Swyer-James-MacLeod Syndrome

Etiology

Initially, Swyer-James-MacLeod syndrome was believed to be congenital in origin, secondary to inborn hypoplasia of the pulmonary artery. Although its definitive cause remains uncertain, it is now widely accepted to be a rare complication of childhood respiratory infections, most commonly bronchiolitis obliterans or pneumonitis. The causative agents implicated in the recurrent pulmonary infections include viruses (measles, respiratory syncytial virus, influenza A, Paramyxovirus morbillivirus, adenovirus types 3, 7, and 21) and bacteria (Bordetella pertussis, Mycobacterium tuberculosis, Mycoplasma pneumoniae).[5][3][6][7][8]

Epidemiology

Due to its rarity, little is known about the overall incidence of Swyer-James-MacLeod syndrome. Despite its first characterization in 1953, the available literature comprises mostly individual case reports and series. One study reported a prevalence of 0.01% in a series of 17,450 reviewed chest radiographs.[8] Many cases remain undiagnosed or are treated as other conditions, such as asthma or bronchiectasis, due to the diagnostic challenges.[9] SJMS has been reported to occur in approximately 4% of patients with bronchiolitis obliterans. For unclear reasons in most patients, there is a preferential involvement of the left lung.[10][11]

Pathophysiology

Swyer-James-MacLeod syndrome, also known as Swyer-James syndrome and Bret syndrome, is considered a result of postinfectious obliterative bronchiolitis. 

Bronchiolitis obliterans (or obliterative bronchiolitis) describes a clinical syndrome of small airway obstruction that is irreversible to bronchodilators. It is triggered by the injury of the bronchiolar epithelium and possibly the adjacent alveoli. This damage, which occurs during early childhood, hinders the normal development of the alveolar ducts.

The injury may be caused by a range of factors, with respiratory infections playing a major role in Swyer-James-MacLeod syndrome. While complete recovery is possible, the repair process may lead to a surplus proliferation of granulation tissue, resulting in narrowing or complete obliteration of the small airways. Unilateral recurrent small airway obstruction involving terminal bronchi and bronchioles occurring early in life triggers an inflammatory response, which leads to the development of submucosal fibrosis.[10] The resulting luminal irregularity further contributes to airway occlusion, becoming more permanent. This, in turn, causes alveolar air trapping, eventually resulting in emphysema, which is defined as permanent overdistention of the airspaces distal to the terminal bronchioles.[1] Alveolar wall destruction leads to the loss of elastic recoil, causing airway collapse during exhalation and air trapping. Therefore, the typical appearance of unilateral hyperlucency can be found on radiographs.

The other, and perhaps more important, factor responsible for the radiographic hyperlucency of a single hemithorax is the reduction of the pulmonary blood flow. Fibrosis of the interalveolar septae leads to obstruction of the pulmonary capillary bed and reduces blood flow to the major pulmonary artery branches. Moreover, hyperinflation of alveoli, as seen in emphysema, creates additional mechanical resistance to blood flow through the capillary beds. Since this process occurs early in life, arterial development is thwarted, resulting in hypoplastic pulmonary vasculature.[12]

Additionally, reduced ventilation of the diseased lung or segment also leads to compensatory vasoconstriction of the pulmonary vessels, leading to a functional restriction of the arterial flow, which contributes further to the radiographic hyperlucency.[4][1][13] Functional hypoplasia of the bronchial vasculature may impair the growth of the affected lung, leading to a lung that is either small or normal in size.[3] In some patients with Swyer-James-MacLeod syndrome, bronchiectasis may develop proximal to bronchiolitis obliterans and is likely a sequela of chronic infections.

Histopathology

Histopathological studies in patients with Swyer-James-MacLeod syndrome (SJMS) are scarce and based solely on the limited number of cases that required surgical intervention.

Histological studies of the diseased lung frequently demonstrate emphysema with dilated bronchioles and cystic dilatation of the alveoli, as well as constrictive bronchiolitis.[14] Emphysema is usually patchy and may be of the panacinar type.[15][1] Other potential changes include mucus plugging and chronic inflammation.[1] Some studies reported hypoplasia of the pulmonary artery and the alveoli.[16] However, there is some speculation that the hypoplasia of the pulmonary vasculature seen on imaging is primarily functional (reflecting reduced blood flow) as some pathological studies resected lungs in SJMS demonstrated a pulmonary artery of normal caliber or only slightly smaller than expected.[1]

History and Physical

Many patients with Swyer-James-MacLeod syndrome are asymptomatic, whereas some suffer from recurrent pulmonary infections. Some patients are diagnosed in childhood, others incidentally during adulthood when undergoing investigations for a different reason (such as the symptoms of asthma or recurrent chest infections).[15] This rare condition poses a diagnostic challenge as its presentation may be non-specific and mimic other respiratory conditions, including Congenital lobar emphysema(CLE), pneumothorax, or localized pulmonary interstitial emphysema, bronchopulmonary sequestration, Poland syndrome, etc.

When symptomatic, patients most often present with recurrent pulmonary infections or exertional dyspnea.[17][1][18] Other symptoms include wheezes, dyspnea on exertion, reduced exercise tolerance, cough (often productive) with or without hemoptysis, and pleuritic chest pain.[3] Most patients, however, are asymptomatic.[10]

The main physical findings include reduced chest expansion, hyper-resonant on percussion, and decreased breath sounds on the affected side.[3] In cases where the mediastinum is shifted to the affected side, the apex beat may also be displaced.[19][10]

Evaluation

Swyer-James-MacLeod syndrome has a broad spectrum of clinical presentations. Because of its rarity, there are no recommended guidelines regarding diagnostic work-up.

• The first line investigation is usually a posteroanterior chest radiograph, which will reveal reduced bronchovascular markings, a small hilar shadow, and hyperlucency of the diseased segment or lobe.[10] These findings are more prominent on expiration, when the diaphragm on the affected side rises to a lesser extent as the lung deflates only partially, demonstrating a degree of air trapping.[3][4] On expiration, the difference in transradiancy becomes even more obvious as the normal lung deflates and becomes more opaque. The mediastinum may also shift to the affected side but will move towards the normal side on expiration.
• Computed tomography (CT) of the chest is usually the modality of choice used to assess the extent and distribution of the disease. It may demonstrate emphysema, bullae, bronchiectasis, atelectasis, and scarring.[10] Moreover, previous studies showed that CT chest is much more sensitive than plain radiograph as it often demonstrates bilateral lung involvement, and the changes may be inhomogeneous. The scanning protocol should also include some expiratory slices to demonstrate air trapping clearly.[20] Bronchiectasis, present in about 30% of patients with Swyer-James-MacLeod syndrome, may be either of the cylindrical or the saccular type.[10] Distinguishing between the two types is essential, as it predicts the clinical course and prognosis.[2] Patients with saccular type bronchiectasis tend to suffer from more severe exacerbations and have poorer outcomes. If bronchiectasis is suspected based on the clinical features, a high-resolution CT of the chest is advised to ensure the diagnosis is not missed using the conventional CT and to allow correct differentiation.
• A ventilation/perfusion scan may reveal a unilateral matched ventilation and perfusion defect of the diseased area. Some advocate it as the first-line investigation (following a chest radiograph) in the evaluation of patients with suspected Swyer-James-MacLeod syndrome.[21]
• CT pulmonary angiography is not essential but would demonstrate hypoplasia of the pulmonary vasculature in the affected lung or segment.[10]
• SJMS commonly shows a restrictive pattern on pulmonary function tests. Patients with bronchiectasis may have a mixed restrictive-obstructive or even predominantly obstructive defect, where the airflow obstruction is irreversible with bronchodilators.[22][8][23] The total lung capacity(TLC) may be slightly reduced.[23]
• Testings such as alpha-1 antitrypsin deficiency are helpful to exclude rare inherited causes of bronchiectasis/emphysema.[10]

The diagnostic criteria for this syndrome require one of the following:[24]

1. Unilateral loss of lung volume with hyperlucency as demonstrated by chest X-ray
2. Unilateral reduction in vascularity on a computed tomographic scan of the chest
3. Unilateral loss of perfusion on technetium Tc 99m lung scan

Treatment / Management

The management of Swyer-James-MacLeod syndrome is patient-centered and delivered using the interprofessional team approach.

Conservative management is the mainstay of treatment.

Prevention and prompt treatment of recurrent respiratory infections: Primary prevention such as pneumococcal and influenza vaccination is necessary.[10] Mucolytics may be helpful in patients with bronchiectasis. Chest physiotherapy employing techniques like percussion and postural drainage are important to ensure efficient sputum clearance.[23] Corticosteroids and inhaled bronchodilators are also used.[10] In cases of respiratory failure, long-term oxygen therapy may be indicated. Patients should also be referred for pulmonary rehabilitation to maximize respiratory function.(B3)

Surgical intervention is reserved for (1) patients with recurrent pulmonary infections, (2) patients who fail to respond, or (3) patients whose symptoms are not adequately controlled with optimal medical management. Surgical options include pneumonectomy or lung volume reduction surgery, such as lobectomy or segmentectomy.[14] This has previously been achieved without significant morbidity but with a dramatic improvement of symptoms and respiratory function.[1] Lung volume reduction surgery has been particularly successful in patients with significant hyperinflation (secondary to emphysema), as it may exert a favorable effect on the mechanics of the airways, diaphragm, and chest wall.[14](B3)

An interesting new approach has also been proposed in one study, where patients underwent occlusion of the main bronchus while the lung was left in place.[25] It was postulated that this procedure is less traumatic than pneumonectomy as the operation is carried out through a small thoracotomy without the need to enter the pleural space. The disconnected lung acts as a biological prosthesis preventing the herniation and hyperexpansion of the remaining healthy lung and mediastinal displacement. Any possible infection was successfully avoided with the help of bronchial washings and the use of high-dose wide-spectrum antibiotics before and after the surgery. Within two years after surgery, fibroatelectasis of the severed lung is expected to develop, and the inflammation should resolve. Moreover, it is believed that this strategy can be successfully utilized specifically in Swyer-James-MacLeod syndrome because there is no blood flow to the affected lung; if a healthy lung were occluded, right to left shunt and hypoxemia would develop.[25](B3)

Differential Diagnosis

The unilateral hyperlucency of the lung can be due to reduced pulmonary blood flow or hyperinflation of terminal airways. Therefore, conditions with one or both of those features can mimic Swyer-James-MacLeod syndrome.

The differential diagnosis includes both congenital and acquired lung disorders.

• Congenital lobar emphysema (CLE) is a developmental condition of the lower respiratory tract characterized by alveolar overdistention within one or multiple pulmonary lobes.[26] It is believed to be the result of many different abnormalities of bronchopulmonary development. A quarter of cases are caused by obstruction of the developing airway early in life. This leads to air trapping and progressive terminal airway hyperinflation, as more air enters the affected lung segments during inspiration than leaves during expiration (the so-called “ball-valve” mechanism). Characteristic findings on chest X-ray are: (1) distension of the affected lobe, (2) mediastinal shift with compression and atelectasis of the contralateral lung, (3) flattened diaphragm due to hyperinflation.
• Localized pulmonary interstitial emphysema is similar to CLE but develops as a complication of mechanical ventilation at high airway pressures in infants.[27] It may be caused by obstruction of the larger airways by a foreign body, a mass (such as a bronchogenic cyst, bronchopulmonary sequestration, congenital pulmonary airway malformation, congenital diaphragmatic hernia, or pulmonary artery sling), or airway collapse, which may occur if the airway is floppy (like in congenital bronchial atresia).[28][29][30][31][32]
• Pulmonary development abnormalities include pulmonary agenesis, aplasia, and hypoplasia, where a lobe or lung, its bronchi, or vasculature fails to develop completely or partially.[33] This leads to unilateral hyper-expansion and radiographic appearance of hyperlucency closely resembling that seen in Swyer-James-MacLeod syndrome.
• Poland syndrome is a spectrum of congenital chest wall anomalies of unclear etiology, comprising hypo- or agenesis of the anterior chest wall muscles (such as pectoralis major, pectoralis minor, latissimus dorsi, serratus anterior and intercostal muscles), hypoplasia or absence of ipsilateral ribs, and hypoplasia or aplasia of mammary tissue.[34] This gives the radiographic appearance of a unilateral hyperlucent hemithorax, which may mimic Swyer-James-MacLeod syndrome.
• Finally, SJMS may be mistaken for pneumothorax in severe cases, with reduced breath sounds and hyperlucency on a chest radiograph.[12] Careful examination of imaging (especially CT of the chest) as well as clinical assessment allows for the correct diagnosis to be made and prevents unnecessary chest tube placement.

Prognosis

Patients with SJMS generally have a normal life expectancy. While Swyer-James-MacLeod syndrome has a spectrum of manifestations, its clinical course is largely determined by the presence or absence of bronchiectasis. Patients without or only with cylindrical bronchiectasis often suffer from mild respiratory symptoms and tend to improve spontaneously.[2] Those with saccular bronchiectasis, on the other hand, suffer from recurrent episodes of pneumonia and are the ones at the highest risk of requiring surgical intervention.[2]

Complications

The major complication of SJMS is the development of bronchiectasis accompanied by chronic productive cough. Bronchiectasis predisposes patients to further respiratory infections. The presence of bullae also increases the risk of developing a spontaneous pneumothorax and limits the patients' activities in diving or air travel.[35] There have also been reports of SJMS complicated by a lung abscess.[36]

As the lung function gradually declines with time, patients may develop type I respiratory failure and require long-term oxygen therapy. This situation has a significant impact on their independence and quality of life.

Finally, patients requiring surgical procedures are at risk of surgical complications such as infection of surgical sites, nerve damage, pneumothorax, emphysema, and surgical emphysema. However, the risks are extremely small, and in all cases reported to date, patients experienced no morbidity as a result of the surgery, and their lung function improved significantly.[14][25]