Congenital Lobar Emphysema

Etiology

In half of patients with CLE, the underlying etiology is idiopathic. In 25% of the patients, CLE is caused by absent bronchial cartilage, hypoplasia, or dysplasia, resulting in bronchial collapse and, thus, air trapping during expiration. Other CLE etiologies include: 

• Parenchymal diseases
• External bronchial obstruction
• Internal bronchial obstruction [2] 

CLE could be caused by parenchymal disease, including the theory of polyalveolar lobes in which experts have proposed that a 3- to 5-fold increase in the number of alveoli develops in the affected lung lobes compared to normal lobes. The mechanism of underlying air trapping in polyalveolar lobes is not known.[3] CLE could also be due to internal bronchial disease. The bronchial disease can be stenosis, atresia, or bronchomalacia.[4][5] Diseases from structures adjoining lungs or bronchi (eg, vessels and mediastinal masses) may also cause CLE.[6]

Epidemiology

The incidence of CLE among live births is 1 out of 20,000 to 30,000.[1] The occurrence is more in men than women, with a ratio of 3 to 1. CLE is more common in infants, with 33% of the cases being symptomatic at birth, and is extremely rare among adults. Due to the severity of symptoms, most are diagnosed within the first 6 months of birth. The left upper lobe is most commonly involved (43%), followed by the right middle lobe (32%) and right upper lobe (21%). The involvement of the lower lobe is rare and only seen in 2% of cases.[2] A quarter of the cases are caused by deformity of bronchial cartilages, and another quarter are due to obstruction of bronchi. CLE is also associated with anomalies of other systems, especially cardiac, in up to 20% of the cases.[7]

Reproductive outcomes vary significantly among different racial and ethnic groups, with Black individuals experiencing a greater incidence of preterm births, low birth weights, and infant mortality compared to White individuals. Studies have shown that the prevalence of certain birth defects differs among these groups. While the overall risk of congenital anomalies is similar between White and Asian individuals, Asians have a higher likelihood of developing craniofacial and musculoskeletal anomalies, according to research results by Egbe A et al (2015).[8][9]

Pathophysiology

CLE is a rare cystic lung malformation characterized by the overinflation of a pulmonary lobe. This hyperinflation of alveoli causes a mediastinal shift to the opposite side, compressing the contralateral lung and leading to the collapse of the remaining lung. Although 90% of cases present before 6 months of age, CLE can manifest as late as 5 years old, with boys more commonly affected than girls. The primary symptoms include respiratory distress, dyspnea, recurrent respiratory tract infections, and cyanosis. Literature reviews indicate that the left upper lobe is most frequently impacted, followed by the middle and right upper lobes, with the lower lobes rarely affected.[10]

Histopathology

Congenital cystic pulmonary lesions are represented by the following entities: congenital pulmonary airway malformation (CPAM), formerly congenital cystic adenomatoid malformation, extralobular and intralobular sequestration, CLE (overexpansion), and bronchogenic cyst. The developmental model of CPAM histogenesis by Stocker proposed perturbations designated as CPAM type 0 to type 4 without known or specific pathogenetic mechanisms along the airway from the bronchus to the alveolus.[11] Additionally, mutational events may occur either at the bodily level in KRAS (CPAM types 1 and possibly 3) or germline variants in congenital acinar dysplasia, formerly CPAM type 0, and pleuropulmonary blastoma, type I, formerly CPAM type 4. The potential for overt malignant progression exists in the case of pleuropulmonary blastoma type I and CPAM type 1 in some cases to well-differentiated mucinous adenocarcinoma. On the other hand, CPAM type 2 is an acquired lesion resulting from an interruption in lung development secondary to bronchial atresia. The latter is also regarded as the etiology of extralobular and intralobular sequestration, whose pathologic features are similar, if not identical, to CPAM type 2. These observations have provided important insights into the pathogenetic mechanisms in the development of the CPAMs since the Stocker classification.[12]

Histologically, no tissue destruction was observed, such as in acquired emphysema. Additionally, no destruction of alveolar walls and septum occurs, and normal acinus structure is present. However, no acinar maturation with age and overinflated alveoli are observed. The primary forms of CLE are hypoalveolar and polyalveolar. In many CLE cases, normal numbers of radial alveoli are present. Nonetheless, no remarkable progression with age is noted compared to normal individuals, inferring that acinar development in the concerned lung ends in the postpartum period. In the hypoalveolar form, fewer than the expected number of alveoli are present, while the polyalveolar form has more alveoli than expected.[3] The airways and arteries are normal in number, size, and structure.

History and Physical

Persistent wheezing in infants frequently requires a thorough etiological investigation for accurate diagnosis. Early onset and the lack of a symptom-free period between wheezing episodes can suggest the presence of malformations. One of them is CLE, a prevalent bronchopulmonary malformation marked by the overinflation of a lung lobe without parenchymal destruction. CLE presents as respiratory distress due to lung lobe overexpansion, compressing adjacent lobes, leading to air entrapment during expiration and recurrent respiratory distress, typically identified during the neonatal stage or later in childhood.[13]

Almost 50% of the patients are symptomatic at birth, and the other 50% become symptomatic within the first 6 months of life. The patient usually presents with difficulty in feeding and breathing, wheezing, retractions, and cyanosis. A history of chronic cough and recurrent respiratory infections is commonly noted. Due to overlapping symptoms, some patients are misdiagnosed with pneumonia or pneumothorax instead of CLE.[4] Lobes affected with CLE are overinflated; thus, ventilation and perfusion are impaired. Due to progressive overinflation, adjacent organs are compressed, leading to further impairment of ventilation or perfusion and, ultimately, respiratory failure. On physical examination, wheezing and rhonchi can frequently be auscultated. The affected lobe is hyperresonant on percussion, and breath sounds are diminished in the area. Congenital cardiac defects are typically associated with CLE.[14]

Evaluation

Clinicians should have a high clinical suspicion for CLE to be able to diagnose patients presenting with symptoms in a timely fashion. Patients with CLE develop air-trapping and hyperinflation in the affected lobes, which are also poorly perfused. Pediatric and adult radiologists need to be familiar with the radiological features of CLE to maximize diagnostic accuracy. Additionally, patients with CLE can be diagnosed prenatally. Affected fetal lungs with CLE can show hyperechogenicity without abnormal blood flow and may also be accompanied by polyhydramnios or mediastinal shift. Magnetic resonance imaging (MRI) is also safe prenatally to confirm the diagnosis.[15][16]

A chest radiograph is typically the initial imaging study performed, which may reveal a distended, hyperlucent affected lobe with a fine vascular network, with this distension pushing the mediastinum and compressing the ipsilateral lobe (see Image. Congenital Lobar Emphysema). A chest computed tomography (CT) scan is preferred for a more specific diagnosis and to determine the topography, which helps evaluate the affected lobe and surrounding structures. CT scan of the chest with intravenous contrast can help evaluate the vascular anomalies related to CLE. The left upper lobe is most commonly affected (43%), followed by the right middle lobe (32%) and the right upper lobe (21%), with the lower lobes being rarely affected (<1%). Bilateral CLE has been documented but is uncommon.[17][18]

MRI with 3-dimensional and vascular sequences is an alternative diagnostic tool that does not require contrast injection and helps identify malformations with a vascular component. In atypical cases, bronchoscopy may be performed to rule out an intrabronchial foreign body, mucous plug, or bronchial anomaly contributing to emphysema. Lung scintigraphy is valuable for visualizing ventilation and perfusion disorders in the affected area and distinguishing CLE from compensatory emphysema.[19][20] However, the definitive diagnosis is typically confirmed through pathological examination following surgical excision, the standard CLE treatment.

Treatment / Management

The clinical severity of patients with CLE defines the treatment of choice. Apart from a few patients who are asymptomatic, almost half show symptoms within the first month of birth. Patients with mild or moderate symptoms could be treated conservatively. Lobectomy is the gold standard for treatment in cases with severe symptoms; however, the conservative treatment seems to increase due to antenatal diagnosis and intrauterine regression.[21][22](B2)

In those undergoing lobectomy, all procedures are performed under general anesthesia using a single-lumen endotracheal tube, with patients positioned laterally. For those undergoing open thoracotomy, a muscle-sparing lateral thoracotomy should be employed. The distended lobe usually protrudes from the thoracic cavity once the chest is opened. The pulmonary artery branches are ligated first, followed by the vein, and finally, the bronchus.

For patients having a thoracoscopic lobectomy, CO₂ is insufflated at a pressure of 4 mm Hg, with a maximum of 6 mm Hg, to deflate the lung. Port positions are customized for each patient; an extra port is occasionally used for retraction. During lower lobectomy, the ports are positioned as low as possible. The affected lobe is resected and removed through a mini-thoracotomy. At the end of the procedure, the intrathoracic CO₂ is evacuated, and a small chest tube is inserted.[23][24][25](B3)

Differential Diagnosis

Differential diagnoses that should also be considered when evaluating CLE include:

• Congenital cystic adenomatoid malformations: CLE and congenital cystic adenomatoid malformation type III have similar ultrasound findings, showing a highly echogenic mass. Congenital lobar emphysema is devoid of cystic lesions compared to cystic adenomatoid malformation.[26]
• Pneumonia: Patients with pneumonia present with fever, chest retractions, and cyanosis. The affected lung on the chest radiograph may present with collapse consolidation, which usually improves with antibiotics; unlike CLE, the affected lung in pneumonia is not hyperinflated.[21]
• Tension pneumothorax: Like CLE, patients with tension pneumothorax also present with respiratory distress; the physical examination will reveal hyperresonance and decreased breath sounds on the affected lung, and the chest radiograph will show that the mediastinum deviates to the contralateral lung. Tension pneumothorax is a medical emergency, and patients have hypotension, and it needs prompt decompression. The chest radiograph of the affected lung in tension pneumothorax shows depression of the hemidiaphragm, which is not seen in CLE.[27]
• Congenital diaphragmatic hernia: CLE and congenital diaphragmatic hernia present with hyperlucent lung on chest radiograph and can be differentiated from CLE because of the gas-filled bowel loops in the chest.[28]

Prognosis

The prognosis following surgical resection is excellent in patients with CLE. In a single institution case series, between January 2015 and January 2019, 37 neonates and infants with congenital lobar overinflation were treated, with an average age of 111.43 plus or minus 65.19 days, and 22 were boys. All cases exhibited respiratory distress, and 19 also presented with cyanosis. Fifteen cases had recurrent pneumonia and fever. Clinical findings included diminished breath sounds on the affected side in 30 cases and wheezes in 22 cases. Emphysema was observed in all cases via chest radiograph, and confirmatory chest CT scans were performed. The left upper lobe was affected in 23 cases, the right middle lobe in 7 cases, and the right upper lobe in 7 cases.

Lobectomy was performed on 31 patients, with a mean age of 147.58 plus or minus 81.49 days at the time of surgery, and 19 of these patients were male. Postoperative complications occurred in 5 cases, with 2 requiring postoperative ventilation. No morbidity or mortality was reported. Follow-up periods ranged from 3 months to 1 year, and all patients were doing well except for one who was lost to follow-up after 3 months.[7] In mild and moderate cases, nonsurgical conservative management has good results. In patients with severe symptoms, lobectomy has an excellent prognosis, and mortality with surgery is very low.[29]

Complications

CLE can have the following complications:

• Cyanosis
• Respiratory failure
• Surgical complications due to lobectomy
• Infantile death