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Using BAL Cellular Analysis in Interstitial Lung Disease
The role of bronchoalveolar lavage (BAL) in diagnosing and managing patients with interstitial lung disease (ILD) has always been uncertain and controversial.
BAL findings are usually nonspecific, suggesting rather than proving the existence of any particular noninfectious condition (including interstitial lung disease). That said, in patients with new interstitial opacities and respiratory symptoms (cough, dyspnea), BAL can sometimes be helpful.
Healthy people's BAL fluid contains predominantly macrophages, with only small numbers of nucleated cells (neutrophils, lymphocytes and eosinophils). A wide variety of changes in the numbers and proportions of nucleated cell constituents have been reported in people with ILD. These changes are nondiagnostic, but sometimes the pattern can guide the diagnostic workup. Once in a while, BAL fluid may help confirm a diagnosis of ILD.
BAL Is Not Diagnostic or Prognostic for ILD
ILD can't be diagnosed by BAL cellular analysis alone, except possibly in some cancers and unusual ILDs. Its role is supportive to the diagnostic process. No randomized trials have shown that BAL in the diagnosis of ILD improves outcomes.
If High-Res CT Chest Is Diagnostic for ILD, BAL Not Needed
Routine high-resolution CT of the chest provides valuable diagnostic information, permitting a short differential diagnosis for ILD to be created in most patients with interstitial lung disease. This can obviate the need for bronchoscopy/BAL or other invasive diagnostic evaluation in many patients. Examples:
- Honeycombing throughout the lungs strongly suggests usual interstitial pneumonitis or UIP. BAL cellular analysis will probably not add value to the workup.
- 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, some experts suggest BAL with cellular analysis may be helpful at narrowing the differential diagnosis.
Ideally, bronchoalveolar lavage should be performed relatively soon after the HRCT (within 1 month or so), and the BAL sample collected from an area definitely affected by interstitial lung disease on the HRCT.
BAL Tests for Suspected ILD
Certain tests on bronchoalveolar lavage fluid might support the diagnosis of interstitial lung disease:
- Cell count with differential (neutrophils, lymphocytes, eosinophils, and mast cells). Lymphocyte subset analysis is less helpful than many people believe and is not needed routinely.
- Microbiology (gram stain and culture, for bacteria, fungi and mycobacteria)
- Cytopathology is not always necessary, but is often performed. Metastatic malignancies (breast cancer, lymphoma) can present with interstitial infiltrates and occasionally be diagnosed this way.
Interpreting Differential Cell Counts from BAL in ILD
"Normal" BAL cell counts have been derived from numerous case series: usually about 100 cells/microL, about 85% macrophages, with lymphocytes making up most of the rest (~10%), neutrophils a smaller fraction (<10%), and eosinophils <1%. Smokers may have significantly higher cell counts. Reiterating the point that cellular analysis is only supportive, not diagnostic in the diagnosis of ILD, here are some commonly reported patterns on BAL in patients with ILD:
- Lymphocytic BAL (>30%): Sarcoidosis or hypersensitivity pneumonitis.
- Neutrophilic BAL (>60%): Infection or ARDS
- Eosinophilic BAL (>30%): Acute or chronic eosinophilic pneumonia; coccidioidomycosis
Nonspecific interstitial pneumonitis and UIP / idiopathic pulmonary fibrosis do not have a typical pattern on BAL (usually a mixed cellularity pattern). Chronic aspiration can also produce a mixed cellular pattern, sometimes with lipid-containing macrophages.
Lymphocyte SubsetAnalysis (CD4, CD8 etc)
When a lymphocytic disease (e.g., sarcoidosis, hypersensitivity pneumonitis) is suspected, lymphocyte subset analysis may be helpful, but also may be misleading. The classic patterns are:
- Elevated CD4/CD8 ratio >2 in early, active sarcoidosis (may be lower in chronic or quiescent disease)
- CD4/CD8 < 1 in hypersensitivity pneumonitis.
However, these metrics are neither sensitive nor specific for either condition and people without disease can sometimes also have these "abnormal" patterns. For this reason, some experts advise against checking this parameter in most patients. A very high CD4/CD8 ratio (>4) may help confirm a sarcoidosis diagnosis, if other clinical features are present.
Kilinç G, Kolsuk EA. The role of bronchoalveolar lavage in diffuse parenchymal lung diseases. Curr Opin Pulm Med. 2005 Sep;11(5):417-421.
Welker L et al. Predictive value of BAL cell differentials in the diagnosis of interstitial lung diseases. Eur Respir J. 2004 Dec;24(6):1000-1006.
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.
Drent M et al. Bronchoalveolar lavage in sarcoidosis. Semin Respir Crit Care Med. 2007 Oct;28(5):486-495.