BACKGROUND: Despite some studies identifying a potential association between obesity and chronic obstructive pulmonary disease (COPD) risk, previous research had overlooked the dynamic nature of body weight over time, leading to inconsistent findings. The purpose of this study is to elucidate the relationship between adult weight change and COPD risk by adjusting for potential confounding factors. METHODS: We conducted a retrospective analysis using data from ten NHANES cycles (1999-2018), including adults aged 40-74 years. Weight change patterns were assessed using BMI at three time points and classified into five categories per period. Absolute weight change was also grouped into five levels. Multivariate logistic regression models, incorporating sampling weights, were used to examine associations between weight change and COPD, adjusting for demographic and lifestyle covariates. RESULTS: Compared with participants who maintained normal weight, stable obesity participants had increased risk of COPD from age 25 years to 10 years before the survey (OR = 1.45, 95% CI = 1.15 to 1.83), in the 10 years period before the survey (OR = 1.75, 95% CI = 1.47 to 2.08), and from age 25 years to survey (OR = 1.84, 95% CI = 1.46 to 2.31). Three periods indicate that weight gain in adulthood was associated with risk of COPD. In addition, substantial weight gain of more than 20 kg was associated with a higher risk of COPD. In stratified analyses, we also observed a more significant association between weight change and the risk of COPD in never smokers compared to former smokers. CONCLUSIONS Our study suggested that stable obesity and weight gain in adulthood were associated with an increased risk of COPD compared to those who maintain a normal weight, and that the association between weight gain and the incidence of COPD appears closer in patients who have never smoked.
Humans ; Pulmonary Disease, Chronic Obstructive/etiology* ; Middle Aged ; Male ; Female ; Adult ; Aged ; Retrospective Studies ; Weight Gain ; Obesity/complications* ; Risk Factors ; United States/epidemiology* ; Nutrition Surveys ; Body Mass Index

OBJECTIVE: To investigate the effect of traditional Chinese Five-body balance exercise on patients with preserved ratio impaired spirometry (PRISm). METHODS: Fifteen patients with PRISm and 15 patients diagnosed with chronic obstructive pulmonary disease (COPD) were recruited from the Outpatient Department of Guang'anmen Hospital and Beijing Niujie Health Service Center from April to December, 2023. Participants in both groups attended supervised Five-body balance exercise training twice a week for 12 weeks. Patients with COPD continued their regular medication regimen during the intervention period. The endpoints were mean changes in the 6-min walk test (6MWT), St. George's Respiratory Questionnaire (SGRQ) score, cardiopulmonary exercise testing (CPET), pulmonary function, and scores of COPD assessment test (CAT), modified British Medical Research Council, Self-Rating Anxiety Scale, and Self-Rating Depression Scale from baseline to 12 weeks. Adverse events were monitored throughout the study. RESULTS: The PRISm group showed a significant improvement from baseline to week 12 in 6MWT, SGRQ symptom score, and forced vital capacity (FVC) compared to the COPD group (P<0.05). No significant between-group changes were observed in other outcome measurements (P>0.05). In addition, compared with baseline, both groups exhibited improvements in 6MWT, SGRQ score, and CPET at week 12 (P<0.05). The PRISm group also showed a significant increase in forced expiratory volume in 1 s and FVC, as well as a significant decrease in CAT score at week 12 (P<0.05). No adverse events were reported. CONCLUSION Patients with PRISm may benefit from Five-body balance exercise training, which can improve the exercise capacity, health-related quality of life, and lung function. (Registration No. ChiCTR2200059290).
Humans ; Spirometry ; Male ; Female ; Pulmonary Disease, Chronic Obstructive/therapy* ; Lung/physiopathology* ; Middle Aged ; Exercise Tolerance/physiology* ; Exercise Therapy ; Aged ; Medicine, Chinese Traditional ; Respiratory Function Tests ; East Asian People

Chronic obstructive pulmonary disease (COPD) currently lacks effective treatments to halt disease progression, making the search for preventive and therapeutic drugs a pressing issue. Natural products, with their accessibility, affordability, and low toxicity, offer promising avenues. Investigating the pharmacological effects and related signaling mechanisms of active components from natural products on COPD animal models induced by various triggers has become an important focus. In animal models induced by cigarette smoke, cigarette smoke combined with lipopolysaccharide (LPS), air pollution, elastase, bacterial or viral infections, the active compounds of natural products, such as flavonoids, terpenoids, and phenolics, can exert anti-inflammatory, antioxidant, mucus-regulating, and airway remodeling-inhibiting effects through key signaling pathways including nuclear factor-erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinase (MAPK). These findings not only provide a theoretical basis for the clinical diagnosis and treatment of COPD but also point to new directions for future scientific research.
Pulmonary Disease, Chronic Obstructive/etiology* ; Animals ; Disease Models, Animal ; Biological Products/pharmacology* ; Humans ; NF-kappa B/metabolism* ; Flavonoids/pharmacology* ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Heme Oxygenase-1/metabolism* ; Terpenes/pharmacology* ; Antioxidants/pharmacology* ; NF-E2-Related Factor 2/metabolism* ; Smoke/adverse effects* ; Phenols/therapeutic use*

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is a major chronic respiratory condition with high morbidity and mortality, imposing a serious economic and public health burden. The World Health Organization ranks COPD among the top 4 chronic diseases worldwide. Zangsiwei Qingfei Mixture (ZSWQF), a novel Tibetan herbal formulation independently developed by our research team, has shown therapeutic potential for chronic respiratory diseases. This study aims to evaluate the effects of aerosolized ZSWQF on cigarette smoke-induced COPD in mice and explore its underlying mechanisms. METHODS: Thirty C57 mice were randomly divided into a Control group, a COPD group, and a ZSWQF group. The Control group received saline aerosol inhalation without cigarette smoke exposure; both the COPD group and the ZSWQF group were exposed to cigarette smoke, with the former receiving saline inhalation and the latter treated with ZSWQF aerosol. White blood cell (WBC) count was performed using a fully automatic blood cell analyzer. Serum, alanine transaminase (ALT), and serum creatinine (SCr), as well as interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α levels in serum and bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). BALF cell classification was determined using a hematology analyzer. Lung function was assessed with a small animal pulmonary function system, including airway resistance (RI) and cyclic dynamic compliance (CyDN). Lung tissues were stained with hematoxylin and eosin (HE), and mean linear intercept (MLI) and destruction index (DI) were calculated to evaluate morphological changes. Network pharmacology was applied to identify disease-related and ZSWQF-related targets, followed by intersection and protein-protein interaction (PPI) network analysis, and enrichment analysis of biological functions and pathways. Primary type II alveolar epithelial cell (AEC II) from SD rats were isolated and divided into a Control group, a lipopolysaccharide (LPS) group, a normal serum group, a water extract of ZSWQF (W-ZSWQF) group, a ZSWQF containing serum group, and a MLN-4760 [angiotensin-converting enzyme (ACE) 2 inhibitor]. Western blotting was performed to assess protein expression of ACE, p38 [a mitogen-activated protein kinase (MAPK)], phospho (p)-p38, extracellular signal-regulated kinases 1 and 2 (ERK1/2), p-ERK1/2, c-Jun N-terminal kinase (JNK), p-JNK, inhibitor of nuclear factor-kappa B alpha (IκBα), p-IκBα, and p-p65 subunit of nuclear factor-kappa B (NF-κBp65). RESULTS: WBC counts were significantly higher in the COPD group than in controls (P<0.01) and decreased following ZSWQF treatment (P<0.05). No significant intergroup differences were found in organ weights, ALT, or SCr (all P>0.05). Serum and BALF levels of IL-6, IL-8, and TNF-α, as well as total BALF cells, neutrophils, and macrophages, were elevated in the COPD group compared with controls and reduced by ZSWQF treatment (P<0.05). COPD mice exhibited increased RI, decreased CyDN, marked alveolar congestion, inflammatory infiltration, thickened septa, and higher MLI and DI values versus controls (P<0.05); ZSWQF treatment significantly reduced MLI and DI (P<0.05). Network pharmacology identified 151 potential therapeutic targets for ZSWQF against COPD, with key nodes including TNF, IL-6, protein kinase B (Akt) 1, albumin (ALB), tumor protein p53 (TP53), non-receptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), signal transducer and activator of transcription 3 (STAT) 3, matrix metalloproteinase (MMP)-9, and beta-catenin (CTNNB1). Enrichment analysis indicates involvement of cancer-related, phosphatidylinositol 3-kinase (PI3K)/Akt, hypoxia-inducible factor (HIF)-1, calcium, and MAPK signaling pathways. Western blotting results showed that compared with the LPS group, AEC II treated with ZSWQF-containing serum exhibited decreased expression of ACE, p-p38/p38, p-ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκBα, and p-NF-κBp65, while ACE2 expression was upregulated, consistent with the MAPK/nuclear factor-kappa B (NF-κB) pathway regulation predicted by network pharmacology. CONCLUSIONS Aerosolized ZSWQF provides protective effects in COPD mice by reducing airway inflammation and remodeling.
Animals ; Pulmonary Disease, Chronic Obstructive/etiology* ; Drugs, Chinese Herbal/therapeutic use* ; Mice ; Mice, Inbred C57BL ; Male ; Network Pharmacology ; Smoke/adverse effects* ; Bronchoalveolar Lavage Fluid ; Administration, Inhalation ; Inflammation/drug therapy* ; Tumor Necrosis Factor-alpha ; Lung/drug effects* ; Interleukin-6/blood*

Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease (COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy- and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.
Pulmonary Disease, Chronic Obstructive/physiopathology* ; Autophagy/physiology* ; Humans ; Muscle, Skeletal/pathology* ; Mitophagy ; Animals ; Mitochondria/metabolism* ; Lysosomes

OBJECTIVES: To identify the key genes and immunological pathways shared by type 2 diabetes mellitus (T2DM) and chronic obstructive pulmonary disease (COPD) and explore the potential therapeutic targets of T2DM complicated by COPD. METHODS: GEO database was used for analyzing the gene expression profiles in T2DM and COPD to identify the common differentially expressed genes (DEGs) in the two diseases. A protein-protein interaction network was constructed to identify the candidate hub genes, which were validated in datasets and disease sets to obtain the target genes. The diagnostic accuracy of these target genes was assessed with ROC analysis, and their expression levels and association with pulmonary functions were investigated using clinical data and blood samples of patients with T2DM and COPD. The abundance of 22 immune cells was analyzed with CIBERSORT algorithm, and their relationship with the target genes was examined using correlation analysis. DGIdb database was used for analyzing the drug-gene interactions and the druggable genes followed by gene set enrichment analysis. RESULTS: We identified a total of 175 common DEGs in T2DM and COPD, mainly enriched in immune- and inflammation-related pathways. Among these genes, CXCL12 was identified as the final target gene, whose expression was elevated in both T2DM and COPD (P<0.05) and showed good diagnostic efficacy. Immune cell infiltration correlation analysis showed significant correlations of CXCL12 with various immune cells (P<0.01). GESA analysis showed that high CXCL12 expression was significantly correlated with "cytokine-cytokine receptor interaction". Drug-gene analysis showed that most of CXCL12-related drugs were not targeted drugs with significant cytotoxicity. CONCLUSIONS CXCL12 is a potential common key pathogenic gene of COPD and T2DM, and small-molecule targeted drugs against CXCL12 can provide a new strategy for treatment T2DM complicated by COPD.
Humans ; Pulmonary Disease, Chronic Obstructive/complications* ; Diabetes Mellitus, Type 2/genetics* ; Chemokine CXCL12/metabolism* ; Protein Interaction Maps ; Gene Expression Profiling

OBJECTIVES: To explore the mechanism of Shenqi Buzhong (SQBZ) Formula for alleviating mitochondrial dysfunction in a rat model of chronic obstructive pulmonary disease (COPD) in light of the AMPK/SIRT1/PGC-1α pathway. METHODS: Fifty male SD rat models of COPD, established by intratracheal lipopolysaccharide (LPS) instillation, exposure to cigarette smoke, and gavage of Senna leaf infusion, were randomized into 5 groups (n=10) for treatment with saline (model group), SQBZ Formula at low, moderate and high doses (3.08, 6.16 and 12.32 g/kg, respectively), or aminophylline (0.024 g/kg) by gavage for 4 weeks, with another 10 untreated rats as the control group. Pulmonary function of the rats were tested, and pathologies and ultrastructural changes of the lung tissues were examined using HE staining and transmission electron microscopy. The levels of SOD, ATP, MDA, and mitochondrial membrane potential in the lungs were detected using WST-1, colorimetric assay, TBA, and JC-1 methods. Flow cytometry was used to analyze ROS level in the lung tissues, and the protein expression levels of P-AMPKα, AMPKα, SIRTI, and PGC-1α were detected using Western blotting. RESULTS: The rat models of COPD showed significantly decreased lung function, severe histopathological injuries of the lungs, decreased pulmonary levels of SOD activity, ATP and mitochondrial membrane potential, increased levels of MDA and ROS, and decreased pulmonary expressions of P-AMPKα, SIRTI, and PGC-1α proteins. All these changes were significantly alleviated by treatment with SQBZ Formula and aminophylline, and the efficacy was comparable between high-dose SQBZ Formula group and aminophylline group. CONCLUSIONS SQBZ Formula ameliorates mitochondrial dysfunction in COPD rats possibly by activating the AMPK/SIRT1/PGC-1α pathway.
Animals ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sirtuin 1/metabolism* ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; Rats, Sprague-Dawley ; Male ; Rats ; AMP-Activated Protein Kinases/metabolism* ; Mitochondria/metabolism* ; Disease Models, Animal ; Signal Transduction/drug effects*

OBJECTIVES: To investigate pharmacologically active components of Yiqi Zishen Formula (YZF) and their mechanisms for alleviating airway inflammation in mice with chronic obstructive pulmonary disease (COPD). METHODS: Ultra-high-performance liquid chromatography coupled with quadrupole-orbitrap mass spectrometry was employed to characterize the chemical components in YZF and YZF-medicated rat serum. A compound-disease target network was constructed based on serum components of YZF to screen the key pathways and targets using enrichment analysis. A mouse model of cigarette smoke-induced COPD was used to evaluate the anti-inflammatory effect of YZF and validate the expression of key proteins in network pharmacology-enriched pathways. Fifty male C57BL/6J mice were randomized equally into control group, COPD model group, high- and low-dose YZF treatment groups, and N-acetylcysteine treatment group. Pulmonary function of the mice was assessed using whole-body plethysmography, and lung histopathology, alveolar structure, and airway remodeling were analyzed using HE staining. The levels of IL-1β, IL-6, and TNF‑α in bronchoalveolar lavage fluid (BALF) were determined with ELISA, and pulmonary expressions of PI3K, Akt, phosphorylated Akt (p-Akt), p65, and phosphorylated p65 (p-p65) were detected using immunohistochemistry. RESULTS: We identified a total of 156 chemical components (including 26 flavonoids or flavonoid glycosides, 27 alkaloids, and 11 saponins) in YZF and 43 prototype components in medicated rat serum. Network pharmacology revealed 704 YZF-related targets and 1199 COPD-associated targets. Integrated analysis suggested that the anti-COPD effects of YZF were associated with the PI3K-Akt signaling pathway. In mouse models of COPD, YZF treatment significantly increased mean alveolar number and peak expiratory flow (P<0.05), reduced mean linear intercept, bronchial wall thickness, lung coefficient, and BALF cytokine levels, and suppressed the expressions of PI3K, Akt, p-Akt, p65, and p-p65 in the lung tissues. CONCLUSIONS YZF alleviates COPD symptoms and airway inflammation in mice possibly by inhibiting the PI3K/Akt/NF‑κB pathway through its multiple components that interact with multiple targets.
Animals ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Signal Transduction/drug effects* ; Male ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; NF-kappa B/metabolism* ; Inflammation/drug therapy* ; Rats

PANoptosis is a newly defined type of programmed cell death (PCD), which is triggered by a variety of stimuli and covers three known forms of PCD: apoptosis, pyroptosis and necroptosis. In physiological state, cell death plays an important protective role against pathogen invasion, but its over-activation may aggravate inflammatory response and cause tissue damage. Studies have shown that the occurrence and progression of acute lung injury/acute respiratory distress syndrome (ALI/ARDS), asthma, chronic obstructive pulmonary disease (COPD) and other lung diseases are closely related to PANoptosis. The purpose of this review is to deeply explore the molecular mechanism of PANoptosis and its regulatory factors in lung diseases, in order to discover potential therapeutic targets and provide new targets and innovative ideas for clinical treatment for lung diseases.
Humans ; Lung Diseases ; Apoptosis ; Pyroptosis ; Pulmonary Disease, Chronic Obstructive ; Necroptosis ; Acute Lung Injury

OBJECTIVE: To investigate the relationship between peripheral blood circular RNA Bardet-Biedl syndrome 9 (circBBS9) and circRNA catenin beta 1 (circCTNNB1) and weaning failure of mechanical ventilation in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A prospective, observational cohort study was conducted. The patients with AECOPD who received invasive mechanical ventilation and passed the spontaneous breathing test (SBT) admitted to the First Affiliated Hospital of Hebei North University from January 2022 to February 2024 were selected as the study subjects. According to the outcome of weaning, the patients were divided into failed weaning group and successful weaning group. At admission and before SBT, the expression levels of circBBS9 and circCTNNB1 in peripheral blood were detected by fluorescence quantitative polymerase chain reaction (PCR). General information, acute physiology and chronic health evaluation II (APACHEII) score within 24 hours of admission, vital signs before SBT and the most recent laboratory indicators before SBT of the patients were collected. The differences in circBBS9 and circCTNNB1 expression levels and clinical data between the two groups were compared. Multivariate Logistic regression was used to analyze the influencing factors of the weaning failure. Receiver operator characteristic curve (ROC curve) was used to analyze the predictive value of each index on weaning failure. RESULTS: Ultimately, 132 patients with AECOPD who underwent invasive mechanical ventilation and passed the SBT were enrolled in the study. Among them, 82 patients were successfully weaned from mechanical ventilation, while 50 patients failed to be weaned, resulting in a weaning failure rate of 37.88%. There was no statistically significant difference in the expression levels of circBBS9 and circCTNNB1 in the peripheral blood at admission of patients between the two groups. The expression level of circBBS9 in the peripheral blood before SBT of patients in the failed weaning group was significantly higher than that in the successful weaning group (2^-ΔΔCt: 131.64±30.24 vs. 100.00±21.32), and the expression level of circCTNNB1 was significantly lower than that in the successful weaning group (2^-ΔΔCt: 79.90±16.82 vs. 100.00±26.43), and the differences were statistically significant (both P < 0.05). The APACHEII score within 24 hours of admission and the levels of RSBI, SCr, and PCT before SBT in the failed weaning group were significantly higher than those in the successful weaning group [APACHEII score: 22.54±4.62 vs. 16.56±4.58, RSBI: 81.90±16.56 vs. 63.25±17.00, SCr (μmol/L): 100.20±17.27 vs. 89.93±26.29, PCT (μg/L): 1.08±0.18 vs. 0.87±0.22], and the Alb level before SBT was significantly lower than that in the successful weaning group (g/L: 29.71±2.73 vs. 33.93±2.89), and the differences were statistically significant (all P < 0.05). There was no statistically significant difference in other clinical data between the two groups. Multivariate Logistic regression analysis showed that circBBS9 [odds ratio (OR) = 1.291, 95% confidence interval (95%CI) was 1.049-1.588] and APACHEII score (OR = 2.897, 95%CI was 1.004-8.353), RSBI (OR = 1.413, 95%CI was 1.057-1.890) were independent risk factors for weaning failure (all P < 0.05), and circCTNNB1 (OR = 0.812, 95%CI was 0.688-0.959) and Alb (OR = 0.149, 95%CI was 0.036-0.614) were protective factors (both P < 0.05). ROC curve analysis showed that circBBS9, circCTNNB1, APACHEII score, RSBI, and Alb all had certain value for predicting weaning failure. The area under the ROC curve (AUC) and 95%CI were 0.820 (0.750-0.890), 0.755 (0.674-0.835), 0.827 (0.757-0.897), 0.795 (0.715-0.876), and 0.854 (0.791-0.919), respectively. Using the multivariate Logistic regression equation as the combined indicator, the AUC for predicting weaning failure reached 0.997 (95%CI was 0.993-1.000), which was significantly higher than that of the single indicators including circBBS9, circCTNNB1, APACHEII score, RSBI, and Alb (the Z value was 5.582, 6.093, 5.771, 5.932, and 5.182, respectively, all P < 0.05). CONCLUSIONS High expression of circBBS9 and low expression of circCTNNB1 in the peripheral blood of AECOPD patients receiving invasive mechanical ventilation before SBT are associated with weaning failure. circBBS9, circCTNNB1 combined with APACHEII score, RSBI and Alb are helpful for predicting the failure of weaning in these patients.
Humans ; Pulmonary Disease, Chronic Obstructive/blood* ; Prospective Studies ; Ventilator Weaning ; RNA, Circular/blood* ; Respiration, Artificial ; Male ; Female ; Aged