Chronic obstructive pulmonary disease (COPD) and lung cancer comprise the leading causes of lung disease-related mortality worldwide. Exposure to tobacco smoke is a mutual aetiology underlying the two diseases, accounting for almost 90% of cases. There is accumulating evidence supporting the role of immune dysfunction, the lung microbiome, extracellular vesicles and underlying genetic susceptibility in the development of COPD and lung cancer. Further, epigenetic factors, involving DNA methylation and microRNA expression, have been implicated in both diseases. Chronic inflammation is a key feature of COPD and could be a potential driver of lung cancer development. Using next generation technologies, further studies investigating the genomics, epigenetics and gene-environment interaction in key molecular pathways will continue to elucidate the pathogenic mechanisms underlying the development of COPD and lung cancer, and contribute to the development of novel diagnostic and prognostic tools for early intervention and personalised therapeutic strategies.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterised by chronic inflammation and significant airflow obstruction that is not fully reversible, and is one of the leading causes of morbidity and mortality worldwide. Extracellular vesicles (EVs) (including apoptotic bodies, microvesicles and exosomes) are small membrane-bound vesicles released by nearly all cell types and can be found in various bodily fluids including blood, sputum and urine. EVs are key mediators in cell-cell communication due to their ability to exchange information to recipient cells, influencing physiological and pathological conditions using their bioactive cargo (DNA, RNA, miRNA, proteins and other metabolites).Therefore the main aim of this review is to highlight recent evidence of the potential use of EVs as diagnostic and therapeutic biomarkers for COPD managements, as well as EVs potential role in COPD pathogenesis.As EVs have been under intense investigation as diagnostic and therapeutic biomarkers for lung disease, in relation to COPD, key studies have identified EVs as potential biomarkers to distinguish exacerbations from stable state, and to characterise COPD phenotypes. EVs are also linked to key inflammatory mediators in COPD progression. In addition, bacteria and their EV cargo influence the lung microenvironment. Further recent therapeutic approaches and advances have seen EVs bioengineered as novel drug delivery vehicles, which could potentially have clinical utility for lung diseases such as COPD.

Lung cancer remains the leading cause of cancer related mortality worldwide. We aimed to test whether a simple blood biomarker (extracellular vesicle miRNAs) can discriminate between cases with and without lung cancer. Methods: plasma extracellular vesicles (EVs) were isolated from four cohorts (n = 20 in each): healthy non-smokers, healthy smokers, lung cancer, and stable COPD participants. EV miRNA expression was evaluated using the miRCURY LNA miRNA Serum/Plasma assay for 179 specific targets. Significantly dysregulated miRNAs were assessed for discriminatory power using ROC curve analysis. Results: 15 miRNAs were differentially expressed between lung cancer and healthy non-smoking participants, with the greatest single miRNA being miR-205-5p (AUC 0.850), improving to AUC 0.993 in combination with miR-199a-5p. Moreover, 26 miRNAs were significantly dysregulated between lung cancer and healthy smoking participants, with the greatest single miRNA being miR-497-5p (AUC 0.873), improving to AUC 0.953 in combination with miR-22-5p; 14 miRNAs were significantly dysregulated between lung cancer and stable COPD participants, with the greatest single miRNA being miR-27a-3p (AUC 0.803), with two other miRNAs (miR-106b-3p and miR-361-5p) further improving discriminatory power (AUC 0.870). Conclusion: this case control study suggests miRNAs in EVs from plasma holds key biological information specific for lung cancer and warrants further prospective assessment.

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