Home Educatione-Learning The Value of Bronchoalveolar Lavage in the Diagnosis and Management of Interstitial Lung Disease
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The Value of Bronchoalveolar Lavage in the Diagnosis and Management of Interstitial Lung Disease

PCCSU Volume 25, Lesson 8

PCCSU

The American College of Chest Physicians offers this lesson as a review of a previously offered self-study program. The program provides information on pulmonary, critical care, and sleep medicine issues. CME is no longer available for the PCCSU program.

Objectives

  • Update your knowledge and understanding of pulmonary medicine topics.
  • Update your knowledge and understanding of critical care medicine topics.
  • Update your knowledge and understanding of sleep medicine topics.
  • Learn clinically useful practice procedures.

CME Availability

Effective July 1, 2013, PCCSU Volume 25 is available for review purposes only.

Effective December 31, 2012, PCCSU Volume 24 is available for review purposes only.

Effective December 31, 2011, PCCU Volume 23 is available for review purposes only. CME credit for this volume is no longer being offered

Effective December 31, 2010, PCCU Volume 22 is available for review purposes only. CME credit for this volume is no longer being offered.

Accreditation Statement

The American College of Chest Physicians is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

CME Statement

Credit no longer available as of July 1, 2013.

Disclosure Statement

The American College of Chest Physicians (CHEST) remains strongly committed to providing the best available evidence-based clinical information to participants of this educational activity and requires an open disclosure of any potential conflict of interest identified by our faculty members. It is not the intent of CHEST to eliminate all situations of potential conflict of interest, but rather to enable those who are working with CHEST to recognize situations that may be subject to question by others. All disclosed conflicts of interest are reviewed by the educational activity course director/chair, the Education Committee, or the Conflict of Interest Review Committee to ensure that such situations are properly evaluated and, if necessary, resolved. The CHEST educational standards pertaining to conflict of interest are intended to maintain the professional autonomy of the clinical experts inherent in promoting a balanced presentation of science. Through our review process, all CHEST CME activities are ensured of independent, objective, scientifically balanced presentations of information. Disclosure of any or no relationships will be made available for all educational activities.

CME Availability

Volume 25 Through June 30, 2013
Volume 24 Through December 31, 2012
Volume 23 Through December 31, 2011
Volume 22 Through December 31, 2010

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PCCSU Volume 25 Editorial Board

Editor-in-Chief
Steven A. Sahn, MD, FCCP

Director, Division of Pulmonary and Critical Care Medicine, Allergy, and Clinical Immunology
Medical University of South Carolina
Charleston, SC

Dr. Sahn has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Deputy Editor
Richard A. Matthay, MD, FCCP

Professor of Medicine
Section of Pulmonary and Critical Care Medicine
Yale University School of Medicine
New Haven, CT

Dr. Matthay has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Alejandro C. Arroliga, MD, FCCP
Professor of Medicine
Texas A&M Health Science Center
College of Medicine
Temple, TX

Dr. Arroliga has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Paul D. Blanc, MD, FCCP
Professor of Medicine
University of California, San Francisco
San Francisco, CA

Dr. Blanc has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health, Flight Attendants Medical Research Institute – university grant monies
University of California San Francisco, US Environmental Protection Agency, California Environmental Protection Agency Air Resources Board – consultant fee
Habonim-Dror Foundation Board of Trustees – fiduciary position

Guillermo A. do Pico, MD, FCCP
Professor of Medicine
University of Wisconsin Medical School
Madison, WI

Dr. do Pico has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Ware G. Kuschner, MD, FCCP
Associate Professor of Medicine
Stanford University School of Medicine
Palo Alto, CA

Dr. Kuschner has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Teofilo Lee-Chiong, MD, FCCP
Associate Professor of Medicine
National Jewish Medical Center
Denver, CO

Dr. Lee-Chiong has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

National Institutes of Health – grant monies (from sources other than industry)
Covidien, Respironics, Inc. – grant monies (from industry-related sources)
Elsevier – consultant fee

Margaret Pisani, MD, MPH, FCCP
Assistant Professor of Medicine
Yale University School of Medicine
New Haven, CT

Dr. Pisani has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Stephen I. Rennard, MD, FCCP
Professor of Medicine
University of Nebraska Medical Center
Omaha, NE

Dr. Rennard has disclosed significant relationships with the following companies/organizations whose products or services may be discussed within Volume 25:

AstraZeneca, Biomark, Centocor, Novartis – grant monies (from industry-related sources)

Almirall, Aradigm, AstraZeneca, Boehringer Ingelheim, Defined Health, Dey Pharma, Eaton Associates, GlaxoSmithKline, Medacrop, Mpex, Novartis, Nycomed, Otsuka, Pfizer, Pulmatrix, Theravance, United Biosource, Uptake Medical, VantagePoint – consultant fee/advisory committee

AstraZeneca, Network for Continuing Medical Education, Novartis, Pfizer, SOMA – speaker bureau

Ex Officio
Gary R. Epler, MD, FCCP

Clinical Associate Professor of Medicine
Harvard Medical School
Brigham & Women's Hospital
Boston, MA

Dr. Epler has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within Volume 25.

Lilly Rodriguez
ACCP Staff Liaison

By Keith C. Meyer, MD, MS, FCCP

Dr. Meyer is Professor of Medicine; Medical Director of Lung Transplantation; Director, Interstitial Lung Disease Program and Clinic; and Director, Adult Cystic Fibrosis Program, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.

Dr. Meyer has disclosed no significant relationships with the companies/organizations whose products or services may be discussed within this chapter.

Objectives

  1. Review BAL technique and its importance in evaluating interstitial lung disease (ILD).
  2. Describe characteristics of BAL analysis in healthy individuals.
  3. Examine BAL characteristics and immune cell patterns in different forms of ILD.
  4. Describe the appropriate integration of BAL in diagnostic algorithms for ILD.
  5. Identify limitations of BAL in the differential diagnosis of ILD.
  6. Clarify the utility of BAL in management of ILD.

Key words: bronchoalveolar lavage, interstitial lung disease

Abbreviations: AIP = acute interstitial pneumonia; AM = alveolar macrophage; COP = cryptogenic organizing pneumonia; DAH = diffuse alveolar hemorrhage; EP = eosinophilic pneumonia; HP = hypersensitivity pneumonitis; HRCT = high-resolution CT; IIP = idiopathic interstitial pneumonia; ILD = interstitial lung disease; IPF = idiopathic pulmonary fibrosis; LIP = lymphoid interstitial pneumonia; NSIP = nonspecific interstitial pneumonia; PAP = pulmonary alveolar proteinosis

Making an accurate and confident diagnosis of specific forms of interstitial lung disease (ILD) presents a daunting challenge to clinicians. Because treatment options and prognosis vary considerably among the various types of ILD, making a precise diagnosis is of prime importance to the patient. Clinical findings can be helpful, but additional testing is usually needed. The advent of high-resolution CT (HRCT) of the thorax has revolutionized the diagnostic approach to patients in whom ILD is suspected,1 but additional testing is often required to provide a confident diagnosis. Surgical lung biopsy will usually provide a precise and confident diagnosis if it is performed properly and histopathologic specimens are interpreted by pathologists with adequate knowledge of lung pathology, but surgical lung biopsy entails some degree of risk owing to the significant complications that may occur. Endoscopic biopsies are quite safe if performed properly, but adequate tissue sampling for diagnosis may not be achieved with transbronchial or endobronchial lung biopsy.

BAL was introduced into the clinical arena in the 1970s and gradually became a tool that was used to evaluate patients in whom diffuse infiltrates were seen on chest imaging.2 After a very high degree of initial enthusiasm for its ability to aid in ILD diagnosis and the publication of guidelines for its use in the diagnosis and management of ILD,3,4 it became clear in the 1990s that BAL had some significant limitations in its ability to aid in diagnosing and differentiating specific forms of ILD. However, BAL can often provide highly useful diagnostic information5-7 and may be particularly useful when combined with clinical data and HRCT images that have been interpreted by radiologists who have adequate expertise in thoracic HRCT analysis.

Is Technique Important?

Centers around the world use different protocols for performing BAL, and no up-to-date, peer-reviewed guidelines or consensus statements have been published to guide clinicians who use BAL as a clinical tool to assist with the diagnosis of ILD. Although standardized methods have been proposed for performing BAL,8 no ultimate consensus has been reached for number of aliquots instilled, total volume instilled, whether to include the first retrieved aliquot in the pooled sample of subsequent retrieved aliquots, site of lavage, technique of applying negative pressure to retrieve instilled fluid, and adjustment of BAL results for dilution of epithelial surface liquid. Nonetheless, the BAL technique employed must be adequate to retrieve a specimen that is diagnostically useful.8

For diffuse and relatively uniform lung involvement with the disease process, the right middle lobe and lingula of the left upper lobe are typically chosen as convenient sites that are easily accessed for wedge positioning of the distal bronchoscope in segmental bronchi. These sites will generally give good BAL fluid return in semirecumbent or recumbent patients. If the disease process is less prominent in these locations but more prominent in other areas as assessed by HRCT imaging, the bronchoscopist may choose to target such areas for lavage.

BAL should be performed with multiple aliquots of normal saline with the bronchoscope in a wedge position.8 Some investigators use hand-held syringes with manual suction to retrieve fluid, while others use wall suction or gravity to provide negative pressure to aspirate instilled fluid. Using a hand-held syringe allows instantaneous control of negative pressure while the relative degree of airway patency vs excessive collapse can be simultaneously visualized. The percentage of BAL fluid that is retrieved should be in the range of 30% or greater, with a total instilled volume in the range of 100 to 300 mL with aliquot size ≤60 mL. However, if ILD is superimposed on emphysema, airways may readily collapse with negative pressure, compromising fluid retrieval and the diagnostic usefulness of the BAL cell pattern. Lavage fluid aliquots should be pooled and rapidly transported to the clinical laboratory for further processing and analysis.

BAL fluid processing and preparation of specimens for subsequent analysis should be performed by personnel in certified clinical laboratories who are familiar with protocols for BAL and adhere to good clinical laboratory practice.7,8 Cell counts can be obtained via hemocytometer or an automated analyzer such as a Coulter counter, and the cytospin method is typically used to prepare cells on slides for staining and subsequent microscopic assessment. It is essential that the determination of differential cell counts be performed by personnel who are adequately familiar with the morphologic features of all of the nucleated immune cell types that are potentially present in BAL, including plasma cells and mast cells. If malignancy is a consideration, cell preparations should be reviewed by a cytopathologist. If infection is a consideration, BAL fluid samples should be subjected to appropriate staining, molecular probes, and culture.7 Lymphocyte subsets may be determined if they are considered useful for diagnosis and an adequate facility is available for such analysis. Other monoclonal antibody staining may also prove useful under certain circumstances (see below).

BAL Immune Cell Patterns: What Is Normal?

BAL differential cell counts for nucleated immune cells retrieved via BAL obtained from healthy, nonsmoking adults generally show 85% to 95% macrophages and 5% to 15% lymphocytes with ≤1% eosinophils and ≤3% neutrophils (Table 1).9 Plasma cells, mast cells, and basophils should not be present. The number of RBCs and bronchial epithelial cells should be minimal, and squamous epithelial cells should not be present (the presence of squamous epithelial cells suggests contamination with upper airway secretions or the presence of aspiration). Cigarette smoking increases the total number of cells/mL of BAL fluid but has little effect on cell differential, although the relative percentage of lymphocytes has a tendency to decline and the total number of neutrophils and macrophages tend to increase.10 Alveolar macrophages (AMs) ingest carbonaceous debris and show characteristic inclusions on examination of BAL cytospin preparations.10 Advanced age may affect BAL cell patterns, and BAL samples from healthy elderly subjects without lung disease tend to show an increase in total cells and an increase in lymphocytes and neutrophils.11,12 Therefore, advanced age must be kept in mind as a potential correlate of increased BAL lymphocytes or granulocytes.


Table 1BAL Cell Differential Percentages in Normal, Nonsmoking Adults

Cell Type Percentage on Differential Cell Count
Alveolar macrophages ≥85%
Lymphocytes ≤15%
Neutrophils ≤3%
Eosinophils ≤1%
Bronchial epithelial cells ≤5%
Squamous epithelial cells Nonea

Data are extracted from numerous reports in the literature.
aIf any are present, they should be rare.


 

What BAL Findings Are Useful for ILD Differential Diagnosis?

BAL Fluid Appearance
The bronchoscopist should examine the nature of the retrieved BAL fluid and observe its appearance. If the retrieved fluid becomes increasingly bloody with sequential aliquots, a diagnosis of diffuse alveolar hemorrhage (DAH) is likely.13 If the retrieved fluid has an opaque, whitish to tan coloration and similarly colored debris settles with gravity to the bottom of a collection cup or syringe over a 10- to 15-min period, a diagnosis of pulmonary alveolar proteinosis (PAP) is highly likely and consistent air-space changes will usually be present on HRCT imaging.

Lymphocyte Pattern
A significant BAL lymphocytosis may be present for many forms of ILD (Table 2). Sarcoidosis and hypersensitivity pneumonitis (HP) have been classically associated with BAL lymphocyte differential counts in excess of 25%, and very high percentages have been reported with HP.15-17 However, prominent BAL lymphocytosis may also be observed with drug reactions, cellular nonspecific interstitial pneumonia (NSIP), cryptogenic organizing pneumonia (COP), or lymphoid interstitial pneumonia (LIP); other entities, such as viral pneumonitis, infections associated with granulomatous inflammatory response, or infiltration with malignant lymphocytes, may also cause some degree of BAL lymphocytosis.


Table 2Specific Forms of ILD and Other Disorders Commonly Associated With Elevated Percentages of BAL Nucleated Immune Cells

BAL Cell Type Specific Disorders to Consider
Lymphocytes >15% Sarcoidosis
Hypersensitivity pneumonitis
Pneumotoxic drug reaction
Cellular NSIP > fibrotic NSIP
Collagen tissue disease-associated ILD
[Cryptogenic] organizing pneumonia
Lymphoproliferative disorders (LIP, lymphoma)
Radiation pneumonitis
Chronic beryllium disease
Eosinophils >1% Eosinophilic ILD
   Eosinophilic pneumonia
   Churg-Strauss syndrome
Pneumotoxic drug reaction
Infection (helminthic, fungal, bacterial)
Airway disorders
   Allergic bronchopulmonary aspergillosis
   Asthma
   Bronchitis
Organizing pneumonia
Idiopathic pulmonary fibrosis
Non-IPF IIP
Hodgkin disease
Neutrophils >3% Infection
Acute lung injury
   ARDS
   Acute exacerbation of IPF
Diffuse alveolar damage
Organizing pneumonia
Aspiration pneumonia
IPF
Non-IPF IIP
Sarcoidosis (fibrotic)
HP (advanced, fibrotic)
Airway disorders (COPD, asthma, inhaled irritants)

 


BAL lymphocytosis has been linked to prognosis and response to therapy for some forms of idiopathic interstitial pneumonia (IIP). BAL findings from patients diagnosed with idiopathic pulmonary fibrosis (IPF)—when this diagnostic term did not necessarily exclude other forms of IIP, such as NSIP—suggested that higher BAL lymphocyte differential cell counts were correlated with better prognosis and/or response to therapy.18-20 A more recent, retrospective study demonstrated that BAL lymphocytosis in patients who appear to have fibrotic IIP suggests that the diagnosis is not IPF but rather NSIP, and BAL lymphocytosis was found to correlate with a better prognosis.21 Generally speaking, ILD associated with a prominent BAL lymphocytosis is likely to respond to immunosuppressive pharmacologic therapy.

Eosinophil Pattern
The percentage of eosinophils in epithelial surface liquid may be increased in a variety of specific ILDs and may also be increased in other non-ILD conditions. However, these increases are usually modest, <10%. Considerably increased values for eosinophil percentage on differential cell count, particularly if in excess of 25%, quite likely signal the presence of an eosinophilic pneumonitis,22 especially eosinophilic pneumonia (EP) or a drug reaction. BAL eosinophilia has been linked to more severe disease and worse prognosis in patients with IPF.20,23

Neutrophil Pattern
An increase in BAL neutrophils is nonspecific and is seen with a number of specific ILDs. However, large numbers of neutrophils may reflect relatively acute or ongoing lung injury, such as acute interstitial pneumonia (AIP) or diffuse alveolar damage (DAD). Infection may also be a cause of increased neutrophils and should be ruled out with appropriate stains, molecular probes, and cultures of BAL fluid. The degree of increase in BAL neutrophils has been correlated with disease severity and prognosis for both HP24,25 and IPF,18,19,26 and the presence of increased neutrophils in BAL from patients with sarcoidosis has been associated with more progressive disease that is less likely to respond to immunosuppressive therapy.27

Mixed Patterns
The BAL differential cell count may show a significant increase in more than one cell type (lymphocytes, neutrophils, and/or eosinophils) with various forms of ILD. Examples include pulmonary sarcoidosis with lung fibrosis, which may show increased BAL lymphocytes and neutrophils; IPF, with increased neutrophils and eosinophils in BAL; and COP, which may show increased lymphocytes, neutrophils, and eosinophils in BAL. Elevations of more than one cell type are frequently observed in ILD associated with connective tissue disease.

Macrophages
Total numbers of AMs can be considerably increased in smokers without ILD and in patients who have desquamative interstitial pneumonia/respiratory bronchiolitis with ILD, which are highly associated with cigarette smoking. AMs may have a foamy appearance in HP, cytoplasmic inclusions with viral infection, highly vacuolated cytoplasm that stains positive for fat in chronic aspiration pneumonitis, ingested RBCs and RBC fragments in DAH, or ingested dust particles or asbestos bodies with occupational exposures. AMs will stain positive for hemosiderin if alveolar hemorrhage has occurred and has preceded BAL by 24 to 48 h.

Other Cell Types
Plasma cells, mast cells, and basophils are not usually present in BAL fluid. However, plasma cells may be observed in patients with HP, drug reactions, EP, infection, or malignancy.28 Increased numbers of mast cells have been associated with HP, drug reactions, sarcoidosis, ILD associated with connective tissue disease, COP, EP, IPF, and malignancy.28 Basophils are rarely identified in BAL, and malignant cells may be seen with primary lung neoplasms.

Identification of Specific Cell Types and Subsets
Determination of the T helper (CD4+) and T suppressor (CD8+) lymphocytes was considered useful in making a diagnosis of sarcoidosis (lymphocytosis with high CD4+/CD8+ T-cell ratio)29 vs HP (lymphocytosis with low CD4+/CD8+ ratio),30 and relative numbers of lymphocyte subsets can be readily quantitated via flow cytometry or in situ immunocytochemistry. The finding of a high CD4+/CD8+ T lymphocyte ratio increases the likelihood of sarcoidosis as the diagnosis when combined with BAL lymphocytosis.31,32 However, many patients diagnosed with pulmonary sarcoidosis do not have an elevated CD4+/CD8+ ratio or may even have a low ratio,33 and the clinician must consider age as a factor if the CD4+/CD8+ ratio is increased and the patient is elderly.12 Similarly, the ratio is not necessarily low in HP; it can also be normal or increased.34 It has gradually become clear that T lymphocyte subset ratios are not as useful as once thought (the ratio can be normal or even low in sarcoidosis and can be normal or increased in HP), and routine determination of BAL lymphocyte subset profiles can add considerable cost to BAL analysis. However, the finding of a high percentage of BAL cells that stain positive for CD1a can be diagnostic of Langerhans cell histiocytosis in the appropriate clinical setting,35 and BAL lymphocytes can be analyzed with appropriate antibody staining and/or polymerase chain reaction methods to detect the presence of lymphomatous cells.36

Acute-Onset ILD
BAL may provide highly useful diagnostic information in patients with acute-onset ILD (usually defined as illness of ≤4 weeks’ duration that is characterized by shortness of breath, hypoxemia, and diffuse radiographic infiltrates in a patient who lacks a history of prior lung disease and has no obvious risk factors for ARDS, such as sepsis or trauma) or patients with an exacerbation of preexistent ILD. Diagnostic considerations in acute-onset ILD include infection, AIP, acute EP, DAH, acute HP, acute COP, drug toxicity, or acute exacerbation of previously undiagnosed IPF or other ILD, such as EP, HP, or COP. Examination of BAL fluid can detect infection or hemorrhage, and a finding of a high percentage of eosinophils (≥25%) strongly supports a diagnosis of EP or drug toxicity. Similarly, large numbers of lymphocytes (≥50%) would suggest acute HP or drug toxicity, especially if macrophages have a foamy appearance, plasma cells are present, and a plausible exposure history is obtained. Bronchoscopy with BAL performed at the time of the acute presentation may facilitate diagnosis, lessen the need to perform a surgical lung biopsy, and identify patients with marked BAL lymphocytosis or eosinophilia who are likely to have a good response to antiinflammatory/immunosuppressive agents (eg, corticosteroids).

Screening for Infection
Infection can cause the subacute onset of diffuse lung infiltrates and masquerade as ILD or coexist with noninfectious ILD. BAL fluid should be examined and screened for mycobacterial or fungal infection if clinical suspicion of an infectious etiology appears to warrant such testing. An uncentrifuged BAL fluid specimen can be sent for quantitative bacterial culture if bacterial infection is a possibility, and BAL fluid can be sent for viral studies (culture, stains, or viral nucleic acid probe studies). If clinically indicated, BAL specimens can be cultured for Legionella, Mycoplasma, and Chlamydiae in addition to mycobacteria and fungi, and cytocentrifuged specimens can be stained to detect the presence of intracellular bacteria, Pneumocystis jiroveci, mycobacteria, or fungi.7

How Safe Is BAL?

Postbronchoscopy fever (fever, chills, and extreme malaise) may occur within hours of the BAL procedure as a consequence of proinflammatory mediator release, and these symptoms are more likely to occur if larger volumes of fluid are used for BAL.37 Rarely, acute exacerbation of established ILD has been reported,38 but BAL is quite safe if performed properly and with appropriate monitoring during the procedure.39,40

How Can BAL Be Optimally Used as a Diagnostic Tool in ILD?

Target Area
Patients with ILD are usually evaluated with HRCT imaging, and the bronchoscopist may decide to use the HRCT images to target areas of more prominent change, such as areas of ground-glass attenuation, more prominent nodular profusion, or fine reticulation. However, no studies have demonstrated that the use of HRCT to target certain geographic lung regions that show more prominent parenchymal change (other than traditionally used sites, such as the right middle lobe or lingula) improves the diagnostic yield of BAL.

Combination With Endoscopic Lung Biopsy
When bronchoscopy with BAL is performed, adding transbronchial (or if appropriate, endobronchial mucosa) biopsies to the bronchoscopy procedure adds relatively little risk to the procedure if performed by an expert bronchoscopist with good technique. As an example, BAL can help to rule out infection when granulomatous changes are identified in endoscopic biopsy specimens. The finding of BAL lymphocytosis plus noncaseating granulomata on endoscopic biopsy would lend confidence to a diagnosis of sarcoidosis for a patient with a consistent clinical presentation and thoracic imaging findings. Similarly, lymphocytosis or a mixed BAL cell pattern plus Masson bodies on transbronchial biopsy would provide confidence in a diagnosis of COP.

Integration With Other Diagnostic Testing and Procedures
As with any other diagnostic tissue sampling (endoscopic or surgical lung biopsy), BAL findings must be integrated with clinical data (history, physical examination), appropriate laboratory testing, and thoracic imaging (Fig 1). In the appropriate clinical setting, certain gross and cellular findings in BAL are highly suggestive or even virtually diagnostic of specific ILD entities (Table 3).


L8Fig1

Figure 1. Diagnostic use of BAL findings. VATS = video-assisted thoracoscopic surgery.


Table 3BAL Findings That May Be Especially Useful in ILD Diagnosis

BAL Finding Consistent Interpretation/Suggested Diagnosis
Bloody fluid DAH
Milky appearance with PAS-positive amorphous debris Pulmonary alveolar proteinosis
Lymphocytes ≥25% Sarcoidosis, HP, cellular NSIP, drug reaction, CBD, lymphoproliferative disorder (eg, LIP)
Neutrophils ≥50% Infection, AIP, DAD, AEIPF
Eosinophils ≥25% EP
High hemosiderin score DAH, DAD
CD1a+ cells >4% Langerhans cell histiocytosis

PAS = periodic acid-Schiff stain; CBD = chronic beryllium disease; DAD = diffuse alveolar damage; AEIPF = acute exacerbation of IPF.


 

Is BAL Useful for Chronic Management of ILD?

In the past, BAL cell profiles were thought to be useful in the management of disorders such as sarcoidosis, HP, or scleroderma, but these assertions have not held up over time with the publication of additional clinical research. A role for BAL cell analysis as a guide for treatment over time, to direct and/or monitor pharmacologic interventions, has not been validated. However, BAL may be useful in evaluating acute changes in symptoms and/or lung function, as adverse events or complications, such as respiratory infection, drug reactions, acute exacerbations of ILD, or hemorrhage, may occur; BAL may assist in the identification of a specific complication and facilitate timely intervention. One exception to this generalization is the use of lung lavage to manage PAP, which is considered to be standard of care for management of patients with PAP.41

What is the Future of BAL for ILD Diagnosis and Management?

Newer tools for analyzing BAL cells and fluid that provide genomic and proteomic characterization of cellular and soluble extracellular components of BAL fluid may eventually offer a means of making accurate and confident diagnoses of specific forms of ILD. These tools may provide guidance in choosing effective therapies, monitoring disease activity, and assessing the effectiveness of specific pharmacologic interventions. DNA microarray analysis can identify and monitor expression patterns of a large number of genes and may be useful for detecting expression patterns that are unique to specific types of ILD.42,43 Similarly, proteome analysis with two-dimensional gel electrophoresis, image analysis, and mass spectrometry may enable identification of specific patterns of gene product (eg, cytokines) expression that can differentiate one form of ILD from another.44,45 BAL fluid protein profiles have shown differences among IPF, sarcoidosis, and HP,46-48 and differences in BAL cell gene expression have been shown to differentiate IPF from HP.49 In the near future, these methods may provide a means of using BAL analysis to achieve confident diagnoses of specific ILDs and to select therapies that can optimize management of specific ILDs.

Summary and Conclusions

If BAL is properly performed and analyzed, characterization of BAL fluid specimens with the determination of nucleated immune cell patterns can (when combined with clinical evaluation of the patient, laboratory testing, and adequate thoracic imaging) play an important role in the diagnosis of many specific forms of ILD. Future applications of BAL in the evaluation of patients with ILD—combined with an evolving, improved understanding of the pathogenesis of specific ILD and the development of novel testing using genomic and proteomic characterization of BAL fluids—may provide accurate diagnostic and prognostic information. Additionally, future advances in the characterization of BAL cells and proteins via gene expression analysis and proteome analysis will potentially play a role in choosing novel therapies for specific forms of ILD and in monitoring therapeutic efficacy.


 

References

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