Hydrogen sulfide in precision medicine: connecting basic science, sensing, and clinical application

Facts Hydrogen sulfide (H 2 S) is a key endogenous signaling molecule involved in cardiovascular, neurological, respiratory, and cancer-related pathophysiology. Dynamic monitoring of trace H 2 S levels provides critical insight into disease initiation, progression, and therapeutic response. Emerging spectroscopic techniques, particularly quartz-enhanced photoacoustic spectroscopy (QEPAS), offer unprecedented sensitivity and selectivity for H 2 S detection in biological samples. Breath and skin gas analysis represent promising non-invasive approaches for translating H 2 S sensing from bench to bedside. Open questions What are the precise physiological thresholds of H 2 S concentration that differentiate healthy and pathological states across diverse organ systems? How can QEPAS and other spectroscopic methods be miniaturized and standardized for reliable, real-time clinical use? Can H 2 S modulation be safely targeted in therapy without disturbing other gasotransmitter pathways (nitric oxide and carbon monoxide)? What regulatory and validation frameworks are required to translate H 2 S-based diagnostics into routine clinical practice? Hydrogen sulfide, as a critical endogenous gasotransmitter, plays a significant role in the pathophysiology of various diseases, including cardiovascular diseases, neurodegenerative disorders, respiratory dysfunctions, and cancer. The dynamic fluctuations in hydrogen sulfide concentration are closely associated with the onset and progression of these conditions. The precise monitoring of trace amounts of hydrogen sulfide in biological samples holds substantial value for elucidating disease mechanisms, developing diagnostic biomarkers, and enabling targeted therapies. This review provides a comprehensive overview of the current advancements in hydrogen sulfide detection technologies in medical applications, with a particular focus on the groundbreaking potential of novel spectroscopic techniques in medical diagnostics. This paper through an integrated research approach that bridges hydrogen sulfide biology, sensing technology, and clinical applications-particularly by utilizing breath and skin gas analysis as windows into metabolic and disease states. A core innovation presented in this work is the proposed optimization of the hydrogen sulfide-quartz-enhanced photoacoustic spectroscopy technique for medical settings, which provides a transformative tool for non-invasive disease screening, precise detection, and targeted therapeutic research. The ultimate goal is to bridge the gap between basic research, sensor technology, and clinical needs, driving innovative applications of hydrogen sulfide in precision medicine.