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Background It has been a long-held consensus that immune reactions primarily mediate the pathology of chronic obstructive pulmonary disease (COPD), and that exosomes may participate in immune regulation in COPD. However, the relationship between exosomes and peripheral immune status in patients with COPD remains unclear. Methods In this study, we sequenced plasma exosomes and performed single-cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) from patients with COPD and healthy controls. Finally, we constructed competing endogenous RNA (ceRNA) and protein–protein interaction (PPI) networks to delineate the interactions between PBMCs and exosomes within COPD. Results We identified 135 mRNAs, 132 lncRNAs, and 359 circRNAs from exosomes that were differentially expressed in six patients with COPD compared with four healthy controls. Functional enrichment analyses revealed that many of these differentially expressed RNAs were involved in immune responses including defending viral infection and cytokine–cytokine receptor interaction. We also identified 18 distinct cell clusters of PBMCs in one patient and one control by using an unsupervised cluster analysis called uniform manifold approximation and projection (UMAP). According to resultant cell identification, it was likely that the proportions of monocytes, dendritic cells, and natural killer cells increased in the COPD patient we tested, meanwhile the proportions of B cells, CD4 + T cells, and naïve CD8 + T cells declined. Notably, CD8 + T effector memory CD45RA + (Temra) cell and CD8 + effector memory T (Tem) cell levels were elevated in patient with COPD, which were marked by their lower capacity to differentiate due to their terminal differentiation state and lower reactive capacity to viral pathogens. Conclusions We generated exosomal RNA profiling and single-cell transcriptomic profiling of PBMCs in COPD, described possible connection between impaired immune function and COPD development, and finally determined the possible role of exosomes in mediating local and systemic immune reactions.

Aims Current guidelines recommend a heart team in the decision making for patients with complex coronary artery disease (CAD). However, the decision-making stability of these teams has not been evaluated and the optimum protocol is unknown. We assessed inter-team agreement for revascularization decision-making and influencing factors to inform the development of a heart team protocol. Methods and results This sequential, explanatory mixed methods study included (1) a cross-sectional quantitative study to assess inter-team agreement on treatment strategy for retrospectively enrolled complex CAD patients and (2) a qualitative study that used semi-structured interviews with heart team members to identify factors influencing decision-making discrepancy. We randomly selected 101 complex CAD patients. Sixteen specialists were randomly assigned to 4 heart teams to make decisions for these patients. The primary outcome kappa of inter-team decision-making agreement was moderate (kappa 0.58). Factors influencing decision-making were generated through inductive thematic analysis and were summarized by 3 themes (specialist quality, team composition, meeting process) and 10 subthemes. Recommendations of heart team implementation were generated based on qualitative and quantitative data at 5 levels: specialist selection, specialist training, team composition, team training, and meeting process. A detailed protocol on the integration of guidelines, previous experience and recommendations was generated to establish and deploy a qualified heart team. Conclusions Agreement between heart teams for revascularization decision-making in complex CAD patients was moderate. Potential factors associated with decision discrepancies were summarized and recommendations were generated. A detailed heart team protocol was designed and should be validated in future.