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 BronchoscopicallyProven) 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

Extrinsic Obstruction

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

  • General Comments
    • 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]
    • 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]
  • 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
  • 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)
  • 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

Mechanical Secretion Clearance Modalities

Mucolytics

Antibiotics

  • Empiric Antibiotic Coverage Against the Following Should Be Considered
  • Directed Antibiotic Coverage Against Specific Organisms Recovered from Bronchoscopy
  • 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]

References

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