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1.
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
2.
Rev Prat ; 74(5): 533-536, 2024 May.
Article Fr | MEDLINE | ID: mdl-38833238

WHAT ARE THE INDICATIONS FOR CORTICOSTEROID THERAPY IN COPD? In stable state chronic obstructive pulmonary disease (COPD), inhaled corticosteroids (ICS) should be used in case of frequent exacerbation only, associated with long-term bronchodilators including long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA). When frequent exacerbations persist despite dual inhaled therapy (LABA + CSI or LABA+LAMA), triple inhaled therapy (LAMA+LABA+CSI) is indicated. In COPD exacerbation, the level of evidence for systemic corticosteroids is very low, justifying not to systematically prescribe systemic corticosteroids and when used to restrict this use to short-term (5 days) and low doses.


QUELLES SONT LES INDICATIONS POUR LA CORTICOTHÉRAPIE DANS LA BPCO ? Dans la bronchopneumopathie chronique obstructive (BPCO) à l'état stable, les corticostéroïdes inhalés (CSI) ne sont à utiliser qu'en cas d'exacerbations fréquentes, en association avec des bronchodilatateurs de longue durée d'action de type bêta-2-agoniste de longue durée d'action (LABA) et anticholinergique de longue durée d'action (LAMA). En cas de persistance d'exacerbations fréquentes malgré une bithérapie inhalée (LABA-CSI ou LAMA-LABA), une triple thérapie (LAMA-LABA CSI) peut être proposée. En cas d'exacerbation de BPCO, le niveau de preuve de la corticothérapie systémique est faible, justifiant ne pas recourir à ce traitement de façon systématique ou de le réaliser en cures courtes (cinq jours) et à faibles doses quand il est prescrit.


Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Administration, Inhalation , Adrenal Cortex Hormones/therapeutic use , Adrenal Cortex Hormones/administration & dosage , Bronchodilator Agents/therapeutic use , Bronchodilator Agents/administration & dosage , Drug Therapy, Combination , Glucocorticoids/therapeutic use , Glucocorticoids/administration & dosage
3.
Respir Res ; 25(1): 236, 2024 Jun 06.
Article En | MEDLINE | ID: mdl-38844921

BACKGROUND: The effect of dual systemic antibiotic therapy against Pseudomonas aeruginosa in patients with pre-existing lung disease is unknown. To assess whether dual systemic antibiotics against P. aeruginosa in outpatients with COPD, non-cystic fibrosis (non-CF) bronchiectasis, or asthma can improve outcomes. METHODS: Multicenter, randomised, open-label trial conducted at seven respiratory outpatient clinics in Denmark. Outpatients with COPD, non-CF bronchiectasis, or asthma with a current P. aeruginosa-positive lower respiratory tract culture (clinical routine samples obtained based on symptoms of exacerbation not requiring hospitalisation), regardless of prior P. aeruginosa-status, no current need for hospitalisation, and at least two moderate or one hospitalisation-requiring exacerbation within the last year were eligible. Patients were assigned 1:1 to 14 days of dual systemic anti-pseudomonal antibiotics or no antibiotic treatment. Primary outcome was time to prednisolone or antibiotic-requiring exacerbation or death from day 20 to day 365. RESULTS: The trial was stopped prematurely based in lack of recruitment during the COVID-19 pandemic, this decision was endorsed by the Data and Safety Monitoring Board. Forty-nine outpatients were included in the study. There was a reduction in risk of the primary outcome in the antibiotic group compared to the control group (HR 0.51 (95%CI 0.27-0.96), p = 0.037). The incidence of admissions with exacerbation within one year was 1.1 (95%CI 0.6-1.7) in the dual antibiotic group vs. 2.9 (95%CI 1.3-4.5) in the control group, p = 0.037. CONCLUSIONS: Use of dual systemic antibiotics for 14 days against P. aeruginosa in outpatients with chronic lung diseases and no judged need for hospitalisation, improved clinical outcomes markedly. The main limitation was the premature closure of the trial. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03262142, registration date 2017-08-25.


Anti-Bacterial Agents , Outpatients , Pseudomonas Infections , Pseudomonas aeruginosa , Humans , Male , Female , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas Infections/diagnosis , Pseudomonas Infections/epidemiology , Anti-Bacterial Agents/therapeutic use , Aged , Middle Aged , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification , Denmark/epidemiology , Disease Progression , Treatment Outcome , Hospitalization , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/microbiology , Pulmonary Disease, Chronic Obstructive/diagnosis
4.
Int J Chron Obstruct Pulmon Dis ; 19: 1225-1232, 2024.
Article En | MEDLINE | ID: mdl-38835808

Purpose: The use of inhaled bronchodilators is the mainstay of treatment for patients with chronic obstructive pulmonary disease (COPD). Although the soft mist inhaler (SMI) was developed to overcome the disadvantages of pressurized metered dose and drug powder inhalers, misuse during handling has been frequently observed in many studies. However, few studies have focused on SMI misuse among patients with COPD. Thus, we aimed to assess and identify the risk factors associated with SMI misuse among patients with COPD. Patient and Methods: In this prospective, observational, cross-sectional study, we enrolled patients with COPD who were undergoing SMI treatment between January 2018 and March 2020. An advanced nurse practitioner assessed the participants' handling of the device by using a check list. Results: Among 159 participants, 136 (85.5%) reported inhaler misuse. Duration of COPD and COPD assessment test (CAT) scores were positively associated with inhaler misuse; adherence and education level were negatively associated with inhaler misuse. In the multivariable analysis, a low educational level (less than high school), high CAT score (≥ 10), and short duration of COPD (≤ 2 years) were identified as risk factors for SMI misuse. Conclusion: SMI misuse remains common among patients with COPD. Therefore, clinicians should pay close attention to their patients using SMIs, especially in the early period after the diagnosis of COPD.


Bronchodilator Agents , Nebulizers and Vaporizers , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Male , Female , Cross-Sectional Studies , Risk Factors , Aged , Prospective Studies , Middle Aged , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Administration, Inhalation , Medication Adherence , Equipment Design , Risk Assessment , Educational Status , Lung/physiopathology , Lung/drug effects
5.
Sci Rep ; 14(1): 12923, 2024 06 05.
Article En | MEDLINE | ID: mdl-38839862

This study in older hospitalized patients with heart failure with reduced ejection fraction (HFrEF) aimed to examine the prevalence of beta-blocker prescription and its associated factors. A total of 190 participants were recruited from July 2019 to July 2020. The inclusion criteria included: (1) aged ≥ 60 years, (2) having a diagnosis of chronic HFrEF in the medical records, (3) hospitalized for at least 48 h. The participants had a mean age of 75.5 ± 9.1, and 46.8% were female. Of these, 55.3% were prescribed beta-blockers during admission. To explore the factors associated with beta-blocker prescription, multivariable logistic regression analysis was applied and the results were presented as odds ratios (OR) and 95% confidence intervals (CI). On multivariate logistic regression models, higher NYHA classes (OR 0.49, 95%CI 0.26-0.94), chronic obstructive pulmonary disease (OR 0.17, 95% CI 0.04-0.85), chronic kidney disease (OR 0.40, 95% CI 0.19-0.83), and heart rate under 65 (OR 0.34, 95% CI 0.12-0.98) were associated with a reduced likelihood of prescription. In this study, we found a low rate of beta-blocker prescriptions, with only around half of the participants being prescribed beta-blockers. Further studies are needed to examine the reasons for the under-prescription of beta-blockers, and to evaluate the long-term benefits of beta-blockers in elderly patients with HFrEF in this population.


Adrenergic beta-Antagonists , Heart Failure , Stroke Volume , Humans , Heart Failure/drug therapy , Heart Failure/physiopathology , Female , Adrenergic beta-Antagonists/therapeutic use , Male , Aged , Stroke Volume/drug effects , Aged, 80 and over , Vietnam/epidemiology , Middle Aged , Drug Prescriptions/statistics & numerical data , Hospitalization/statistics & numerical data , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology
8.
Sci Rep ; 14(1): 10361, 2024 05 06.
Article En | MEDLINE | ID: mdl-38710754

Chronic obstructive pulmonary disease (COPD) is a progressive disease that is characterized by chronic airway inflammation. A Japanese herbal medicine, hochuekkito (TJ-41), is prominently used for chronic inflammatory diseases in Japan. This study aimed to analyze the anti-inflammatory effect of TJ-41 in vivo and its underlying mechanisms. We created a COPD mouse model using intratracheal administration of porcine pancreatic elastase and lipopolysaccharide (LPS) and analyzed them with and without TJ-41 administration. A TJ-41-containing diet reduced inflammatory cell infiltration of the lungs in the acute and chronic phases and body weight loss in the acute phase. In vitro experiments revealed that TJ-41 treatment suppressed the LPS-induced inflammatory cytokines in BEAS-2B cells. Furthermore, TJ-41 administration activated the AMP-activated protein kinase (AMPK) pathway and inhibited the mechanistic target of the rapamycin (mTOR) pathway, both in cellular and mouse experiments. We concluded that TJ-41 administration reduced airway inflammation in the COPD mouse model, which might be regulated by the activated AMPK pathway, and inhibited the mTOR pathway.


Anti-Inflammatory Agents , Disease Models, Animal , Drugs, Chinese Herbal , Medicine, Kampo , Pulmonary Disease, Chronic Obstructive , Animals , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/metabolism , Pulmonary Disease, Chronic Obstructive/pathology , Drugs, Chinese Herbal/pharmacology , Anti-Inflammatory Agents/pharmacology , Mice , AMP-Activated Protein Kinases/metabolism , TOR Serine-Threonine Kinases/metabolism , Humans , Lipopolysaccharides , Male , Cytokines/metabolism , Signal Transduction/drug effects , Cell Line , Lung/pathology , Lung/drug effects , Lung/metabolism , Pancreatic Elastase/metabolism , East Asian People
9.
Respir Res ; 25(1): 228, 2024 May 29.
Article En | MEDLINE | ID: mdl-38811970

BACKGROUND: Respiratory viral infections are major drivers of chronic obstructive pulmonary disease (COPD) exacerbations. Interferon-ß is naturally produced in response to viral infection, limiting replication. This exploratory study aimed to demonstrate proof-of-mechanism, and evaluate the efficacy and safety of inhaled recombinant interferon-ß1a (SNG001) in COPD. Part 1 assessed the effects of SNG001 on induced sputum antiviral interferon-stimulated gene expression, sputum differential cell count, and respiratory function. Part 2 compared SNG001 and placebo on clinical efficacy, sputum and serum biomarkers, and viral clearance. METHODS: In Part 1, patients (N = 13) with stable COPD were randomised 4:1 to SNG001 or placebo once-daily for three days. In Part 2, patients (N = 109) with worsening symptoms and a positive respiratory viral test were randomised 1:1 to SNG001 or placebo once-daily for 14 days in two Groups: A (no moderate exacerbation); B (moderate COPD exacerbation [i.e., acute worsening of respiratory symptoms treated with antibiotics and/or oral corticosteroids]). RESULTS: In Part 1, SNG001 upregulated sputum interferon gene expression. In Part 2, there were minimal SNG001-placebo differences in the efficacy endpoints; however, whereas gene expression was initially upregulated by viral infection, then declined on placebo, levels were maintained with SNG001. Furthermore, the proportion of patients with detectable rhinovirus (the most common virus) on Day 7 was lower with SNG001. In Group B, serum C-reactive protein and the proportion of patients with purulent sputum increased with placebo (suggesting bacterial infection), but not with SNG001. The overall adverse event incidence was similar with both treatments. CONCLUSIONS: Overall, SNG001 was well-tolerated in patients with COPD, and upregulated lung antiviral defences to accelerate viral clearance. These findings warrant further investigation in a larger study. TRIAL REGISTRATION: EU clinical trials register (2017-003679-75), 6 October 2017.


Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/virology , Male , Female , Middle Aged , Aged , Administration, Inhalation , Double-Blind Method , Nebulizers and Vaporizers , Sputum/virology , Sputum/metabolism , Treatment Outcome , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Disease Progression , Interferon-beta/administration & dosage
11.
Int J Chron Obstruct Pulmon Dis ; 19: 995-1010, 2024.
Article En | MEDLINE | ID: mdl-38737191

Purpose: To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD). Patients and Methods: Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured. Results: VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively). Conclusion: Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.


Drugs, Chinese Herbal , Exercise Tolerance , Frailty , Lung , Muscle Strength , Pulmonary Disease, Chronic Obstructive , Sarcopenia , Humans , Sarcopenia/physiopathology , Sarcopenia/diagnosis , Sarcopenia/epidemiology , Sarcopenia/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/complications , Male , Female , Aged , Treatment Outcome , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/adverse effects , Middle Aged , Muscle Strength/drug effects , Lung/physiopathology , Lung/drug effects , Time Factors , Exercise Tolerance/drug effects , Frailty/diagnosis , Frailty/physiopathology , Frailty/epidemiology , Comorbidity , Fatigue/physiopathology , Fatigue/drug therapy , Fatigue/diagnosis , Recovery of Function , Functional Status , Frail Elderly , Walking Speed
12.
BMC Pulm Med ; 24(1): 247, 2024 May 19.
Article En | MEDLINE | ID: mdl-38764008

BACKGROUND: High blood eosinophils seem to predict exacerbations and response to inhaled corticosteroids (ICS) treatment in patients with chronic obstructive pulmonary disease (COPD). The aim of our study was to prospectively evaluate for 2 years, blood and sputum eosinophils in COPD patients treated with bronchodilators only at recruitment. METHODS: COPD patients in stable condition treated with bronchodilators only underwent monitoring of lung function, blood and sputum eosinophils, exacerbations and comorbidities every 6 months for 2 years. ICS was added during follow-up when symptoms worsened. RESULTS: 63 COPD patients were enrolled: 53 were followed for 1 year, 41 for 2 years, 10 dropped-out. After 2 years, ICS was added in 12/41 patients (29%) without any statistically significant difference at time points considered. Blood and sputum eosinophils did not change during follow-up. Only FEV1/FVC at T0 was predictive of ICS addition during the 2 year-follow-up (OR:0.91; 95% CI: 0.83-0.99, p = 0.03). ICS addition did not impact on delta (T24-T0) FEV1, blood and sputum eosinophils and exacerbations. After 2 years, patients who received ICS had higher blood eosinophils than those in bronchodilator therapy (p = 0.042). Patients with history of ischemic heart disease increased blood eosinophils after 2 years [p = 0.03 for both percentage and counts]. CONCLUSIONS: Blood and sputum eosinophils remained stable during the 2 year follow-up and were not associated with worsened symptoms or exacerbations. Almost 30% of mild/moderate COPD patients in bronchodilator therapy at enrollment, received ICS for worsened symptoms in a 2 year-follow-up and only FEV1/FVC at T0 seems to predict this addition. History of ischemic heart disease seems to be associated with a progressive increase of blood eosinophils.


Bronchodilator Agents , Eosinophils , Pulmonary Disease, Chronic Obstructive , Sputum , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/physiopathology , Male , Female , Aged , Sputum/cytology , Middle Aged , Follow-Up Studies , Bronchodilator Agents/therapeutic use , Prospective Studies , Forced Expiratory Volume , Adrenal Cortex Hormones/therapeutic use , Administration, Inhalation , Leukocyte Count , Disease Progression , Eosinophilia , Inflammation
13.
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
14.
JAMA Netw Open ; 7(5): e247535, 2024 May 01.
Article En | MEDLINE | ID: mdl-38771577

Importance: While ß-blockers are associated with decreased mortality in cardiovascular disease (CVD), exacerbation-prone patients with chronic obstructive pulmonary disease (COPD) who received metoprolol in the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK-COPD) trial experienced increased risk of exacerbations requiring hospitalization. However, the study excluded individuals with established indications for the drug, raising questions about the overall risk and benefit in patients with COPD following acute myocardial infarction (AMI). Objective: To investigate whether ß-blocker prescription at hospital discharge is associated with increased risk of mortality or adverse cardiopulmonary outcomes in patients with COPD and AMI. Design, Setting, and Participants: This prospective, longitudinal cohort study with 6 months of follow-up enrolled patients aged 35 years or older with COPD who underwent cardiac catheterization for AMI at 18 BLOCK-COPD network hospitals in the US from June 2020 through May 2022. Exposure: Prescription for any ß-blocker at hospital discharge. Main Outcomes and Measures: The primary outcome was time to the composite outcome of death or all-cause hospitalization or revascularization. Secondary outcomes included death, hospitalization, or revascularization for CVD events, death or hospitalization for COPD or respiratory events, and treatment for COPD exacerbations. Results: Among 3531 patients who underwent cardiac catheterization for AMI, prevalence of COPD was 17.1% (95% CI, 15.8%-18.4%). Of 579 total patients with COPD and AMI, 502 (86.7%) were prescribed a ß-blocker at discharge. Among the 562 patients with COPD included in the final analysis, median age was 70.0 years (range, 38.0-94.0 years) and 329 (58.5%) were male; 553 of the 579 patients (95.5%) had follow-up information. Among those discharged with ß-blockers, there was no increased risk of the primary end point of all-cause mortality, revascularization, or hospitalization (hazard ratio [HR], 1.01; 95% CI, 0.66-1.54; P = .96) or of cardiovascular events (HR, 1.11; 95% CI, 0.65-1.92; P = .69), COPD-related or respiratory events (HR, 0.75; 95% CI, 0.34-1.66; P = .48), or treatment for COPD exacerbations (rate ratio, 1.01; 95% CI, 0.53-1.91; P = .98). Conclusions and Relevance: In this cohort study, ß-blocker prescription at hospital discharge was not associated with increased risk of adverse outcomes in patients with COPD and AMI. These findings support use of ß-blockers in patients with COPD and recent AMI.


Adrenergic beta-Antagonists , Myocardial Infarction , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/complications , Adrenergic beta-Antagonists/therapeutic use , Male , Female , Myocardial Infarction/complications , Myocardial Infarction/drug therapy , Myocardial Infarction/mortality , Aged , Middle Aged , Prospective Studies , Longitudinal Studies , Hospitalization/statistics & numerical data
15.
Hu Li Za Zhi ; 71(3): 43-51, 2024 Jun.
Article Zh | MEDLINE | ID: mdl-38817136

BACKGROUND: Poor disease control in patients with chronic obstructive pulmonary disease (COPD) is associated with suboptimal inhaler use. PURPOSE: This study was designed to explore the accuracy of inhaler use and related factors in elderly patients with COPD. METHODS: A cross-sectional survey design was used to recruit patients with COPD from a medical centre in southern Taiwan who were over 65 years old and used inhalers regularly. All of the data as well as information on inhaler use accuracy were collected using a self-designed questionnaire and inhaler operation checklist. Multivariable logistic regression was used to analyse significant correlates of correct inhaler operation. RESULTS: The average age of the 150 participants was 75.0 years (SD = 7.5) years. Most used one type of inhaler only (86.0%). The rate of accurate inhaler operation was 40.7% (n = 61) for the sample, with dry powder inhalers associated with the highest accuracy (64%) and pressurized metered-dose inhalers associated with the lowest accuracy (1.6%). Multivariate logistic regression analysis showed that using a soft mist inhaler (adjusted odds ratio, AOR = 23.29; 95% confidence interval, 95% CI [2.84, 191.07]), using a dry powder inhaler (AOR =15.60, 95% CI [1.99, 122.26]), and higher satisfaction with the inhaler were positively and independently associated with accurate inhaler use (AOR = 1.94, 95% CI [1.09, 3.44]). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Important factors related to inhaler use accuracy include inhaler type and level of patient satisfaction with their inhaler. Healthcare professionals should regularly confirm that older patients are able to use their inhalers correctly and are satisfied with their inhalers.


Nebulizers and Vaporizers , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Aged , Male , Female , Cross-Sectional Studies , Aged, 80 and over
16.
Drug Des Devel Ther ; 18: 1755-1770, 2024.
Article En | MEDLINE | ID: mdl-38808326

Purpose: The aim of this study is to uncover the anti-inflammatory propertity of andrographolide (AGP) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the underlying mechanisms related to the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway. Methods: An in vivo experiment was conducted on murine model of AECOPD through endotracheal atomization of elastase and lipopolysaccharide (LPS). Intraperitoneal AGP was administered four times. NLRP3 inflammasome pathway molecules were examined using real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. By using enzyme-linked immunosorbent assay (ELISA), we tested interleukin (IL)-1ß levels in bronchoalveolar lavage fluid. An in vitro study was conducted to determine how AGP impacts the NLRP3 inflammasome in THP-1 derived macrophages. The levels of molecules involved in the pathway were measured. Furthermore, molecular docking analyses were carried out to investigate the interactions between AGP and pathway targets. Results: In the in vivo study, NLRP3 inflammasome activation was observed in mice experiencing AECOPD. The administration of high-dose AGP demonstrated a mitigating effect on inflammatory cells infiltration in the lungs. Moreover, AGP administration effectively suppressed the expression of NLRP3, apoptosis associated speck-like protein that contains a CARD (PYCARD), cysteinyl aspartate-specific protease-1 (Caspase-1), IL-1ß, and IL-18 at both the genetic and protein levels. In the in vitro experiment, IL-1ß levels were significantly elevated in THP-1 derived macrophages with activated inflammasome compared to the control group. Furthermore, the downregulation of NLRP3, CASP1, and IL1B genes was observed upon the inhibition of NLRP3 expression through small interfering RNA (siRNA). AGP demonstrated inhibitory effects on the gene expression and protein levels of NLRP3, Caspase-1, and IL-1ß. Additionally, molecular docking analysis confirmed that AGP exhibited a favorable binding affinity with all five targets of the pathway. Conclusion: AGP effectively inhibited NLRP3 inflammasome activation and mitigated the inflammatory reaction of AECOPD both in animal models and in vitro experiments, highlighting the potential of AGP as a treatment for AECOPD with anti-inflammatory properties.


Diterpenes , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , Pulmonary Disease, Chronic Obstructive , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/metabolism , Animals , Diterpenes/pharmacology , Diterpenes/chemistry , Diterpenes/administration & dosage , Mice , Inflammasomes/metabolism , Inflammasomes/drug effects , Humans , Mice, Inbred C57BL , Molecular Docking Simulation , Male , Inflammation/drug therapy , Inflammation/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Lipopolysaccharides/pharmacology , Structure-Activity Relationship
17.
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
18.
NPJ Prim Care Respir Med ; 34(1): 13, 2024 May 28.
Article En | MEDLINE | ID: mdl-38806496

The Test of Adherence to Inhalers (TAI) Toolkit links an adherence measurement instrument (the TAI) to proven effective interventions for different causes of non-adherence to inhaled medication. This study aimed to assess the usability and feasibility of the TAI Toolkit in clinical practice. The TAI Toolkit was piloted in eight primary and secondary care settings. Each study site included 10 patients with asthma and/or COPD and suspected non-adherence. Healthcare professionals (HCPs) recorded clinical data and TAI Toolkit outcomes. Data on usability and feasibility were collected in semi-structured interviews and with the System Usability Score (SUS). Of the included patients, 81% were non-adherent, and sporadic non-adherence was the most common (69%). The TAI Toolkit was valued with a mean SUS-score of 85.9 by the HCPs. They found the toolkit to 'be visually attractive', 'easy-to-use' and 'give insight into patients' adherence', thereby offering good potential for its use in clinical practice.


Asthma , Feasibility Studies , Medication Adherence , Nebulizers and Vaporizers , Pulmonary Disease, Chronic Obstructive , Humans , Medication Adherence/statistics & numerical data , Male , Pulmonary Disease, Chronic Obstructive/drug therapy , Female , Middle Aged , Asthma/drug therapy , Administration, Inhalation , Aged , Adult
19.
Int J Chron Obstruct Pulmon Dis ; 19: 1153-1166, 2024.
Article En | MEDLINE | ID: mdl-38813078

Purpose: Real-life research is needed to evaluate the effectiveness of budesonide/glycopyrrolate/formoterol (BGF) in routine COPD primary care management. We assessed the frequency of medication success among patients with COPD who initiated BGF using real-world data. Patients and Methods: Patients with a recorded diagnostic COPD code who started BGF with ≥2 prescriptions within 90-days were identified in the UK Optimum Patient Care Research Database and followed from first prescription until censoring at the end of follow-up (180-days), death, leaving database or end of data at 24/10/2022. The primary outcome was medication success at 90-days post-BGF initiation, defined as no major cardiac or respiratory event (ie no complicated COPD exacerbation, hospitalization for any respiratory event, myocardial infarction, new/hospitalized heart failure, and death) and no incidence of pneumonia. Medication success was also assessed at 180-days post-BGF initiation. Overall real-life medication success was claimed if the lower 95% confidence interval (CI) for the proportion of patients meeting the primary outcome was ≥70% (defined a priori). Results: Two hundred eighty-five patients were included. Prior to BGF initiation, these patients often had severe airflow obstruction (mean ppFEV1: 54.5%), were highly symptomatic (mMRC ≥2: 77.9% (n = 205/263); mean CAT score: 21.7 (SD 7.8)), with evidence of short-acting ß2-agonist (SABA) over-use (≥3 inhalers/year: 62.1%, n=179/285), repeat OCS prescriptions (≥2 courses/year: 33.0%, n = 95/285) and multiple primary care consultations (≥2 visits/year: 61.1%, n = 174/285). Overall, 39.6% of patients (n = 113/285) switched from previous triple therapies. Real-life medication success was achieved by 96.5% of patients (n = 275/285 [95% CI: 93.6, 98.3]) during 90-days treatment with BGF and by 91.8% (n = 169/184 [95% CI: 86.9, 95.4]) of patients at 180-days. The prescribed daily dose of SABA remained stable over the study period. Conclusion: The majority of patients initiating BGF experienced real-life medication success reflecting the absence of severe cardiopulmonary events. These benefits were apparent after 90-days of treatment and sustained over 180-days.


Adrenergic beta-2 Receptor Agonists , Bronchodilator Agents , Databases, Factual , Glycopyrrolate , Primary Health Care , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/physiopathology , Male , Female , Aged , Treatment Outcome , Bronchodilator Agents/administration & dosage , Bronchodilator Agents/adverse effects , Middle Aged , Time Factors , Adrenergic beta-2 Receptor Agonists/administration & dosage , Adrenergic beta-2 Receptor Agonists/adverse effects , United Kingdom , Glycopyrrolate/administration & dosage , Glycopyrrolate/adverse effects , Budesonide, Formoterol Fumarate Drug Combination/administration & dosage , Budesonide, Formoterol Fumarate Drug Combination/adverse effects , Budesonide, Formoterol Fumarate Drug Combination/therapeutic use , Lung/physiopathology , Lung/drug effects , Muscarinic Antagonists/administration & dosage , Muscarinic Antagonists/adverse effects , Drug Combinations , Retrospective Studies , Glucocorticoids/administration & dosage , Glucocorticoids/adverse effects , Aged, 80 and over
20.
NPJ Prim Care Respir Med ; 34(1): 10, 2024 May 10.
Article En | MEDLINE | ID: mdl-38729942

This study aimed to investigate the real-world standardisation and adherence of medical treatment regimens in patients with chronic obstructive pulmonary disease (COPD) in the community for making future management strategy. The follow-up data and treatment information of patients with COPD, which were collected through the Management Information Center of COPD (MICCOPD) in 21 community health service centres in Songjiang District, a countryside region of Shanghai. Concordance between the pharmaceutical treatment plan and recommendation of 2017 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report during the follow-up management period, as well as the medication adherence by patients,were analysed. Out of the 2044 patients diagnosed with COPD, 814 patients (39.8%) who had an initial record of medication use were found to meet the inclusion criteria. The most common medication regimens were long-acting beta-agonist plus inhaled corticosteroids (35.9%) and oral bronchodilators (41.9%). Among these 814 patients, 45.7%, 38.0%, 31.6% and 14.6% adhered to the treatment after 6, 12, 18 and 24 months of follow-up, respectively. The concordance rate with the regimens recommended by the 2017 GOLD guidelines was 35.5% at baseline, 35.5% at 6 months, 32.7% at 12 months, 35.4% at 18 months and 37% at 24 months. The compliance and guideline consistency rates of patients with COPD in the community under the management of general practitioners need to be improved. Enhancing general practitioner proficiency in the prevention and management of COPD and increasing patient awareness of the condition, are crucial standardising and improving adherence to initial and follow-up COPD treatments.


Bronchodilator Agents , Medication Adherence , Pulmonary Disease, Chronic Obstructive , Humans , Pulmonary Disease, Chronic Obstructive/drug therapy , Male , Female , Aged , Middle Aged , Medication Adherence/statistics & numerical data , Bronchodilator Agents/therapeutic use , China , Internet , Adrenal Cortex Hormones/therapeutic use , Adrenergic beta-Agonists/therapeutic use , Administration, Inhalation
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