Using BAL Cellular Analysis in Interstitial Lung Disease: 2012 ATS Guideline
The role of bronchoalveolar lavage (BAL) in diagnosing and managing patients with interstitial lung disease (ILD) has always been uncertain and controversial. An American Thoracic Society (ATS) expert panel including Keith Meyer, Ganesh Raghu, Brent Wood et al reviewed 35 years of published literature and authored a clinical practice guideline on the use of BAL in patients with suspected ILD, published in the May 1 2012 AJRCCM.
BAL Is Not Diagnostic or Prognostic for ILD
Authors strongly emphasize that BAL cellular analysis by itself is “insufficient to diagnose the specific type of ILD, except in malignancies and some rare ILDs,” and that it has “no firmly established prognostic value and cannot predict the response to therapy.”
There are no controlled clinical trials [showing] routine BAL in patients with ILD improves patient-important outcomes. However, [our] clinical experience suggests that the results from BAL (cellular analysis, staining and culture for mycobacterial and fungal infection, cytopathology) may provide strong support or clues for a diagnosis or help narrow the differential diagnosis … [T]here are insufficient data to confirm that BAL cell analysis is beneficial and, therefore, it is impossible to weigh [benefits vs. risks and costs] … [Therefore,] BAL cellular analyses should be [elected] on a case-by-case basis until [better evidence is published].
Given those caveats, here are the highlights from this ATS guideline on use of BAL for evaluation & management of ILD.
BAL Advised Only If High-Res CT Chest Is Non-Diagnostic
Authors point out that routine high-resolution CT of the chest provides such valuable diagnostic information that a short differential diagnosis for ILD can be made in most patients with interstitial lung disease, without bronchoscopy/BAL or other invasive diagnostic evaluation.
- In patients with extensive honeycomb change throughout the lungs (the radiographic pattern of usual interstitial pneumonitis or UIP), BAL cellular analysis is not suggested.
- If, when taken together with the other clinical and historical findings, high-resolution CT of the chest is diagnostic for another form of ILD, BAL cellular studies are not advised. Sarcoidosis, pulmonary Langerhans cell histiocytosis, and UIP are the most well-characterized radiographically and the “most diagnosable” ILD subtypes from HRCT findings alone.
If HRCT is non-diagnostic for the ILD subtype, authors suggest BAL with cellular analysis may be helpful at narrowing the differential diagnosis.
Recommended BAL Tests for Suspected ILD
When BAL is performed in the workup of ILD, authors recommend a cell count with differential be collected (neutrophils, lymphocytes, eosinophils, and mast cells — but not routine lymphocyte subset analysis).
Microbiological tests (gram stain and culture, including for fungi and mycobacteria) and cytopathology should be considered “if clinically indicated.”
Interpreting Differential Cell Counts from BAL in ILD
The notion of using relative increases in inflammatory cell subpopulations to diagnose a type of ILD is highly fraught and unscientific, but “may support a specific type of ILD or help narrow the differential diagnosis, when considered in the context of the clinical and radiological findings.”
“Normal” BAL cell counts have been derived from numerous case series. The following are from never-smokers and non-smokers (smokers have significantly higher cell counts):
|BAL cell ct.||Observed normal ranges|
|Total count||103-158 cells/microL|
|Macrophages||80 – 95%|
|Lymphocytes||4 – 15%|
|Neutrophils||1 – 4%|
|Eosinophils||0.1 – 0.5%|
Authors suggest the following BAL cell differential patterns are the most helpful in the diagnosis of ILD:
|BAL Cellular Pattern||ILD Subtypes to Consider More Highly|
|Lymphocytes > 25%||Granulomatous lung disease (sarcoidosis, hypersensitivity pneumonitis), NSIP, berylliosis, drug reaction, COP, LIP, or lymphoma|
|Lymphocytes > 50%||Hypersensitivity pneumonitis or cellular NSIP|
|Eosinophils > 25%||Diagnostic of eosinophilic lung disease, if clinical features are present|
|Neutrophils > 50%||Pneumonia, aspiration pneumonia, lung abscess, acute lung injury|
|Mast cell > 1% with lymphocyte > 50% and neutrophils > 3%||Hypersensitivity pneumonitis|
ATS Recommends Not Performing Lymphocyte Subset Analysis (CD4, CD8 etc) Routinely.
Authors feel lymphocyte subset analysis, if performed routinely, is “rarely helpful and potentially misleading.” Rather, it should be used after a lymphocytosis is identified on BAL cell differential, or in cases when a lymphocytic disease is suspected.
Even when a lymphocytic disease (e.g., sarcoidosis, hypersensitivity pneumonitis) is suspected, lymphocyte subset analysis may be misleading or difficult to interpret. The classic patterns (elevated CD4/CD8 ratio in sarcoidosis, and reduced in HP) are neither sensitive nor specific, may change throughout the disease course, and may be present in normal subjects. An elevated CD4/CD8 ratio may be most useful in the diagnosis of sarcoidosis: in cases when the ratio is > 4 and other findings of sarcoidosis are present, authors suggest the CD4/CD8 ratio provides additional evidence for sarcoid.
ATS Recommendations for BAL in ILD: Summary
Bronchoalveolar lavage (BAL) is not necessary for most patients with ILD, including those with a usual intersitial pattern (UIP) on high-resolution chest CT (HRCT). BAL may help direct the diagnosis of an ILD subtype in some patients with nondiagnostic HRCT of the chest. BAL cellular analysis cannot diagnose ILD subtype alone, nor can it predict outcome or response to therapy.
In those patients in whom BAL for ILD is performed:
- Collect the BAL sample from an abnormal area of lung as seen on high-resolution CT.
- A minimum of 5 mL must be collected; 10-20 mL is better. 30% of the total instilled volume should be collected to ensure a reliable cell differential; <10% collected is particularly unreliable.
- Perform differential cell count on the BAL sample: macrophages, lymphocyte, eosinophil, and neutrophil counts (in another section, they advise mast cells be checked as well). Microbiology and cytopathology should be collected when clinical suspicion warrants it.
- Lymphocyte subset analysis (e.g., CD4/CD8 ratios) should not be performed routinely.
With gratitude to: Meyer KC et al. An Official American Thoracic Society Clinical Practice Guideline: The Clinical Utility of Bronchoalveolar Lavage Cellular Analysis in Interstitial Lung Disease. AJRCCM 2012;185:1004-1014.