Right Middle Lobe Syndrome

Etiology

The obstructive type of middle lobe syndrome usually results from extrinsic compression of the right middle lobe bronchus resulting from peribronchial lymphadenopathy or tumors that exploit the anatomic peculiarities of the right middle lobe bronchus[3]. It can classify into two subtypes: intraluminal or extraluminal obstruction.

Extrinsic compression may involve a plethora of tumors, including hamartomas, primary lung cancers, and distant metastasis from unknown primaries.[3][4] The most common etiology of the obstructive type is often subject to mediation by peribronchial lymphadenopathy secondary to granulomatous diseases, endemic fungal infections, and various mycobacterial species.[4][5][6][7][8] Other more exotic etiologies that cause an intraluminal obstruction, described in previous literature as isolated case reports, include sarcoidosis, aspiration, mucus plugs, and broncholiths.[9]

In the nonobstructive type, there is no identifiable obstruction on bronchoscopic evaluation, and the physiological basis of the recurrent atelectasis is poorly understood. The collateral ventilation of the middle lobe constitutes a zone of high resistance in comparison to the upper lobes, as a result of the higher ratio of pleural to the non-pleural surface area. The hypothesis is that ineffective collateral ventilation may play a significant role in the pathophysiology of middle lobe syndrome. Nonobstructive middle lobe syndrome is usually due to transient hypoventilation in the setting of chronic inflammatory and infectious changes (in conditions like cystic fibrosis) due to a wide array of infections, pulmonary infarcts, bronchopulmonary cysts, or disease processes that predispose to bronchiectasis.[10][9]

Epidemiology

Epidemiological data on middle lobe syndrome is very limited. There have been scattered case series and nationwide studies demonstrating a higher female to male ratio with women presenting later in age than their male counterparts.[9][11] Additionally, the poorly understood nonobstructive variant of middle lobe syndrome due to chronic inflammation is the most common etiology, accounting for over 60% of known cases.[3]

Pathophysiology

The pathophysiology of middle lobe syndrome varies by type. In obstructive middle lobe syndrome, there is a noticeable decrease in endoluminal diameter in the right middle lobe bronchus or left lingular bronchus due to extraluminal or intraluminal obstruction. The right middle lobe bronchus, in particular, is susceptible to near or total obstruction due to a smaller intraluminal diameter than other lobar bronchi.[12] Similarly, female patients have globally smaller intraluminal diameters compared to their male counterparts, thus providing anatomical evidence for a female predisposition epidemiologically.[12] Furthermore, the fissures of the middle lobe and lingula insulate these segments from collateral ventilation, thus reducing the likelihood of auto-correction of atelectasis and decreasing mucus clearance.[13][14]

History and Physical

A keen sense of awareness towards certain distinguishing features in the history and physical examination can raise the index of suspicion for diagnosis. The patients with middle lobe syndrome usually present with a constellation of symptoms such as chronic cough, hemoptysis, dyspnea, and features consistent with recurrent pneumonia. However, the most important aspect of history is an intrusive, recurrent, difficult to treat pneumonia. Physical exam findings would include wheezing, rhonchi, decreased breath sounds, tachypnea, and possibly diaphoresis during periods of concomitant pneumonia. In rare cases, features such as failure to thrive or cachexia may present as well, depending on the underlying etiology responsible for middle lobe syndrome.

Evaluation

There is a myriad of tests and imaging modalities available to assist in the diagnosis of middle lobe syndrome; however, none is satisfactorily sensitive or specific enough to be considered the gold standard for diagnosis. Initial evaluation with a PA and lateral chest X-ray would seem appropriate; however, these plain films may be normal in patients who have intermittent obstructions or recurrent pneumonia.[2] The classic silhouette sign with the right heart border obscured by a right middle lobe infiltrate may be present in AP or PA projections.[13] Nevertheless, a radiographic evaluation may best focus on identifying the underlying cause of the condition. Bronchoscopy, complete blood count, and/or CT chest may further help elucidate the underlying disease process responsible for the syndrome. 

Treatment / Management

Treatment for middle lobe syndrome, whether it is obstructive or non-obstructive, is directed at diagnosing and treating the underlying disease process. Agents directed towards optimizing pulmonary function (mucolytics, chest physiotherapy, bronchodilators, and antibiotics) are cornerstones of treatment and would most likely benefit all types of middle lobe syndrome irrespective of underlying etiology[15] Targeted antibiotic therapy towards Pseudomonas species is a strong recommendation, as the underlying structural changes associated with middle lobe syndrome enable it to be a viable medium for pseudomonal infections.(B2)

In obstructive type middle lobe syndrome, fiberoptic or rigid bronchoscopy would help remove foreign bodies or evaluate intrabronchial tumors. Clinicians have occasionally used insufflation with fiberoptic bronchoscopy for lobar collapse. However, there is no robust data regarding this approach, and it should only receive consideration on a case-by-case basis.[16][17] Ultimately, surgical intervention may play an essential role, if conservative and bronchoscopic management fails to produce favorable results. One study demonstrated that one-third of patients were successfully treated with conservative management, while one-third of patients went on to undergo surgical intervention.[18] The role of surgical intervention and possible lobectomy is only limited to obstructive MLS and data is limited to sporadic case reports in children. (B2)

Differential Diagnosis

Differentials include, but are not limited to cystic fibrosis, bronchiectasis, aspergillosis, pulmonary sequestration, tuberculosis infection, asthma, chronic obstructive pulmonary disease, immunodeficiency, ciliary disorders, and other rare causes.