Etiology and Pathogenesis

Laryngomalacia is the most common congenital abnormality of the extrathoracic airway. Structural abnormalities that occur in some cases include shortened aryepiglottic folds; a flaccid, omega-shaped epiglottis; and prolapsing arytenoid cartilages. Poor tone and coordination of the laryngeal muscles caused by neuromuscular immaturity contributes to inspiratory collapse of laryngeal structures.

Laryngeal atresia is a life-threatening condition that occurs when the occluded laryngeal lumen fails to recanalize at 10 weeks of gestation. Incomplete recanalization can result in laryngeal webs, which are often associated with DiGeorge or velocardiofacial syndromes. Congenital subglottic stenosis is similar in pathogenesis; however, the defect occurs below the glottis at the level of the cricoid cartilage. Laryngeal clefts develop between 25 and 35 days in utero because of abnormal separation of the trachea from the foregut.

Tracheomalacia may be either primary or secondary, the latter being more common. In primary tracheomalacia, there is an intrinsic weakness of the tracheal cartilage and sometimes shortening of the cartilage rings so that the posterior membrane comprises a greater proportion of the tracheal circumference. Secondary tracheomalacia results from extrinsic compression of the airway in association with cardiovascular abnormalities such as double aortic arch, or it may be a complication of prolonged intubation, tracheostomy placement, or severe tracheobronchitis.

Tracheoesophageal fistula (TEF) occurs when there is incomplete mesodermal septation of the primitive foregut. The trachea is anatomically abnormal, causing primary malacia. In 85% of cases, there is a proximal blind-ending pouch with a distal fistula (Figure 39-1). The pouch expands and compresses the trachea, thus also causing secondary malacia. Less common types include the H-type fistula and upper esophageal fistula with distal atresia. The fistulae are often small and found between the larynx and the thoracic inlet.

Figure 39-1 Tracheoesophageal fistula.

Tracheal stenosis refers to a fixed narrowing of the trachea either from extrinsic compression or from an intrinsic abnormality. Intrinsic tracheal stenosis is usually associated with complete cartilaginous tracheal rings. The rings completely encircle the trachea, and there is absence of the posterior membranous portion. Complete rings are commonly seen in association with a left pulmonary artery sling. The left pulmonary artery arises from the right pulmonary artery and then passes around the right side and behind the carina and then between the trachea and esophagus. Tracheal atresia is rare and usually caused by a malformation of the laryngotracheal groove.

Bronchial abnormalities include bronchomalacia, which may be diffuse from intrinsic airway properties, or isolated because of local compression or damage (e.g., after prolonged mechanical ventilation). Williams-Campbell syndrome is a severe form with marked deficiency of airway cartilage. Mounier-Kuhn syndrome is congenital tracheobronchomegaly associated with tracheomalacia and bronchiectasis. Anatomic abnormalities of the bronchi include a tracheal bronchus or “pig bronchus” in which an abnormal bronchus arises from the trachea proximal to the carina rather than from the right main bronchus; it usually supplies a segment of the right upper lobe. An aberrant “bridging bronchus” occurs when the right lower lobe bronchus arises from the left bronchial tree.

Clinical Presentation

Airway abnormalities can present with immediate respiratory distress after birth or their presentation may be subtle (e.g., an abnormal cry or difficulty feeding). Inspiratory stridor is often a key feature in laryngeal abnormalities. Increased inspiratory airflow or effort accentuates the stridor (e.g., during crying, feeding or upper respiratory tract infections). Laryngomalacia is associated with other congenital anomalies in 20% of cases. Episodes of recurrent croup in the first 18 months of life or episodes of croup that continue past 5 or 6 years of age should always raise the possibility of a fixed upper airway narrowing such as laryngeal web or subglottic stenosis. Laryngeal clefts can present with the triad of stridor, excessive salivation, and a muted cry. They, similar to the H-type TEF, are also associated with coughing during feedings. Other diagnostic considerations for stridor to consider include congenital hemangiomas and laryngeal cysts.

Patients with tracheomalacia and bronchomalacia may present with a harsh “barking” cough and homophonous wheeze, representing intrathoracic obstruction. Some cases are misdiagnosed as difficult-to-treat asthma. Symptoms of TEF can be varied and include recurrent coughing with feeds, choking or cyanotic spells, and frothing. If symptoms are mild, the diagnosis can be delayed beyond infancy. Recurrent infection in the same location of the lung can point to a structural bronchial anomaly, including stenosis or malacia.

Evaluation and Management

In most cases of laryngomalacia, a careful history and physical examination are sufficient to make a diagnosis. However, when symptoms are associated with failure to thrive or other laryngeal malformations are being considered, a flexible endoscopy should be performed. Anteroposterior and lateral airway radiographs may also help to localize a fixed anatomic narrowing. If a laryngeal cleft is suspected, a contrast swallow can demonstrate the defect, but a rigid bronchoscopy is also usually necessary. Laryngomalacia is usually a benign entity that resolves without intervention within the first 2 years of life, but aryepiglottoplasty has been used to treat cases associated with severe airway obstruction. Surgical excision or laser ablation is used to treat many laryngeal anomalies, including webs and cysts. Surgery for subglottic stenosis, if warranted, may involve a cricoid split or laryngotracheoplasty. Rarely in these cases or with laryngeal clefts, a tracheostomy is needed to allow for staged repair.

Tracheobronchial abnormalities usually require rigid or flexible bronchoscopy for diagnosis. Areas of extrinsic airway compression should prompt imaging by computed tomography (CT) or magnetic resonance imaging (MRI) to define the offending lesion. Patients with significant obstructive symptoms from tracheomalacia may benefit from an aortopexy, tracheostomy with or without continuous positive airway pressure (CPAP), or use of bronchoconstrictor drugs. Bronchomalacia, if severe, may also require use of CPAP; complications relating to impaired airway clearance often require chest physiotherapy and antibiotic administration.

In suspected cases of TEF, the diagnosis is made by injecting contrast via a nasogastric tube in the prone position and monitoring by fluoroscopy as the tube is withdrawn up from the midesophagus. Surgical repair involves a cervical approach in most cases with ligation of the fistula and either primary or subsequent repair of the atresia. Recurrent laryngeal nerve injury is a risk of the procedure.

Etiology and Pathogenesis

These lesions occur early in lung development, and the degree to which they affect the rest of the lung depends on their size and position. Classification of parenchymal lesions is a controversial topic, but most authors agree that descriptive terms based on imaging (e.g., presence or absence of cysts) are preferable to the assignment of histologic terms until a tissue diagnosis is made.

Congenital lobar emphysema (CLE) describes cases of an overdistended, hyperlucent lobe (Figure 39-2). The most commonly affected region is the left upper lobe (42% of cases). CLE may be caused by partial bronchial obstruction producing a ball-valve effect or a deficiency of bronchial cartilage. Less commonly, alveolar hyperplasia produces a polyalveolar lobe.

Figure 39-2 Congenital lobar emphysema.

Congenital cystic adenomatoid malformation (CCAM) or congenital pulmonary airway malformation (CPAM) represents a broad spectrum of hamartomatous defects resulting from developmental arrest during morphogenesis of the bronchial tree. Genetic defects, including mutations in the platelet-derived growth factor B gene, have been proposed to trigger abnormal cell signaling and proliferation resulting in these defects. Histologically, there are five types, although some are not cystic, and only type 3 is adenomatoid. Type 1 is the most common, occurring in 50% of cases. It is usually localized to a single lobe with no regional predilection (Figure 39-3). The cysts are lined with bronchial cells and hyperplastic mucous cysts. In rare situations, this hyperplasia extends into surrounding parenchyma and is reclassified as bronchoalveolar carcinoma. Type 2 is the next most common histologic pattern consisting of bronchiolar cell hyperplasia within the cysts.

Figure 39-3 Congenital bronchogenic and pulmonary cysts.

Bronchogenic cysts are a type of foregut duplication cyst produced when a segment of bronchial-type tissue separates from the developing bronchial tree. The cysts are lined with ciliated bronchial epithelium and contain cartilage in their walls, which differentiates them from simple foregut cysts. The majority of these cysts are located in the mediastinum close to the main carina and usually do not communicate with the tracheobronchial tree (see Figure 39-3).

Pulmonary sequestrations are generally thought to be masses of nonfunctioning pulmonary tissue derived from accessory foregut budding. They have no connection with the tracheobronchial tree and receive their arterial supply from the systemic circulation; in 20% of cases, the systemic artery is subdiaphragmatic in origin. Whereas extralobar sequestrations usually have both arterial and venous systemic blood supply, the venous drainage of intralobar sequestrations is by pulmonary veins (Figure 39-4). Extralobar sequestrations are covered by their own pleura; in contrast, intralobar sequestrations are surrounded by the same visceral pleura as the rest of the lung. In 40% of cases of extralobar sequestration, there are associated anomalies, including hindgut duplications or congenital heart defects. Histologically, in both types, there are cystic, nonaerated bronchial and alveolar tissue.

Figure 39-4 Bronchopulmonary sequestration.

Pulmonary hypoplasia is defined as lung weight more than 2 standard deviations below the normal range for age. Causes include congenital diaphragmatic hernia (CDH), oligohydramnios, thoracic cage anomalies, and giant omphalocele. In cases of CDH, pulmonary hypoplasia most likely occurs before abdominal contents migrate into the thorax, but the additional insult of a space-occupying lesion further contributes to hypoplasia (Figure 39-5).

Figure 39-5 Congenital diaphragmatic hernia.

Clinical Presentation

Because of improvements in ultrasound imaging techniques, many parenchymal lung lesions are now detected antenatally at the time of prenatal screening. Postnatally, infants may present early with progressive tachypnea and respiratory distress without signs of upper airway obstruction (no stridor). With large thoracic lesions that interfere with fetal swallowing, there may be a history of polyhydramnios and possible premature labor. In cases of CLE and CCAM, mediastinal shift or pneumothorax may be appreciated on examination. High-output cardiac failure can be present in cases of pulmonary sequestration with significant arteriovenous shunting, but most cases of sequestration are asymptomatic, at least initially. In cases of pulmonary hypoplasia, the precipitating factor may be evident on examination (e.g., a “bell-shaped” chest wall deformity of thoracic dystrophy or scaphoid abdomen of CDH). Other features concerning for possible CDH include mediastinal shift with apparent dextrocardia (90% of cases are left sided), decreased breath sounds over the affected side, and audible bowel sounds in the chest resulting from visceral herniation.

Many parenchymal lesions may remain asymptomatic initially but present in later life as recurrent pneumonia in the same location if they become infected; less commonly, an abscess will develop within the lesion. Some lesions will be identified coincidentally on a chest radiograph as a focal solid or cystic mass or area of hyperlucency. Rarely, cystic lesions can present in later life with a pneumothorax or hemothorax or even undergo malignant transformation.

Evaluation and Management

Etiology and Pathogenesis

Pulmonary vascular malformations are rare congenital anomalies, but when present, they can cause significant morbidity. Pulmonary arteriovenous malformations (AVMs) can be found as isolated lesions or in association with another parenchymal anomaly (e.g., sequestration). Most commonly, they occur in association with hereditary hemorrhagic telangiectasia. Alveolar capillary dysplasia (ACD) is a life-threatening malformation of poorly developed alveolar capillaries often associated with misalignment of the pulmonary veins, which travel in the bronchoarterial bundle rather than in the septae. Scimitar syndrome is another rare vascular anomaly involving aberrant pulmonary venous drainage, usually of the right lung to the inferior vena cava below the diaphragm.

Clinical Presentation

Large PAVMs present with evidence of right-to-left shunting with cyanosis, exercise limitation, and occasionally cardiac failure. Patients often have evidence of digital clubbing and a systolic murmur. Occasionally, a bruit can be heard over the AVM; this can be accentuated by having the patient inspire against a closed glottis (Mueller maneuver). Hemoptysis is also a concerning feature. There may be evidence of telangiectasias on the lips, under the tongue, between the fingers, or elsewhere. Scimitar syndrome can also present in infancy with cardiac failure and respiratory distress. Here, however, the shunt is left to right, cyanosis is absent, and the respiratory distress is likely the result of associated pulmonary hypoplasia or congenital heart disease. ACD presents with progressive respiratory failure and pulmonary hypertension in early life that is typically refractory to all forms of treatment. These infants will improve with ECMO but will not tolerate its withdrawal.

Evaluation and Management

The chest radiograph can be normal or it may reveal only poorly defined opacities or a “vascular blush.” In cases of scimitar syndrome, the typical scimitar sign representing the anomalous vein can be seen. A contrast echocardiogram (“bubble study”) in which agitated saline is injected can disclose the late phase shunt typical of PAVMs. High-resolution contrast CT scanning, pulmonary angiography, or cardiac catheterization, however, is usually necessary for definitive diagnosis. PAVMs can often be managed by embolization using coils or sclerosing agents, but surgical resection is occasionally required. The prognosis in cases of multiple AVMs is poor, and lung transplantation may be the only recourse in some instances. Scimitar syndrome can be managed expectantly or initially by coil embolization of the anomalous vessel. If correction is required, however, definitive surgery with redirection of the anomalous vein to the left atrium is eventually required. Diagnosis of ACD can only be made by lung biopsy. If not managed with lung transplantation as soon as possible, the condition is fatal.

Future Directions

As antenatal screening has become more routine and imaging techniques have improved, we now know that many of these lesions regress spontaneously. Physicians thus are being faced with the dilemma of when to intervene and how best to follow those lesions treated expectantly. Additionally, some malformations are only diagnosed incidentally. Therefore, there is a need for documentation of long-term outcomes of all cases of congenital lung lesions, including those treated antenatally.

Nomenclature of congenital lung parenchymal lesions remains confusing, with various terms used by different authors; for example, CCAM, CPAM, and cystic congenital thoracic malformation all refer to a similar but unclear diagnosis. A universal classification system needs to be developed to avoid confusion over diagnosis.

Strategies for postnatal diagnosis also continue to be refined with MRI in particular offering an imaging modality free of radiation. Controversy remains also as to whether “compensatory” lung growth occurs in infants with pulmonary hypoplasia. Many infants who are temporized in infancy and early childhood may well outgrow their pulmonary vascular supply as teenagers or young adults, thus rendering them the sickest in this complex group. Ongoing research is addressing methods of stimulating lung growth both in and ex utero for infants with pulmonary hypoplasia.