Congenital lobar emphysema

INTRODUCTION — Congenital lobar emphysema (CLE), also known as congenital alveolar overdistension, is a developmental anomaly of the lower respiratory tract that is characterized by hyperinflation of one or more of the pulmonary lobes [1,2]. Other terms for CLE include congenital lobar overinflation and infantile lobar emphysema [3-5].

EPIDEMIOLOGY — CLE is a rare congenital malformation with a prevalence of 1 in 20,000 to 1 in 30,000 [6]. CLE was diagnosed in 10 of 70 patients with congenital malformations of the lung seen from 1970 to 1995 at Children's National Medical Center in Washington, D.C. [7]. A case series indicated that CLE comprised 53 of 506 (10.5 percent) congenital lung malformations treated by 11 collaborating children's hospitals [8]. Depending upon the pattern of referrals, other tertiary medical centers may treat one or two cases per year [3,9].

Males appear to be affected more than females, in a ratio of 3:1 [1]. The reason for the male predominance is unknown [1,3,5].

PATHOGENESIS — Progressive lobar hyperinflation is likely the final common pathway that results from a variety of disruptions in bronchopulmonary development. These result from abnormal interactions between embryonic endodermal and mesodermal components of the lung. Disturbances may lead to changes in the number of airways or alveoli or alveolar size [10]. However, a definitive causative agent cannot be identified in approximately 50 percent of cases [11].

The most frequently identified cause of CLE is obstruction of the developing airway, which occurs in 25 percent of cases [1]. Airway obstruction can be intrinsic or extrinsic, with the former being more common. This leads to the creation of a "ball-valve" mechanism, in which a greater volume of air enters the affected lobe during inspiration than leaves during expiration, producing air trapping.

Intrinsic obstruction often is caused by defects in the bronchial wall, such as deficiency of bronchial cartilage. This results in airway collapse during expiration. Intraluminal obstruction caused by meconium or mucous plugs, granulomas, or mucosal folds can cause partial obstruction of a lower airway. Extrinsic compression may be caused by vascular anomalies, such as a pulmonary artery sling or anomalous pulmonary venous return, or intrathoracic masses, such as foregut cysts and teratomas. Additionally, bronchial atresia has been identified as a common finding in CLE and other congenital cystic pulmonary malformations [12].

PATHOLOGY — CLE is characterized by overdistention of one or more lobes of the lung [13]. This leads to compression of the remaining lung tissue and herniation of the affected lobe across the anterior mediastinum into the opposite chest, causing displacement of the mediastinum.

The different pulmonary lobes are variably affected by CLE. The left upper lobe is affected most often (40 to 50 percent of cases) [1,3,14,15]. The distribution in right middle, right upper, and lower lobes is 25 to 35, 20, and 2 to 10 percent, respectively. CLE affecting multiple lobes is rare.

Gross inspection of tissue specimens typically demonstrates hyperexpansion of the affected lobe with parenchymal pallor (picture 1). Histologic findings are variable [3]. They range from simple, uniformly enlarged distal airways and airspaces (picture 2) to a polyalveolar form. In the latter, the conducting airways are normal in size and number, but the alveoli within the gas exchange units are enlarged and increased in number. True emphysematous changes are lacking in both types, leading some experts to use the term congenital lobar overinflation rather than emphysema. Abnormal cartilage, granulation tissue, mucosal folds, or other anomalies occasionally are detected.

CLINICAL FEATURES — Affected infants usually are symptomatic in the neonatal period [8]. Approximately 25 to 33 percent of cases present at birth, 50 percent by one month of age, and nearly all by six months of age [1,3].

Progressive respiratory distress develops rapidly in some infants, while others have a more gradual, insidious onset [1,3-5,7,9,16,17], and some may remain asymptomatic for years [18,19]. The severity depends upon the size of the affected lobe, the compression of surrounding lung tissue, and the extent of mediastinal shift.

Infants typically have tachypnea and increased work of breathing and often have cyanosis [1,3,4,7,9]. Recurrent pneumonia or poor feeding with failure to thrive are less frequent presentations that may occur in milder forms.

Physical examination reveals respiratory distress that often is accompanied by wheezing caused by airway compression. Breath sounds are decreased over the involved lobe, which is hyperresonant to percussion. Depending upon the extent of mediastinal shift, the cardiac point of maximal impulse may be displaced.

Other congenital anomalies often accompany CLE and may be apparent on examination. Cardiovascular anomalies are present in 14 percent of cases [1]. Renal, gastrointestinal, musculoskeletal, and cutaneous disorders also may occur.

DIAGNOSIS — The diagnosis of CLE often can be made from its characteristic appearance on a chest radiograph (image 1) [5,17]. The chest film typically demonstrates distension of the affected lobe and mediastinal shift, with compression and atelectasis of the contralateral lung. The diaphragm often appears flattened because of hyperinflation.

If the chest radiograph is obtained immediately after birth, the affected lobe may appear opacified due to retained fetal lung fluid. As the fluid is absorbed and the lobe becomes filled with air, progressive hyperinflation develops.

Computed tomography (CT) of the chest or magnetic resonance imaging (MRI) may help establish the diagnosis of CLE in atypical cases and may demonstrate an intrinsic or extrinsic source of airway obstruction [17,20,21]. Studies with contrast may also demonstrate vascular causes of airway compression and resultant emphysematous changes. Alternatively, echocardiography may identify vascular structures causing airway compression.

CT may establish a diagnosis of CLE in some infants with persistent respiratory distress and a nondiagnostic chest radiograph [22]. It also is helpful to define cystic pulmonary lesions detected by prenatal ultrasonography [11]. Rarely, CT findings are nondiagnostic and definitive diagnosis is possible only on histologic evaluation [23].

Ventilation/perfusion lung scans demonstrate decreased ventilation and perfusion in the affected lobe [1]. However, they usually are not necessary for the diagnosis of CLE. Bronchoscopy also is usually not necessary for diagnosis but may identify a source of airway obstruction.

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

Prenatal diagnosis — CLE sometimes is detected by prenatal ultrasonography. A case series reported that 24.5 percent of CLEs, compared with 73.1 percent of other congenital abnormalities, were identified on prenatal ultrasound. However, in all of these cases, CLE was initially misidentified as congenital pulmonary airway malformation (CPAM; previously known as congenital cystic adenomatoid malformation [CCAM]), bronchopulmonary sequestration, or unspecified. CLE lesions have increased echogenicity and/or a cystic appearance and usually can be differentiated from other congenital lung lesions [24,25]. CLE lesions may decrease in size during pregnancy, similar to other congenital lung lesions [11,24]. The imaging abnormality may even disappear on prenatal ultrasound and become apparent again on postnatal evaluation [26]. Predictors of severe respiratory distress or mortality include polyhydramnios, fetal hydrops, and lung to thorax transverse area ratio (L/T value) of less than 0.25 [27].

Differential diagnosis — The radiographic appearance of hyperlucency of the lung can be caused by a reduction in pulmonary blood flow or by a hyperinflation process with normal or reduced pulmonary blood flow. Thus, CLE can mimic a variety of congenital and acquired disorders [28,29]:

●Pneumothorax or localized pulmonary interstitial emphysema – Localized pulmonary interstitial emphysema typically develops in infants who are mechanically ventilated at high airway pressures. Definitive diagnosis prevents potential complications related to unnecessary interventions such as tube thoracostomy [30]. The emphysematous lobe in CLE usually has linear bronchovascular and alveolar markings, while these markings are absent in pneumothorax. (See "Pulmonary air leak in the newborn".)

●Localized pulmonary hyperinflation – This can be caused by obstruction of the airway by a foreign body, congenital bronchial atresia, or by a mass such as a bronchogenic cyst or a pulmonary artery sling (anomalous origin of the left pulmonary artery). (See "Airway foreign bodies in children" and "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula".)

●Space-occupying chest lesions – Space-occupying lesions usually are easily distinguished from CLE by the radiographic findings. These include CPAM, bronchopulmonary sequestration, and congenital diaphragmatic hernia. (See "Bronchopulmonary sequestration" and "Congenital pulmonary airway malformation".)

●Pulmonary growth abnormalities – Pulmonary growth abnormalities including agenesis of the pulmonary vasculature and agenesis of a lung can mimic CLE by causing hyperinflation of the contralateral lung. (See "Radiographic appearance of developmental anomalies of the lung", section on 'Agenesis'.)

●Swyer-James-MacLeod syndrome (SJM), also known as unilateral hyperlucent lung syndrome, is an uncommon disease that results in decreased pulmonary vascularity and hyperinflation that may be confined to one lung or one lobe, with or without bronchiectasis [31]. SJM is now thought to be a postinfective form of bronchiolitis obliterans. Infections with adenovirus, measles, Bordetella pertussis, tuberculosis, Mycoplasma pneumoniae, respiratory syncytial virus, and influenza A have been implicated [32-34]. CLE and other developmental pulmonary anomalies, such as unilateral pulmonary artery agenesis, may mimic the findings of SJM on plain radiograph but are distinct entities [35]. These disorders usually can be distinguished from SJM by further evaluation with CT and/or ventilation and perfusion scanning.

In contrast to CLE, many patients with SJM are asymptomatic and only diagnosed when chest radiographs are obtained for other indications. Airflow obstruction is generally present on pulmonary function testing, and ventilation/perfusion scanning often reveals a matched ventilation and perfusion defect of the affected lung [35,36]. In SJM, the affected lung typically has normal to small lung size, whereas in CLE, the affected lobe is expanded. Complications of SJM include recurrent infection in areas of bronchiectasis, lung abscess, and spontaneous pneumothorax [37,38]. Treatment is generally conservative, but pneumonectomy can be considered in patients with severe bronchiectasis complicated by recurrent infections [33,34,39].

●Poland syndrome – Poland syndrome is a constellation of congenital anomalies that include hypogenesis of the muscles of the anterior chest wall and breast tissue. This can lead to a unilateral hypolucency of the chest radiograph, which is differentiated from intrathoracic causes of hypolucency by chest CT [28]. (See "Chest wall diseases and restrictive physiology", section on 'Poland syndrome'.)

TREATMENT — The management of CLE depends on whether symptoms are present. The vast majority of lesions are symptomatic and require early resection. For asymptomatic patients, conservative management usually is appropriate because they are unlikely to develop complications. By contrast, the management of asymptomatic patients with other types of congenital abnormalities of the lower airway is controversial, with arguments made for and against surgical resection [40,41]. This is because these other lesions may be associated with risks for infection or malignancy, which is not the case in CLE. (See "Congenital pulmonary airway malformation", section on 'Asymptomatic patients'.)

Symptomatic patients — The appropriate treatment of CLE in newborns with respiratory distress is surgical resection of the affected lobe [42-45]. Historically, this was done by open thoracotomy, but minimally invasive techniques are now often used for resection of these lesions, resulting in decreased morbidity [46]. Case series show good outcomes for symptomatic patients managed with surgery [16,47,48]. In long-term follow-up, patients treated with surgery may have generalized overinflation on chest radiography and pulmonary function abnormalities that are proportional to the volume of lung that was excised; wheezing is the most common clinical symptom [48,49].

Asymptomatic patients — Conservative management is reasonable in infants and older children who have no or minimal symptoms [50], although some infants who are asymptomatic at birth may develop progressive respiratory symptoms over time, which may require surgical management. The conservative approach for infants and older children with mild symptoms is supported by a small number of case series that demonstrated clinical, and sometimes radiologic, improvement in patients treated conservatively and similar long-term outcomes in mildly symptomatic patients treated surgically or conservatively, as illustrated by the following observations:

●In a report of 30 children with CLE diagnosed over a 27-year period, nine were followed conservatively [47]. The duration of follow-up ranged from 1 month to 17 years, and all patients demonstrated decreased hyperexpansion of the affected lobe.

●In a report of 20 children (0 to 17 years) with CLE who were treated at a single institution between 1995 and 2002, eight were identified antenatally [19]. Among the 11 patients who were symptomatic at presentation, six with mild symptoms were managed conservatively and showed spontaneous clinical and/or radiologic improvement during follow-up ranging from six months to eight years.

●A report of 14 children (25 days to 2.5 years) with CLE who were treated at a single institution between 1991 and 1998 included four children who had mild symptoms and presented at an older age, who were followed conservatively [16]. These children became asymptomatic during the follow-up period of three months to four years, although radiographic abnormalities persisted.

●In a study from 1976, outcomes at an average age of 10 years were similar in six patients with CLE who were treated surgically and five who were managed conservatively [48]. Patients who were managed conservatively had no or minimal symptoms in the neonatal period, and all were asymptomatic at follow-up. Chest radiographs showed localized overinflation of the affected lobe and minimal compression of the remaining lung parenchyma. They had decreased forced vital capacity (FVC), large trapped-gas volume, and reduced forced expiratory flows (FEF) at low lung volumes that were proportional to the unventilated volumes of lung that were chronically obstructed and are similar to the pulmonary function abnormalities in patients treated with surgery.

SUMMARY AND RECOMMENDATIONS

●Pathogenesis – Congenital lobar emphysema (CLE), also known as congenital alveolar overdistension, is a developmental anomaly of the lower respiratory tract that is characterized by hyperinflation of one or more of the pulmonary lobes. Some cases are attributable to obstruction of the developing airway, which leads to air trapping. Many infants have associated anomalies, particularly of the cardiovascular system. (See 'Pathogenesis' above.)

Hyperinflation of one or more lobes of the lung leads to compression of the remaining lung tissue and herniation of the affected lobe across the anterior mediastinum into the opposite chest, causing displacement of the mediastinum. (See 'Pathology' above.)

●Clinical presentation – Approximately 25 percent of cases present at birth, 50 percent by one month of age, and nearly all by six months of age. Infants typically have tachypnea and increased work of breathing and often have cyanosis. Recurrent pneumonia or poor feeding with failure to thrive are less frequent presentations that may occur in milder forms. (See 'Clinical features' above.)

●Diagnosis – The diagnosis of CLE often can be made from its characteristic appearance on a chest radiograph (image 1). The chest film typically demonstrates distension of the affected lobe and mediastinal shift, with compression and atelectasis of the contralateral lung. Some cases are detected by prenatal ultrasonography. (See 'Diagnosis' above.)

●Differential diagnosis – The radiographic appearance of CLE should be differentiated from pneumothorax or localized pulmonary interstitial emphysema (or, pulmonary air leak), which typically develops in mechanically ventilated infants. The differential diagnosis includes other space-occupying lesions such as congenital pulmonary airway malformation (CPAM), bronchopulmonary sequestration, bronchogenic cyst, congenital diaphragmatic hernia, and Swyer-James-MacLeod syndrome (SJM; unilateral hyperlucent lung syndrome). (See 'Differential diagnosis' above.)

●Management – For newborns with respiratory distress due to CLE, treatment consists of surgical resection of the affected lobe. For infants and older children who have no or minimal symptoms, conservative management is reasonable. Some infants who are asymptomatic at birth may also develop progressive respiratory symptoms over time and may require surgical management. (See 'Treatment' above.)