Inflammation is an essential mechanism of various diseases. The development and resolution of inflammation are complex immune-modulation processes which induce the involvement of various types of immune cells. Specialized pro-resolving lipid mediators (SPMs) have been demonstrated to be signaling molecules in inflammation. SPMs are involved in the pathophysiology of different diseases, especially respiratory diseases, including asthma, pneumonia, and chronic obstructive pulmonary disease. All of these diseases are related to the inflammatory response and its persistence. Therefore, a deeper understanding of the mechanisms and development of inflammation in respiratory disease, and the roles of the SPM family in the resolution process, might be useful in the quest for novel therapies and preventive measures for pulmonary diseases.

The endoplasmic reticulum (ER) is an integral organelle for maintaining protein homeostasis. Multiple factors can disrupt protein folding in the lumen of the ER, triggering ER stress and activating the unfolded protein response (UPR), which interrelates with various damage mechanisms, such as inflammation, apoptosis, and autophagy. Numerous studies have linked ER stress and UPR to the progression of chronic obstructive pulmonary disease (COPD). This review focuses on the mechanisms of other cellular processes triggered by UPR and summarizes drug intervention strategies targeting the UPR pathway in COPD to explore new therapeutic approaches and preventive measures for COPD.

Exercise rehabilitation training has emerged as one of the most promising modalities for enhancing clinical outcomes and overall well-being in patients with chronic obstructive pulmonary disease (COPD). Distinct exercise prescriptions yield different clinical benefits in this population. Endurance training has been demonstrated to significantly improve exercise capacity, alleviate dyspnea, and enhance health-related quality of life metrics. High-intensity interval training offers a time-efficient approach to boosting cardiorespiratory fitness and metabolic function. Resistance training addresses progressive muscle atrophy through targeted myofiber recruitment, thereby augmenting musculoskeletal performance and translating to enhanced exercise tolerance in patients with COPD. Exercise-mediated rehabilitation attenuates COPD progression and mitigates acute exacerbation risks via multifactorial mechanisms such as mitigation of inflammatory responses, reduction of oxidative stress, and improvement of endothelial cell function. Elucidating the pathophysiological mechanisms underlying exercise-induced benefits will pave the way for precision rehabilitation protocols, ultimately advancing COPD disease management paradigms, refining patient-centered outcome measures, and achieving sustainable health optimization in this clinical cohort.

Background: Soluble Epoxide Hydrolase (sEH) metabolizes anti-inflammatory epoxyeicosatrienoic acids and critically affects airway inflammation in chronic obstructive pulmonary disease (COPD). Considering the excessive endoplasmic reticulum stress is associated with the earlier onset of COPD. The role of sEH and endoplasmic reticulum stress in the pathogenesis of COPD remains unknown. Method: 16 weeks of cigarette-exposed mice were used to detect the relationship between sEH and endoplasmic reticulum stress in COPD. Human epithelial cells were used in vitro to determine the regulation mechanism of sEH in endoplasmic reticulum stress induced by cigarette smoke. Results: sEH deficiency helps reduce emphysema formation after smoke exposure by alleviating endoplasmic reticulum stress response. sEH deficiency effectively reverses the upregulation of phosphorylation IRE1α and JNK and the nuclear expression of AP-1, alleviating the secretion of inflammatory factors induced by cigarette smoke extract. Furthermore, the treatment with endoplasmic reticulum stress and IRE1α inhibitor downregulated cigarette smoke extract-induced sEH expression and the secretion of inflammatory factors. Conclusion: sEH probably alleviates airway inflammatory response and endoplasmic reticulum stress via the IRE1α/JNK/AP-1 pathway, which might attenuate lung injury caused by long-term smoking and provide a new pharmacological target for preventing and treating COPD.

To investigate the predictive value of the equivalent of carbon dioxide at the anaerobic threshold (EqCO₂@AT) for acute exacerbations (AE) in patients with chronic obstructive pulmonary disease (COPD). This retrospective cohort study included 79 patients with COPD who underwent baseline pulmonary function testing and cardiopulmonary exercise testing (CPET). EqCO₂@AT = 30 was used only as an empirical threshold for descriptive stratification, rather than as an outcome-derived cutoff. Patients were also classified into non-AE and AE groups according to annualized exacerbation frequency. Baseline characteristics, pulmonary function, and CPET parameters were compared between groups. Logistic regression was used to evaluate the association between EqCO₂@AT and AE risk. Predictive performance was assessed using receiver operating characteristic curves, calibration analysis, decision curve analysis, Kaplan–Meier analysis, and a simplified nomogram. Of the 79 patients, 16 were classified into the low EqCO₂@AT group and 63 into the high EqCO₂@AT group. Patients with higher EqCO₂@AT were older, had lower BMI, greater smoking exposure, lower FEV₁% predicted and DLCO% predicted, reduced exercise capacity, and higher ventilatory inefficiency parameters. Compared with the non-AE group, the AE group had worse lung function, lower exercise capacity, and higher VE/VCO₂ slope and EqCO₂@AT. EqCO₂@AT was associated with AE risk in univariable analysis (OR 1.122, 95% CI 1.027–1.226, P = 0.011) and remained significant after adjustment for age, BMI, and FEV₁% predicted (OR 1.269, 95% CI 1.110–1.450, P < 0.001). The AUC of EqCO₂@AT alone was 0.739, whereas the combined model achieved an AUC of 0.850. Kaplan–Meier analysis showed significantly lower AE-free survival in the high EqCO₂@AT group (log-rank P = 0.002). The simplified nomogram provided an individualized visual tool for AE risk estimation. Elevated EqCO₂@AT is associated with impaired ventilatory efficiency, reduced exercise capacity, and increased AE risk in COPD. A model incorporating EqCO₂@AT, age, BMI, and FEV₁% predicted showed good predictive performance and may support individualized AE risk stratification. These findings suggest that CPET-derived ventilatory efficiency parameters may provide clinically useful information beyond conventional pulmonary function assessment, although validation in larger multicenter prospective cohorts is still required.

Cigarette smoke–induced airway epithelial injury is a central pathological feature of chronic obstructive pulmonary disease (COPD) and is closely associated with mitochondrial dysfunction. Excessive dynamin-related protein 1 (DRP1)–mediated mitochondrial fission contributes to epithelial oxidative stress and apoptosis; however, the endogenous regulatory mechanisms limiting aberrant DRP1 activation in the airway epithelium remain poorly understood. Epoxyeicosatrienoic acids (EETs), lipid mediators metabolized by soluble epoxide hydrolase (EPHX2), have been implicated in lung protection, but their role in regulating mitochondrial dynamics in cigarette smoke–exposed airway epithelium has not been established. Wild-type and EPHX2^-/- mice were exposed to chronic cigarette smoke to evaluate mitochondrial morphology, oxidative stress, epithelial apoptosis, and lung mechanics. In vitro, BEAS-2B airway epithelial cells were exposed to cigarette smoke extract (CSE) with pharmacological or genetic modulation of EET signaling. Mitochondrial structure and function, including reactive oxygen species production, mitochondrial membrane potential, and DRP1 phosphorylation status, were assessed using confocal microscopy, transmission electron microscopy, and immunoblotting. Chronic cigarette smoke exposure induced marked mitochondrial fragmentation, increased oxidative stress, and epithelial apoptosis, accompanied by enhanced DRP1 activation. Genetic deletion of EPHX2 or exogenous EET supplementation preserved mitochondrial network integrity and significantly attenuated DRP1-mediated mitochondrial fission in both in vivo and in vitro models. In vivo, restoration of inhibitory DRP1 Ser637 phosphorylation was associated with reduced mitochondrial fragmentation, whereas in vitro EETs promoted inhibitory DRP1 Ser637 phosphorylation via activation of the cAMP/PKA signaling pathway, thereby limiting pathological mitochondrial fission and mitigating epithelial cell injury. EETs act as endogenous modulators of mitochondrial dynamics in airway epithelial cells. By restraining DRP1-mediated mitochondrial fission, EET signaling protects against cigarette smoke–induced mitochondrial dysfunction and epithelial injury, supporting the EPHX2–EET axis as a mechanistically and clinically relevant pathway for further translational investigation in COPD. The online version contains supplementary material available at 10.1186/s12931-026-03657-8.