Disorders of the Pleura¶

Chapter 305 | Part 7: Disorders of the Respiratory System · Part 7 – Respiratory Disorders · Chapter 305

Key Clinical Points¶

Light's criteria (Pleural fluid (PF) protein/serum protein >0.5, PF LDH/serum LDH >0.6, and PF LDH >2/3 upper normal serum limit) distinguish exudates from transudates but misidentify ~25% of transudates as 'pseudoexudates' (often due to diuresed transudates).
Pleural fluid NT-proBNP >1500 pg/mL is suggestive of an effusion secondary to congestive heart failure and correlates well with serum values.
Chylothorax is identified by a milky appearance and triglyceride levels >1.2 mmol/L (110 mg/dL).
Hemothorax is established if the pleural fluid hematocrit is more than one-half of that in the peripheral blood.
Complicated parapneumonic effusions (empyema) are indicated by: pH <7.20, glucose <60 mg/dL, loculation, or a positive Gram stain.
Malignant pleural effusions typically portend a poor prognosis (<6-month survival) and are generally not curable with chemotherapy.
Primary spontaneous pneumothorax recurs in approximately one-half of patients; thoracoscopy with stapling of blebs is nearly 100% successful in preventing recurrence.
Tuberculous pleuritis is suggested by high levels of TB markers: adenosine deaminase (ADA) >40 IU/L or interferon γ >140 pg/mL.
Pleural fluid amylase elevation suggests esophageal rupture or pancreatic disease.
Trapped lung (fibrothorax) is identified by a thick pleural rind, pneumothorax ex vacuo (air on imaging after thoracentesis), or recurrence of effusion shortly after drainage.

1. DEFINITION & OVERVIEW¶

• Pleural Space: Located between the lung and chest wall; contains a thin layer of fluid serving as a coupling system. • Pressure Dynamics: Maintained at approximately -3 to -5 cmH2O due to balance between lung elastic recoil (visceral pleura) and chest wall expansion (parietal pleura). • Pathology: Invasion by organisms, inflammatory cells, cancer cells, or introduction of air, blood, or chyle leads to significant disease. • Pleural Effusion: Defined as an excess quantity of fluid in the pleural space. • Fluid Dynamics: Fluid enters from capillaries (parietal pleura), lung interstitium (visceral pleura), or peritoneal cavity; lymphatics normally remove 20x more fluid than is formed. • Mechanism of Effusion: Occurs when hydrostatic-oncotic balance is disturbed, overwhelming lymphatic drainage. • Presentation: Most commonly presents as shortness of breath and occasionally chest pain.

2. EPIDEMIOLOGY¶

• Incidence: Approximately 1.5 million Americans develop exudative pleural effusions annually from bacterial pneumonia, malignancy, viral infection, and pulmonary embolism.

3. ETIOLOGY & PATHOPHYSIOLOGY¶

3.1 Transudative vs. Exudative Mechanisms¶

• Transudative Effusions: Result from systemic factors (hydrostatic-oncotic pressures) altering fluid balance. • Exudative Effusions: Result from local factors (inflammation, infection, malignancy) altering fluid balance. • Diagnostic Distinction: Based on LDH and protein levels; Light's criteria misidentify ~25% of transudates as "pseudoexudates" (often diuresed transudates). • Alternative Criteria: If clinical suspicion for transudate is high despite exudative markers, use Serum to pleural fluid protein gradient (SPPG) or serum to pleural fluid albumin gradient (SPAG) >3.1 g/dL and elevated pleural fluid cholesterol.

3.2 Transudative Pleural Effusions¶

• Common Causes: 1. Congestive heart failure 2. Cirrhosis 3. Nephrotic syndrome 4. Peritoneal dialysis 5. Superior vena cava obstruction 6. Myxedema 7. Urinothorax

3.3 Exudative Pleural Effusions¶

• Neoplastic: Metastatic disease, Mesothelioma. • Infectious: Bacterial, Tuberculosis, Fungal, Viral, Parasitic. • Pulmonary Embolism. • Gastrointestinal Disease: Esophageal perforation, Pancreatic disease, Intraabdominal abscesses, Diaphragmatic hernia, After abdominal surgery, Endoscopic variceal sclerotherapy, After liver transplant. • Collagen Vascular Diseases: Rheumatoid pleuritis, Systemic lupus erythematosus, Drug-induced lupus, Sjögren syndrome, Granulomatosis with polyangiitis (Wegener), Churg-Strauss syndrome. • Other Causes: 6. Post–coronary artery bypass surgery 7. Asbestos exposure 8. Sarcoidosis 9. Uremia 10. Meigs' syndrome 11. Yellow nail syndrome 12. Drug-induced pleural disease (Nitrofurantoin, Dantrolene, Methysergide, Bromocriptine, Procarbazine, Amiodarine, Dasatinib) 13. Trapped lung 14. Radiation therapy 15. Post–cardiac injury syndrome 16. Hemothorax 17. Iatrogenic injury 18. Ovarian hyperstimulation syndrome 19. Pericardial disease 20. Chylothorax

4. CLINICAL FEATURES¶

4.1 General Presentation¶

• Primary Symptoms: Dyspnea (often out of proportion to the effusion size) and chest pain. • Malignancy: Symptomatic treatment; poor prognosis (<6-month survival). • Tuberculosis: Fever, weight loss, dyspnea, pleuritic chest pain. • Chylothorax: Dyspnea; large effusion on radiograph. • Mesothelioma: Chest pain and shortness of breath. • Hepatic Hydrothorax: Severe dyspnea. • Parapneumonic Effusion: Acute febrile illness, pleuritic chest pain, sputum production, leukocytosis. • Anaerobic Infection: Subacute illness, weight loss, leukocytosis, mild anemia.

4.2 Pneumothorax Features¶

• Definition: Presence of gas in the pleural space. • Spontaneous: Occurs without antecedent trauma. ◦ Primary: No underlying lung disease. ◦ Secondary: Present with underlying lung disease. • Traumatic: Result of penetrating or nonpenetrating chest injuries. • Tension Pneumothorax: Pressure in pleural space is positive throughout the respiratory cycle.

5. DIFFERENTIAL DIAGNOSIS¶

5.1 Diagnostic Clues¶

• Asbestos: Diagnosis by exclusion. • Malignancy: Confirmed via cytology; if negative, use CT/ultrasound-guided biopsy of thickening or nodules; definitive via thoracoscopic biopsy. • Chylothorax: Triglyceride level >1.2 mmol/L (110 mg/dL). • Hemothorax: Hematocrit > 1/2 of peripheral blood hematocrit. • Esophageal Rupture / Pancreatic Disease: Elevated pleural fluid amylase. • Intraabdominal Abscess: Fever, predominantly polymorphonuclear cells in fluid, no pulmonary parenchymal abnormalities. • Tuberculosis: High markers: ADA >40 IU/L or interferon γ >140 pg/mL. • Parapneumonic Effusion: Suspected in any patient with bacterial pneumonia.

6. INVESTIGATIONS & DIAGNOSIS¶

• Initial Imaging: Chest X-ray (lateral decubitus), CT, or Ultrasound to evaluate extent and identify features. • Thoracentesis: Perform to determine transudate vs exudate. • Light's Criteria Application: 1. Pleural fluid protein / serum protein >0.5 2. Pleural fluid LDH / serum LDH >0.6 3. Pleural fluid LDH > 2/3 upper normal serum limit → If any met: Exudate. → If none met: Transudate (Treat for CHF, cirrhosis, nephrosis). • Specific Testing for Exudates: 1. Glucose: <60 mg/dL suggests Malignancy, Bacterial infection, or Rheumatoid pleuritis. 2. NT-proBNP: >1500 pg/mL suggests heart failure (correlates well with serum values). 3. Amylase: High levels suggest esophageal rupture or pancreatic disease. 4. Eosinophils: Suggest drug-induced pleural disease. 5. Triglycerides & Cholesterol: Identify Chylothorax. 6. Hematocrit: Identify Hemothorax. 7. Congo Red Staining: Identify Amyloidosis. 8. Flow Cytometry: Identify Lymphoma. 9. TB Markers: ADA >40 IU/L or interferon γ >140 pg/mL. • Evaluation of Complexity: 1. Use CT/Ultrasound to identify loculation or septations (indicates complicated parapneumonic effusion). 2. Identify 'Trapped Lung' via: Pleural manometry, thick pleural rind, pneumothorax ex vacuo (air on imaging after thoracentesis), or recurrence of effusion shortly after drainage. • Routine Analysis: In addition to appearance, obtain glucose level, differential cell count, microbiologic studies, and cytology. • Decision Pathway (Flowchart 1): 1. Pleural effusion identified → Thoracentesis/LDH & Protein measurement. 2. Are any Light's criteria met? (PF/serum protein >0.5, PF/serum LDH >0.6, or PF LDH >2/3 upper normal serum limit). - No → Transudate → Treat CHF, cirrhosis, nephrosis. - Yes → Exudate → Proceed to next step. 3. Is Glucose <60 mg/dL? - Yes → Consider: Malignancy, Bacterial infections, Rheumatoid pleuritis. - No → Proceed to next step. 4. Pulmonary embolism (PE) suspected? (via spiral CT or lung scan). - Yes → Treat for PE. - No → Proceed to next step. 5. Pleural fluid markers for TB positive? (ADA >40 IU/L or interferon γ >140 pg/mL). - Yes → Treat for TB. - No → Proceed to next step. 6. Are symptoms improving? - Yes → Observe. - No → Consider thoracoscopy or image-guided pleural biopsy.

7. MANAGEMENT & TREATMENT¶

7.1 Malignant Pleural Effusion¶

Symptomatic Treatment: Primary approach due to poor prognosis.
Intervention for Severe Dyspnea: → Option 1: Small indwelling catheter for regular home drainage. → Option 2: Tube thoracostomy with chemical pleurodesis (sclerosing agent) OR thoracoscopy with drainage and surgical pleurodesis.

7.2 Chylothorax¶

Initial Treatment: Chest tube + octreotide + modification of diet (eliminate enteral fat).
Advanced Intervention: Percutaneous transabdominal thoracic duct blockage or ligation of the thoracic duct.
Note: Avoid prolonged tube thoracostomy to prevent malnutrition and immunologic incompetence.

7.3 Hemothorax¶

Initial Step: Tube thoracostomy for continuous quantification of bleeding.
Assessment: Check pleural fluid hematocrit (must be > 1/2 of peripheral blood to confirm).
Intervention: If drainage is required, consider surgical or interventional options.

7.4 Parapneumonic Effusion (PPE)¶

Identify Complicated PPE (Empyema):
Loculated fluid
pH <7.20
Glucose <60 mg/dL
Positive Gram stain or culture
Gross pus
Management of Fibrinopurulent Fluid: → If not fully drained by thoracentesis, use chest tube. → Consider instillation of fibrinolytic agent (e.g., tPA 10 mg) and deoxyribonuclease (5 mg). → Perform thoracoscopy to break down adhesions if recurrence occurs. → Surgical decortication should be considered when these measures are ineffective.

7.5 Pneumothorax¶

Primary Spontaneous Pneumothorax: → Asymptomatic/Mild: Observation. → Symptomatic: Needle aspiration or tube drainage. → Recurrent or non-expanding lung: Thoracoscopy with stapling of blebs and pleurodesis (nearly 100% success in preventing recurrence).
Secondary Pneumothorax: Requires prompt management due to lack of pulmonary reserve.

7.6 Other Conditions¶

Hepatic Hydrothorax: Treat as ascites; if persistent, consider pleurodesis, TIPS, or liver transplant.
Trapped Lung: If management fails, surgical decortication is indicated.

8. PROGNOSIS & COMPLICATIONS¶

• Malignancy: Poor prognosis (<6-month survival); often not curable with chemotherapy. • Recurrence: ~50% of primary spontaneous pneumothoraces recur; thoracoscopy/pleurodesis prevents this. • Progression: Effusions can progress from exudative → fibrinopurulent → organizing phase (pleural peel). • Trapped Lung: Result of fibrous restrictive peel; requires decortication if other measures fail.

9. SPECIAL CONSIDERATIONS¶

• Chylothorax: No obvious trauma → lymphangiogram and chest CT to assess thoracic duct. • Mesothelioma: Diagnosis via image-guided needle biopsy or thoracoscopy. • Tuberculous Pleuritis: Treatment of pleural and pulmonary TB is identical. • Drug-induced: Associated fluid may be eosinophilic. • Meigs' Syndrome: Benign ovarian tumors causing ascites and effusion. • Ovarian Hyperstimulation Syndrome: Can cause eosinophilic fluid.

10. KEY PEARLS & CLINICAL TRAPS¶

• Pseudoexudates: ~25% of transudates are misidentified as exudates by Light's criteria. • Symptom Disproportion: Dyspnea is often disproportionately severe relative to the size of the effusion. • Pleural Fluid Analysis: Always include glucose, differential cell count, microbiologic studies, and cytology. • Hemothorax Threshold: Hematocrit > 1/2 peripheral blood → Hemothorax. • Chylothorax Threshold: Triglycerides > 1.2 mmol/L (110 mg/dL). • Tuberculosis Markers: ADA >40 IU/L or interferon γ >140 pg/mL. • Trapped Lung Indicators: Pleural manometry, thick pleural rind, pneumothorax ex vacuo, or rapid recurrence after drainage.

Reference Tables¶

TABLE 305-1 Differential Diagnoses of Pleural Effusions Transudative Pleural Effusions 1. Congestive heart failure 2.…¶

Harrison's 22e, p.2268

Transudative Pleural Effusions
1. Congestive heart failure
  2. Cirrhosis
  3. Nephrotic syndrome
  4. Peritoneal dialysis
  5. Superior vena cava obstruction
  6. Myxedema
  7. Urinothorax
Exudative Pleural Effusions
1. Neoplastic diseases
  a. Metastatic disease
  b. Mesothelioma
  2. Infectious diseases
  a. Bacterial infections
  b. Tuberculosis
  c. Fungal infections
  d. Viral infections
  e. Parasitic infections
  3. Pulmonary embolization
  4. Gastrointestinal disease
  a. Esophageal perforation
  b. Pancreatic disease
  c. Intraabdominal abscesses
  d. Diaphragmatic hernia
  e. After abdominal surgery
  f. Endoscopic variceal sclerotherapy
  g. After liver transplant
  5. Collagen vascular diseases
  a. Rheumatoid pleuritis
  b. Systemic lupus erythematosus
  c. Drug-induced lupus
  d. Sjögren syndrome
  e. Granulomatosis with polyangiitis (Wegener)
  f. Churg-Strauss syndrome
  6. Post–coronary artery bypass surgery
  7. Asbestos exposure
  8. Sarcoidosis
  9. Uremia
  10. Meigs’ syndrome
  11. Yellow nail syndrome
  12. Drug-induced pleural disease
  a. Nitrofurantoin
  b. Dantrolene
  c. Methysergide
  d. Bromocriptine
  e. Procarbazine
  f. Amiodarone
  g. Dasatinib
  13. Trapped lung
  14. Radiation therapy
  15. Post–cardiac injury syndrome
  16. Hemothorax
  17. Iatrogenic injury
  18. Ovarian hyperstimulation syndrome
  19. Pericardial disease
  20. Chylothorax

TABLE 305-2 Disease-Specific Pleural Fluid Tests

SUSPECTED DISEASE	TESTS
Pancreatic disease or esophageal rupture	Pleural fluid amylase
Congestive heart failure	Pleural fluid N-terminal pro-brain natriuretic peptide (NT-proBNP)
Hemothorax	Pleural fluid hematocrit
Amyloidosis	Congo red staining