Abstract
BACKGROUND: In pulmonary sarcoidosis, alveolar macrophages (AMs) undergo epithelioid transformation, but their quantitative morphologic characteristics and association with systemic disease markers remain incompletely defined. RESEARCH QUESTION: Do enlargement and activation features of AMs in bronchoalveolar lavage (BAL) samples correlate with systemic markers of sarcoidosis activity (ACE and sIL-2R)? METHODS: BAL cells from 16 biopsy-confirmed sarcoidosis cases and 4 healthy controls were cytocentrifuged, Diff-Quik®-stained, and analyzed using a digital planimetric microscope. Cell area (CA) of 50 randomly selected AMs per subject (total = 1,000) was quantified and categorized as small, medium, large, or extra-large based on control mean ± SD cutoffs. Nonparametric tests and principal component analysis (PCA) were applied to examine associations among CA, morphological features, serum ACE, and sIL-2R. RESULTS: The mean CA was 31% greater in sarcoidosis than in controls (368.2 ± 169.3 μm(2) vs. 281.4 ± 90.9 μm(2); p < 0.001), with higher proportions of large/extra-large AMs (41% vs. 14%; p < 0.001). Vacuolation, rosette formation, and membrane ruffling were hallmarks of AM activation, correlating strongly with serum ACE and sIL-2R but not with the BALF CD4/CD8 ratio. CONCLUSION: AM enlargement and activation features are quantitative, reproducible surrogates of disease activity in pulmonary sarcoidosis. Clinical implications: Quantitative assessment of alveolar macrophage morphology may aid in assessment and monitoring of sarcoidosis activity and treatment response.