months following lung transplantation; known risk factors (eg, early evidence of bronchial ischemia, early rejection, and severe reperfusion edema).
• Nonspecific findings of stenosis on FVL, CT; stenosis at anastomotic site on bronchoscopy.
• Biopsy not typically needed unless another etiology is suspected.

• As for patients with PITS.

• Chronic symptoms weeks to months following injury.
• Nonspecific findings of stenosis on FVL, CT, and bronchoscopy.
• Biopsy not typically needed unless another etiology is suspected.

• As for patients with PITS.

• Acute symptoms following injury or chronic symptoms as the injury resolves.
• Nonspecific CT and bronchoscopic findings that vary depending on the nature of the injury. Tracheal wall thickening on CT and mucosal inflammation or pseudomembranes on bronchoscopy may be seen with active tracheitis while fibrotic structure may be seen with old healed inflammation.
• Biopsy not typically needed unless another etiology is suspected.

• Treatment depends on presentation. For example, a hematoma may need to be drained, pseudomembranes may need to be removed bronchoscopically, and a healed fibrous stricture may be treated similarly to PITS.

• Acute symptoms of tracheobronchitis with tracheal wall thickening on CT; bronchoscopy may show airway erythema and edema, pseudomembranes, blistering, ulceration, bronchorrhea, fibrin casts, or evidence of charring.
• Late symptoms due to fibrotic stenosis during healing similar to PITS (above) may also occur.
• Biopsy may not be needed unless another etiology or complication, such as bronchial polyposis is suspected.

• Supportive therapy for acute symptoms.
• Treated as for patients with PITS for late fibrous structures.

• Subacute or chronic symptoms. History of aspiration event may be present.
• CT, bronchoscopy, and biopsy may show residual remnants of aspirated foreign body with nonspecific inflammation or evidence of vegetable or other foreign matter.
• Biopsy may not be needed unless another etiology is suspected.

• Acute phase involves removal of the foreign body.
• Old fibrotic scar is treated with principles similar to patients with PITS.

• Younger patients with chronic upper airway symptoms including hemoptysis, but symptoms may be acutely life-threatening if severe. Underlying diagnosis not always evident but may include fever, renal disease, joint pain, rashes, eye involvement.
• Subglottic stenosis on CT and bronchoscopy is classic finding and involvement may be multifocal (eg, ulcerations and inflammatory pseudotumors).
• Biopsy needed to confirm the diagnosis and inform therapy.

• Treat underlying cause with appropriate systemic therapy (eg, corticosteroids and rituximab for GPA).
• Patients who failed systemic therapy or have severe disease are generally treated with local bronchoscopic techniques including a combination of dilation and local thermal ablation or stenting. Bronchoscopic injection of corticosteroids or mitomycin C may be combined with repeat dilation/ablation for recurrence.
• Surgery or tracheostomy may be the only option in recurrent or resistant cases.

• Chronic upper airway symptoms. Underlying diagnosis not always evident but may include small joint arthritis, lung parenchymal, or skin involvement.
• CT findings may show arthritis or subluxation of CAJ and evidence of RA in the pleura or lung parenchyma; and laryngoscopy/bronchoscopy findings may show abnormal CAJ, vocal cord paralysis, inflammatory stricture.
• Biopsy generally needed but may show nonspecific inflammation.

• Treatment principles similar to patients with vasculitis (eg, RA-specific anti-inflammatories with or without local bronchoscopic therapies).
• Consideration may need to be given for CAJ surgery if the joint is unstable.

• Chronic symptoms. Underlying sarcoidosis typically present.
• CT findings vary depending on the mechanism of stenosis (eg, enlarged lymph nodes causing compression, upper lobe fibrosis, hilar calcification). Bronchoscopy findings also vary but may show extrinsic compression or inflammatory/fibrotic stricture. Multiple sites may be evident, so thorough inspection is warranted, including the supraglottis.
• Biopsy showing noncaseating granulomas useful to confirm the diagnosis. Sometimes amyloidosis is seen.

• Treatment principles similar to patients with vasculitis (eg, systemic glucocorticoids with or without local bronchoscopic therapies) but may vary depending on the mechanism involved in stenosis.

• Chronic or recurrent acute symptoms. Underlying diagnosis may be evident with relapsing ear and nose involvement. Anterior trachea may be tender.
• CT may show loss of destruction and loss of cartilaginous support. Bronchoscopy and findings may be nonspecific with inflammation and narrowing.
• Biopsy generally not needed if diagnosis is clear from organ involvement elsewhere or biopsy material is obtained from other tissue (eg, ear). Biopsy may be unrevealing if the stenosis is due to old, healed scar.

• Treatment principles similar to patients with vasculitis (eg, combination systemic glucocorticoids plus cyclophosphamide with or without local bronchoscopic therapies). Stenting may be needed for areas of tracheomalacia due to cartilage loss.

• Chronic symptoms. Underlying diagnosis typically evident (eg, bloody diarrhea, weight loss, colitis).
• CT and bronchoscopy may be nonspecific and subglottic involvement is the most common site of involvement.
• Biopsy findings may show lymphoplasmacytic inflammation.

• Treatment principles similar to patients with vasculitis. Optimal anti-inflammatory therapy is unknown for laryngotracheal disease. Consider glucocorticoids plus local therapy.

• Chronic symptoms. Underlying diagnosis may not be evident but may include lymphadenopathy, pancreatitis, cholangitis, or other organ involvement.
• CT and bronchoscopy vary depending on the pathogenic mechanism (eg, extrinsic compression, direct airway all involvement).
• Biopsy findings may show lymphoplasmacytic infiltrates enriched in IgG4-positive plasma cells, with abundant storiform fibrosis.

• Treatment principles similar to patients with vasculitis. Optimal anti-inflammatory therapy unknown for laryngotracheal disease. Consider glucocorticoids plus local therapy.

• Chronic symptoms. Underlying diagnosis typically evident (eg, bone and joint involvement, serologic evidence of SLE).
• CT and bronchoscopy and with nonspecific findings of inflammatory or fibrotic stricture, typically in subglottis location.
• Biopsy findings may show granulomatous inflammation and varied levels of vasculitic inflammation and fibrin deposits.

• Treatment principles similar to patients with vasculitis. Optimal anti-inflammatory therapy unknown for laryngotracheal disease. Consider glucocorticoids with or without local therapy.

• Subacute or chronic symptoms, history of current or old tuberculosis.
• CT may show evidence of active or old infection (eg, upper lobe infiltrate, cavities, scarring, fistula) but may be normal or show evidence of extrinsic obstruction from involved lymph nodes. Bronchoscopy may reveal pseudomembranes and an inflammatory, ulcerated stricture (if active infection) or a fibrotic stricture (if due to healed tuberculosis).
• Washings and biopsy may reveal evidence of active infection (eg, acid fast positive caseating granulomas) or nonspecific inflammation or fibrosis if the stricture is due to old healed or treated tuberculosis.

• Patients with acute infection should be treated with appropriate antimicrobial therapy unless stenosis is severe, in which case local bronchoscopic dilation/ablation may be needed. Pseudomembranes may be bronchoscopically removed, if present. Bronchoscopic surveillance is needed to follow the course of treated airway disease since stenosis can occur despite treatment.
• For patients with fibrous strictures from old, healed disease, treat as for patients with PITS.

• Symptoms may be acute in those with active infection (eg, ulcerative tracheitis, pseudomembranes, or thick mucus plugs in patients with Aspergillus) or chronic in those with older healed tracheal infection.
• CT may show thickened tracheal wall due to infectious tracheitis or a stricture with healed infection; in patients with Histoplasma, enlarged lymph nodes (sometimes calcified) or fibrosing mediastinitis may be seen. Bronchoscopy may show ulcerative tracheitis, pseudomembranes, and mucus plugs in patients with active Aspergillus infection, extrinsic compression in patients with Histoplasma. Fibrotic stenosis may be seen in those with healed infection.
• Washings and biopsy may also reveal evidence of active infection while nonspecific inflammation or fibrosis may be seen if the stricture is due to old healed or treated infection.

• Treatment principles similar to patients with mycobacterial infection.

Viral – Herpes simplex virus is the most common with both direct involvement and subsequent fibrosis. CMV and RSV are less common. RRP due to HPV is rare.

• Symptoms may be acute in those with tracheal stenosis due to active tracheitis or chronic in those with older healed tracheal infection.
• CT may show thickened tracheal wall due to infectious tracheitis or a stricture if the infection has resolved. Bronchoscopy may show tracheitis or pseudomembranes in patients with active infection; washings and biopsy may also reveal evidence of active infection while nonspecific inflammation or fibrosis may be seen if the stricture is due to healed infection. Patients with RRP may have classic smooth polypoid lesions (papillomas) throughout the endobronchial tree on visual inspection and have HPV on microbiologic testing; malignant conversion on biopsy is rare.
• Washings and biopsy may also reveal evidence of active infection while nonspecific inflammation or fibrosis may be seen if the stricture is due to old healed or treated infection.

• Treatment principles similar to patients with mycobacterial infection.
• In RRP, the focus of therapy is debulking with local ablative techniques with or without systemic therapy (eg, interferon gamma). There is no cure.

Infectious-related (eg, Corynebacterium, Mycobacterium, Staphylococcus aureus, Mycoplasma, Hemophilus, Aspergillus, CMV, HSV, and RSV).

• Typically, acute symptoms if infectious or inhalation injuries are the cause but may be chronic if inflammatory conditions are the cause.
• CT and bronchoscopy may show edematous airways with inflammatory material is admixed with fibrin deposit in a layering fashion along the airway wall.
• Histology may show nonspecific inflammatory material. Bronchial washings and tissue should be sent for culture and microbiologic analysis.

• Pseudomembranes may be bronchoscopically removed, if present.
• Treat underlying cause (inflammation or infection).
• Treat as for PITS if old fibrotic stenosis is present.

• Preferentially affects males. May be asymptomatic or present chronically.
• May be an incidental finding on CT. Both CT and bronchoscopy show long segment narrowing with 1 to 3 mm calcified nodules arising from the anterior cartilaginous elements of the trachea; the posterior wall is spared.
• Biopsy typically done to exclude serious pathologies. Histologically, it is characterized by osseous and cartilaginous submucosal nodules connected to tracheal cartilage.

• Local debulking of cartilaginous growth is mainstay of therapy (eg, with endobronchial laser).
• Surgery or tracheostomy for recurrent or resistant cases, respectively.

• Chronic symptoms more likely although hemoptysis may occur if ulceration is present.
• CT may reveal a tracheal mass. Bronchoscopy findings vary depending on the etiology.
• Bronchoscopic biopsy or, in many cases, surgical removal is generally needed.

• Local bronchoscopic therapy, such as electrocautery, laser, argon plasma coagulation, or cryotherapy.
• If above fails, or if the diagnosis is uncertain or carcinoid is suspected, then surgery may be preferred.

• Chronic, slowly progressive symptoms. Commonly affects individuals in their fifth and sixth decade and has slight predilection for females.
• CT and bronchoscopy show circumferential subglottic stenosis as the main site of involvement, but other sites may be affected. Calcification may be seen. Bronchoscopy may also show mucosal nodularity, bronchial wall thickening, mucosal hyperemia and edema, and airway wall rigidity. Amyloid deposits can range in appearance from circumscribed, small superficial yellow lesions to erythematous, raised cobblestoning of the airway.
• Biopsy may reveal amyloid deposits with typical apple-green birefringence under polarized light on Congo red staining or yellow-green birefringence under polarized light.

• Systemic therapy may be needed for patients with secondary amyloidosis only but is generally not needed for primary tracheal amyloidosis.
• As a general rule, extensive debulking is generally not performed to avoid inducing an aggressive fibrotic response.
• Symptomatic patients with focal disease may be treated with local therapy, such as argon laser.
• Patients with circumferential disease may be treated with mucosal sparing surgery (surgical removal of small pieces of tissue). Corticosteroid or mitomycin C injection into the surgical bed to limit a fibrotic response is sometimes used but of unclear benefit.
• Balloon dilation and stents are transient therapies that may be a bridge to tissue removal.
• For patients with resistant or severe disease, repeat local therapy may be needed and external beam radiation can be considered in cases of immunoglobulin light chain amyloid. Surgery or tracheostomy are additional options.

• Acute symptoms during acute flares or chronic symptoms due to scarring. Evidence of mucosal or skin lesions in other sites.
• CT may reveal edema and airway thickening; and bronchoscopy may show ulceration, erosions, and intense inflammation in acute flares, while a fibrotic stricture may be seen in those with scarring due to healing. Bullae are unusual.
• Biopsy findings may show friable mucosa and erosions. Mucosal lesions may not be suitable for histopathology (due to crush artifact) but can be used to obtain direct immunofluorescence. Identification of extrapulmonary lesions and antibasement membrane zone antibodies may be needed to facilitate the diagnosis.

• Systemic therapy for the underlying acute disease (eg, corticosteroids and doxycycline).
• Local bronchoscopic therapy, such as dilation and stenting with lesional injection with corticosteroids sometimes needed.
• Surgery or tracheostomy is rarely performed for severe or resistant cases of fibrotic scar. Surgery can be challenging as the tissue is prone to rescarring and decreased healing.

• Acute symptoms if early in the course or chronic symptoms months to years after irradiation.
• Larynx and upper trachea most frequent sites of stricture formation on CT and bronchoscopy.
• Biopsy is nonspecific and may just show inflammation (if subacute acute) or fibrosis.

• Bronchoscopic dilation or stent placement.
• Tracheostomy may be needed in rare cases of resistant or severe stenosis.
• Surgery problematic due to friable airways (during the acute phase) and anatomic distortion (during the chronic fibrotic phase).

• Chronic symptoms. Large goiter or lymph nodes may be evident on examination.
• CT and bronchoscopy may show reason for extrinsic compression (mass, lymph nodes, large goiter, malignant mass, fibrosing mediastinitis).
• Biopsy may not be necessary unless malignant invasion is suspected or sampling of lymph nodes is needed.

• Treat underlying disorder.
• Stent is a temporary solution while therapy of the underlying cause of compression is ongoing.

• Slowly progressive chronic symptoms often associated with airway and/or pulmonary artery or superior vena cava obstruction in individuals located in regions endemic for Histoplasma.
• CT may show old Histoplasma-related calcification and an enlarged mediastinum with heterogeneous, circumferential fibrosis of other mediastinal structures (eg, esophagus, great vessels).
• Biopsy of the mediastinum shows dense fibrosis and minimal inflammation but is not always necessary if classic findings are present but may be needed if malignancy is suspected.

• Airway stents and balloon dilation are a mainstay of treatment since most cases are due to a fibrotic reaction to old Histoplasma infection. Treatment with antifungals, glucocorticoids, or other anti-inflammatory agents are not generally effective. The latter may be tried in cases that are idiopathic or due to autoimmune disorders or IgG4 disease.
• Surgery may be reserved for resistant cases (eg, tracheal resection or removal of mediastinal tissue) but has a high morbidity and mortality and response is variable.
• Tracheostomy may be an option, depending on the location and severity.

• Older patients with chronic bronchial symptoms. Tracheal obstruction is rare.
• The broncholith may be seen on CT and bronchoscopy and may be freely mobile or attached to the airway wall. Associated complications may also be seen on CT (eg, postobstructive atelectasis, fistulization).
• Histopathology on expectorated or removed stones shows laminated necrosis with extensive calcification and occasionally microorganisms may be seen (eg, fungi, tuberculosis).

• Depending on the location, broncholiths may be removed bronchoscopically (intraluminal) or surgically (extraluminal).
• Local ablative therapies (eg, laser lithotripsy) may be needed for mixed intraluminal/extraluminal broncholiths.

• More likely to present in children.
• CT and bronchoscopy may show vascular rings or tracheal webs or laryngocele.
• Biopsy generally not needed.

• Webs may be amenable to balloon dilation, while laryngoceles generally need resection.

• Almost exclusively in females in the third to sixth decade, possible familial component.
• Short segment (eg, 1 to 3 cm in length), and circumferential subglottic stenosis on CT and bronchoscopy in the absence of findings elsewhere.
• Biopsy shows keloid-like fibrosis. No underlying causes are evident. Additional serology and pathology staining may be needed to rule out rare and serious causes.

• Local bronchoscopic mucosal sparing surgery (eg, 3 radial incisions) combined with gentle dilation.
• Recurrence is treated with repeat local therapies with or without intralesional injection of corticosteroids or mitomycin C.
• Patients with complex lesions not responsive to repeated local therapy should be evaluated for surgical resection or reconstruction.