Extracellular Vesicles in Exhaled Breath Condensate as Emerging Biomarkers in Lung Cancer

Exhaled breath condensate (EBC) has emerged as a noninvasive liquid biopsy medium that captures aerosolized material from the respiratory tract and may provide insight into local lung biology. Within this matrix, extracellular vesicles (EVs) can carry DNA, RNA, proteins, and lipids that reflect cellular origin and may report tumor-associated inflammation, airway remodeling, and microenvironmental changes. This review summarizes current evidence on the molecular composition, origin, and biogenesis of EVs detected in EBC, with emphasis on their potential for early lung cancer detection and longitudinal disease monitoring. Proteomic, transcriptomic, and genomic analyses have identified tumor-associated signatures, including cytokines, driver mutations, and epigenetic alterations, while lipidomic profiling may capture oxidative, inflammatory, and metabolic stress. Recent methodological advances in EV enrichment, microfluidics, single-vesicle analytics, and digital assays are improving the sensitivity of low-biomass EBC analyses. However, EBC-derived EV research remains technically challenging, and standardization of collection, EV isolation, molecular analysis, and reporting is essential. Artificial intelligence (AI) and machine learning (ML) may support integration of multi-omic and clinical data, particularly when validated in prospective cohorts. Together, these developments position EBC-derived EVs as an emerging, patient-friendly, lung-proximal platform for biomarker discovery and future precision oncology applications, while underscoring the need for source-resolved validation and clinical translation studies.