Real-Time Breath Diagnostics: Linking Molecular Pathways, Measurement Technologies, and Clinical Translation

Diagnostic latency limits time-sensitive care and early detection, and exhaled breath provides a rapid, repeatable window into metabolic and inflammatory chemistry. We review real-time breath sampling and analytical technologies and evaluate their readiness for clinical adoption, with emphasis on molecular pathways reflected in the breath volatilome and in exhaled breath condensate. Real-time mass spectrometry enables kinetic VOC profiling and targeted quantification, while humidity-aware sensors and wearable condensate platforms extend monitoring beyond the laboratory. Pathway-anchored interpretation links breath readouts to ketone handling, isoprenoid metabolism, nitric oxide signaling, lipid peroxidation, uremic nitrogen handling, and microbiome-host co-metabolism, but performance remains vulnerable to confounding, drift, and non-representative comparators. Translation requires standardized breath fraction control, traceable features, robust quality systems, and governed device algorithm stacks so that breath outputs inform decisions and outcomes.