Bronchoalveolar Lavage

Anatomy and Physiology

The anatomy and physiology of BAL involve a meticulous understanding of the respiratory system, the bronchial tree, and the alveolar structures. The respiratory system comprises the upper respiratory tract (nose, pharynx, larynx) and the lower respiratory tract (trachea, bronchi, bronchioles, and alveoli). The bronchial tree extends from the trachea and branches into the bronchi, further divided into bronchioles. Alveoli are tiny, air-filled sacs located at the distal ends of bronchioles where gas exchange occurs. The lower respiratory tract is particularly interesting in BAL, as it typically targets specific subsegments of the bronchial tree and the alveoli, allowing for localized sampling.

The respiratory system's primary function is to facilitate gas exchange, with oxygen entering the bloodstream and carbon dioxide being expelled. Alveoli are populated by specialized cells, including alveolar macrophages, which play a crucial role in immune defense by engulfing and clearing foreign particles. BAL retrieves fluid and cellular material from the lower respiratory tract, providing diagnostic information about cellular composition, infection, inflammation, and other pathological processes.

Understanding the intricate interplay between the anatomy and physiology of the respiratory system is essential for performing and interpreting BAL effectively in a clinical setting. This knowledge allows healthcare professionals to gain valuable diagnostic information and contribute to managing respiratory disorders.

Indications

A substantial proportion of pathological diseases affecting the lungs manifest at the alveolar level. BAL emerges as a valuable diagnostic tool, enabling the collection and subsequent analysis of the alveolar milieu. Common applications of BAL encompass investigations into opportunistic and atypical respiratory infections in patients who are immunocompromised and explore unexplained radiographic pulmonary infiltrates or hypoxemia.[3][4] Additionally, BAL plays a crucial role in shedding light on the diagnosis of various noninfectious conditions such as diffuse alveolar hemorrhage, pulmonary alveolar proteinosis, eosinophilic pneumonia, hypersensitivity pneumonitis, interstitial lung diseases, chronic berylliosis, and the presence of malignant cells or leukemic infiltrates.[5][6]

Contraindications

BAL is generally a safe procedure, but there are certain contraindications and situations where caution should be exercised. Contraindications to BAL include:

• Severe respiratory distress
• Severe hypoxemia
• Hemodynamic instability
• Coagulopathy
• Thrombocytopenia is a relative contraindication for fiberoptic bronchoscopy (cutoff of 20,000 to 50,000/μL). In contrast to the proposed platelet count cutoff (50,000 to 75,000 platelets/μL) for transbronchial biopsies, BAL is contraindicated if the platelet count is below 20,000 platelets/μL.
• Uncooperative patients
• Recent cardiac events
• Severe uncontrolled hypertension
• Unprotected airway
• Severe pulmonary hypertension
• Active respiratory tract bleeding
• Elevated intracranial pressure [7][8][9]

Contraindications may vary based on individual patient factors, institutional protocols, and clinical context. The decision to perform BAL should be carefully considered, and potential risks and benefits should be weighed. Additionally, consultation with a healthcare provider and a thorough assessment of the patient's overall health status is crucial in determining the appropriateness of the procedure in each case.

Equipment

A bronchoscopy cart should be brought to the bedside, and all equipment should be examined and verified to be working. All flushes and equipment needed should be prepared before beginning the procedure. A BAL requires specialized equipment to ensure the procedure is conducted safely and effectively. Here is a list of equipment typically used in the performance of BAL:

• Bronchoscope with a light source
• Bite block
• Sampling vials: 1 culture, 1 cytology
• 10 mL syringe to blow up the cuff (if the patient is intubated)
• 250 mL bag of normal saline
• Suction catheter and tubing
• 3-way stopcock
• 60 ml syringes (x3)
• Gauze
• 1 specimen cup
• 18 gauge needle
• Sterile lubricant
• Sputum trap
• Sterile drapes or towels
• Personal protective equipment (eg, gloves, gown, mask, and hat)
• Pulse oximeter
• Oxygen delivery device
• Sedatives as needed
• Bronchial brush or cytology brush (optional) 
• In some cases, a bronchial brush may collect additional cellular material from the bronchial walls. 
• Biopsy forceps (optional)
• These may be employed if a simultaneous biopsy is needed for diagnostic purposes. 

The specific equipment used may vary based on institutional protocols, the patient's condition, and the purpose of the BAL (diagnostic or therapeutic). Adherence to infection control practices and guidelines is crucial to prevent complications and ensure patient safety.

Personnel

Performing a BAL involves a team of healthcare professionals with specialized skills and roles. The personnel required for a BAL procedure may include:

• Clinician to perform the procedure
• This is usually a pulmonologist, intensivist, or thoracic surgeon.
• Nurse
• They assist during the procedure. Their responsibilities may include preparing the patient, providing support during the bronchoscopy, and monitoring their vital signs.
• Respiratory therapist (if needed)
• If the patient is on a ventilator, they may adjust ventilator settings as required. 
• Anesthesiologist or anesthetist (if needed)
• They are necessary when the patient requires sedation or anesthesia.
• Radiology technologist (if imaging is used)
• They are needed in certain situations when fluoroscopy or other imaging modalities are utilized during and after the procedure.

The personnel involved can vary based on institutional practices, the complexity of the procedure, and the patient's needs. Additionally, adherence to infection control measures and proper training in bronchoscopy equipment are fundamental to ensuring a successful and safe BAL procedure.

Preparation

Preparing to perform a BAL involves a comprehensive series of steps to ensure the safety and efficacy of the procedure. The initial phase thoroughly evaluates the patient's medical history, focusing on respiratory symptoms, cardiac issues, and relevant past procedures. Taking note of smoking status, vaping, and smoke exposure history is also essential to give the substantial effect smoking has on the cellular composition of BAL, namely many more neutrophils and macrophages than in nonsmokers. Furthermore, neutrophil elastase, matrix metalloproteinase-2, and metalloproteinase-9 activities and protein levels were elevated in both vapers' and smokers' BAL relative to nonsmokers.[10]

Obtaining informed consent is a crucial step wherein the BAL's purpose, potential risks, and benefits are explained to the patient. Pre-procedure instructions are provided, covering fasting requirements and medication management. Patient monitoring equipment, including a pulse oximeter, is readied to track oxygen saturation and pulse rate during the procedure. Adequate oxygen administration is recommended to avoid hypoxia during the BAL procedure and maintain pulse oximetry of more than 90% to 92%.[11] Sometimes, transient hypoxia occurs during and shortly after BAL due to alveolar filling with liquid. Therefore, patients with low or borderline oxygen saturation at baseline require special attention. In a clinical trial on 36 outpatients randomized to standard therapy or high-flow nasal cannula (HFNC) during fiberoptic bronchoscopy for BAL, HFNC improved gas exchange, preserved lung volume, and diaphragm function.[12]

The meticulous preparation of equipment is important, with checks performed on the functionality of the bronchoscope, suction devices, and containers for sample collection. Coordination with the BAL team, comprising nurses, respiratory therapists, and anesthesiologists if needed, ensures a collaborative approach. If applicable, pre-procedure medications are administered according to institutional protocols. Patient positioning is carefully executed in preparation for the procedure, typically in a semirecumbent or supine position.

If the patient is on the ventilator, the clinician must look at the ventilator settings and estimate the patient's ability to maintain oxygenation and ventilation during and after the procedure. The following are ventilator settings that signify the patient can likely tolerate a BAL from a respiratory standpoint: 

• Positive end-expiratory pressure <14 cm H₂O
• Ability to tolerate decreased minute ventilation 
• Low fraction of inspired oxygen requirements before initiating the procedure

The ventilator settings should be adjusted to ensure continued minute ventilation and adequate oxygenation throughout the procedure. Settings should be adjusted to maintain at least the preprocedure minute ventilation delivered to the patient before changing the ventilator or medicating the patient. The following are recommended ventilator changes:

• Turn FIO₂ to 100%.
• Change the mode to 1 with mandatory minute ventilation. This is usually volume control/assist control, allowing continued minute ventilation despite relative airway obstruction. 
• Allows for a high respiratory rate
• Allows for a small tidal volume
• Decrease flow rates by lengthening inspiratory time.
• Adjust "high-pressure" limits and alarms to accommodate increased pressures.

In addition to ventilator settings, the patient's overall clinical picture should be assessed to ensure they can tolerate a BAL. The following parameters should also be evaluated:

• The absence of elevated ICP 
• Acute changes in minute ventilation and airway pressures will acutely elevate ICP
• Minimal coagulopathy
• International normalized ratio <1.5 
• Platelet count >20,000
• Endotracheal tube or tracheostomy size ≥7.5 mm diameter

Parameters not within these recommendations suggest increased risk and the benefits of the BAL versus these risks should be considered. 

Sterile normal saline, instilled during the lavage, is prepared and made readily available. All personnel wear appropriate personal protective equipment to maintain a sterile environment. Verification of emergency equipment, including resuscitation tools, is undertaken in anticipation of unforeseen complications. A final review confirms patient identification, the targeted subsegment of the lung, and the completeness of documentation, including consent forms and pre-procedure checklists.

Effective communication with the patient throughout the process is prioritized, reassuring and addressing any last-minute concerns. Postprocedure planning includes monitoring for immediate complications, observing vital signs, and providing appropriate patient care instructions. This systematic and thorough approach ensures not only the safety of the procedure but also contributes to a positive patient experience and the accurate acquisition of diagnostic results.

Technique or Treatment

Patient Monitoring

Patients must be monitored during BAL to maintain adequate hemodynamics, minute ventilation, and oxygen saturation throughout the procedure. This is accomplished through the following:

• Continuous pulse oximetry
• Continuous electrocardiogram monitoring
• Continuous or every 5 minutes blood pressure monitoring 

Administer sufficient topical anesthetics to the tracheobronchial tree to prevent the patient from coughing during the procedure.[13] Additionally, sedation is required to ensure patient comfort, safety, and cooperation.[14] This may involve a combination of benzodiazepines and opiates or propofol, which can also be used for sedation.[15][16] The healthcare team must be aware of the potential side effects of medications used during the procedure, and the patient must be monitored for any of these.

BAL Technique

Performing a BAL involves a standardized procedure with some variability in its performance despite guidelines from societies such as the American Thoracic Society and the British Thoracic Society. BAL is conducted after introducing a bronchoscope into the tracheobronchial tree and airway inspection before biopsies or brushing are taken, as this minimizes the potential introduction of bronchial wall debris and additional red blood cells into the most distal airways, which could alter the composition of the lavage fluid. The flexible bronchoscope, with an outer diameter ranging from 3 to 6 mm, is guided into the targeted lung subsegment and wedged into a bronchiole.

Room temperature physiological saline, ranging from 20 to 60 mL (or 50 mL in at least 3 aliquots), is injected and withdrawn gradually 3 to 5 times, not exceeding a maximum of 300 mL. Mild suction is applied to prevent airway collapse, with intermittent suctioning recommended. Adequate return, defined as 30% or more of instillation, is required, with 10 to 20 mL needed for cellular and infectious workup. The procedure is aborted if only 5% of each aliquot returns, indicating retained fluid.

Factors affecting low BAL fluid recovery include male sex, older age (>65 years), smoking, history of emphysema and chronic obstructive pulmonary disease, and the bronchus used for the procedure (bronchi other than the middle lobe bronchus or lingula).[17][18] When no further fluid can be aspirated, a second saline-filled syringe is connected to the bronchoscope, and the procedure is repeated until a third lavage is completed. Usually, the recovery of BAL fluid is less in the first sample and increases with subsequent aliquots. 

In cases of localized pulmonary disease, often identified through radiological imaging such as chest x-rays or computed tomography of the chest, the bronchoscope is meticulously guided to the specific affected region. Then, it is carefully wedged into the subsegment, ensuring the distal airway is ideally centered in the imaging field. Conversely, when dealing with diffuse diseases exhibiting heterogeneous patterns on imaging, the preferred sites for lavage are typically the right middle lobe or lingula. Since bronchoscopy is typically conducted with the patient lying supine, the anterior projection of these segments utilizes gravity to optimize maximal BAL. If accessibility to these segments is limited, either lower lobe's superior or anterior segment may serve as an alternative. Theoretically, this process allows for the lavage of up to 1 million alveoli.[19][20] For patients suspected of diffuse alveolar hemorrhage, the recommendation is to perform 3 sequential BALs at the same site. Visual inspection of the recovered samples is crucial, specifically assessing for any increase in hemorrhagic appearance from the first syringe to the third.

BAL Fluid Assessment

While the collection of BAL samples lacks standardization, experts advise adherence to a recommended protocol to minimize contamination and artifacts. The gathered lavage fluid should be meticulously pooled and mixed, and its volume should be accurately documented. For transportation exceeding 1 hour, storing the fluid on ice is advisable. Research indicates that cells in BAL fluid maintain viability for up to 4 hours at room temperature.

The analysis of BAL fluid typically involves examining white and red cells. Esterase staining is employed to distinguish immature macrophages from large lymphocytes. Additional stains may be applied to assess the presence of iron, malignant cells, inorganic dust, and microorganisms. In general, if the BAL specimen contains fewer than 2 million total cells, exhibits fewer than 10 alveolar macrophages per high-power field, displays a high number of red cells (indicative of trauma), or shows degenerative changes, the specimen may not be considered reliable for making a valid diagnosis.

Notably, in healthy nonsmoking adults, the average number of cells recovered from BAL fluid varies from 100,000 to 150,000 cells/mL. Smoking elevates cell numbers by 4- to 6-fold, predominantly comprising macrophages.[21][22]

The lack of good evidence supporting specific normal values for BAL prompts us to focus on critical cell line cut-offs that aid in diagnosing various conditions:

Neutrophilia (>5%)

• Associated diagnoses: idiopathic pulmonary fibrosis, acute respiratory distress syndrome, infections, and connective tissue disorders

Eosinophilia (>25%)

• Suggestive of eosinophilic lung diseases: acute eosinophilic pneumonia, chronic eosinophilic pneumonia, and Churg-Strauss syndrome

Lymphocytosis (>50%)

• Implicates HP
• When lymphocytes are ≥15%, cluster of differentiation (CD)4/CD8 ratios can be assessed.
• Elevated CD4/CD8
• Indicates hypersensitivity pneumonitis (chronic or smoker), sarcoidosis (CD4+/CD8+ >4 is highly specific), berylliosis, asbestosis, Crohn disease, and connective tissue disorders
• Normal CD4/CD8
• Suggests tuberculosis and malignancies
• Low CD4/CD8
• Associated with acute hypersensitivity pneumonitis, silicosis, drug-induced lung disease, human immunodeficiency virus infection, and cryptogenic organizing pneumonia [23]

The lymphocyte types (eg, CD4 and CD8) can be assessed using immunofluorescent labeled monoclonal antibodies or flow cytometry. Flow cytometry offers advantages such as the identification of leukemic infiltrates and efficiency in counting a larger number of cells. After incubation, the collected BAL fluid cells are passed through a flow cytometer to calculate the CD4 to CD8 ratio.

• Per the American Thoracic Society recommendation, a lymphocyte differential count ≥25% signifies the presence of inflammatory lung disease, encompassing granulomatous diseases (sarcoidosis, hypersensitivity pneumonitis, chronic beryllium disease), cellular nonspecific interstitial pneumonia, drug reactions, lymphoid interstitial pneumonia, cryptogenic organizing pneumonia, or lymphoma.

Complications

BAL is considered a safe procedure but carries risks and potential complications like any medical intervention. The following are possible complications associated with BAL:

•  Fever
  • One of the most common complications associated with BAL
  • Usually self-limited 
  • Often related to the volume of lavage fluid instilled and may be more common with larger lavage volumes
• Hypoxemia 
  • The other most common complication associated with BAL
  • May occur during or after the procedure. 
  • Often related to the volume of lavage fluid instilled and may be more common with larger lavage volumes.
  • Decreased PaO₂ after BAL can be explained by the release of inflammatory mediators induced by the instilled fluid in the respiratory segments; the return of oxygenation to baseline can take several hours in cases of pulmonary parenchymal disease [13]
• Bleeding
  • Minimal bleeding may occur, particularly in patients with underlying coagulation disorders
  • Significant bleeding is rare but can occur, especially if the patient has a bleeding tendency or is on anticoagulant medications
  • Risk factors for bleeding include coagulopathies, thrombocytopenia, platelet dysfunction, severe uremia, hepatic failure, pulmonary hypertension, and superior vena cava syndrome [24]
• Infection
  • There is a potential risk of introducing infection into the lower respiratory tract during the procedure; strict adherence to aseptic techniques helps minimize this risk
• Bronchospasm
  • More prevalent in those with preexisting respiratory conditions such as asthma
  • Can be managed with a bronchodilator
• Pneumothorax
  • These are rare
  • More prevalent in patients with underlying lung disease
• Allergic reactions
• Transient hemodynamic change
  • More commonly seen when conscious sedation is used
• Acute exacerbation of underlying lung disease
  • In rare cases, BAL has been associated with acute exacerbations of underlying lung conditions, such as exacerbation of idiopathic pulmonary fibrosis

The overall risk of complications is relatively low, and BAL is generally considered a well-tolerated and valuable diagnostic procedure. The benefits of obtaining diagnostic information often outweigh the potential risks, primarily when the procedure is performed by trained and experienced medical professionals in a controlled clinical setting. As with any medical procedure, the decision to perform BAL should be based on a careful assessment of the patient's risk factors and the potential diagnostic benefits.

Clinical Significance

The cellular and noncellular tests of BAL fluid are valuable tools in assessing various respiratory disorders using cell count cutoffs or ratios (as outlined earlier in the BAL technique section). A bloody return on BAL establishes a definitive diagnosis of diffuse alveolar hemorrhage.[25] In addition, the accumulation of hemosiderin-laden macrophages or siderophages can confirm a histopathological diagnosis of diffuse alveolar hemorrhage via BAL analysis.[26] Likewise, a definitive diagnosis of a disease such as pulmonary Langerhans cell histiocytosis, also known as eosinophilic granuloma of the lung, can be confirmed with the presence of cells that express CD-1a, S100, and CD207 in the BAL fluid.[27][28] Moreover, staining for periodic acid-Schiff in BAL fluid collected from the distal airway can help identify pulmonary alveolar proteinosis. 

BAL is also an excellent method of obtaining specimens to rule out opportunistic infections in immunocompromised individuals. Combining culture results with cytology may show viral intranuclear or intracytoplasmic inclusion bodies on examination of pulmonary epithelial cells, which may help identify viruses like herpes simplex and cytomegalovirus. BAL is also beneficial for detecting fungi and mycobacteria, which may not always be identified in blood. A disadvantage of BAL is that many potentially pathogenic microorganisms may have colonized the airways without any clinical disease. Hence, their recovery may not be meaningful.[29][30]

The differential cell counts on BAL fluid have been reported to be helpful in certain lung disorders. However, BAL results alone often lack specificity and require interpretation and other clinical and radiographic details.[31] For example, BAL fluid analysis and cell count are unreliable diagnostic tools for amiodarone-induced pneumonitis.[32]

BAL is also useful in evaluating individuals with occupational exposures to asbestos and other silicates. These macrophage-ingested occupational dust particles are usually visible in the fluid under polarized light. BAL cytology is also helpful in evaluating patients with malignancies of the airways.

In addition, BAL fluid can be assessed for a variety of microbiologic analyses, including the following:

• Acid-fast bacilli for mycobacterial culture and stain
• Qualitative or quantitative bacterial culture 
• Direct fluorescent antigen detection for Legionella 
• Specific microbial cultures (such as for Nocardia, actinomycosis, mycobacterial, fungal, and viral culture)
• Fluorescent or silver stain for Pneumocystis jirovecii 
• Galactomannan enzyme immunoassay for fungal antigen detection that is commonly used to diagnose invasive aspergillosis

Other conditions that BAL fluid analysis can help in the clinical assessment are:

• Chronic beryllium disease
• A beryllium-lymphocyte proliferation test confirms beryllium exposure and differentiation between sarcoidosis and chronic beryllium disease.[33]
• Cryptogenic organizing pneumonia
• Interleukin (IL)-9 and IL-9R-positive lymphocytes are reported to be more commonly seen in cryptogenic organizing pneumonia than other types of ILDs, such as nonspecific interstitial pneumonia and sarcoidosis.[34]
• Drug-induced pneumonitis
• A cell count is important in the assessment of these cases and typically shows a lymphocytic cellular pattern (>15% lymphocytes) and an eosinophilic pattern (>1% eosinophils).[23]
• Hypersensitivity pneumonitis
• BAL cellular determination is helpful as a differential count of >1% mast cells, >50% lymphocytes, and >3% neutrophils suggest acute hypersensitivity pneumonitis.
• Interstitial pneumonia
• Lymphoid interstitial pneumonia
• Lymphoma

The limitation of BAL in certain pulmonary disorders, as a normal BAL fluid cell profile, does not exclude histopathological abnormalities in the lung. In addition, caution should be exercised when the epithelial cell count exceeds 5%, as this suggests a suboptimal sample. 

Usually, BAL is performed for diagnostic purposes. However, BAL is uniquely used to treat Pulmonary alveolar proteinosis. This is called whole lung lavage and involves instilling 30 to 50 liters of sterile saline through a double-lumen endotracheal tube while the patient is under general anesthesia.

Enhancing Healthcare Team Outcomes

Effective patient-centered care and optimal outcomes in BAL procedures require a collaborative and well-coordinated effort among various healthcare professionals, including physicians, advanced practitioners, nurses, and pharmacists. Physicians play a crucial role in diagnosing and guiding treatment, while advanced practitioners contribute their expertise in managing complex cases. Nurses ensure proper patient preparation and assist during the procedure, emphasizing patient safety and comfort. Pharmacists play a vital role in medication management and ensuring the safe administration of drugs related to BAL. Interprofessional communication is essential for sharing critical information and coordinating care seamlessly. Care coordination involves aligning efforts to streamline the BAL process, from pre-procedure preparations to post-procedural care, ensuring a holistic approach to patient well-being. Regular team collaboration enhances patient-centered care by fostering a comprehensive understanding of individual patient needs, improving outcomes, prioritizing patient safety, and optimizing overall team performance in the context of BAL.