Expanding role of cell-free DNA for the early diagnosis and monitoring of pulmonary diseases

ABSTRACT: Circulating cell-free DNA (cfDNA) has firmly established itself as a cornerstone of liquid biopsy, advancing the noninvasive diagnosis and monitoring of pulmonary diseases. Its molecular characteristics, particularly methylation profiles, fragmentation patterns, and mutations, now enable a range of clinical applications-from early detection of lung cancer to rapid pathogen identification and severity assessment in pneumonia, and to precise risk stratification in chronic conditions such as chronic obstructive pulmonary disease and asthma. Beyond diagnostic applications, dynamic changes in cfDNA levels and profiles provide critical insights into disease monitoring across a spectrum of pulmonary disorders. While challenges in detection sensitivity, analytical standardization, and clinical validation remain, the ongoing integration of multi-omics data and artificial intelligence is refining the predictive power of cfDNA-based models. Future developments are expected to consolidate the role of cfDNA analysis as an indispensable tool in precision pulmonology, ultimately transforming diagnostic pathways and enabling more personalized, proactive management of respiratory health.