Cognitive impairment has been found in chronic obstructive pulmonary disease (COPD) patients. However, the structural alteration of the brain and underlying mechanisms are poorly understood.

Background: To explore patterns of brain structural alteration in chronic obstructive pulmonary disease (COPD) patients with different levels of lung function impairment and the associations of those patterns with cognitive functional deficits using voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) analyses based on high-resolution structural MRI and diffusion tensor imaging (DTI). Methods: A total of 115 right-handed participants (26 severe, 29 moderate, and 29 mild COPD patients and a comparison group of 31 individuals without COPD) completed tests of cognitive (Montreal Cognitive Assessment [MoCA]) and pulmonary function (forced expiratory volume in 1 s [FEV1]) and underwent MRI scanning. VBM and TBSS analyses were used to identify changes in grey matter density (GMD) and white matter (WM) integrity in COPD patients. In addition, correlation analyses between these imaging parameter changes and cognitive and pulmonary functional impairments were performed. Results: There was no significant difference in brain structure between the comparison groups and the mild COPD patients. Patients with moderate COPD had atrophy of the left middle frontal gyrus and right opercular part/triangular part of the inferior frontal gyrus, and WM changes were present mainly in the superior and posterior corona radiata, corpus callosum and cingulum. Patients with severe COPD exhibited the most extensive changes in GMD and WM. Some grey matter (GM) and WM changes were correlated with MoCA scores and FEV1. Conclusions: These findings suggest that patients with COPD exhibit progressive structural impairments in both the GM and the WM, along with impaired levels of lung function, highlighting the importance of early clinical interventions.

Microplastics (MPs) induce mitochondrial dysfunction and iron accumulation, contributing to mitochondrial macroautophagy/autophagy and ferroptosis, which has increased susceptibility to the exacerbation of chronic obstructive pulmonary disease (COPD); however, the underlying mechanism remains unclear. We demonstrated that MPs intensified inflammation in COPD by enhancing autophagy-dependent ferroptosis (ADF) in vitro and in vivo. In the lung tissues of patients with COPD, the concentrations of MPs, especially polystyrene microplastics (PS-MPs), were significantly higher than that of the control group, as detected by pyrolysis gas chromatography mass spectrometry (Py-GCMS), with increased iron accumulation. The exposure to PS-MPs, 2 μm in size, resulted in their being deposited in the lungs of COPD model mice detected by optical in vivo imaging, and observed in bronchial epithelial cells traced by GFP-labeled PS-MPs. There were mitochondrial impairments accompanied by mitochondrial reactive oxygen species (mito-ROS) overproduction and significantly increased levels of lysosome biogenesis and acidification in pDHBE cells with PS-MP stimulation, triggering occurrence of ferritinophagy and enhancing ADF in COPD, which triggered acute exacerbation of COPD (AECOPD). Reestablishing autophagy-dependent ferroptosis via mitochondria-specific ROS scavenging or ferroptosis inhibition alleviated excessive inflammation and ameliorated AECOPD induced by PS-MPs. Collectively, our data initially revealed that MPs exacerbate ferroptosis via mito-ROS-mediated autophagy in COPD, which sheds light on further hazard assessments of MPs on human respiratory health and potential therapeutic agents for patients with COPD.

Non-coding RNAs play an important role in the pathogenesis of pulmonary arterial hypertension (PAH). The aim of this study was to characterize the therapeutic role of melatonin as well as the underlying molecular mechanism (its effects on the expression of H19 and its downstream signaling pathways) in the treatment of PAH. Real-time PCR and western blot analysis were performed to evaluate the expression of H19, miR-200a, miR-675, insulin-like growth factor-1 receptor (IGF1R), and programmed cell death 4 (PDCD4). The value of systolic pulmonary artery pressure (SPAP) and the ratio of medial thickening in the monocrotaline (MCT) group were increased, whereas the melatonin treatment could decrease these values to some extent. The weights of RV (right ventricle), LV (left ventricle) + IVS (interventricular septal), and RV/(LV + IVS) in the MCT group were much higher than those in the MCT + melatonin and control groups. In addition, the expression of H19, miR-675, IGF1R mRNA, and IGF1R protein in the MCT group was the highest, whereas their expression in the control group was the lowest. The expression of miR-200, PDCD4 mRNA, and PDCD4 protein in the MCT group was the lowest, whereas their expression in the control group was the highest. Furthermore, H19 directly suppressed the expression of miR-200a, whereas miR-675-3p and miR-200a directly inhibited the expression of IGF1R and PDCD4, respectively. Finally, melatonin treatment inhibited cell proliferation; upregulated the expression of H19, miR-675-3p, and PDCD4; and downregulated the expression of miR-200a and IGF1R. This study demonstrated the role of H19-miR-675-3p-IGF1R- and H19-miR-200a-PDCD4-signaling pathways in the melatonin treatment of PAH.