Exosomes in selected high-burden pulmonary diseases: biomarkers, multiomics, engineering strategies, and clinical translation

Exosomes, often discussed within the broader field of extracellular vesicles (EVs), are increasingly recognized as mediators of intercellular communication and as potential platforms for liquid biopsy and cell-free therapy in pulmonary medicine. This narrative review summarizes recent preclinical, translational, and early clinical evidence regarding exosome-based biomarkers and therapeutic strategies in selected high-burden pulmonary diseases, including chronic obstructive pulmonary disease (COPD), asthma, pulmonary fibrosis, acute lung injury/acute respiratory distress syndrome (ALI/ARDS), and lung cancer. We discuss disease-specific exosomal cargo signatures, methodological considerations for pulmonary samples, multiomics-based biomarker discovery, engineered exosome delivery platforms, and current clinical and regulatory barriers. Exosomal miRNAs, proteins, and surface markers show promise for noninvasive diagnosis and prognosis, but most candidate biomarkers still require validation in large, multicenter, disease-specific cohorts. Similarly, mesenchymal stromal cell-derived, epithelial cell-derived, and engineered exosomes have demonstrated anti-inflammatory, antifibrotic, regenerative, or antitumor effects in preclinical models, whereas robust clinical efficacy data remain limited. Standardized isolation, characterization, potency assays, biodistribution assessment, good manufacturing practice-compliant production, and product-specific regulatory pathways will be essential for future clinical translation.