Tracheomalacia

Etiology

Although there is no internationally agreed classification system, the etiology of the disease can be divided into three main categories: congenital defects in tracheal integrity, acquired conditions weakening the whole or partial tracheal structure, and conditions causing extrinsic compression of the airway.[2] The first group refers to conditions that cause immaturity of the trachea; the other two groups refer to conditions in which a normally developed trachea undergoes a degeneration process.

Congenital Defects in Tracheal Integrity

Numerous diseases may cause immaturity of the tracheobronchial cartilage and, in turn, congenital tracheomalacia. Systemic conditions like Ehlers Danlos and bronchopulmonary dysplasia can result in an innately weakened trachea. There are many childhood syndromes associated with tracheomalacia. There is a significant incidence of coexisting congenital heart diseases and tracheoesophageal fistula (a tracheal defect may be present in up to 75% of the patients with tracheoesophageal fistula) or esophageal atresia.[2][4][5] 

Some conditions may compromise the normal development of the trachea in the area where they exert compression. Among these conditions that compromise the tracheal integrity, there are vascular rings; they primarily result from the persistence of the double aortic arch after the second month of fetal life and determine a localized alteration of the development of the trachea (and esophagus). Apart from the double aortic arch, which accounts for approximately 40% of the congenital vascular compressions, other conditions including a right aortic arch, a left-sided origin of the (right) innominate artery, a right-sided origin of the left common carotid artery, or an anomalous origin of the left pulmonary artery from the right pulmonary artery can provoke tracheal compression.

In adults, congenital tracheomalacia can be due to Mounier-Kuhn syndrome. It is a rare disease produced by the atrophy of elastic fibers in the trachea and main bronchi, which induces tracheobronchial flaccidity, dilatation, and collapse. The syndrome is often associated with Ehlers-Danlos syndrome, Marfan syndrome, and cutis laxa. The disorder, also referred to as tracheobronchomegaly, can occur at various ages but is usually diagnosed in young adults with recurrent bronchopulmonary infections with chronic non-productive or productive cough, dyspnoea, hemoptysis, and wheezing. However, clinical manifestations vary from paucisymptomatic cases (chronic cough) to severe cases with bronchiectasis or bullous emphysema, which can lead to severe impairment of respiratory function. Although Mounier-Kuhn syndrome may have a link to a genetic defect, research has yet to identify any gene alteration.[6]

Acquired Conditions Weakening the Tracheal Structure

There are multiple potential causes for acquired tracheomalacia. Inflammatory processes such as tracheobronchitis, recurrent polychondritis, and chronic lung conditions such as bronchiectasis can weaken the structure of the airway, predisposing it to collapse. Recurrent polychondritis is a rare autoimmune rheumatic disease characterized by episodes of painful and destructive inflammation of the cartilage and other connective tissues in various organs. Acquired diffuse tracheobronchial collapse is often a finding in chronic obstructive pulmonary disease (COPD). Other conditions such as prolonged intubation, surgery (e.g., pulmonary resection), chest trauma, or foreign bodies can cause segmental disease. Neoplastic pathologies in the respiratory tract (e.g., cylindroma) may also affect the structure of the airway leading to tracheomalacia.[2][7][8]

Extrinsic Compressions

Disease processes extrinsic to the respiratory system, such as cardiovascular masses (e.g., vascular aneurysms and dilated cardiomyopathy), non-pulsatile fixed compressions including large thyroid goiters, and intrathoracic neoplastic diseases may externally compress on the airway leading to tracheomalacia.

Epidemiology

Primary congenital tracheomalacia is rare, and the exact disease incidence and prevalence are uncertain. A proportion of the disease likely goes undiagnosed as often it may resolve spontaneously. A single-center retrospective study where 512 bronchoscopies were analyzed found the estimated incidence of disease to be at least 1 in 2100 children.[9] The secondary forms have a variable incidence according to the underlying pathology. Of note, recurrent intubation and duration of intubation represent the most common cause of adult-acquired tracheomalacia.[10] The reported incidence of tracheobronchomalacia in individuals suffering from COPD is 7 to 15%.[11] Mounier-Kuhn syndrome is a rare disorder, as only approximately 300 cases have been reported to date.

Pathophysiology

The trachea connects the larynx to the distal airways, and its structural support derives from 16 to 20 rings of hyaline cartilage. The rings form a "U" shape as they are incomplete at the posterior aspect, which is covered by a posterior membrane. A variety of disease processes can disrupt this support structure, causing narrowing of the lumen of the trachea (reduced anterior-posterior airway caliber) with associated loss of the semicircular shape and bulging of the posterior membranous wall. This narrowing of the trachea causes the symptoms experienced by patients. Under normal conditions, a modest expiratory collapse of the trachea constitutes a condition of frequent occurrence; in the infant, during forced expiration, a reduction of the tracheal lumen can be achieved up to 30% of its diameter. A tracheal collapse capable of producing an obstacle to lung ventilation must be greater than 50% of the tracheal diameter. In these cases, clinically evident expression of tracheomalacia occurs.[12]

History and Physical

Symptoms may be persistent or intermittent, depending on the severity and extent of the disease. Due to expiratory flow obstruction, patients can present with expiratory stridor. Moreover, alteration of the clearance of secretions can be expressed as productive cough and increased susceptibility to upper airway infections. Furthermore, while intrathoracic collapse occurs during expiration, extrathoracic malacia (upper malacia) results in inspiratory collapse. Infants may be asymptomatic; however, the trachea may become easily compressed while swallowing a food bolus, leading to failure to thrive.[13] 

In congenital forms, the expiratory stridor begins after 4-6 weeks and increases during times of increased airflow, such as activity, coughing, crying, or feeding, and in the supine position, while it decreases at rest. A worsening after meals indicates a possible association with GER (a potential cause). Again, crying is normal, as is the children's weight. Children affected by compression due to vascular rings lie with the head and neck hyperextended to stretch the trachea and reduce its compression. 

Apart from stridor, the clinical picture of tracheomalacia can encompass different symptoms and signs, including inspiratory retractions of supraclavicular and intercostal spaces, hoarseness, aphonia, breathing difficulties, and feeding problems. Furthermore, recurrent respiratory infections can exacerbate these symptoms and, if severe, can lead to respiratory distress, apnea, cyanosis, and airway obstruction, which may require intubation.[13] However, congenital tracheomalacia, if not associated with other pathologies, is not extended to other respiratory tracts and generally resolves in 12 to 24 months. Abnormal expiratory noises usually characterize auscultation despite a normal inspiration.

The clinician needs to take a thorough history, focusing primarily on any respiratory symptoms, as well as information regarding the perinatal period, prematurity, any surgical procedures or intubations performed, and feeding and growth in young children. Subglottic airway pathology should be considered in children presenting with recurrent episodes of croup and atypical wheeze.[14]

Patients with other causes of subglottic airway narrowing may present similarly. Therefore, a thorough physical examination should include a full assessment of the head and neck and the cardio-respiratory systems. Syndromic features may indicate potential concurrent disease. A small proportion of patients with cutaneous haemangiomas (especially facial) may have subglottic hemangiomas.[15]

Evaluation

Although the diagnosis is by endoscopy, diagnostic imaging has an important role in the etiological definition, especially in identifying external compressions in secondary tracheomalacia. For instance, cine fluoroscopy combined with contrast swallow may give information regarding the degree of tracheal collapse and delineate esophageal abnormalities and external tracheal compression. It is of high specificity and low sensitivity; however, the exam is a useful adjunct to endoscopy, mainly when other imaging modalities are unavailable.[16] Many centers also use tracheobronchography as an alternative method alongside bronchoscopy for diagnosis.[17]

Multidetector or ultrafast computed tomography (CT) imaging allows a quick airway assessment. Other mediastinal structures can also be studied if using contrast. When paired with bronchoscopy, it demonstrates good diagnostic accuracy.[18] Nevertheless, CT is associated with radiation exposure, and in young children, this may require sedation, which can change airway dynamics.[19] These issues are potentially solvable by using lower doses of radiation in expiratory phase scans and free-breathing cine-multidetector CT imaging, respectively.[20][21]

The gold standard investigation is direct visualization of the airway during spontaneous respiration via bronchoscopy; this is often undertaken alongside other imaging methods, as previously described. Bronchoscopy can demonstrate the narrowing of the lumen of the trachea with associated loss of the semicircular shape and bulging of the posterior membranous wall. There are currently no studies comparing rigid bronchoscopy to flexible bronchoscopy, and it is accepted that each has its benefits and drawbacks.[22][23]

A variety of imaging techniques may give further information about the disease. Plain radiographs might not show tracheal abnormalities; however, other abnormalities such as vascular anomalies and respiratory pathologies may be visible. Although the literature pertaining to the use of dynamic magnetic resonance imaging (MRI) in the assessment of tracheomalacia is limited, it provides excellent delineation of the anatomy along with no radiation. Thanks to advances in technology, cine-MRI may enable a dynamic airway assessment. The technique is, however, time-consuming and may require intubation or sedation in younger children. Novel imaging approaches such as ultrashort echo-time magnetic resonance imaging (UTE MRI) can represent an interesting solution for assessing tracheomalacia dynamically in neonates without sedation and ionizing radiation.[24]

Pulmonary function tests may show an obstructive pattern and provide supportive evidence; however, they should not be used in isolation to diagnose tracheomalacia.[25]

Treatment / Management

Depending on the extent of the disease and other associated conditions, tracheomalacia can be treated conservatively, with medical management, or with surgery. The management of these patients is best when accomplished by an interprofessional team with input from various specialists.

Congenital and mild acquired disease may resolve spontaneously; therefore, these patients should be treated conservatively with adequate monitoring. Healthcare team members should advise parents on appropriate immunizations, vaccinations, and passive smoking avoidance. Although clinicians use bronchodilators, anti-muscarinic agents, mucolytics, and antibiotics, there is currently little evidence for their benefit.[2]

Chest physiotherapy may be necessary to help the management of secretions and prevent airway infections. Prevention and management of GER are mandatory, and specific feeding regimes are required to avoid aspiration and ensure adequate growth and development.[7][26]

In adults, tracheomalacia may be an incidental finding, and if they do not suffer from any symptoms, a conservative approach should be adopted. Often there is a concurrent disease such as COPD that requires simultaneous management. Continuous positive pressure ventilation (CPAP) is an option for those who fail conservative management. Surgery is the very last resort.[2]

The literature regarding the efficacy of medical treatment options is limited, and the majority of the evidence has its basis in small retrospective studies. There is anecdotal evidence supporting the use of nebulized hypertonic saline in aiding the clearing of mucus and prophylactic antibiotics.[27] Any co-existing diseases require appropriate concurrent management. In the acute setting, CPAP may provide ventilatory pressure support, although there are no prospective or randomized trials to guide treatment algorithms.

Patients with severe symptoms and acquired disease are more likely to require surgical intervention; this is particularly true of patients who experience apneic spells, failure to thrive, recurrent pneumonia, and cyanotic episodes.[28] It is essential to look for the presence of a tracheoesophageal fistula during surgery and correct it if required.(A1)

Stenting is an option for very severe disease. There are a variety of different options for intraluminal stenting; however, each poses its own potential issues. Granulation tissue, vascular erosion, and mucosal hyperplasia can occur in various stents. Although silicone stents may be easier to remove, they require a general anesthetic and insertion via rigid bronchoscopy.[29] Although often patients experience short-term improvement of symptoms from stenting, the longevity of resolution of symptoms is unpredictable.[30] Thus, stenting is inappropriate for diffuse disease, as one cannot stent the entire respiratory tree. If the patient can tolerate stenting, definitive surgical treatment (for example, tracheobronchoplasty) is an option.[31] In patients with short segmental disease, tracheal resection and anastomosis are a consideration in centers with the appropriate expertise.[32](B2)

Historically, surgery involved tracheostomy, which allows long-term mechanical ventilation if required and a degree of airway stenting. Clinicians can perform tracheostomy either surgically or percutaneously. However, the relative morbidity can be high; therefore, clinicians should reserve this option for end-stage disease or either proximal or diffuse disease.[13][28](A1)

Aortopexy is a surgical approach to tracheomalacia and a favored option in many centers. The approach provides an anterior lifting of the aorta that is sutured to the posterior surface of the sternum. Nevertheless, there are different surgical approaches and different techniques. Aortopexy is most commonly performed in the anterior direction. It involves the anterior fixation of the ascending aorta and may be performed via a left anterior thoracotomy, partial sternotomy, or thoracoscopically.[33] 

Key procedural steps may include the movement of overlying vessels to the back of the sternum, elevation of the pulmonary arteries, and occasionally direct suturing to the trachea if required. These techniques aim to increase the space within the mediastinum and therefore relieve potential external compressive forces on the trachea. If the clinician places sutures in the vessel, a balance between suture strength and the risk of hemorrhage is a consideration. Recently, there have been encouraging results from a single-center study looking at posterior aortopexy, which may address the inwards collapse of the membranous posterior wall of the trachea during inspiration.[34](B3)

Differential Diagnosis

Clinicians must consider different clinical conditions that manifest themselves with the typical symptoms of tracheomalacia (e.g., stridor) in the differential diagnosis:

• Laryngomalacia
• Subglottic stenosis
• Vocal cord paralysis
• Epiglottitis
• Inhaled foreign body
• Recurrent respiratory papillomatosis

Laryngomalacia is a condition characterized by foreshortened aryepiglottic folds with laxity in the supraglottic structures (such as the epiglottis), resulting in an inward collapse during inspiration. Patients can present with feeding difficulties and inspiratory stridor, which is worse when lying flat. The stridor is usually not present at birth but appears in the first 4 to 6 weeks of life, then increases in the following months, and is exacerbated by crying. Nevertheless, laryngomalacia often resolves by the age of 2. It is diagnosable using flexible nasendoscopy.

Subglottic stenosis commonly results from repeated trauma from either intubations or high-sited tracheostomies, though it is frequently idiopathic. Autoimmune and connective tissue diseases are also important causes of subglottic stenosis. Patients often have biphasic stridor, which does not typically change with position. These patients may be mistaken for children with recurrent croup episodes. Diagnosis is via endoscopic examination, either flexible nasendoscopy or bronchoscopy.

Vocal cord paralysis can either be congenital or acquired. If unilateral, patients may have weak phonation or hoarseness with potential issues with swallowing and aspiration. If bilateral, this is a potential airway emergency, and the patient can present with stridor and severe dyspnea but will often have a near-normal voice and cry. The unilateral form is most commonly due to dysfunction of the recurrent laryngeal nerve (compression, surgical trauma, neoplastic invasion). The bilateral acquired vocal cord paralysis with adduction is a serious iatrogenic condition, whereas the bilateral congenital form is usually associated with CNS problems such as perinatal asphyxia or hemorrhagic stroke, hydrocephalus, or Arnold-Chiari malformation. Diagnosis is via laryngoscopy, flexible nasendoscopy, or bronchoscopy.

Epiglottitis and other infections of the airway may cause stridor and dysphagia. The clinical picture develops acutely and requires rapid treatment.

Patients with foreign body aspiration usually have a history of choking after swallowing an object. Plain radiographs will show the foreign body if it is radio-opaque. Ventilating bronchoscopy may be both diagnostic and therapeutic for these patients. It is particularly important to determine if the foreign body is of organic material or a button battery, as both can significantly damage the respiratory epithelial lining.

Recurrent respiratory papillomatosis in children is an uncommon but potentially life-threatening, benign viral neoplasm of the respiratory tract. This condition is characterized by recurrent growth of polyps due to the human papillomavirus (types 6 and 11, classically), especially in the larynx but also in the tracheal and distally. Patients may have symptoms of upper airway obstruction and have a hoarse cry and phonation. The diagnosis is with flexible nasendoscopy or bronchoscopy, confirmed via biopsy of a lesion.

Prognosis

For patients with congenital disease and mild symptoms, the prognosis is generally favorable, and symptoms tend to resolve by around the age of 2 years. Patients with other co-existing comorbidities tend to have persistent symptoms until later in childhood. Those whose symptoms persist until adulthood may have a degree of exercise intolerance.[13] The prognosis of the secondary conditions depends on the pathology that produced the alteration and on the degree of the lesion.

Complications

Complications of untreated tracheomalacia involve potential airway obstruction, recurrent respiratory infections, and failure to thrive.[13] The main objective of treatment is to reduce the likelihood of developing these complications; however, the treatment options are not without risks. Early complications from tracheostomy include bleeding, infection, recurrent laryngeal nerve damage, and false passage. Later issues include a trachea-esophageal fistula, a fistula between the trachea and innominate artery, and subglottic stenosis.[35] Aortopexy poses potential risks of pneumothorax, pleural effusion, atelectasis, phrenic nerve palsy, and bleeding.[36]