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1.
Int J Tuberc Lung Dis ; 28(6): 287-294, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38822484

BACKGROUNDGiven the high prevalence of asthma-chronic obstructive pulmonary disease overlap (ACO) in Vietnam, there is an urgent need to establish a simplified strategy for categorising patients as either having asthma or chronic obstructive pulmonary disease (COPD). This classification would streamline the application of treatment recommendations outlined by the Global Initiative for Asthma (GINA) and the Global Initiative for Chronic Obstructive Lung Disease (GOLD).METHODSPatients with obstructive lung function were classified as having COPD, asthma, or ACO based on GINA/GOLD guidelines. We hypothesised that ACO-like asthma (ACO-A) would present with positive skin prick tests (SPTs) or early onset of symptoms without a history of tuberculosis (TB), while those with ACO-like COPD (ACO-B) would exhibit negative SPTs and late onset of symptoms and/or a history of TB.RESULTSAmong 235 patients, the prevalence of asthma, ACO-A, ACO-B, and COPD was respectively 21%, 22%, 17%, and 40%. Allergic history, rhinitis, and childhood asthma were associated with ACO-A, while high cumulative smoking was correlated with ACO-B. Socio-economic and demographic parameters, medical history, clinical features, smoking habits, lung function, and para-clinical investigations significantly differed between "all asthma" (i.e., individuals with asthma combined with ACO-A) and "all COPD" (i.e., individuals with COPD combined with ACO-B).CONCLUSIONBased on SPTs, history of TB, and onset age, ACO patients may be defined as people with asthma or COPD..


Asthma , Phenotype , Pulmonary Disease, Chronic Obstructive , Humans , Middle Aged , Male , Female , Prevalence , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/diagnosis , Adult , Asthma/epidemiology , Asthma/diagnosis , Vietnam/epidemiology , Aged , Skin Tests , Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome/epidemiology , Asthma-Chronic Obstructive Pulmonary Disease Overlap Syndrome/diagnosis
2.
Int J Chron Obstruct Pulmon Dis ; 19: 1177-1196, 2024.
Article En | MEDLINE | ID: mdl-38826697

Objective: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence, morbidity, and mortality. Chuankezhi (CKZ) injection, a Chinese patent medicine, has been commonly used for treating COPD. This study evaluated the clinical efficacy of CKZ injections in COPD patients and explored potential underlying mechanisms by integrating meta-analysis and network pharmacology. Research Methods: Randomized controlled trials (RCTs) were search in database by Web of Science, Cochrane Library and PubMed as of November 2022 for literature collection, and the Review Manager 5.4 was used to analyze the data. Through the network pharmacology method, the chemical components and their targets, as well as the disease targets were further analyzed. Results: A total of 15 RCTs including 1212 patients were included. The results of meta-analysis showed that CKZ injection can significantly improve the clinical effective rate (RR = 1.25, 95% CI: 1.14 to 1.36), and the clinical advantage was that it can significantly reduced acute exacerbation rate (RR = 0.29, 95% CI: 0.12 to 0.70) and COPD assessment test (CAT) scores (MD =-4.62, 95% CI:-8.966 to-0.28). A total of 31 chemical compounds and 178 potential targets for CKZ injection were obtained from the online databases. Molecular docking revealed that most key components and targets could form stable structure. Conclusion: This systematic review with meta-analysis and network pharmacology demonstrates that CKZ could effectively improve the clinical efficacy and safety in the treatment of COPD. Such efficacy may be related to an anti-inflammatory effect and immunoregulation of CKZ via multiple components, multiple targets and multiple pathways.


Drugs, Chinese Herbal , Network Pharmacology , Pulmonary Disease, Chronic Obstructive , Randomized Controlled Trials as Topic , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Humans , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/administration & dosage , Treatment Outcome , Lung/drug effects , Lung/physiopathology , Anti-Inflammatory Agents/administration & dosage , Middle Aged , Male , Aged , Female , Injections
3.
Int J Chron Obstruct Pulmon Dis ; 19: 1167-1175, 2024.
Article En | MEDLINE | ID: mdl-38826698

Purpose: To develop a novel method for calculating small airway resistance using computational fluid dynamics (CFD) based on CT data and evaluate its value to identify COPD. Patients and Methods: 24 subjects who underwent chest CT scans and pulmonary function tests between August 2020 and December 2020 were enrolled retrospectively. Subjects were divided into three groups: normal (10), high-risk (6), and COPD (8). The airway from the trachea down to the sixth generation of bronchioles was reconstructed by a 3D slicer. The small airway resistance (RSA) and RSA as a percentage of total airway resistance (RSA%) were calculated by CFD combined with airway resistance and FEV1 measured by pulmonary function test. A correlation analysis was conducted between RSA and pulmonary function parameters, including FEV1/FVC, FEV1% predicted, MEF50% predicted, MEF75% predicted and MMEF75/25% predicted. Results: The RSA and RSA% were significantly different among the three groups (p<0.05) and related to FEV1/FVC (r = -0.70, p < 0.001; r = -0.67, p < 0.001), FEV1% predicted (r = -0.60, p = 0.002; r = -0.57, p = 0.004), MEF50% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001), MEF75% predicted (r = -0.71, p < 0.001; r = -0.60, p = 0.002) and MMEF 75/25% predicted (r = -0.64, p = 0.001; r = -0.64, p = 0.001). Conclusion: Airway CFD is a valuable method for estimating the small airway resistance, where the derived RSA will aid in the early diagnosis of COPD.


Airway Resistance , Hydrodynamics , Lung , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive , Tomography, X-Ray Computed , Humans , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Male , Retrospective Studies , Female , Middle Aged , Aged , Forced Expiratory Volume , Lung/physiopathology , Lung/diagnostic imaging , Vital Capacity , Computer Simulation , Radiographic Image Interpretation, Computer-Assisted , Respiratory Function Tests/methods
4.
Nutrients ; 16(10)2024 May 16.
Article En | MEDLINE | ID: mdl-38794746

BACKGROUND: Cytokine storm and oxidative stress are present in chronic obstructive pulmonary disease (COPD). Individuals with COPD present high levels of NF-κB-associated cytokines and pro-oxidant agents as well as low levels of Nrf2-associated antioxidants. This condition creates a steroid-resistant inflammatory microenvironment. Lacticaseibacillus rhamnosus (Lr) is a known anti-cytokine in lung diseases; however, the effect of Lr on lung inflammation and oxidative stress in steroid-resistant COPD mice remains unknown. OBJECTIVE: Thus, we investigated the Lr effect on lung inflammation and oxidative stress in mice and macrophages exposed to cigarette smoke extract (CSE) and unresponsive to steroids. METHODS: Mice and macrophages received dexamethasone or GLPG-094 (a GPR43 inhibitor), and only the macrophages received butyrate (but), all treatments being given before CSE. Lung inflammation was evaluated from the leukocyte population, airway remodeling, cytokines, and NF-κB. Oxidative stress disturbance was measured from ROS, 8-isoprostane, NADPH oxidase, TBARS, SOD, catalase, HO-1, and Nrf2. RESULTS: Lr attenuated cellularity, mucus, collagen, cytokines, ROS, 8-isoprostane, NADPH oxidase, and TBARS. Otherwise, SOD, catalase, HO-1, and Nrf2 were upregulated in Lr-treated COPD mice. Anti-cytokine and antioxidant effects of butyrate also occurred in CSE-exposed macrophages. GLPG-094 rendered Lr and butyrate less effective. CONCLUSIONS: Lr attenuates lung inflammation and oxidative stress in COPD mice, suggesting the presence of a GPR43 receptor-dependent mechanism also found in macrophages.


Lacticaseibacillus rhamnosus , Macrophages , Oxidative Stress , Pulmonary Disease, Chronic Obstructive , Receptors, G-Protein-Coupled , Animals , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/metabolism , Oxidative Stress/drug effects , Receptors, G-Protein-Coupled/metabolism , Mice , Humans , Macrophages/drug effects , Macrophages/metabolism , Male , Cytokines/metabolism , Inflammation Mediators/metabolism , Mice, Inbred C57BL , Disease Models, Animal , Smoke/adverse effects , Dexamethasone/pharmacology , Butyrates/pharmacology , Lung/drug effects , Lung/metabolism
5.
PLoS One ; 19(5): e0303858, 2024.
Article En | MEDLINE | ID: mdl-38781270

OBJECTIVE: The study aims to explore the driving forces behind physical activity engagement among patients with chronic obstructive pulmonary disease, focusing on motivation, opportunity, and capability. DESIGN: A phenomenological qualitative study applied the motivation, opportunity, and capability model, conducted in two respiratory units of a Chinese university hospital. METHODS: Participants, selected by age, gender, and illness duration, included inpatients during the interview sessions and those recently discharged within six months. One-on-one semi-structured interviews were recorded, transcribed, and analyzed by the Colaizzi seven-step method. RESULTS: Seventeen participants diagnosed with chronic obstructive pulmonary disease for over one year aged between 66 (range: 42-96) participated. Three major themes were identified: Inspiring participation motivation-transitioning from recognizing significance to habit formation; Offering participation opportunities-reiterating demand for personalized strategies and ideal environmental settings; Enhancing participation capability-addressing strategies for overcoming fears, setting goals, ensuring safety, and adjusting activity levels. CONCLUSIONS: This research underscores the vital role of inspiring participation motivation, offering opportunities, and enhancing the capability for participation in effective engagement. Advocating increased attention from healthcare departments, fostering interdisciplinary collaboration, improving activity guidance and counseling effectiveness, and considering individual preferences can significantly benefit those patients with chronic obstructive pulmonary disease who hesitate or are unable to participate in physical activities, thereby increasing the dose of non-leisure time physical activity.


Exercise , Motivation , Pulmonary Disease, Chronic Obstructive , Qualitative Research , Humans , Pulmonary Disease, Chronic Obstructive/psychology , Pulmonary Disease, Chronic Obstructive/therapy , Middle Aged , Male , Female , Aged , Adult , Aged, 80 and over , Exercise/psychology
6.
Ital J Pediatr ; 50(1): 104, 2024 May 23.
Article En | MEDLINE | ID: mdl-38783314

Short-acting bronchodilators are a class of medications commonly used to treat asthma, chronic obstructive pulmonary disease, and other respiratory conditions. The use of these medications has evolved over time as we have gained a better understanding of their effectiveness and safety in the pediatric population. This comprehensive review synthesizes the current understanding of short-acting ß2-agonists and short-acting anticholinergics in children. It addresses indications, contraindications, safety considerations, and highlights areas where further research is needed to guide the most effective use of short-acting bronchodilators.


Bronchodilator Agents , Humans , Bronchodilator Agents/therapeutic use , Child , Asthma/drug therapy , Cholinergic Antagonists/therapeutic use , Adrenergic beta-2 Receptor Agonists/therapeutic use , Pulmonary Disease, Chronic Obstructive/drug therapy
7.
Int J Chron Obstruct Pulmon Dis ; 19: 1079-1091, 2024.
Article En | MEDLINE | ID: mdl-38783895

Purpose: To develop and validate a nomogram for assessing the risk of developing hypercapnic respiratory failure (HRF) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Patients and Methods: From January 2019 to August 2023, a total of 334 AECOPD patients were enrolled in this research. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression to determine independent predictors and develop a nomogram. This nomogram was appraised by the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow goodness-of-fit test (HL test), decision curve analysis (DCA), and clinical impact curve (CIC). The enhanced bootstrap method was used for internal validation. Results: Sex, prognostic nutritional index (PNI), hematocrit (HCT), and activities of daily living (ADL) were independent predictors of HRF in AECOPD patients. The developed nomogram based on the above predictors showed good performance. The AUCs for the training, internal, and external validation cohorts were 0.841, 0.884, and 0.852, respectively. The calibration curves and HL test showed excellent concordance. The DCA and CIC showed excellent clinical usefulness. Finally, a dynamic nomogram was developed (https://a18895635453.shinyapps.io/dynnomapp/). Conclusion: This nomogram based on sex, PNI, HCT, and ADL demonstrated high accuracy and clinical value in predicting HRF. It is a less expensive and more accessible approach to assess the risk of developing HRF in AECOPD patients, which is more suitable for primary hospitals, especially in developing countries with high COPD-related morbidity and mortality.


Disease Progression , Hypercapnia , Nomograms , Predictive Value of Tests , Pulmonary Disease, Chronic Obstructive , Respiratory Insufficiency , Humans , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/complications , Male , Female , Aged , Hypercapnia/diagnosis , Hypercapnia/physiopathology , Respiratory Insufficiency/diagnosis , Respiratory Insufficiency/physiopathology , Respiratory Insufficiency/etiology , Risk Assessment , Risk Factors , Middle Aged , Reproducibility of Results , Prognosis , Nutrition Assessment , Aged, 80 and over , Hematocrit , Retrospective Studies , Sex Factors , Decision Support Techniques , Activities of Daily Living , Nutritional Status
8.
J Vis Exp ; (207)2024 May 10.
Article En | MEDLINE | ID: mdl-38801265

Chronic obstructive pulmonary disease (COPD) is a major public health problem. Due to the restriction of expiratory airflow, it is characterized by emphysematous destruction of the lungs. Shortness of breath is one of the main clinical symptoms. Auricular acupressure is a clinical therapy characteristic of Chinese medicine that treats the disease by compressing ear points. Usually, the seeds of Vaccaria segetalis are used to stimulate ear points, which has the effect of regulating qi and alleviating wheezing. In this paper, we propose this characteristic therapy of traditional Chinese medicine (TCM) for the clinical symptoms of wheezing of lung and kidney qi deficiency type in stable COPD patients. Ear points are selected as the treatment protocol for Lung (CO14), Spleen (CO13), Kidney (CO10), Shen Men (TF4), and Ping Chuan (AT1.2.4i) points. The protocol describes a case study using auricular acupressure for a patient with chronic obstructive pulmonary disease to relieve wheezing symptoms.


Acupressure , Pulmonary Disease, Chronic Obstructive , Respiratory Sounds , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Disease, Chronic Obstructive/complications , Humans , Acupressure/methods , Male , Acupuncture, Ear/methods
9.
Age Ageing ; 53(5)2024 May 01.
Article En | MEDLINE | ID: mdl-38783755

BACKGROUND: Patients with congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and dementia are underrepresented in specialist palliative home care (SPHC). However, the complexity of their conditions requires collaboration between general practitioners (GPs) and SPHC teams and timely integration into SPHC to effectively meet their needs. OBJECTIVE: To facilitate joint palliative care planning and the timely transfer of patients with advanced chronic non-malignant conditions to SPHC. METHODS: A two-arm, unblinded, cluster-randomised controlled trial. 49 GP practices in northern Germany were randomised using web-based block randomisation. We included patients with advanced CHF, COPD and/or dementia. The KOPAL intervention consisted of a SPHC nurse-patient consultation followed by an interprofessional telephone case conference between SPHC team and GP. The primary outcome was the number of hospital admissions 48 weeks after baseline. Secondary analyses examined the effects on health-related quality of life and self-rated health status, as measured by the EuroQol 5D scale. RESULTS: A total of 172 patients were included in the analyses. 80.4% of GP practices had worked with SHPC before, most of them exclusively for cancer patients. At baseline, patients reported a mean EQ-VAS of 48.4, a mean quality of life index (EQ-5D-5L) of 0.63 and an average of 0.80 hospital admissions in the previous year. The intervention did not significantly reduce hospital admissions (incidence rate ratio = 0.79, 95%CI: [0.49, 1.26], P = 0.31) or the number of days spent in hospital (incidence rate ratio = 0.65, 95%CI: [0.28, 1.49], P = 0.29). There was also no significant effect on quality of life (∆ = -0.02, 95%CI: [-0.09, 0.05], P = 0.53) or self-rated health (∆ = -2.48, 95%CI: [-9.95, 4.99], P = 0.51). CONCLUSIONS: The study did not show the hypothesised effect on hospitalisations and health-related quality of life. Future research should focus on refining this approach, with particular emphasis on optimising the timing of case conferences and implementing discussed changes to treatment plans, to improve collaboration between GPs and SPHC teams.


Heart Failure , Palliative Care , Primary Health Care , Pulmonary Disease, Chronic Obstructive , Quality of Life , Humans , Palliative Care/methods , Male , Female , Aged , Germany , Pulmonary Disease, Chronic Obstructive/therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Aged, 80 and over , Heart Failure/therapy , Heart Failure/diagnosis , Dementia/therapy , Chronic Disease , Home Care Services , Patient Care Team , Time Factors , Interdisciplinary Communication , Delivery of Health Care, Integrated/organization & administration
10.
Cells ; 13(10)2024 May 17.
Article En | MEDLINE | ID: mdl-38786086

Although Chronic Obstructive Pulmonary Disease (COPD) is highly prevalent, it is often underdiagnosed. One of the main characteristics of this heterogeneous disease is the presence of periods of acute clinical impairment (exacerbations). Obtaining blood biomarkers for either COPD as a chronic entity or its exacerbations (AECOPD) will be particularly useful for the clinical management of patients. However, most of the earlier studies have been characterized by potential biases derived from pre-existing hypotheses in one or more of their analysis steps: some studies have only targeted molecules already suggested by pre-existing knowledge, and others had initially carried out a blind search but later compared the detected biomarkers among well-predefined clinical groups. We hypothesized that a clinically blind cluster analysis on the results of a non-hypothesis-driven wide proteomic search would determine an unbiased grouping of patients, potentially reflecting their endotypes and/or clinical characteristics. To check this hypothesis, we included the plasma samples from 24 clinically stable COPD patients, 10 additional patients with AECOPD, and 10 healthy controls. The samples were analyzed through label-free liquid chromatography/tandem mass spectrometry. Subsequently, the Scikit-learn machine learning module and K-means were used for clustering the individuals based solely on their proteomic profiles. The obtained clusters were confronted with clinical groups only at the end of the entire procedure. Although our clusters were unable to differentiate stable COPD patients from healthy individuals, they segregated those patients with AECOPD from the patients in stable conditions (sensitivity 80%, specificity 79%, and global accuracy, 79.4%). Moreover, the proteins involved in the blind grouping process to identify AECOPD were associated with five biological processes: inflammation, humoral immune response, blood coagulation, modulation of lipid metabolism, and complement system pathways. Even though the present results merit an external validation, our results suggest that the present blinded approach may be useful to segregate AECOPD from stability in both the clinical setting and trials, favoring more personalized medicine and clinical research.


Biomarkers , Proteomics , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/blood , Proteomics/methods , Male , Female , Cluster Analysis , Aged , Biomarkers/blood , Middle Aged , Disease Progression , Proteome/metabolism , Case-Control Studies
11.
Cells ; 13(10)2024 May 20.
Article En | MEDLINE | ID: mdl-38786101

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized, at least in part, by autoimmunity through amplified T helper 1 and 17 (Th1 and Th17) immune responses. The loss of immune tolerance controlled by programmed death-ligand 1 (PD-L1) may contribute to this. OBJECTIVES: We studied the tolerogenic role of PD-L1+ dendritic cells (DCs) and their subtypes in relation to specific T cell immunity and the clinical phenotypes of COPD. METHODS: We used flow cytometry to analyze PD-L1 expression by the DCs and their subtypes in the peripheral blood mononuclear cells (PBMCs) from normal participants and those with COPD. T cell proliferation and the signature cytokines of T cell subtypes stimulated with elastin as autoantigens were measured using flow cytometry and enzyme-linked immunosorbent assays (ELISA), respectively. MEASUREMENT AND MAIN RESULTS: A total of 83 participants were enrolled (normal, n = 29; COPD, n = 54). A reduced PD-L1+ conventional dendritic cell 1 (cDC1) ratio in the PBMCs of the patients with COPD was shown (13.7 ± 13.7%, p = 0.03). The decrease in the PD-L1+ cDC1 ratio was associated with a rapid decline in COPD (p = 0.02) and correlated with the CD4+ T cells (r = -0.33, p = 0.02). This is supported by the NCBI GEO database accession number GSE56766, the researchers of which found that the gene expressions of PD-L1 and CD4, but not CD8 were negatively correlated from PBMC in COPD patients (r = -0.43, p = 0.002). Functionally, the PD-L1 blockade enhanced CD4+ T cell proliferation stimulated by CD3/elastin (31.2 ± 22.3%, p = 0.04) and interleukin (IL)-17A production stimulated by both CD3 (156.3 ± 54.7, p = 0.03) and CD3/elastin (148 ± 64.9, p = 0.03) from the normal PBMCs. The PD-L1 blockade failed to increase IL-17A production in the cDC1-depleted PBMCs. By contrast, there was no significant change in interferon (IFN)-γ, IL-4, or IL-10 after the PD-L1 blockade. Again, these findings were supported by the NCBI GEO database accession number GSE56766, the researchers of which found that only the expression of RORC, a master transcription factor driving the Th17 cells, was significantly negatively correlated to PD-L1 (r = -0.33, p = 0.02). CONCLUSIONS: Circulating PD-L1+ cDC1 was reduced in the patients with COPD, and the tolerogenic role was suppressed with susceptibility to self-antigens and linked to rapid decline caused by Th17-skewed chronic inflammation.


B7-H1 Antigen , Dendritic Cells , Immune Tolerance , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/immunology , Dendritic Cells/immunology , Dendritic Cells/metabolism , B7-H1 Antigen/metabolism , Female , Male , Middle Aged , Aged , Leukocytes, Mononuclear/metabolism , Leukocytes, Mononuclear/immunology , Cytokines/metabolism
12.
Cells ; 13(10)2024 May 20.
Article En | MEDLINE | ID: mdl-38786103

Cigarette smoke is one of the main factors in Chronic Obstructive Pulmonary Disease (COPD), a respiratory syndrome marked by persistent respiratory symptoms and increasing airway obstruction. Perturbed NAD+/NADH levels may play a role in various diseases, including lung disorders like COPD. In our study, we investigated the preventive effect of NADH supplementation in an experimental model of COPD induced by cigarette smoke extract (CSE). N = 64 mice randomly distributed in eight groups were injected with NADH (two doses of 100 mg/kg or 200 mg/kg) or dexamethasone (2 mg/kg) before being exposed to CSE for up to 9 weeks. Additionally, NADH supplementation preserved lung antioxidant defenses by preventing the functional loss of key enzymes such as superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase, and the expression levels of glutathione (GSH) (n = 4, p < 0.001). It also reduced oxidative damage markers, such as malondialdehyde (MDA) and nitrites (n = 4, p < 0.001). A marked increase in tissue myeloperoxidase activity was assessed (MPO), confirming neutrophils implication in the inflammatory process. The latter was significantly ameliorated in the NADH-treated groups (p < 0.001). Finally, NADH prevented the CSE-induced secretion of cytokines such as Tumor Necrosis Factor alpha (TNF-α), IL-17, and IFN-y (n = 4, p < 0.001). Our study shows, for the first time, the clinical potential of NADH supplementation in preventing key features of COPD via its unique anti-inflammatory and antioxidant properties.


Disease Models, Animal , Mice, Inbred BALB C , NAD , Pneumonia , Pulmonary Disease, Chronic Obstructive , Animals , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/prevention & control , Pulmonary Disease, Chronic Obstructive/etiology , NAD/metabolism , Mice , Pneumonia/prevention & control , Pneumonia/metabolism , Pneumonia/pathology , Injections, Intraperitoneal , Smoke/adverse effects , Oxidative Stress/drug effects , Male , Antioxidants/metabolism , Antioxidants/pharmacology , Cytokines/metabolism , Lung/pathology , Lung/metabolism , Lung/drug effects , Peroxidase/metabolism
13.
Respir Res ; 25(1): 218, 2024 May 24.
Article En | MEDLINE | ID: mdl-38789950

OBJECTIVE: To evaluate the predictive value of PD-1 expression in T lymphocytes for rehospitalization due to acute exacerbations of COPD (AECOPD) in discharged patients. METHODS: 115 participants hospitalized with COPD (average age 71.8 ± 6.0 years) were recruited at Fujian Provincial Hospital. PD1+T lymphocytes proportions (PD1+T%), baseline demographics and clinical data were recorded at hospital discharge. AECOPD re-admission were collected at 1-year follow-up. Kaplan-Meier analysis compared the time to AECOPD readmissions among groups stratified by PD1+T%. Multivariable Cox proportional hazards regression and stratified analysis determined the correlation between PD1+T%, potential confounders, and AECOPD re-admission. ROC and DCA evaluated PD1+T% in enhancing the clinical predictive values of Cox models, BODE and CODEX. RESULTS: 68 participants (59.1%) were AECOPD readmitted, those with AECOPD readmission exhibited significantly elevated baseline PD-1+CD4+T/CD4+T% and PD-1+CD8 + T/CD8 + T% compared to non-readmitted counterparts. PD1+ T lymphocyte levels statistically correlated with BODE and CODEX indices. Kaplan-Meier analysis demonstrated that those in Higher PD1+ T lymphocyte proportions had reduced time to AECOPD readmission (logRank p < 0.05). Cox analysis identified high PD1+CD4+T and PD1+CD8+T ratios as risk factors of AECOPD readmission, with hazard ratios of 1.384(95%CI [1.043-1.725]) and 1.401(95%CI [1.013-1.789]), respectively. Notably, in patients aged < 70 years and with fewer than twice AECOPD episodes in the previous year, high PD1+T lymphocyte counts significantly increased risk for AECOPD readmission(p < 0.05). The AECOPD readmission predictive model, incorporating PD1+T% exhibited superior discrimination to the Cox model, BODE index and CODEX index, AUC of ROC were 0.763(95%CI [0.633-0.893]) and 0.734(95%CI [0.570-0.899]) (DeLong's test p < 0.05).The DCA illustrates that integrating PD1+T% into models significantly enhances the utility in aiding clinical decision-making. CONCLUSION: Evaluation of PD1+ lymphocyte proportions offer a novel perspective for identifying high-risk COPD patients, potentially providing insights for COPD management. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR, URL: www.chictr.org.cn/ ), Registration number: ChiCTR2200055611 Date of Registration: 2022-01-14.


Programmed Cell Death 1 Receptor , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/blood , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/immunology , Male , Female , Aged , Programmed Cell Death 1 Receptor/metabolism , Prospective Studies , Middle Aged , Disease Progression , Patient Readmission , Cohort Studies , Hospitalization/statistics & numerical data , Hospitalization/trends , Aged, 80 and over , Follow-Up Studies , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
14.
Int J Mol Sci ; 25(10)2024 May 07.
Article En | MEDLINE | ID: mdl-38791100

Chronic obstructive pulmonary disease (COPD) is comprised of histopathological alterations such as pulmonary emphysema and peribronchial fibrosis. Matrix metalloproteinase 9 (MMP-9) is one of the key enzymes involved in both types of tissue remodeling during the development of lung damage. In recent studies, it was demonstrated that deflamin, a protein component extracted from Lupinus albus, markedly inhibits the catalytic activity of MMP-9 in experimental models of colon adenocarcinoma and ulcerative colitis. Therefore, in the present study, we investigated for the first time the biological effect of deflamin in a murine COPD model induced by chronic exposure to ozone. Ozone exposure was carried out in C57BL/6 mice twice a week for six weeks for 3 h each time, and the treated group was orally administered deflamin (20 mg/kg body weight) after each ozone exposure. The histological results showed that deflamin attenuated pulmonary emphysema and peribronchial fibrosis, as evidenced by H&E and Masson's trichrome staining. Furthermore, deflamin administration significantly decreased MMP-9 activity, as assessed by fluorogenic substrate assay and gelatin zymography. Interestingly, bioinformatic analysis reveals a plausible interaction between deflamin and MMP-9. Collectively, our findings demonstrate the therapeutic potential of deflamin in a COPD murine model, and suggest that the attenuation of the development of lung tissue damage occurs by deflamin-regulated MMP-9 catalytic activity.


Disease Models, Animal , Matrix Metalloproteinase 9 , Mice, Inbred C57BL , Ozone , Pulmonary Disease, Chronic Obstructive , Animals , Matrix Metalloproteinase 9/metabolism , Ozone/pharmacology , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/pathology , Pulmonary Disease, Chronic Obstructive/chemically induced , Mice , Lung/pathology , Lung/drug effects , Lung/metabolism , Male
15.
Arq Bras Cardiol ; 121(4): e20230578, 2024.
Article Pt, En | MEDLINE | ID: mdl-38695473

BACKGROUND: Currently, excess ventilation has been grounded under the relationship between minute-ventilation/carbon dioxide output ( V ˙ E - V ˙ CO 2 ). Alternatively, a new approach for ventilatory efficiency ( η E V ˙ ) has been published. OBJECTIVE: Our main hypothesis is that comparatively low levels of η E V ˙ between chronic heart failure (CHF) and chronic obstructive pulmonary disease (COPD) are attainable for a similar level of maximum and submaximal aerobic performance, conversely to long-established methods ( V ˙ E - V ˙ CO 2 slope and intercept). METHODS: Both groups performed lung function tests, echocardiography, and cardiopulmonary exercise testing. The significance level adopted in the statistical analysis was 5%. Thus, nineteen COPD and nineteen CHF-eligible subjects completed the study. With the aim of contrasting full values of V ˙ E - V ˙ CO 2 and η V ˙ E for the exercise period (100%), correlations were made with smaller fractions, such as 90% and 75% of the maximum values. RESULTS: The two groups attained matched characteristics for age (62±6 vs. 59±9 yrs, p>.05), sex (10/9 vs. 14/5, p>0.05), BMI (26±4 vs. 27±3 Kg m2, p>0.05), and peak V ˙ O 2 (72±19 vs. 74±20 %pred, p>0.05), respectively. The V ˙ E - V ˙ CO 2 slope and intercept were significantly different for COPD and CHF (27.2±1.4 vs. 33.1±5.7 and 5.3±1.9 vs. 1.7±3.6, p<0.05 for both), but η V ˙ E average values were similar between-groups (10.2±3.4 vs. 10.9±2.3%, p=0.462). The correlations between 100% of the exercise period with 90% and 75% of it were stronger for η V ˙ E (r>0.850 for both). CONCLUSION: The η V ˙ E is a valuable method for comparison between cardiopulmonary diseases, with so far distinct physiopathological mechanisms, including ventilatory constraints in COPD.


FUNDAMENTO: Atualmente, o excesso de ventilação tem sido fundamentado na relação entre ventilação-minuto/produção de dióxido de carbono ( V ˙ E − V ˙ CO 2 ). Alternativamente, uma nova abordagem para eficiência ventilatória ( η E V ˙ ) tem sido publicada. OBJETIVO: Nossa hipótese principal é que níveis comparativamente baixos de η E V ˙ entre insuficiência cardíaca crônica (ICC) e doença pulmonar obstrutiva crônica (DPOC) são atingíveis para um nível semelhante de desempenho aeróbico máximo e submáximo, inversamente aos métodos estabelecidos há muito tempo (inclinação V ˙ E − V ˙ CO 2 e intercepto). MÉTODOS: Ambos os grupos realizaram testes de função pulmonar, ecocardiografia e teste de exercício cardiopulmonar. O nível de significância adotada na análise estatística foi 5%. Assim, dezenove indivíduos elegíveis para DPOC e dezenove indivíduos elegíveis para ICC completaram o estudo. Com o objetivo de contrastar valores completos de V ˙ E − V ˙ CO 2 e η E V ˙ para o período de exercício (100%), correlações foram feitas com frações menores, como 90% e 75% dos valores máximos. RESULTADOS: Os dois grupos tiveram características correspondentes para a idade (62±6 vs 59±9 anos, p>.05), sexo (10/9 vs 14/5, p>0,05), IMC (26±4 vs 27±3 Kg m2, p>0,05), e pico V ˙ O 2 (72±19 vs 74±20 % pred, p>0,05), respectivamente. A inclinação V ˙ E − V ˙ CO 2 e intercepto foram significativamente diferentes para DPOC e ICC (207,2±1,4 vs 33,1±5,7 e 5,3±1,9 vs 1,7±3,6, p<0,05 para ambas), mas os valores médios da η E V ˙ foram semelhantes entre os grupos (10,2±3,4 vs 10,9±2,3%, p=0,462). As correlações entre 100% do período do exercício com 90% e 75% dele foram mais fortes para η E V ˙ (r>0,850 para ambos). CONCLUSÃO: A η E V ˙ é um método valioso para comparação entre doenças cardiopulmonares, com mecanismos fisiopatológicos até agora distintos, incluindo restrições ventilatórias na DPOC.


Exercise Test , Heart Failure , Oxygen Consumption , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/physiopathology , Male , Middle Aged , Female , Heart Failure/physiopathology , Exercise Test/methods , Aged , Oxygen Consumption/physiology , Respiratory Function Tests , Exercise Tolerance/physiology , Pulmonary Ventilation/physiology , Reference Values , Echocardiography , Chronic Disease , Carbon Dioxide
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