Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula

INTRODUCTION — Congenital anomalies of the respiratory tract include malformations located anywhere from the nose to the alveoli. Anomalies of the intrathoracic airways, including the trachea, bronchi, and lower airways, are reviewed here. Disorders of the upper respiratory tract are discussed separately. (See "Congenital anomalies of the nose" and "Congenital anomalies of the jaw, mouth, oral cavity, and pharynx" and "Congenital anomalies of the larynx".)

TRACHEOESOPHAGEAL FISTULA AND ESOPHAGEAL ATRESIA — Tracheoesophageal fistula (TEF) is a common congenital anomaly of the respiratory tract, with an incidence of approximately 1 in 3500 to 1 in 4500 live births [1-4].

Classification — TEF typically occurs with esophageal atresia (EA). EA and TEF are classified according to their anatomic configuration (figure 1) [5]. Type C, which consists of a proximal esophageal pouch and a distal TEF, accounts for 84 percent of cases. TEF occurs without EA (H-type fistula) in approximately 4 percent [6-8]. Other rare variations have been reported [9,10].

There are associated anomalies in approximately one-half of the cases of TEF and EA, often as part of the VACTERL association (vertebral defects, anal atresia, cardiac defects, TEF, renal anomalies, and limb abnormalities) or CHARGE syndrome (coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities) and, especially, with congenital heart or genitourinary defects [3,4,8,11-13]. (See "Congenital anomalies: Epidemiology, types, and patterns", section on 'Association' and "Renal hypodysplasia", section on 'Genetic disorders'.)

Pathogenesis — TEF and EA are caused by a defect in the lateral septation of the foregut into the esophagus and trachea. The fistula tract is thought to derive from a branch of the embryonic lung bud that fails to undergo branching because of defective epithelial-mesenchymal interactions [14,15].

Clinical features — The clinical presentation of TEF depends upon the presence or absence of EA. In cases with EA (95 percent), polyhydramnios occurs in approximately two-thirds of pregnancies [16]. However, many cases are not detected prenatally [17]. Additional clinical features relate to the presence of the VACTERL association (a constellation of malformations including vertebral, anal, cardiac, TEF, renal, and limb defects) [11].

Infants with EA become symptomatic immediately after birth, with excessive secretions that cause drooling, choking, respiratory distress, and inability to feed. A fistula between the trachea and distal esophagus leads to gastric distension. Reflux of gastric contents through the TEF results in aspiration pneumonia and contributes to morbidity.

Patients with H-type TEFs may present early if the defect is large, with coughing and choking associated with feeding as the milk is aspirated through the fistula [8]. However, smaller defects of this type may not be symptomatic in the newborn period. In one series, the delay in diagnosis ranged from 26 days to 4 years [18]. These patients typically have a prolonged history of mild respiratory distress associated with feeding or recurrent episodes of pneumonia. On occasion, the diagnosis may be delayed for longer periods and even into adulthood [19,20].

Diagnosis — The diagnosis of EA can be made by attempting to pass a catheter into the stomach. In affected infants, the catheter cannot be passed farther than approximately 10 to 15 cm. This finding can be confirmed with an anterior-posterior chest radiograph that demonstrates the catheter curled in the upper esophageal pouch (image 1). A distal TEF may be suspected based on chest radiographs; both anterior-posterior and lateral views will reveal a gas-filled gastrointestinal tract (image 1). When the diagnosis is uncertain or a proximal TEF is suspected, a small amount of water-soluble contrast material placed in the esophageal pouch under fluoroscopic guidance will confirm the presence of EA (image 2). Barium should not be used as the contrast agent, because it causes pneumonitis if aspirated into the lungs (image 3). The contrast material must be removed immediately to avoid regurgitation and aspiration.

Diagnosis of H-type (ie, without EA) TEF is more challenging. Demonstration of the fistula should be attempted with an upper gastrointestinal series using thickened water-soluble contrast material (image 4). The traditional method requires a pull-back technique in which the distal esophagus is filled first and then the catheter is pulled in a cephalad direction [8]. Subsequent studies have suggested equal or better diagnostic sensitivity with contrast swallow radiography [21]. However, the fistulous tract may be missed in these studies. In that case, esophageal endoscopy and bronchoscopy may be used to detect the TEF (picture 1). Demonstration of the fistula may be accomplished by the appearance in the esophagus of a small amount of methylene blue that is injected into the trachea. Improved computed tomography (CT) technology has led to increasing use of three-dimensional CT scanning, with airway reconstruction as an additional modality for the diagnosis of TEF [22-24]. However, CT scanning is not necessary if the TEF has been adequately identified on contrast radiography [25].

Because TEF/EA is often part of a constellation of other abnormalities (CHARGE syndrome or VACTERL association), evaluation for other anomalies is appropriate. Echocardiography and renal ultrasonography should be performed in all infants in whom TEF has been identified. Consideration may be given to additional evaluations (eg, contrast enema, limb radiographs) if clinically indicated.

Initial management — Treatment of TEF consists of surgical separation of the trachea and esophagus by ligation of the fistula. With H-type TEF, a cervical approach can be used in most cases [7,26].

In cases with EA, primary anastomosis of the esophageal segments with simultaneous fistula ligation is preferred and typically is performed as soon as possible. Preoperatively, the esophageal remnant is evacuated by continuous suction to avoid pooling of secretions and soiling of the respiratory tract. Advances in the medical management of these infants combined with newer surgical techniques have improved outcomes [27-35]. Primary repair may not be possible if the distance between esophageal segments is large [36]. In that case, the first-line option is to delay the repair for two to nine months to allow for esophageal growth, which often permits primary repair [37,38]. If this is not possible, alternatives include esophageal lengthening by traction, interposition of the jejunum or colon, and gastric transposition [38-42]. Historically, preterm infants had high morbidity if surgical intervention (ligation and anastomosis) was performed in the first few days of life. For this reason, in very low birth weight infants (<1500 g), a staged approach with early TEF separation and subsequent EA anastomosis is used for some patients; outcomes for this group have improved over time [43].

Postoperatively, feedings are reintroduced after surgical healing and then increased as tolerated. Gastrostomy is rarely needed if a primary anastomosis is successful.

Because patients with TEF often have complicated gastroesophageal reflux (GER) due to impaired esophageal peristalsis (see 'Outcomes' below), common practice is to treat with a proton pump inhibitor (PPI) for at least one year after TEF repair and longer for those with evidence of ongoing GER [44]. Although two multicenter studies found no benefits of acid suppression on complications including stricture formation, leak, or pneumonia, these outcomes probably have low sensitivity for acid-related esophageal disease [45,46]. Thus, acid suppression is appropriate in patients with clinical evidence of peptic disease, but benefits of empiric therapy have not been established.

Infants with TEF are at increased risk for feeding difficulties and may benefit from consultation with a feeding specialist to avoid a chronic feeding disorder.

Outcomes — The prognosis for H-type TEF (ie, without EA) is generally good [3,47]. Outcomes of infants with EA and TEF are more guarded and depend upon associated abnormalities [48], especially abnormalities of the pulmonary vasculature or parenchyma [49].

●Survival – In a large case series of infants with EA or EA and TEF, survival was 87 percent overall and 72 percent among those with syndromic EA [50]. Compared with infants with nonsyndromic EA, the risk of death was threefold higher in those with VACTERL association and sixfold higher in those with non-VACTERL syndromes, including trisomy 21 and CHARGE syndrome. The gap length of the EA (the distance between the two esophageal pouches) also may determine the prognosis [51].

●Gastrointestinal complications – Complications after EA and TEF repair include:

•Anastomotic leak (approximately 15 percent) [52].

•Esophageal stricture (approximately 35 percent) [52]; esophageal stricture has been successfully managed with endoscopic balloon dilation [53,54].

•Recurrent fistulae (approximately 3 percent) [52]. Residual tracheal diverticulum without complete fistula formation has also been reported (image 5) [55]. There was associated tracheomalacia in 15 percent of cases. (See 'Tracheomalacia' below.)

•Gastrointestinal motility disorders, including disturbed peristalsis and delayed gastric emptying are common and contribute to GER and aspiration [56]. A systematic review reported the following outcomes in adulthood [57]:

-Dysphagia – 50 percent

-GER disease (GERD) with esophagitis – 40 percent

-GERD without esophagitis – 57 percent

-Barrett esophagus – 6 percent (approximately 4 times that if the general population) [57,58]

-Esophageal cancer (squamous cell) – 1 percent (approximately 50 times that in the general population >40 years) [57,59]

(See "Barrett's esophagus: Surveillance and management".)

●Respiratory complications – Respiratory function abnormalities and respiratory tract infections are common after EA and TEF repair and warrant monitoring [60]. In many cases, these problems persist on long-term follow-up [58,61-69]. The systematic review of long-term outcomes described above reported the following pooled estimated prevalences [57]:

•Respiratory tract infections – 24 percent

•Asthma (clinician-diagnosed) – 22 percent

•Wheeze – 35 percent

•Persistent cough – 15 percent

Bronchiectasis develops in 15 to 25 percent of patients after EA and TEF repair when determined by advanced imaging [49,70,71]. The likely mechanisms are poor cough efficiency and/or recurrent aspiration, leading to respiratory infections. (See "Bronchiectasis in children: Pathophysiology and causes", section on 'Aspiration'.)

Long-term management — Both pulmonary and gastrointestinal abnormalities may persist throughout adulthood. Long-term management focuses on early detection and aggressive management of these common complications, ideally guided by a multidisciplinary team with surgical specialists as well as specialists in pediatric pulmonology, gastroenterology, and otolaryngology [70]. Specific recommendations have been made by an expert panel, primarily based on expert opinion with limited clinical evidence [44]:

●All children and adults should be routinely monitored for symptoms of GERD, dysphagia, aspiration, and nutritional status. These pathologies have similar or overlapping symptoms, especially in young children.

●All patients should undergo at least three surveillance endoscopies during childhood to detect early esophagitis. Routine endoscopic surveillance should be continued in adulthood every 5 to 10 years.

●Patients with symptoms of GERD or dysphagia should be evaluated with an esophageal contrast study and endoscopy. Occasionally, patients may also have respiratory symptoms if the esophageal obstruction compresses the trachea. Esophagitis should be managed aggressively with PPIs and esophageal strictures with dilation and PPIs. Asymptomatic patients do not require routine screening or dilation for strictures.

●Patients with respiratory symptoms should be carefully evaluated for anatomic abnormalities, including anastomotic stricture, laryngeal cleft, vocal cord paralysis, congenital esophageal stenosis, recurrent fistula, or congenital vascular malformations [49,72]. Acid suppression alone probably does not improve respiratory symptoms and may actually predispose to respiratory infection.

●Fundoplication has a limited role in patients with TEF because their underlying esophageal dysmotility predisposes to post-fundoplication complications (eg, esophageal stasis and, possibly, to aspiration) [73]. However, fundoplication may be considered in selected patients, such as those with poorly controlled GERD despite maximal PPI therapy, long-term dependency on transpyloric feeding, or cyanotic spells due to GERD. Eosinophilic esophagitis should be excluded before proceeding to fundoplication.

All patients and their families should be educated about these health risks and the importance of clinical and endoscopic surveillance, and these issues should be incorporated into well-organized transition to care by an adult gastroenterologist. (See "Barrett's esophagus: Surveillance and management".)

TRACHEOMALACIA — Tracheomalacia is a relatively common anomaly of the upper respiratory tract characterized by dynamic collapse of the trachea during breathing, resulting in airway obstruction [74,75]. Because most lesions are intrathoracic, airway collapse typically occurs during expiration. Extrathoracic lesions in the cervical trachea are rare and lead to collapse during inspiration. Tracheobronchomalacia is the more general term for dynamic collapse of large or smaller conducting airways.

Tracheomalacia is often classified as congenital (primary) or acquired (secondary) [76]. There are multiple causes of both congenital and acquired tracheomalacia. Congenital disorders that are associated with tracheomalacia include anything leading to in utero tracheal compression (eg, congenital heart disease with cardiomegaly or intrathoracic masses), craniofacial anomalies and other genetic syndromes, mucopolysaccharidoses, connective tissue diseases, and others. Acquired causes include those related to chronic barotrauma (from positive pressure ventilation, eg, in premature infants with bronchopulmonary dysplasia), infection, or inflammation.

Tracheomalacia can be further categorized by the underlying pathophysiology:

●Acquired defect in the cartilaginous support of the trachea due to prolonged positive pressure ventilation or an infectious/inflammatory process. This process explains the occurrence of tracheomalacia in many premature infants with bronchopulmonary dysplasia.

●Extrinsic tracheal compression by the heart and mediastinal vessels, tumors, lymph nodes, or other masses [77-79]. This type can be congenital or acquired.

●Intrinsic defect in the cartilaginous portion of the trachea, leading to an increased proportion of membranous trachea. The lack of sufficient rigid support results in airway collapse.

Tracheomalacia is a frequent complication of surgical repair of esophageal atresia (EA) and TEF, developing in 30 to 40 percent of cases. (See 'Tracheoesophageal fistula and esophageal atresia' above.)

Clinical features — Signs and symptoms depend upon the location and severity of the tracheal lesion. Intrathoracic lesions typically present with a recurrent harsh, barking, or croup-like cough, whereas extrathoracic lesions cause inspiratory stridor; both may result in respiratory distress [75]. A greater extent of collapse is associated with earlier presentation. Infants and young children with tracheobronchomalacia tend to have more frequent respiratory illnesses and delayed recovery from these illnesses as compared with control patients, but the site and severity of the malacia does not predict the respiratory illness profile [80]. In addition, there is an association between tracheomalacia and protracted bacterial bronchitis. The mechanism of this association has not been established but may include ineffective cough and poor mucus clearance due to tracheal collapse when coughing [81]. More recently, an association between tracheomalacia and bronchiectasis has been identified [82]. Thus, children with a history of tracheomalacia should have long-term surveillance for respiratory symptoms. Development of a chronic wet or productive cough suggests protracted bacterial bronchitis, which can lead to bronchiectasis. Management of protracted bacterial bronchitis is discussed separately. (See "Causes of chronic cough in children", section on 'Protracted bacterial bronchitis'.)

Diagnosis — The evaluation of a child for possible tracheomalacia is generally undertaken if there is a high index of suspicion based on history and physical examination, as above. Dynamic airway endoscopy is the diagnostic tool of choice [83]. Changes in airway caliber during fluoroscopy and contrast bronchography occasionally can establish a diagnosis but are less commonly used than endoscopy. Chest radiographs have little utility in making a diagnosis of tracheomalacia because most affected patients have normal chest radiographs when they inspire and hold their breath. In a study of 144 patients evaluated using airway radiographs, microlaryngoscopy (examination of the supraglottic structures with a small endoscope), and bronchoscopy, sensitivity of the radiograph to detect tracheomalacia was only 62 percent [84].

Definitive diagnosis usually is made by bronchoscopy during spontaneous breathing [75,85]. With this technique, the trachea is observed to collapse during expiration (picture 1) [83]. Noninvasive diagnosis of this disorder may be improved by newer imaging techniques, including multidetector CT, in which end-expiratory and end-inspiratory images are obtained [75,86]. Children older than age five are usually able to voluntarily perform the breathing maneuvers that are necessary for this technique; younger children and infants usually require endotracheal intubation. Free-breathing cine CT does not require patient cooperation with respiratory maneuvers and has been successfully applied to the diagnosis of tracheomalacia in young children [87,88]. A combined approach using endoscopy and three-dimensional CT scan also has been advocated [89,90].

Standard CT or magnetic resonance imaging (MRI) are not well suited for primary diagnosis of tracheobronchomalacia, because images are generally obtained at end inspiration and malacia may not be evident. However, in some cases, these imaging studies may be helpful in defining the extent of the lesion [91,92]. Newer dynamic CT and MRI technology are promising as diagnostic alternatives [75,76]. Angio-MRI can be used to diagnose vascular anomalies, which can cause extrinsic tracheobronchial compression and are sometimes associated with tracheomalacia [93].

Management — The long-term prognosis of this disorder is good in those children who have no associated problems. Most affected infants improve spontaneously by 6 to 12 months of age as airway caliber increases and cartilage develops. However, some remain symptomatic or have exercise intolerance as adults [75].

Intervention may be needed in children with life-threatening episodes of airway obstruction, recurrent infection, respiratory failure, or failure to thrive [94]. Interventions include:

●Continuous positive airway pressure (noninvasive or invasive via tracheostomy) has been the most widely used therapy [75,76].

●Surgical approaches such as tracheal reconstruction and the placement of external tracheal stents have been described [95-98]. Posterior tracheopexy (surgical suspension of the trachea) has shown promise for patients with severe tracheomalacia in reports from a single center [99,100].

●Customized external airway stents (either three-dimensionally printed personalized external airway stents or custom-fitted external bioresorbable plates) are a new technology for airway stenting [85,101,102]. Although a number of groups have reported their application in small numbers of patients, external stents are not in widespread use.

●Experiences with a variety of endoscopically placed intraluminal stents have been reported [85,94]. Metallic and silicone endoluminal stents are generally avoided in children because of many complications with long-term use [75,103,104]. Expanding metallic stents, in particular, have been associated with a high incidence of complications and are used only in life-threatening situations [105,106]. Absorbable mesh stents have been used in several European centers, with promising results, but are not commonly used in the United States [85,94].

●Aortopexy, the surgical suspension of the aorta from the sternum, has been reported as an effective treatment for severe tracheomalacia due to a number of different etiologies. In addition to decreasing the compression of the trachea caused by some vascular malformations, aortopexy pulls the anterior tracheal wall toward the sternum, improving airway patency [107-110].

INTRINSIC TRACHEAL OBSTRUCTION — Intrinsic obstruction of the tracheal lumen usually is caused by hemangiomas, hamartomas, or webs [78,111,112]. Affected patients present with stridor or fixed, monophonic "wheezing" (a noise similar to that heard in asthma but caused by tracheal narrowing rather than increased lower airways resistance) and respiratory distress that ranges from mild to severe, depending upon the extent of tracheal narrowing. The stridor can be inspiratory, expiratory, or both.

Bronchoscopy is required to establish the diagnosis, although high-resolution imaging studies may identify large lesions. Therapy consists of surgical resection of the obstructing lesion, except for airway hemangiomas, for which systemic propranolol is generally the first line of therapy. The long-term prognosis usually is good. (See "Infantile hemangiomas: Management".)

TRACHEAL ATRESIA

●Definition and types – Tracheal atresia, also known as agenesis or aplasia of the trachea, is a rare, usually lethal disorder [113]. The defect consists of partial or complete absence of the trachea below the larynx (picture 1) [83]. The lower respiratory tract often is connected to the gastrointestinal tract via a distal tracheo- or bronchoesophageal fistula. Lack of a fistula between the airway and esophagus is incompatible with life [114,115].

Tracheal atresia is classified based upon the presence and extent of the tracheal remnant [111,116-119]. Several classification systems have been proposed; the most widely applied recognizes three distinct lesions (figure 2) [120]:

•Type I – A short segment of trachea connects to the anterior esophagus

•Type II – The airway and esophagus are fused at the level of the carina with no tracheal remnant

•Type III – Right and left mainstem bronchi directly adjoin the esophagus

●Clinical features – As with many of the congenital anomalies of the respiratory tract, tracheal atresia may be diagnosed by prenatal ultrasound [121,122]. Ultrasound features include symmetrically enlarged lungs or other features of congenital high airway obstruction; polyhydramnios may be present if esophageal occlusion is also present. (See "Congenital pulmonary airway malformation: Prenatal diagnosis and management", section on 'Differential diagnosis'.)

The signs of tracheal atresia are immediately apparent at birth. The infant is cyanotic with severe respiratory distress, has no audible cry, and cannot be intubated or ventilated [111,123-125]. Males are affected more often than females (2:1), and other congenital anomalies are present in 90 percent of cases [124].

Tracheal atresia may be part of a pattern of congenital malformations that overlaps with, but is distinct from, the VACTERL association [126,127]. Other reports have described tracheal agenesis in association with a spectrum of congenital anomalies described as TACRD (tracheal agenesis/atresia, complex congenital cardiac abnormalities, radial ray defects, and duodenal atresia) [128]. In case series of fetuses with tracheal atresia, most had other congenital abnormalities, which included pulmonary (pulmonary hypoplasia or lobular simplification), gastrointestinal (esophageal, gastric, biliary or duodenal, or anal anomalies), genitourinary, and cardiovascular defects [127,129].

●Pathogenesis – Tracheal agenesis results from abnormal development of the laryngotracheal groove early in gestation [111,130]. The cause is unknown and is likely heterogeneous. One mechanism that would also account for the associated anomalies involves abnormal epithelial-mesenchymal interactions [127]. Alternatively, disrupted vascular development in a primary developmental field may result in the anomalies of foregut derivatives in some patients.

●Outcome – Historically, tracheal atresia has been considered lethal. However, resuscitation may be possible if a proximal TEF is present and the trachea can be intubated by passing a tube through the esophagus and fistula into the trachea [85,131,132]. Additionally, emergency tracheostomy may be performed and is lifesaving [133]. If the infant can be resuscitated, surgical correction can be attempted, although the prognosis for survival remains guarded at best [134,135]. The development of ex utero intrapartum treatment (EXIT; or fetal surgery) has marginally improved the prognosis for infants diagnosed with tracheal atresia on prenatal ultrasound. A number of case reports describe the successful management of infants with tracheal atresia after EXIT surgery [136,137].

CONGENITAL TRACHEAL STENOSIS

●Definition and variants – Congenital tracheal stenosis is a rare anomaly that occurs less often than laryngeal or other tracheal malformations [138,139]. The narrowing results from complete or nearly complete rings of cartilage. Three patterns are seen [111]:

•Segmental stenosis that can occur anywhere in the tracheobronchial tree (50 percent)

•Generalized or complete stenosis/hypoplasia (30 percent)

•Funnel-shaped lesion often associated with a pulmonary artery sling (20 percent)

Tracheal stenosis often is associated with other malformations of the respiratory tract, esophagus, or skeleton [85,140]. However, in a small series of premature infants with tracheal stenosis, none had accompanying abnormalities [141].

Note that congenital tracheal stenosis is distinct from and far less common than acquired tracheal stenosis (eg, subglottic stenosis), which may occur as a consequence of intubation or airway trauma associated with prematurity and bronchopulmonary dysplasia. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Glottic and subglottic damage'.)

●Clinical features – The age at onset and severity of symptoms depend upon the degree of stenosis. Complete stenosis presents in newborns, whereas segmental or funnel-shaped lesions may become symptomatic later. Infants typically present with severe respiratory distress, cyanosis, and feeding difficulty. Other findings may include inspiratory stridor or a monophonic expiratory wheeze refractory to bronchodilator therapy. Older patients can present with these findings or recurrent pneumonia [142].

Life-threatening deterioration may result when inflammation or mucus plugs cause further tracheal narrowing. Endotracheal intubation usually can be performed in these patients, although advancing the endotracheal tube may not be possible.

●Diagnostic evaluation – Chest radiographs or fluoroscopy (with or without contrast) occasionally can demonstrate narrowing of the trachea (image 6). However, bronchoscopy usually is needed to confirm the diagnosis (picture 1) [83]. CT or MRI may be useful to define the extent of narrowing [91,92]. Advances in CT technology with three-dimensional airway reconstruction have led to the development of "virtual tracheobronchoscopy," which has enhanced the diagnosis of tracheobronchial anomalies [143,144].

●Management – Tracheal stenosis requires surgical correction, which can include less invasive procedures such as balloon dilation, stent placement, and laser treatment or traditional surgical approaches, primarily slide tracheoplasty for long-segment defects and resection with end-to-end anastomosis for short-segment defects [85,145,146]. Surgical repair of tracheal stenosis requires expert planning and execution due to complex issues with anesthesia and surgery and associated risks [147].

●Outcome – Historically, the outcome of isolated short-segment stenosis has been relatively good, whereas long-segment stenosis has been considered incompatible with survival. However, as mentioned above, advances in surgical management have decreased the mortality rate of severely affected patients [145,148].

Mortality risk remains significant when tracheal stenosis is associated with other conditions. In one series, 5 of 16 infants with tracheal stenosis died, although all who died presented with cardiovascular lesions [149]. In another report, patients with tracheal stenosis often required prolonged ventilator support (median duration 59 days) [150]. However, the duration of ventilation and extent of narrowing at dynamic contrast bronchography did not predict survival.

TRACHEAL CARTILAGINOUS SLEEVE — A tracheal cartilaginous sleeve (TCS) is a rare anomaly in which the anterior portions of the tracheal cartilages are fused into a continuous segment ("sleeve") of cartilage. It is most commonly associated with genetic craniosynostosis syndromes (Pfeiffer, Apert, Crouzon, Saethre-Chotzen, Beare-Stevenson, and others) [151]. TCS is especially common when these syndromes are associated with variants in the FGFR2 (particularly p.W290C, p.S252W and p.C342 variants), FGFR3, and TWIST1 genes [151-154]. These syndromes are typically associated with significant upper airway obstruction, including obstructive sleep apnea, but may also be complicated by severe, life-threatening lower airway obstruction caused by the TCS. (See "Overview of craniosynostosis" and "Craniosynostosis syndromes".)

Diagnosis of TCS can be challenging because cartilaginous abnormalities are not easily detected by MRI or CT. Neck ultrasonography may be useful to identify the anomaly [152,155]. Airway endoscopy is often needed to confirm the diagnosis of TCS. In some cases, the cartilaginous sleeve is first diagnosed during an attempted tracheostomy and may complicate the procedure. Hence, it is critical to perform complete airway examination when evaluating infants with these syndromes. Many affected patients require long-term tracheostomy.

ANOMALIES OF TRACHEOBRONCHIAL ARBORIZATION — Tracheal bronchus, tracheal trifurcation, and bridging bronchus are developmental anomalies of the major bronchi that originate during the embryonic stage of development. Bronchial atresia, stenosis, or malacia are developmental anomalies of the smaller conducting airways that tend to originate later in gestation when the more distal airways are formed.

The arborization anomalies are often associated with congenital tracheal or tracheobronchial stenosis and may be accompanied by congenital cardiovascular anomalies [156-159]. They also can be associated with congenital malformations such as bronchogenic cysts. (See 'Other lower airway anomalies' below.)

The radiographic appearance of these malformations and other developmental anomalies of the lung is discussed in detail separately. (See "Radiographic appearance of developmental anomalies of the lung".)

Tracheal bronchus — Tracheal bronchus refers to an abnormal bronchus that originates from the trachea, carina, or other bronchus and is directed to the upper lobes (figure 3) [160]. In a series of 35 cases, most cases originated from the bronchus (69 percent) rather than the trachea (23 percent) or carina (8 percent) [161]. In another large series, tracheal bronchus accounted for 7.5 percent of tracheobronchial anomalies [162]. Most cases involve the right upper lobe. A specific malformation in which a single right upper lobe bronchus arises from the right side of the trachea above the carina is known as bronchus suis (or "pig bronchus") (image 7) because it is the normal anatomic configuration seen in swine and other ruminant animals.

Tracheal bronchus is a common airway malformation, with an incidence of 0.1 to 5 percent [163,164]. The defect in embryogenesis that results in this disorder is uncertain. Possible mechanisms include abnormalities in migration, selection, or reduction of airways during development [165].

Tracheal bronchus usually is asymptomatic and considered an incidental finding on bronchoscopy performed for unrelated reasons. However, affected children can have respiratory morbidity. In one series, 18 patients ranging from 1 day to 54 months of age presented with recurrent pneumonia (50 percent), stridor (33 percent), respiratory distress (11 percent), or thoracic mass (6 percent) [166]. Most of them had other congenital anomalies. Other presentations include prolonged right upper lobe atelectasis complicating endotracheal intubation and mechanical ventilation [167] and lobar emphysema [168]. The diagnosis is made at bronchoscopy or by CT [161,169-171]. (See "Radiographic appearance of developmental anomalies of the lung".)

No specific therapy is indicated if the patient is asymptomatic. Recurrent pneumonia and localized bronchiectasis are managed with antibiotics and pulmonary toilet, including postural drainage and chest physiotherapy. Patients who do not respond to medical management may require lobectomy. The prognosis for patients with this anomaly typically is excellent.

Tracheal trifurcation — Tracheal trifurcation describes airway anatomy that includes three main bronchi originating at the level of the carina [158,172]. It is often seen in conjunction with congenital cardiovascular disease, tracheobronchial stenosis, and/or other airway or pulmonary abnormalities. Symptoms may be subtle if trifurcation is an isolated anomaly or masked by other symptoms when seen as part of a constellation of anomalies. Diagnosis generally includes bronchoscopy and CT imaging.

Bridging bronchus — Bridging bronchus describes airway anatomy in which the right middle and lower lobes are supplied by an aberrant airway originating at the left mainstem bronchus [173]. The aberrant airway crosses or "bridges" the mediastinum. Bridging bronchus is typically seen in association with a pulmonary artery sling or other congenital cardiovascular abnormalities. (See "Vascular rings and slings" and "Isolated ventricular septal defects (VSDs) in infants and children: Anatomy, clinical features, and diagnosis".)

Individuals with bridging bronchus are generally symptomatic (acute distress, chronic wheezing, recurrent infection) because of the associated airway stenosis or obstruction. Diagnosis is made through direct bronchoscopic imaging or advanced CT or MRI imaging. Surgical management is often needed for symptomatic individuals and must be tailored to specific tracheobronchial abnormalities and any associated cardiovascular abnormalities.

OTHER LOWER AIRWAY ANOMALIES

Bronchial atresia — Bronchial atresia typically is identified as an incidental finding on a chest radiograph obtained in an asymptomatic older child or adult [174]. Because no communication with the normal tracheobronchial tree exists, infection is unusual. Because most patients are asymptomatic, it is difficult to estimate its prevalence. However, one study of population screening of males with chest radiographs identified bronchial atresia in 1.2 cases per 100,000 [175]. Surgery is indicated only for symptomatic lesions.

This condition appears on chest radiograph as a hyperinflated or hyperlucent area that may compress adjacent tissue and cause a shift of the mediastinum (image 8). The hyperinflation is thought to result from unidirectional flow through collateral airways (pores of Kohn, canals of Lambert). A left-sided predominance occurs for unknown reasons [111]. When the appearance is atypical, diagnosis can be confirmed by CT.

Some authors have suggested that bronchial atresia may represent a common pathogenic pathway for a variety of congenital lung malformations including intralobar sequestration, congenital cystic adenomatoid malformation, and congenial lobar emphysema [176]. This theory is plausible based on common histopathologic findings among these lesions [177,178]. (See "Bronchopulmonary sequestration" and "Congenital pulmonary airway malformation" and "Congenital lobar emphysema".)

Bronchial stenosis — Bronchial stenosis refers to a narrowing of a bronchus at any point in the bronchial tree; congenital bronchial stenosis may be associated with complete tracheal rings [158]. This condition can involve one or more bronchi. Like airway malacia, it can also be congenital or acquired. Congenital bronchial stenosis is most often found in infants with congenital heart disease or as part of a constellation of abnormalities associated with a genetic syndrome; isolated congenital bronchial stenosis is rare [179]. Affected patients present in infancy with wheezing refractory to bronchodilators and recurrent pneumonia. The chest radiograph typically shows hyperinflation and air trapping. Acquired bronchial stenosis can result from trauma or surgical intervention, retained foreign bodies, chronic inflammation associated with rheumatic diseases, or infection.

Bronchoscopy can confirm the diagnosis in lesions that are proximal. Detection of distal lesions is limited by the size of the patient and the bronchoscope. Airway imaging with CT or MRI reconstruction may detect lesions that are more peripheral, although these techniques can miss smaller lesions [91,92].

Management is supportive. This approach includes antibiotics to treat infection and chest physiotherapy to mobilize secretions, although supporting evidence for the latter is unavailable. Most cases need no intervention, and symptoms usually resolve as the airways grow. However, surgical resection sometimes is indicated in children with serious or recurrent infections who fail medical management.

Bronchomalacia — Bronchomalacia refers to dynamic narrowing of the bronchi. It is a relatively common abnormality of the lower airway and often is associated with tracheomalacia [180]. Causes include congenital absence of cartilage, extrinsic airway compression, and acquired intrinsic narrowing after infection or lung or heart-lung transplant [77,181,182].

The clinical presentation of this disorder is similar to tracheomalacia and bronchial stenosis. Affected patients present between 1 and 12 months and rarely before 1 month of age [183]. Typical features include recurrent infections and respiratory distress in severe cases. A fixed expiratory "wheeze" (a noise similar to that heard in asthma but caused by bronchial narrowing rather than increased lower airways resistance) is heard on auscultation.

The diagnosis is made with bronchoscopy or CT imaging with airway reconstruction; the selection of diagnostic tests depends on local resources and expertise [182,184-186]. Management is similar to that for tracheomalacia. Most patients require no intervention, although unusual cases need continuous positive airway pressure to prevent lobar collapse [183]. Patients with severe respiratory distress may require surgical repair of anomalous vessels, suspension of the involved airway (bronchopexy), airway stents, or lobectomy [77,187,188].

Bronchial obstruction — Numerous disorders can cause extrinsic or intrinsic obstruction of the lower airways. Extrinsic obstruction or compression usually results from aberrant blood vessels, although it may be caused by congenital cystic malformations such as bronchogenic cyst (see 'Bronchogenic cyst' below). Intrinsic obstruction can be caused by acquired lesions such as bronchial webs, enlarged mediastinal lymph nodes, hamartomas, plasmacytomas, and other tumors.

These conditions are rare and typically present with recurrent infection distal to the obstruction. The diagnosis is made by endoscopy or high-resolution imaging studies. Surgery is performed to exclude malignancy and prevent the recurrence of symptoms. It usually is curative.

Bronchogenic cyst

●Anatomy and embryology – Bronchogenic cysts arise from anomalous budding of the foregut during development and represent part of the spectrum of bronchopulmonary foregut malformations [165,189,190]. They can occur at any point throughout the tracheobronchial tree. Cervical, intrapleural, cutaneous, esophageal, cardiac, and subdiaphragmatic retroperitoneal bronchogenic cysts are unusual occurrences but have been reported [191-202]. These lesions, although rare, are among the most common lower respiratory tract malformations [203-207].

●Clinical features – Affected patients typically present during the second decade of life with recurrent coughing, wheezing (which may simulate asthma), and pneumonia, but they may become symptomatic in infancy or adulthood [207-211]. Newborns with rapidly enlarging central cysts can develop respiratory distress, cyanosis, and feeding difficulty [212-215]. Bronchogenic cysts also may be detected as neck masses or incidental findings on chest radiographs.

●Diagnosis – Bronchogenic cysts appear on chest radiographs as round water-density masses that may have air-fluid levels associated with previous or current infection (image 9) [216,217]. CT typically shows sharply marginated cystic mediastinal masses of soft tissue or water attenuation (image 10) [217]. Lesions that appear solid on CT usually can be characterized as cystic by MRI. The radiographic appearance of bronchogenic cysts and other developmental anomalies of the lung is discussed in detail separately. (See "Radiographic appearance of developmental anomalies of the lung".)

Gross pathologic examination demonstrates unilocular cysts that are filled with thick, clear fluid and do not communicate with the tracheobronchial tree (picture 2) [217]. On histologic examination, the cyst is lined by respiratory epithelium with occasional foci of squamous metaplasia; the wall resembles that of larger airways and contains smooth muscle, glands, and cartilage (picture 3). The presence of cartilage plates is the most reliable diagnostic criterion.

●Management – The management of a bronchogenic cyst consists of surgical excision by partial or total lobectomy. This procedure is curative. Controversy exists regarding the need for resection when patients are asymptomatic. We suggest surgery in all cases because of the likelihood of eventual development of symptoms and the potential for serious illness [208]. In addition, malignant degeneration may occur with this disorder, as in other congenital cystic anomalies [218]. Although surgical excision is typically straightforward, operative complications have been reported [219-221]. The prenatal ultrasound identification of large cysts compressing cardiovascular structures warrants in utero thoracentesis to prevent fetal hydrops [212].

SUMMARY AND RECOMMENDATIONS

●Tracheal anomalies

•Tracheoesophageal fistula (TEF) – A common congenital anomaly of the respiratory tract that typically occurs with esophageal atresia (EA) (figure 1). Infants with EA often have a history of polyhydramnios and present with excessive oral secretions and inability to feed. Those with a fistula between the trachea and the distal esophagus may have abdominal distension and aspiration pneumonia. Motility disorders and respiratory function abnormalities are common after TEF repair and warrant close monitoring and proactive management. (See 'Tracheoesophageal fistula and esophageal atresia' above.)

•Tracheomalacia – A relatively common anomaly of the upper respiratory tract characterized by dynamic collapse of the trachea during breathing. Intrathoracic lesions are most common and tend to cause symptoms during expiration (eg, a croup-like cough), whereas extrathoracic lesions cause inspiratory stridor. The diagnosis of tracheomalacia is made by bronchoscopy during spontaneous breathing (picture 1); standard radiography is not sufficient to make the diagnosis. (See 'Tracheomalacia' above.)

•Rare tracheal anomalies – These include:

-Tracheal atresia, which may be identified on prenatal ultrasound or present at birth with cyanosis, severe respiratory distress, and no audible cry; it is usually lethal at birth. (See 'Tracheal atresia' above.)

-Congenital tracheal stenosis, which is characterized by segmental, funnel-shaped, or generalized stenosis, caused by rings of cartilage (picture 1). The presentation varies markedly depending on the degree and type of stenosis. (See 'Congenital tracheal stenosis' above.)

-Tracheal cartilaginous sleeve (TCS), which is characterized by the fusing of the anterior portions of the tracheal cartilages into a continuous segment of cartilage; it usually is associated with a genetic craniosynostosis syndrome. (See 'Tracheal cartilaginous sleeve' above.)

●Bronchial anomalies

•Tracheal bronchus – An abnormal bronchus that originates from the trachea, carina, or other bronchus and is directed to the upper lobes (figure 3). It is a relatively common airway anomaly and is usually asymptomatic. (See 'Tracheal bronchus' above.)

•Bronchial stenosis – Narrowing of the bronchi at any point in the bronchial tree. This condition can be focal or diffuse and is often associated with bronchial arborization anomalies (tracheal bronchus, tracheal trifurcation, or bridging bronchus). Affected patients present in infancy with wheezing refractory to bronchodilators and recurrent pneumonia. The chest radiograph typically shows hyperinflation and air trapping. (See 'Bronchial stenosis' above and 'Anomalies of tracheobronchial arborization' above.)

•Bronchomalacia – The dynamic narrowing of the bronchi during respiration; this may be caused by congenital absence of cartilage, extrinsic airway compression, and acquired intrinsic narrowing after infection. Symptoms include a fixed expiratory wheeze in an infant and sometimes recurrent infections and respiratory distress. (See 'Bronchomalacia' above.)

•Bronchogenic cysts – Unilocular fluid-filled lesions, usually in the lungs or mediastinum; they do not communicate with the tracheobronchial tree. Affected patients typically present during the second decade of life with recurrent coughing, wheezing (which may simulate asthma), and pneumonia. (See 'Bronchogenic cyst' above.)