Monocyte Subset Predicts Clinical Outcomes in Fibrotic Hypersensitivity Pneumonitis

This study aimed to identify circulating immune cell populations associated with disease severity and progression in fibrotic hypersensitivity pneumonitis (fHP). Using single-cell RNA sequencing of peripheral blood mononuclear cells from 33 fHP patients (NCT02958917) and 36 sex-matched healthy controls (GSE196735, pools 1-3), we identified significant shifts in immune cell composition. Compared to controls, fHP patients exhibited a marked increase in classical monocytes (CD14⁺), non-classical monocytes (CD16⁺), and myeloid-derived dendritic cells. Classical monocytes, in particular, were strongly correlated with baseline lung fibrosis severity—quantified by data-driven texture analysis of high-resolution computed tomography—and with reduced progression-free survival. Pathway analysis revealed that monocytes from patients with severe disease were enriched for inflammatory and metabolic processes, whereas those from patients with poor outcomes showed upregulation of interferon and NF-κB signaling. These findings highlight peripheral monocytes as promising prognostic biomarkers in fHP and suggest their role in driving fibrotic progression through dysregulated immune responses.