Bronchoalveolar Lavage

General indications:

• Non-resolving pneumonia
• Diffuse lung infiltrates (interstitial and/or alveolar)
• Suspected alveolar hemorrhage
• Quantitative cultures for ventilator associated pneumonia
• Infiltrates in an immunocompromised host
• Exclusion of diagnosable conditions by BAL, usually infection
• Research

BAL can be diagnostic in the appropriate clinical setting for:

• Alveolar hemorrhage
• Malignancies
  • Lymphangitic carcinomatosis
  • Bronchoalveolar carcinoma
  • Other malignancies
• Infections
  • PCP
  • Mycobacterial
  • Bacterial
  • Fungal
  • Viral

Equipment

• Flexible bronchoscope
• Sterile collection trap
• Suction tubing
• Sterile saline
• Vacuum source
• Syringe
• Optional 3 way stop-cock
• Lidocaine 1-2%

Preparation and Anesthesia

1. Obtain informed consent.
2. If an outpatient procedure, the patient should be accompanied by a person designated to drive the patient.
3. BAL should be planned to be performed prior to any other bronchoscopic procedure.
4. Review radiographs to determine ideal site of alveolar lavage.
   • In diffuse infiltrates, the right middle lobe (RML) or the lingula in the supine patient is preferred.
5. Prepare bronchoscope, collection trap, and tubing. ( Click for image)
6. Prepare supplemental oxygen and monitoring equipment.
   • ECG, pulse-oximetry, BP cuff.
7. Premedicate with bronchodilators and/or warm the saline solution for those at risk for bronchospasm.
8. Position patient, preferably in supine position when approaching RML or lingula.
9. Apply monitors and supplemental oxygen.
10. Sedation with a benzodiazepine and a narcotic will allow patient comfort and minimize cough reflex.
    • Example: midazolam (adult dose 1 to 2.5 mg IV) and fentanyl (adult dose 25-100 mcg IV).
    • Topical anesthesia with lidocaine should be minimized.
      • Up to 8.2 mg/kg was found to be safe in a single study (endorsed as the maximum safe limit by the British Thoracic Society), but this amount is rarely necessary.
      • Conventional proposed maximum limits vary from 4-5 mg/kg. At our institution, we generally use the limit of 5 mg/kg of 2% lidocaine. Reduced limits are advised in those with liver or cardiac disease.

Technique

1. Perform preparatory steps and obtain adequate sedation. (See Preparation and Anesthesia)
2. Plan to perform the BAL preceding any other planned bronchoscopic procedure to avoid specimen contamination.
   • Avoid suctioning prior to obtaining BAL specimen.
   • If needed however, the suction channel should be thoroughly rinsed with saline prior to the BAL.
3. Minimize use of topical anesthesia as there may be bacteriostatic effects of lidocaine.
   • Typically, we use the minimum amount of 2% lidocaine topically that is necessary to minimize coughing with a typical upper limit of 4-5 mg/kg.
4. Advance bronchoscope until wedged in a desired subsegmental bronchus at the desired location.
   • Avoidance of bronchial trauma is particularly important in the patient with suspected alveolar hemorrhage.
5. Infuse 20mL of saline with a syringe, observing the flow of saline at the distal tip of the bronchoscope.
6. Maintaining wedge position, apply gentle suction (50-80mmHg), collecting the lavage specimen in the collection trap.
7. Repeat steps 5 and 6, up to 5 times as needed (total 100-120 mL), to obtain an adequate specimen (40-60 mL - usually 40-70% recovery of total instillate).
   • Observe for flow of bubbles returning from the alveolar space.
     
     
   • Gentle re-orientation of bronchoscope tip may allow better return of fluid.
   • Distal airways may collapse at higher negative suction pressures.
   • Reduction in pressure or intermittent suctioning may help with distal airway collapse.
   • Instructing the patient to inhale and exhale deeply may also help improve return of specimen.
   • Higher aliquots and higher total volume can occasionally be used (up to 300 mL).
8. BAL specimen should be processed as soon as possible with desired tests ordered.
9. Patient should be observed for a minimum of 1 hour after the procedure, with continued monitoring.

Common tests/Analysis

Gross observation

• Pulmonary alveolar proteinosis
  • Opaque or translucent brownish or sandy colored fluid, sediments out into two layers if left to sit
• Alveolar hemorrhage
  • Sequentially more hemorrhagic with each aliquot

Cell count and differential

• Alveolar macrophages (Normal >80%)
• Neutrophils (Normal <3%)
  • Nonspecific, but suggests active alveolitis
  • IPF, ARDS, infection, connective tissue disorders, Wegener's granulomatosis, pneumoconiosis
• Eosinophilia (Normal <1-2%)
  • Low to moderate eosinophilia (5-20%): Drug induced lung disease (e.g. minocycline, nitrofurantoin, penicillin), infections (parasitic, mycobacterial, fungal), asthma, malignancies (infrequently), other interstitial pneumonias occasionally (BOOP or COP, IPF/UIP, ILD associated with Connective tissue disorders)
  • Moderate to marked eosinophilia (>20%): ABPA, Churg-Strauss syndrome, Acute eosinophilic pneumonia, chronic eosinophilic pneumonia, idiopathic hypereosinophilic syndrome
• Lymphocytosis (Normal <15%)
  • Lymphocytosis can be found in a variety of conditions as listed below, but is not sufficiently sensitive and specific to recommend for routine clinical practice? Commonly noted associations are listed below.
    • Elevated CD4/CD8: Active sarcoidosis, berylliosis, asbestosis, Crohns disease, connective tissue disorders
    • Normal CD4/CD8: Tuberculosis, malignancies
    • Low CD4/CD8: Hypersensitivity pneumonitis, silicosis, drug-induced lung disease, HIV infection, BOOP (COP)
    • Others: Lymphoma, viral pneumonia, alveolar proteinosis
• Erythrocytes
  • Elevated erythrocyte count - early sign of alveolar hemorrhage (first several hours)
  • Phagocytosed erythrocytes - alveolar hemorrhage within 48 hours
  • Hemosiderin laden macrophages - alveolar hemorrhage > 48hours

Microbiology

• Cultures
• Stains and Immunohistochemistry
  • Gram stain: Bacterial
  • KOH preparation: Fungal
  • Periodic acid-Schiff (PAS): Pulmonary alveolar proteinosis
  • Auramine-rhodamine, Auramine-O, or Ziehl-Neelson: Mycobacterial
  • Modified acid fast stain (Kinyoun): Nocardia
  • Silver methenamine: Pneumocystis carinii pneumonia, fungal
  • Direct fluorescent antibody testing (DFA) for Legionella
• Polymerase chain reaction (PCR)
  • Mycobacteria tuberculosis
  • Possible for numerous pathogens but clinical utility still unclear
• Quantitative or semiquantitative cultures
  • Particularly for ventilator associate pneumonia
    • Diagnostic of infection if organism identified:

      -	Pneumocystis carinii
      -	Toxoplasma gondii
      -	Strongyloides stercoralis
      -	Legionella pneumophila
      -	Cryptococcus neoformans
      -	Histoplasma capsulatum
      -	Mycobacterium tuberculosis
      -	Mycoplasma pneumoniae
      -	Influenza A and B viruses
      -	Respiratory syncytial virus

    • Colonization by organism possible:

      -	Bacteria
      -	Herpes, cytomegalovirus
      -	Aspergillus
      -	Candida
      -	Atypical mycobacteria

Cytology

• Foamy macrophages
  • Nonspecific finding but can be seen in patients using amiodarone
• Malignancies
  • Lymphangitic carcinomatosis
  • Lymphoma
  • Bronchoalveolar carcinoma and other primary lung malignancies
  • Extrapulmonary malignancies
• Sulfur granules
  • Actinomycetes
• Hemosiderin Laden Macrophages
  • 20% is highly specific and sensitivie for alveolar hemorrhage, although a spectrum of findings can be seen depending on the timing and severity of the hemorrhage. Subclinical hemorrhage is thought to be possible at a level as low as 5%.
• Langerhans cells
  • >5% suggestive of Pulmonary Langerhans cell histiocytosis
  • Also CD1a (OKT6) or S100
• Cytomegalic cells
  • Viral pneumonias (cytomegalovirus, herpes)
• Oil red O stain
  • Indicates neutral fat droplets that can be seen in fat embolism
• Fat and Lipid stain (e.g. Sudan III)
  • Lipoid pneumonia (aspiration)
  • Lipid-laden alveolar macrophage index > 100 (Sensitivity of 100%, Specificity 57%)

Other

• Dust particle inclusions
  • Pneumoconioses, asbestos exposure
• Electron microscopy (Rarely indicated if ever for clinical purposes)
  • Birbeck granules or "X" bodies (pentilaminar cytoplasmic inclusions) - indicates Langerhans cells
  • Myelin like ultrastructure with lamellar bodies and myelin - alveolar proteinosis

Complications/Adverse events

• No complications in up to 95%
• Cough
• Transient fever (2.5%)
• Transient chills and myalgias
• Transient infiltrates in most (resolves in 24 hours)
• Bronchospasm (<1%)
• Transient fall of lung function
• Transient decrease in baseline PaO2
• In patients with already severely compromised respiratory status, the loss of lung function may necessitate the need for mechanical ventilation. Ideally, BAL in these patients should be avoided, but could be done after intubation if the patient progresses to this point.

References

1. Wang K, Mehta A, Turner J, editors. Flexible Bronchoscopy. 2 ed. Ann Arbor, MI: Blackwell Science; 2004.
2. Prakash UBS, editor. Bronchoscopy. First ed. New York, NY: Raven Press, Ltd.; 1994.
3. British Thoracic Society Bronchoscopy Guidelines Committee aSoSoCCoBTS. British Thoracic Society guidelines on diagnostic flexible bronchoscopy. Thorax 2001;56 Suppl 1:i1-21.
4. Costabel U. Atlas of Bronchoalveolar Lavage. First ed. Phildaelphia, PA: Chapman and Hall; 1998.