Large airway diseases

Introduction
• The large extrapulmonary airways
• Trachea
• Mainstem bronchi
• Right bronchus intermedius
Trachea
• Length 10 – 16 cm
• Proximal 1/3 extra-thoracic
• Distal 2/3 intra-thoracic
• Composed of 16 – 22 C-shaped cartilages connected posteriorly by a
membranous wall
• Trachealis muscle
• Runs longitudinally along the posterior membrane
• Innervated by the vagus nerve (muscarinic)
Trachea
• The posterior membrane moves inward in exhalation
• During cough, it decreases the cross-section and increases the cough velocity
• Histology
• Tracheobronchial mucosa has a pseudo-stratified columnar epithelium, has
mucus-producing goblet cells, sub-mucosal gland duct opening, cough
receptors
Clinical features
• Most serious manifestations of tracheal disorders
• Acute onset of stridor or wheezes
• Respiratory distress
• For stridor or dyspnea at rest: diameter is decreased > 75% (< 5 mm)
• Most common symptoms
• Cough
• Sputum production
• Dyspnea
• Hemoptysis
• Wheeze
Diagnostic approach
Pulmonary function test
• First step
• Features of flow-volume curve highly suggestive of the disease
• Sudden drop in expiratory flow
• Plateau of inspiratory and expiratory flow
• Notching of expiratory flow
• Oscillation of expiratory flow
• Diameter of the trachea < 8mm to produce abnormality
• In malacia, CT findings and airflow limitation are not correlated
• PFT relied upon to determine physiologic significance
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Chest imaging
• Second step
• CT without contrast is the test of choice
• If a mediastinal tissue is suspected to impinge on the airway, contrast is
needed
• In tracheobronchomalacia and excessive dynamic airway collapse,
inspiratory, end-expiratory and/or dynamic CT images should be
obtained
Bronchoscopy
• Definitive procedure
• Narrow band imaging makes blood vessels look very dark
• More sensitive than white light bronchoscopy for dysplasia
• Radial probe ultrasound
• Dynamic bronchoscopy
• Flexible bronchoscopy during quiet breathing, forced breathing manoeuvers
and cough
• Ultra-thin bronchoscopes are needed for severely obstructed airways
Stenosis and malacia
• Tracheobronchial stenosis
• Relatively fixed narrowing of large airways
• Tracheobronchial malacia
• Weakness of the cartilaginous large airway wall
Stenosis
• Benign or malignant
• Intrinsic stenosis
• Exophytic growth
• Focal stricture
• Granulation tissue
• Airway wall thickening
• Extrinsic stenosis
Malacia
• Malacia of intra-thoracic large airway limits airflow only during
expiration
• Can be missed on standard CT-scans obtained at end-inspiration
Intrinsic disorders
Benign tracheal stenosis
• Idiopathic laryngotracheal stenosis
• Mucosal and submucosal hypertrophy
• Spares the cartilage
• Almost exclusively in women
• Post-intubation tracheal stenosis
• Cuff pressure > mucosal capillary pressure (30 cmH2O)
• Mucosa dies by necrosis and becomes fibrotic
• Risk factors: women, obesity, DM, HTN, cardiovascular disease
Benign tracheal stenosis
• Post-tracheostomy tracheal stenosis
• Damage of cartilage during placement or subsequent injury by tube or cuff
• Incidence increasing
• Risk factors: percutaneous technique, size > 6, obesity
• Post-infectious tracheal stenosis
• Mostly TB
• Granulomatous infection: fungus, Klebisella rhinoscleromatis, HPV
Benign tracheal stenosis
• Other causes
• GPA, sarcoidosis, amyloidosis, IBD
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Malignant airway disease
• Primary tracheal tumors are rare and usually malignant
Tracheobronchopathia osteochondroplastica
• Benign disorder of trachea and mainstem bronchi
• Submucosal cartilaginous or bony nodules
• Connect to airway cartilage and protrude into lumen
• Spare the posterior wall
• Often detected incidentally
• Unknown etiology
• Posterior wall spared
• Feature differentiating it from amyloidosis, sarcoidosis, fibroma, carcinoma
Tracheobronchopathia osteochondroplastica
• Symptoms
• Cough, dyspnea, wheezes, recurrent airway infection
• Mistaken for asthma or chronic bronchitis
• Large nodules cause hemoptysis, lobar obstruction, post-obstructive
pneumonia
• Hoarseness and sore throat if located in subglottis
Tracheobronchopathia osteochondroplastica
• Diagnosed during airway inspection
• Biopsy not needed and often unsuccessful (heavily calcified)
• If done: cartilaginous or osseous metaplasia
• Treatment
• Goal: ameliorate symptoms
• Forceps removal, laser extraction, cryotherapy, external beam radiation,
stenting, surgical resection if failure, tracheostomy as last resort
Tracheobronchial amyloidosis
• Causes
• Chronic inflammation
• Plasma cell dyscrasias
• Heritable mutations promoting fibrillogenesis
• Senescence
Tracheobronchial amyloidosis
• Amyloid involvement of respiratory tract is uncommon
• Five subtypes
• Tracheobronchial
• Nodular (solitary or multiple)
• Senile pulmonary
• Mediastinal-hilar
• Diffuse interstitial
Tracheobronchial amyloidosis
Tracheobronchial amyloidosis
• Rare (1.1% of all amyloidosis)
• Idiopathic
• Not associated with other diseases
• Peak age 50-60 years
• M=F
Tracheobronchial amyloidosis
Tracheobronchial amyloidosis
• CT
• Diffuse circumferential wall thickening and nodularity of the trachea and
mainstem bronchi
• Bronchoscopy
• Diffuse mucosal edema, hyperemia, friable mucosa
• Or small occluding nodules or masses
• Lesions can be sessile, nodular, or polypoid
Tracheobronchial amyloidosis
Tracheobronchial amyloidosis
• Biopsy
• Amorphous hyaline material, positive Congo red staining, and yellow-green
birefringence under polarized light
• Treatment
• Goal: maintain patent airway
• Neodymium-doped yttrium aluminum garnet (Nd:YAG) laser, argon plasma
coagulation, stent placement, freezing, and resection
• If not amenable to endobronchial intervention: radiation therapy
• Systemic therapy not efficacious
• Surgical intervention if failure
Infections
TB
• Endobronchial TB is common
• Stenosis in 90% despite adequate treatment
• Most common symptom is intractable cough
• CT
• Circumferential tracheal thickening, deformation of rings, stenosis
• Bronchoscopy
• Mucosal ulcers, erythema, edema, hyperplastic inflammatory polyps
Infections
Fungal infections
• Aspergillus fumigatus, mucormycosis
• CT may show parenchymal involvement
• Bronchoscopy
• White plaques, hyperemic mucosa, sticky secretions
• White material may represent calcium deposited by Aspergillus
• Biopsy of the plaque can be diagnostic
• If lesions do not respond to antifungals
• Tracheal balloon dilation, laser therapy, stent placement, surgical resection
Infections
Bacterial infections
• Klebsiella rhinoscleromatis
• Infects the nares and paranasal sinuses
• Can infection the upper airway and trachea
• Mikulicz cells in the nodules are pathognomonic: macrophages with small
nuclei containing the bacterium
• Endemic in Africa, South America
• Ultimately results in chronic granulomatous inflammation
• Treatment by surgical resection and long-term antibiotic
Infections
Respiratory papillomatosis
• Juvenile form
• Perinatal infection with HPV
• Presents in childhood
• Benign airway papillomas
• Subtypes 6 and 11 cause > 90% of cases
• Subtypes 16 and 18 carry a risk of malignant transformation
Infections
Respiratory papillomatosis
• Adult form
• More common in men and smokers
• Caused by HPV transmitted by oral sex
• Papillomas rarely recur after resection
• Treatment by endobronchial resection with adjuvant medical therapy
• Intralesional cidofovir and bevacizumab have shown promise
Inflammatory causes
Relapsing polychondritis
• Rare autoimmune disorder
• Inflammation of cartilage in ear, nose, joints, large airways
• Airways involved in 50% of cases, mostly larynx and trachea
• Repeated episodes lead to obstruction from malacia and/or stenosis
• CT
• Thickened cartilage with sparing of posterior membrane
• PET
• High activity in the cartilage (distinguishes active from fibrotic lesions)
• Treatment by immunosuppression
Inflammatory causes
Relapsing polychondritis
• Treatment by immunosuppression with steroids
• If worsening
• Positive pressure ventilation
• Tracheal stenting
• Tracheostomy
Inflammatory causes
Sarcoidosis
• Lung involved in > 90% of cases
• Endobronchial involvement in 70% of cases
• Tracheal involvement is uncommon (1-3% of cases)
• Intrinsic granulomatous infiltration or extrinsic compression by mediastinal LN
• Proximal 1/3 > distal parts
• Bronchoscopy: cobblestone mucosa with whitish granulomatous material in
areas of stenosis
• Treatment by systemic steroids
• If reversible obstruction on spirometry: inhaled steroids or bronchodilators
Inflammatory causes
GPA
• Tracheobronchial tree affected in 12-23% of cases
• GPA affects men and women equally
• However, > 90% of tracheal stenosis patients are women
• CT
• Circumferential smooth or nodular mucosal thickening
• Irregular borders
• Ulceration
• Cartilage rings can be narrowed and deformed
Inflammatory causes
GPA
• Bronchoscopy
• Subglottic stenosis
• Tracheal stenosis
• Tracheal ulcers
• Inflammatory pseudopolyps
• Transbronchial biopsy is insensitive (< 20% yield)
• Treatment
• Systemic steroids + (cyclophosphamide or rituximab)
• If stenosis persists or recurs: endobronchial therapies
Inflammatory causes
IBD
• Uncommon tracheal involvement
• 0.2% of UC
• 0.4% of CD
• Pulmonary and GI exacerbations occur simultaneously
• CT
• Tracheobronchial wall thickening
• Bronchoscopy
• Ulcers in mucosa, severe narrowing, cobblestoning
• Treatment by high dose of steroids
Broncholithiasis
• Calcified material eroding into the lumen leading to inflammation and
obstruction
• Calcified LN from earlier granulomatous infection, endemic fungal disease or
silicosis
• Foreign material
• Hamartoma
• Carcinoid tumor
• Calcified tracheal cartilage rings protruding into the lumen
• In severe cases, a fistula can develop
Broncholithiasis
• Diagnosis is by CT scan
• Bronchoscopy can miss the lesion
• Treatment
• Conservative: cough suppression, treatment of pneumonia
• If symptoms escalate: bronchoscopic removal by forceps, Nd:YAG lasers can
be effective, surgery if failure
Vascular malformations
• Tracheal varices are rare
• Can cause massive hemoptysis if biopsied
• Bronchoscopy
• Polypoid tracheal nodules with dilated mucosal vessels
• CT
• Mediastinal collateral vessels distinguish varices from other causes of nodules
Tracheobronchomalacia and excessive
dynamic airway collapse
• Both diseases can present together
Tracheobronchomalacia and excessive
dynamic airway collapse
TBM
• Weakness of cartilaginous anterolateral wall of the trachea and
mainstem bronchi
• Caused by cartilage breakdown
• Results in excessive collapse during exhalation
Tracheobronchomalacia and excessive
dynamic airway collapse
TBM
• Often acquired
• Chronic airway inflammation: chronic bronchitis, cystic fibrosis, GERD
• Cartilage inflammation: relapsing polychondritis
• Chronic extrinsic compression: goiter or tumors
• Cartilage necrosis: ET tubes, tracheostomy tubes
• Radiation
• Tracheobronchomegaly (Mounier-Kuhn syndrome)
Tracheobronchomalacia and excessive
dynamic airway collapse
EDAC
• Exaggerated bulging of the posterior tracheal membrane
• Increased transmural pressure gradient during exhalation
• Weakening of the muscular posterior membrane
• Found in chronic obstructive airway disease
Tracheobronchomalacia and excessive
dynamic airway collapse
• Diagnosis
• Cross-section area on bronchoscopy or CT decreases > 50% during forced
exhalation
• This threshold may be inadequate to define an abnormal collapse
• Collapse requiring treatment usually approaches 95-100%
• Therefore, flow-volume curves can be better indicators than visual
assessement
Tracheobronchomalacia and excessive
dynamic airway collapse
• Treatment
• Symptomatic: treat the underlying disease
• If medical treatment ineffective: CPAP, stents, surgery
Extrinsic disorders
Fibrosing mediastinitis
• Rare
• Exaggerated granulomatous response in mediastinal LN to
• Histoplasma capsulatum
• TB
• Aspergillus flavus
• Sarcoidosis
• IgG4-related disease
• Can also cause pulmonary arterial and venous compression
• CXR shows a widened medastiunm
• CT with contrast needed
• No standard treatment
Fistulas
• Tracheo-esophageal fistulas can be congenital or acquired
• Acquired
• Esophageal cancer (in 5-15% of patients)
• Lung cancer (in 1% of patients)
• Benign conditions: prolonged intubation, tracheostomy, surgery, radiation
• Symptoms: cough with eating or drinking, recurrent aspiration,
dysphagia, malnutrition
• In cancer patients, survival is few weeks to months
Fistulas
• CT, barium esophagram or symptoms can suggest TEF and airway
inspection is needed
• Heaped, irregular margins with secretions from the esophagus escaping to
the trachea
• Small fistulas are difficult to identify: oral administration of methylene blue
before bronchoscopy can help
Fistulas
• Treatment
• Benign disease: surgery
• Malignant disease: stenting of trachea and/or esophagus
• Esophageal stent: if esophageal stenosis and no tracheal obstruction
(airway obstruction can occasionally occur after placement)
• Tracheal stent: performed first if tracheal obstruction, concern of
development of obstruction, or esophagus has no stenosis
• Patency maintained by daily nebulization of bronchodilators and saline
solution
Fistulas
• Double stenting
• Tracheal obstruction + stenotic esophageal tumor
• Very large fistula
• Tracheal obstruction after esophageal stent placement
• Double stenting can increase the size of the fistula and prevent healing
• It should be avoided in patients with a potential of cure, long-term survival or
surgical correction
Emerging therapies
3D printed airway stents
• Precisely fitting the patient’s trachea
• Mold made from 3D CT reconstruction
Tracheal replacement
• Resection with end-to-end anastomosis is limited by the involvement
of > 4cm of trachea
• For long resections
• Synthetic prosthetics
• Allografts
• Autologous tissue
• Tracheal transplantation
• None meets criteria for ideal replacement: lateral rigidity and stiffness,
longitudinal flexibility, air-tightness, support of a functional ciliated
respiratory epithelium, biocompatibility, and absence of need for
immunosuppression