Middle Lobe Syndrome (Brock Syndrome)

History, Definition, and Epidemiology

History

In 1948, Graham First Described the Middle Lobe Syndrome in 12 Patients with Atelectasis and Nontuberculous Pneumonitis of the Right Middle Lobe (Postgrad Med, 1948) [MEDLINE]
- These Cases Had Presumed (But Not Bronchoscopically–Proven) Airway Compression by Peribronchial Enlarged Lymph Nodes
In 1955, Effler and Ervin Published a Review on the Anatomic and Clinical Features of the Middle Lobe Syndrome (Am Rev Tuberc, 1955) [MEDLINE]
- They Defined Middle Lobe Syndrome as a “Suppurative Process Which is Characterized by Recurrent Pneumonitis, Productive Cough, Recurrent Fever, and Frequent Hemoptyses”
- They Stated “The Middle Lobe Syndrome Begins with a Phase of Obstructive Pneumonitis and Terminates with a Phase in Which There is Destruction of the Lung Parenchyma Distal to the Point of Obstruction”
In 1966, Culiner Described the Middle Lobe Syndrome as “Obstructive Atelectasis of This Lobe, with the Obstruction Being Attributed to Compression by Peribronchial Nodes” (Dis Chest, 1966) [MEDLINE]

Definition

Middle Lobe Syndrome is Most Consistently Defined in the Medical Literature as Recurrent or Chronic Right Middle Lobe Atelectasis (Collapse or Volume Loss) (see Atelectasis) (Postgrad Med, 1948) [MEDLINE] (Dis Chest, 1966) [MEDLINE] (Thorax, 1980) [MEDLINE] (Respiration, 2012) [MEDLINE]
- A Similar Syndrome May Occur in the Lingula, Being Termed the “Lingula Syndrome” (Chest, 2004) [MEDLINE]

Epidemiology

Middle Lobe Syndrome is Considered to Be a Rare Clinical Entity, But its Epidemiology Has Not Been Well-Described in the Medical Literature (Thorax, 1980) [MEDLINE] (Respiration, 2012) [MEDLINE]
- Middle Lobe Syndrome Has Been Described in Childen and Adults of Both Sexes
- Middle Lobe Syndrome Has Been Described in Both Primary and Tertiary Care Settings
- Non-Obstructive Middle Lobe Syndrome Appears to Be More Common than Obstructive Middle Lobe Syndrome (Clin Respir J, 2009) [MEDLINE]
Incidence
- In a National Study from Iceland, the Incidence of Middle Lobe Syndrome Requiring Surgical Resection was Defined (JAMA, 1966) [MEDLINE]
  - Male: 1.43 milion males per year
  - Female: 2.94 milion females per year
Sex-Predominance
- Middle Lobe Syndrome is More Common in Females
  - The F:M Ratio is 1.5-3.0 in Most Studies (Respiration, 2012) [MEDLINE]
Family History of Atopy
- Family History of Atopy, Asthma, Chronic Obstructive Pulmonary Disease are Present in Up to 50% of Cases (Thorax, 1980) [MEDLINE] (Clin Respir J, 2009) [MEDLINE] (Respiration, 2012) [MEDLINE]
Familial Clustering
- Familial Clustering Has Been Reported

Etiology

Obstructive Middle Lobe Syndrome

Intrinsic Obstruction

Infection
- Actinomycosis (see Actinomycosis)
- Echinococcosis (see Echinococcosis) (BMJ Case Rep, 2016) [MEDLINE]
- Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex)
  - However, as Noted Below, Most Cases of Middle Lobe Syndrome Associated with Nontuberculous Mycobacteria Have a Patent Right Middle Lobe Bronchus (Dis Chest, 1966) [MEDLINE]
  - Endobronchial Submucosal “Pearls” May Be Seen in HIV Patients (Biopsy of These is Usually Positive for Acid-Fast Bacilli)
- Mycobacterium Tuberculosis (Tuberculosis) (see Tuberculosis)
- Nocardiosis (see Nocardiosis)
Neoplasm
- Epidemiology
  - Neoplasms (Benign and Malignant) Account for Approximately 25% of Middle Lobe Syndrome Cases (Although Many Middle Lobe Syndrome Studies Have Excluded Patients with Identifiable Neoplasms) (Respiration, 2012) [MEDLINE]
- Types of Neoplasms
  - Bronchial Adenoma (see Bronchial Adenoma)
  - Hamartoma (see Hamartoma)
  - Lung Cancer (see Lung Cancer)
  - Endobronchial Metastases (see Lung Metastases-Endobronchial)
    - Breast Cancer (see Breast Cancer): most common tumor to metastasize to airway
    - Cervical Cancer (see Cervical Cancer)
    - Chronic Lymphocytic Leukemia (CLL) (see Chronic Lymphocytic Leukemia)
    - Colorectal Cancer (see Colorectal Cancer)
    - Endometrioma (see Endometrioma)
    - Esophageal Cancer (see Esophageal Cancer)
    - Germ Cell Tumor (see Germ Cell Tumor)
    - Head and Neck Cancer (see Head and Neck Cancer)
    - Hepatocellular Carcinoma (see Hepatocellular Carcinoma)
    - Hodgkin Lymphoma (see Hodgkin Lymphoma)
    - Kaposi Sarcoma (see Kaposi Sarcoma)
    - Lymphoma (see Lymphoma)
    - Melanoma (see Melanoma)
    - Ovarian Cancer (see Ovarian Cancer)
    - Plasmacytoma (see Multiple Myeloma)
    - Renal Cell Cancer (see Renal Cancer)
    - Sarcoma
    - Testicular Cancer (see Testicular Cancer)
    - Thymic Carcinoma (see Thymoma)
    - Thyroid Cancer (see Thyroid Cancer)
    - Urothelial Cell Carcinoma (Transitional Cell Carcinoma) (see Urothelial Cell Carcinoma)
Mucoid Impaction (see Mucoid Impaction)
- Allergic Bronchopulmonary Aspergillosis (ABPA) (see Allergic Bronchopulmonary Aspergillosis) (Eur Respir J, 1993) [MEDLINE]
- Asthma (see Asthma): predominantly seen in pediatric cases with history of asthma or atopy
- Bacillus Calmette-Guerin (BCG) (see Bacillus Calmette-Guerin)
- Cystic Fibrosis (CF) (see Cystic Fibrosis)
- Distal to Central Airway Obstruction (from Bronchial Atresia, Bronchial Carcinoid, Bronchogenic Cyst, etc)
- Lung Cancer (see Lung Cancer)
- Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex
- Sjogren’s Syndrome (see Sjogren’s Syndrome)
Other Endobronchial Mass/Nodule/Anatomic Distortion
- Airway Foreign Body (see Airway Foreign Body): more commonly occurs in children
- Amyloidosis (see Amyloidosis): due to endobronchial amyloidosis
- Broncholithiasis (see Broncholithiasis): due to erosion of broncholith from adjacent lymph nodes into the right middle lobe bronchus
- Sarcoidosis (see Sarcoidosis): due to endobronchial granuloma
- Silicosis (see Silicosis): due to endobronchial silicosis
- Tracheobronchopathia Osteochondroplastica (TPO) (see Tracheobronchopathia Osteochondroplastica) (Adv Respir Med, 2017) [MEDLINE]: due to endobronchial nodules

Extrinsic Obstruction

Peribronchial Lymphadenopathy
- Epidemiology
  - Peribronchial Lymphadenopathy is the Most Common Etiology of Extrinsic Compression of the Right Middle Lobe Bronchus (Chest, 1966) [MEDLINE]
- Granulomatous Mediastinitis Disorders Which Cause Peribronchial Lymphadenopathy (see Granulomatous Mediastinitis and Fibrosing Mediastinitis)
  - Blastomycosis (see Blastomycosis)
  - Histoplasmosis (see Histoplasmosis): most common etiology in the US
  - Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex)
  - Mycobacterium Fortuitum (see Mycobacterium Fortuitum)
  - Mycobacterium Tuberculosis (Tuberculosis) (see Tuberculosis): common cause in the US
  - Sarcoidosis (see Sarcoidosis)
- Fibrosing Mediastinitis Disorders Which Cause Peribronchial Lymphadenopathy (see Granulomatous Mediastinitis and Fibrosing Mediastinitis)
  - Blastomycosis (see Blastomycosis)
  - Familial Multifocal Fibrosclerosis
  - Histoplasmosis (see Histoplasmosis)
  - Hodgkin Lymphoma (Nodular Sclerosing) (see Hodgkin Lymphoma)
  - Methysergide (see Methysergide)
  - Paraffin Plombage (Pneumonolysis): previously used to treat tuberculosis
  - Radiation Therapy (see Radiation Therapy)
  - Sarcoidosis (see Sarcoidosis)
  - Silicosis (see Silicosis)
  - Traumatic Mediastinal Hematoma
  - Mycobacterium Tuberculosis (Tuberculosis) (see Tuberculosis)
- Other Disorders Which Cause Peribronchial Lymphadenopathy
  - Asbestos (see Asbestos)
  - Metastases to Peribronchial Lymph Nodes
Other Extrinsic Etiology
- Cardiovascular Anomaly
- Esophageal Traction Diverticulum (see Esophageal Diverticulum) (Can Med Assoc J, 1981) [MEDLINE]
- Situs Inversus (see Situs Inversus)

Non-Obstructive Middle Lobe Syndrome (“Peripheral Middle Lobe Syndrome”)

General Comments

Non-Obstructive Middle Lobe Syndrome is Characterized by Absence of Demonstrable Right Middle Lobe Bronchus Obstruction by Bronchoscopy
Non-Obstructive Cases May Also Manifest Pathology in the Lingula on the Left Side (“Lingula Syndrome”) (Chest, 2004) [MEDLINE]
Non-Obstructive Middle Lobe Syndrome Commonly Manifests as Recurrent Pneumonia in Association with Asthma, Bronchitis, or Cystic Fibrosis (JAMA, 1966) [MEDLINE] (J Maine Med Assoc, 1972) [MEDLINE] (Arch Dis Child, 1992) [MEDLINE]

Infection

Actinomycosis (see Actinomycosis)
Aspergillus (see Aspergillus)
Blastomycosis (see Blastomycosis)
Bordetella Pertussis (see Bordetella Pertussis)
Chlamydophila Psittaci (Psittacosis) (see Psittacosis)
Echinococcosis (see Echinococcosis)
Haemophilus Influenza (see Haemophilus Influenza)
Histoplasmosis (see Histoplasmosis)
Moraxella Catarrhalis (see Moraxella Catarrhalis)
Mycobacterium Avium Complex (MAC) (see Mycobacterium Avium Complex)
- Most Cases of Middle Lobe Syndrome Associated with Nontuberculous Mycobacteria Have a Patent Right Middle Lobe Bronchus (Dis Chest, 1966) [MEDLINE]
- In 1992, the “Lady Windermere Syndrome” was Described in a Series of Female Patients (n = 29) with MAC Infection Initially in Middle Lobe or Lingular Distributions (in the Absence of Airway Obstruction or Predisposing Pulmonary Disease) (Chest, 1992) [MEDLINE]
  - Lady Windermere was a Fastidious Female Character in the Victorian-Era (1892) Oscar Wilde Play, “Lady Windermere’s Fan”
  - The Authors Hypothesized that Voluntary Suppression of Cough May Have Led to the Development of Nonspecific Inflammation in the Poorly-Draining Middle Lobe or Lingula, Upon Which MAC Infection then Occurred
Mycobacterium Fortuitum (see Mycobacterium Fortuitum)
- Most Cases of Middle Lobe Syndrome Associated with Nontuberculous Mycobacteria Have a Patent Right Middle Lobe Bronchus (Dis Chest, 1966) [MEDLINE]
Mycobacterium Tuberculosis (Tuberculosis) (see Tuberculosis)
Nocardiosis (see Nocardiosis)
Staphylococcus Aureus (see Staphylococcus Aureus)
Streptococcus Pneumoniae (Pneumococcus) (see Streptococcus Pneumoniae)

Other

Asthma (see Asthma)
- Epidemiology
  - Predominantly Seen in Pediatric Cases with History of Asthma or Atopy
  - In a Series of Asthmatic Children with Middle Lobe Syndrome, Haemophilus Influenzae and Streptococcus Pneumoniae were the Predominant Organisms Recovered (see Haemophilus Influenzae and Streptococcus Pneumoniae) (Arch Dis Child, 1992) [MEDLINE]
Bronchogenic Cyst (see Bronchogenic Cyst)
Cystic Fibrosis (CF) (see Cystic Fibrosis)
Idiopathic Middle Lobe Syndrome
- Physiology
  - Unclear Pathogenesis
Primary Ciliary Dyskinesia (see Primary Ciliary Dyskinesia)
Pulmonary Infarction (see Pulmonary Infarction)
Sjogren’s Syndrome (see Sjogren’s Syndrome)
- Physiology
  - Lymphocytic Bronchiolitis in the Atelectatic Lobes (Med J Aust, 2006) [MEDLINE]

Physiology

Obstructive Middle Lobe Syndrome

Mechanisms

Intrinsic Obstruction Due to Obstructing Endobronchial Lesion (Tumor, Mucous Plug, Mucoid Impaction, etc)
Extrinsic Compression of the Middle Lobe Bronchus (by Peribronchial/Hilar Lymph Nodes Which Encircle the Right Middle Lobe Bronchus)

Therapy

Surgery is the Typically the Preferred Therapy

Non-Obstructive Middle Lobe Syndrome (“Peripheral Middle Lobe Syndrome”)

Epidemiology

Non-Obstructive Middle Lobe Syndrome (Characterized by an Absence of Airway Obstruction by Chest CT and/or Bronchoscopy) Accounts for the Majority of Middle Lobe Syndrome Cases (Respiration, 2012) [MEDLINE]
Non-Obstructive Type May Also Occur in Other Lobes of the Lung, Most Commonly the Lingula

Possible Mechanisms (Respiration, 2012) [MEDLINE]

Right Middle Lobe Bronchus Has a Narrow Diameter, Long Length, and an Acute Takeoff Angle, Creating Poor Conditions for Drainage (and Poor Clearance of Mucous)
- Right Middle Lobe Bronchus Typically Has a “Fish-Mouth” Configuration (as Does the Lingular Bronchus)
- Embryologic Factors
  - Early in Embryologic Development, the Smaller Left Endodermal Bud is Directed More Laterally than the Caudally-Located Right Endodermal Bud, Resulting in Asymmetry of the Mainstem Bronchi
  - Later in Embryologic Development, the Right Main Lung Bud Forms Three Lung Buds and the Left Lung Bud Forms Only Two Buds (Corresponding to the Later Pulmonary Lobes)
Right Middle Has Relatively Poor Collateral Ventilation (as Compared to the Upper Lobes)
- Right Middle Lobe is Anatomically Surrounded by Two Fissures (with Scant Parenchymal Bridges), Which Impedes Collateral Ventilation (Similar Anatomic Features Occur in the Lingula)
- Poor Right Middle Lobe Collateral Ventilation (Especially in Patients with Complete Fissures) and Relative Anatomical Isolation Decrease the Probability of Reinflation Once Atelectasis Has Occurred (Radiology, 1983) [MEDLINE]
- Right Middle Lobe Has a Greater Ratio of Pleural Surface to Nonpleural Surface, as Compared to the Upper Lobes
- Collateral Ventilation in the Right Middle Lobe of Young Normal Subjects is Characterized by High Resistance and a Long-Time Constant, Relative to the Upper Lobes (Am Rev Respir Dis, 1978) [MEDLINE]
Infection in the Right Middle Lobe
Inflammation in the Right Middle Lobe

Therapy

Medical Management is the Typically the Preferred Therapy

Association of Middle Lobe Syndrome with the Development of Bronchiectasis (see Bronchiectasis)

Recurrent or Chronic Right Middle Lobe Syndrome May Result in Bronchiectasis
- Due to Recurrent and/or Chronic Infection/Inflammation
Bronchiectasis Occurs in 50% of Cases (Respiration, 2012) [MEDLINE]

Diagnosis

Bronchoscopy (see Bronchoscopy)

Required to Rule Out Endobronchial Pathology and Collect Specimens for Microbiologic Processing
- Bronchoscopy is Abnormal in Approximately 40% of Cases
- The Most Common Abnormalities Found are Right Middle Lobe Bronchial Stenosis or Endobronchial Tumor
Endobronchial Ultrasound (EBUS) (seeEndobronchial Ultrasound)
- Useful to Detect Lymphadenopathy and Calcification

Chest X-Ray (CXR)/Chest Computed Tomography (Chest CT) (see Chest X-Ray and Chest Computed Tomography)

Findings
- Normal: chest imaging may be normal in cases with intermittent or recurrent atelectasis
- Right Middle Lobe Infiltrate
- Right Middle Lobe Atelectasis
  - On the Lateral Chest X-Ray: Anterior Wedge-Shaped Density with Base Toward Pleura and Apex Pointing Toward the Hilum
- Right Middle Lobe Bronchiectasis

Clinical

Pulmonary Manifestations

Chest Pain (see Chest Pain)

Epidemiology
- May Occur (Clin Respir J, 2009) [MEDLINE]

Cough (see Cough)

Epidemiology
- Occurs in 30-50% of Cases (Clin Respir J, 2009) [MEDLINE] (Respiration, 2012) [MEDLINE]
Clinical
- May Be Chronic or Recurrent
- May Be Productive

Dyspnea (see Dyspnea)

Epidemiology
- May Occur (Clin Respir J, 2009) [MEDLINE]

Wheezing (see Wheezing)

Epidemiology
- May Occur
Clinical
- Wheezing May Be Localized in Cases with an Obstructive Etiology of the Middle Lobe Syndrome

Right Middle Lobe Atelectasis

Diagnosis
- May Be Incidentally Noted on Chest X-Ray (CXR) or Chest Computed Tomography (CT) (see Chest X-Ray and Chest Computed Tomography)
  - On the Posteroanterior Chest X-Ray, There is Obscuration of the Right Heart Border (Because the Medial Segment of the Right Middle Lobe is Adjacent to the Right Atrium)
  - On the Lateral Chest X-Ray, There is Triangle of Increased Density Between the Minor Fissure and the Lower Half of the Major Fissure
  - Chest CT Scan is Useful to Evaluate Bronchial Patency, Assess for Lymphadenopathy, Assess for Calcifications, and Detect Other Etiologies of Extrinsic Right Middle Lbe Airway Compression (Radiology, 1983) [MEDLINE]
- Bronchoscopy (see Bronchoscopy)
  - Bronchoscopy is Critical to Evaluate for the Presence of Airway Abnormalities
  - Bronchoscopic Sampling (Bronchoalveolar Lavage) is Useful to Collect Diagnostic Specimens
    - Bacteria Studies: Gram stain, bacterial culture, etc
    - Fungal Studies: fungal stain, fungal culture, etc
    - Mycobacterial Studies: acid-fast bacterial (AFB) stain, mycobacterial culture, TB PCR, etc
    - Cytologic Studies: to rule out malignancy
- Endobronchial Ultrasound (EBUS)
  - Useful to Assess for Lymphadenopathy and Calcifications
Clinical
- May Be Persistent or Intermittent
- Decreased Breath Sounds Over the Right Middle Lobe

Pneumonia

Physiology
- Post-Obstructive Pneumonia (see Community-Acquired Pneumonia)
  - In One Histopathologic Study of Right Middle Lobe Syndrome Cases Cured Surgically (n = 60), 60% Had Chronic Suppurative Infection, 33% Had Neoplasm, and 7% Had Tuberculosis (Med Interne, 1982) [MEDLINE]
- May Be Recurrent (Requiring Multiple Courses of Antibiotics, Bronchodilators, etc)
Clinical
- Cough (see Cough)
- Fatigue (see Fatigue)
- Fever/Chills (see Fever)
- Hemoptysis (see Hemoptysis)
- Weight Loss (see Weight Loss)
- Vocal Fremitus (E->A Changes) Over the Right Middle Lobe: due to alveolar filling

Bronchiectasis (see Bronchiectasis)

Epidemiology
- Bronchiectasis Occurs in 50% of Cases (Respiration, 2012) [MEDLINE]
Physiology
- Due to Poor Secretion Clearance and Chronic/Recurrent Infection

Treatment

General Measures

Early Intervention (Especially in Children) May Helpt to Avoid Chronic Atelectasis or the Development of Bronchiectasis (Chest, 2005) [MEDLINE]
Avoidance of Airway Irritants
Avoidance of Tobacco Exposure (see Tobacco)

Treatment of Underlying Asthma (If Present) (see Asthma)

Bronchodilators: see below
Inhaled Corticosteroids (see Corticosteroids)
Other Standard Measures

Bronchodilators

Short-Acting β2-Adrenergic Receptor Agonists (SABA’s) (see Β2-Adrenergic Receptor Agonists)
- Albuterol (Ventolin, Salbutamol, etc) (see Albuterol)
Long-Acting/Ultra Long-Acting β2-Adrenergic Receptor Agonists (LABA’s) (see Β2-Adrenergic Receptor Agonists)
- Formoterol (Foradil, Oxeze, Oxis, Atock, Atimos, Perforomist) (see Formoterol)
- Olodaterol (Striverdi Respimat) (see Olodaterol)
- Salmeterol (Serevent) (see Salmeterol)
- Vilanterol (see Vilanterol)
Short-Acting Muscarinic Receptor Antagonists (SAMA’s) (see Muscarinic Antagonists)
- Ipratropium Bromide (Atrovent) (see Ipratropium Bromide)
Long-Acting Muscarinic Receptor Antagonists (LAMA’s) (see Muscarinic Antagonists)
- Tiotropium (Spiriva) (see Tiotropium)

Mechanical Secretion Clearance Modalities

Not Well-Studied in the Treatment of Middle Lobe Syndrome (Chest, 2005) [MEDLINE]
Modalities
- Chest Physical Therapy (CPT) (see Chest Physical Therapy)
- Flutter Valve (see Flutter Valve)
- High-Frequency Oscillation Respiratory Therapy (Vest) (see High-Frequency Oscillation Respiratory Therapy)
- Postural Drainage
  - May Be Useful (Chest, 2005) [MEDLINE]

Mucolytics

N-Acetylcysteine (Mucomyst) (see N-Acetylcysteine)

Antibiotics

Empiric Antibiotic Coverage Against the Following Should Be Considered
- Haemophilus Influenzae (see Haemophilus Influenzae)
- Moraxella Catarrhalis (see Moraxella Catarrhalis)
- Streptococcus Pneumoniae (see Streptococcus Pneumoniae)
Directed Antibiotic Coverage Against Specific Organisms Recovered from Bronchoscopy
- Mycobacteria
- Pseudomonas Aeruginosa (see Pseudomonas Aeruginosa): may be present in some difficult cases
Low-Dose Roxithromycin (Macrolide) Therapy
- May Be Useful (Especially if Bronchiectasis is Present) (Respiration, 2001) [MEDLINE]
Use of Nebulized Antibiotics Has Not Been Well Studied in Middle Lobe Syndrome

Bronchoscopy (see Bronchoscopy)

Bronchoscopy May Be Useful to Enhance Secretion Clearance
Intrabronchial Air Insufflation: to treat lobar collapse
Balloon Dilation/Argon Plasma Coagulation/Electrocautery/Cryosurgery/Laser Therapy/Stent Placement: may be used in some cases

Surgical Resection (see Pulmonary Lobectomy)

Right Middle Lobectomy May Be Required in Some Cases
- Cases with Obstructive Right Middle Lobe Syndrome are More Amenable to Surgical Intervention
Indications for Right Middle Lobectomy
- Resistant/Complex Cases (Which are Unresponsive to Medical Therapy) and Who Have Proven Right Middle Lobe Bronchial Obstruction (Clin Respir J, 2009) [MEDLINE]
- Resistant/Complex Cases with Chronic Atelectasis (>6 Months) Despite Medical Therapy: especially if patient has associated debilitating symptoms (such as persistent cough, fever, failure to thrive, etc)
- Recurrent Hemoptysis, Not Amenable to Interventional Radiology Angioembolization (see Hemoptysis)
- Presence of Malignancy (or Concern for Underlying Malignancy) in Right Middle Lobe
Surgical Approach
- Video-Assisted Thoracoscopic Approach is Feasible for the Surgical Management of Middle Lobe Syndrome in Selected Patients with No Severe Calcified Lymph Nodes Surrounding the Hilus Pulmonis (World J Surg, 2017) [MEDLINE]

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