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ETHNOPHARMACOLOGICAL RELEVANCE: Sea buckthorn (Hippophae rhamnoides), a traditional Tibetan medicinal herb, exhibits protective effects against cardiovascular and respiratory diseases. Although Sea buckthorn extract (SBE) has been confirmed to alleviate airway inflammation in mice, its therapeutic effect and underlying mechanism on chronic obstructive pulmonary disease (COPD) requires further clarification. AIM OF THE STUDY: To elucidate the alleviative effect and molecular mechanism of SBE on lipopolysaccharides (LPS)/porcine pancreatic elastase (PPE)-induced COPD by blocking ferroptosis. METHODS: The anti-ferroptotic effects of SBE were evaluated in human BEAS-2B bronchial epithelial cells using CCK8, RT-qPCR, western blotting, and transmission electron microscopy. Transwell was employed to detect chemotaxis of neutrophils. COPD model was induced by intranasally administration of LPS/PPE in mice and measured by alterations of histopathology, inflammation, and ferroptosis. RNA-sequencing, western blotting, antioxidant examination, flow cytometry, DARTS, CETSA, and molecular docking were then used to investigate its anti-ferroptotic mechanisms. RESULTS: In vitro, SBE not only suppressed erastin- or RSL3-induced ferroptosis by suppressing lipid peroxides (LPOs) production and glutathione (GSH) depletion, but also suppressed ferroptosis-induced chemotactic migration of neutrophils via reducing mRNA expression of chemokines. In vivo, SBE ameliorated LPS/PPE-induced COPD phenotypes, and inhibited the generation of LPOs, cytokines, and chemokines. RNA-sequencing showed that p53 pathway and mitogen-activated protein kinases (MAPK) pathway were implicated in SBE-mediated anti-ferroptotic action. SBE repressed erastin- or LPS/PPE-induced overactivation of p53 and MAPK pathway, thereby decreasing expression of diamine acetyltransferase 1 (SAT1) and arachidonate 15-lipoxygenase (ALOX15), and increasing expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Mechanistically, erastin-induced elevation of reactive oxygen species (ROS) was reduced by SBE through directly scavenging free radicals, thereby contributing to its inhibition of p53 and MAPK pathways. CETSA, DARTS, and molecular docking further showed that ROS-generating enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) may be the target of SBE. Overexpression of NOX4 partially impaired the anti-ferroptotic activity of SBE. CONCLUSION: Our results demonstrated that SBE mitigated COPD by suppressing p53 and MAPK pro-ferroptosis pathways via directly scavenging ROS and blocking NOX4. These findings also supported the clinical application of Sea buckthorn in COPD therapy.
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Ferroptosis , Hippophae , Extractos Vegetales , Enfermedad Pulmonar Obstructiva Crónica , Especies Reactivas de Oxígeno , Proteína p53 Supresora de Tumor , Ferroptosis/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Animales , Humanos , Especies Reactivas de Oxígeno/metabolismo , Hippophae/química , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteína p53 Supresora de Tumor/metabolismo , Ratones , Masculino , Ratones Endogámicos C57BL , Línea Celular , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Modelos Animales de Enfermedad , Simulación del Acoplamiento MolecularRESUMEN
Purpose: This study aimed to investigate the proportion and risk factors of paroxysmal atrial fibrillation (AF) and atrial arrhythmias (AA) in patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Vietnam. Patients and Methods: A prospective observational study was conducted at two major hospitals in Hanoi, Vietnam, from January 2022 to January 2023. A total of 197 AECOPD patients were recruited. ECG and 24-hour Holter ECG were used to diagnose paroxysmal AF and AA. Results: The prevalence of paroxysmal AF and AA were 15.2% and 72.6%, respectively. Factors associated with a higher likelihood of paroxysmal AF included aging 75 years old and above (aOR = 3.15; 95% CI: 1.28 to 8.48), Premature atrial complex (PAC) with 500 or more (aOR = 3.81; 95% CI: 1.48 to 10.97) and severity of COPD as group C and D (aOR = 3.41; 95% CI: 1.28 to 10.50). For AA, aging 75 years old and above (aOR = 2.25; 95% CI: 1.28 to 5.20), smoking (aOR = 2.10; 95% CI: 1.07 to 4.23) and P wave dispersion (PWD) with 40 milliseconds or more (aOR = 3.04; 95% CI: 1.54 to 6.19) were associated with a higher likelihood of AA. Conclusion: Overall, our findings highlight the associated factors with the paroxysmal AF and AA among AECOPD patients. This underscores the importance of a multifaceted approach to risk assessment and management in this vulnerable population, focusing not only on respiratory symptoms but also on comprehensive cardiovascular evaluation and intervention.
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Fibrilación Atrial , Progresión de la Enfermedad , Hospitalización , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Anciano , Fibrilación Atrial/epidemiología , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/terapia , Masculino , Prevalencia , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Factores de Riesgo , Vietnam/epidemiología , Hospitalización/estadística & datos numéricos , Factores de Edad , Medición de Riesgo , Anciano de 80 o más Años , Complejos Atriales Prematuros/epidemiología , Complejos Atriales Prematuros/diagnóstico , Complejos Atriales Prematuros/fisiopatología , Electrocardiografía AmbulatoriaRESUMEN
Background: The associations between gut microbiota and chronic obstructive pulmonary disease (COPD) have gained increasing attention and research interest among scholars. However, it remains unclear whether gut microbiota serves as a causal factor for COPD or if it is a consequence of the disease. Therefore, we investigated the causal relationship between COPD and gut microbiota, with intention of providing novel insights and references for clinical diagnosis and treatment. Methods: Based on the genome-wide association study (GWAS) data, we employed MR-Egger regression, random-effects inverse variance-weighted (IVW) method, and weighted median method for bidirectional Mendelian randomization (MR) analysis. We conducted Cochran's Q test for heterogeneity assessment and performed multivariable analysis, sensitivity analysis, and heterogeneity testing to validate the reliability and stability of results. Results: Utilizing MR analysis, mainly employing the IVW method, we detected a collective of 11 gut microbiota species that exhibited associations with COPD. Among them, Bacteroidia, family XIII, Clostridium innocuum group, Barnesiella, Collinsella, Lachnospiraceae NK4A136 group, Lachnospiraceae UCG004, Lachnospiraceae UCG010, and Bacteroidales were found to be protective factors for COPD. On the other hand, Holdemanella and Marvinbryantia were identified as risk factors for COPD. Individuals with elevated levels of Holdemanella exhibited a 1.141-fold higher risk of developing COPD compared to their healthy counterparts, and those with increased levels of Marvinbryantia had a 1.154-fold higher risk. Reverse MR analysis yielded no evidence indicating a causal relationship between gut microbiota and COPD occurrence. Conclusion: Our study established a causal link between 11 specific gut microbiota species and COPD, offering novel insights and valuable references for targeted therapies in the clinical management of COPD. However, our results were mainly based on the analysis of database, and further clinical studies are needed to clarify the effects of gut microbiota on COPD and its specific protective mechanism.
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Microbioma Gastrointestinal , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/microbiología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/genética , Humanos , Factores de Riesgo , Disbiosis , Medición de Riesgo , Bacterias/genética , Bacterias/aislamiento & purificación , Bacterias/clasificación , Predisposición Genética a la Enfermedad , Fenotipo , Pulmón/microbiología , Pulmón/fisiopatología , Factores ProtectoresRESUMEN
Adherence to COPD treatment plays a crucial role in patient health outcomes. Understanding the correlation between treatment adherence and health status is vital for clinicians to develop effective disease management strategies. This study aimed to examine treatment adherence and its impact on the health status of COPD patients, specifically focusing on the effects of adhering to inhaled medications and breathing exercises. A cross-sectional study involving 420 outpatients diagnosed with COPD was conducted. The study encompassed administering questionnaires, observing patient breathing exercises, and measuring ventilatory function. Results showed that only 36.9% of participants adhered to treatment, with 44.7% following inhaler protocols and 36.9% regularly engaging in breathing exercises. The patients who were non-adherent exhibited a 0.3-fold increase in disease severity compared to the adherent group (p = .002). These findings suggest that consistent adherence to treatment, including inhaled medications and breathing exercises, may positively affect health status by reducing disease severity and airway obstruction in COPD patients. To address this, we recommend that home care clinicians implement a post-discharge assessment and intervention program. This program should focus on educating patients about the importance of treatment adherence and promoting behaviors that reinforce adherence to prescribed therapies.
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Estado de Salud , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Masculino , Femenino , Estudios Transversales , Anciano , Persona de Mediana Edad , Pacientes Ambulatorios , Cumplimiento de la Medicación/estadística & datos numéricos , Encuestas y Cuestionarios , Cumplimiento y Adherencia al Tratamiento/estadística & datos numéricos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are associated with high mortality, morbidity, and poor quality of life and constitute a substantial burden to patients and health care systems. New approaches to prevent or reduce the severity of AECOPD are urgently needed. Internationally, this has prompted increased interest in the potential of remote patient monitoring (RPM) and digital medicine. RPM refers to the direct transmission of patient-reported outcomes, physiological, and functional data, including heart rate, weight, blood pressure, oxygen saturation, physical activity, and lung function (spirometry), directly to health care professionals through automation, web-based data entry, or phone-based data entry. Machine learning has the potential to enhance RPM in chronic obstructive pulmonary disease by increasing the accuracy and precision of AECOPD prediction systems. OBJECTIVE: This study aimed to conduct a dual systematic review. The first review focuses on randomized controlled trials where RPM was used as an intervention to treat or improve AECOPD. The second review examines studies that combined machine learning with RPM to predict AECOPD. We review the evidence and concepts behind RPM and machine learning and discuss the strengths, limitations, and clinical use of available systems. We have generated a list of recommendations needed to deliver patient and health care system benefits. METHODS: A comprehensive search strategy, encompassing the Scopus and Web of Science databases, was used to identify relevant studies. A total of 2 independent reviewers (HMGG and CM) conducted study selection, data extraction, and quality assessment, with discrepancies resolved through consensus. Data synthesis involved evidence assessment using a Critical Appraisal Skills Programme checklist and a narrative synthesis. Reporting followed PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: These narrative syntheses suggest that 57% (16/28) of the randomized controlled trials for RPM interventions fail to achieve the required level of evidence for better outcomes in AECOPD. However, the integration of machine learning into RPM demonstrates promise for increasing the predictive accuracy of AECOPD and, therefore, early intervention. CONCLUSIONS: This review suggests a transition toward the integration of machine learning into RPM for predicting AECOPD. We discuss particular RPM indices that have the potential to improve AECOPD prediction and highlight research gaps concerning patient factors and the maintained adoption of RPM. Furthermore, we emphasize the importance of a more comprehensive examination of patient and health care burdens associated with RPM, along with the development of practical solutions.
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Aprendizaje Automático , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Humanos , Monitoreo Fisiológico/métodos , Telemedicina , Calidad de VidaRESUMEN
RESEARCH QUESTION: From the perspectives of healthcare professionals (HCPs) and people with chronic obstructive pulmonary disease (COPD) known to tertiary care, what influences successful referrals to a pulmonary rehabilitation program (PRP)? METHODS: This cross-sectional qualitative study was informed by a critical realist perspective. We purposively sampled people with COPD and HCPs who deliver COPD care and used semi-structured interviews and focus groups to explore determinants of a successful referral to a PRP. Interviews were recorded, transcribed verbatim and analysed using reflexive thematic analysis. RESULTS: Data were available on 38 HCPs and 15 people with COPD. We generated three core themes pertaining to successful referrals. The first theme was that HCPs should be mindful of how professional responsibilities (such as their personal value and interest in a PRP, their degree of understanding of PRPs, and the organisational culture the PRPs are embedded within) shape decision-making during a therapeutic interaction. The second theme, there's more to me than my COPD, characterised psychological perceptions that shape a person's readiness to engage in a PRP. The third theme, communication is a two-way street that requires careful navigation, characterised the interpersonal dynamic between HCP and patient, and how dedicated conversations about PRPs can encourage successful referrals. CONCLUSION: Therapeutic interactions that include dedicated conversations about PRPs can foster successful referrals among people with COPD. During these interactions, HCPs should take the time to understand and carefully unpack psychological perceptions whilst imparting value, interest and enthusiasm for PRPs. Doing so can shape patient engagement toward referral success.
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Comunicación , Participación del Paciente , Enfermedad Pulmonar Obstructiva Crónica , Investigación Cualitativa , Derivación y Consulta , Humanos , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Enfermedad Pulmonar Obstructiva Crónica/psicología , Estudios Transversales , Masculino , Participación del Paciente/psicología , Femenino , Persona de Mediana Edad , Anciano , Grupos Focales , Personal de Salud/psicología , Toma de Decisiones , AdultoRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a severe condition affecting millions worldwide, leading to numerous annual deaths. The absence of significant symptoms in its early stages promotes high underdiagnosis rates for the affected people. Besides pulmonary function failure, another harmful problem of COPD is the systemic effects, e.g., heart failure or voice distortion. However, the systemic effects of COPD might provide valuable information for early detection. In other words, symptoms caused by systemic effects could be helpful to detect the condition in its early stages. OBJECTIVE: The proposed study aims to explore whether the voice features extracted from the vowel "a" utterance carry any information that can be predictive of COPD by employing Machine Learning (ML) on a newly collected voice dataset. METHODS: Forty-eight participants were recruited from the pool of research clinic visitors at Blekinge Institute of Technology (BTH) in Sweden between January 2022 and May 2023. A dataset consisting of 1246 recordings from 48 participants was gathered. The collection of voice recordings containing the vowel "a" utterance commenced following an information and consent meeting with each participant using the VoiceDiagnostic application. The collected voice data was subjected to silence segment removal, feature extraction of baseline acoustic features, and Mel Frequency Cepstrum Coefficients (MFCC). Sociodemographic data was also collected from the participants. Three ML models were investigated for the binary classification of COPD and healthy controls: Random Forest (RF), Support Vector Machine (SVM), and CatBoost (CB). A nested k-fold cross-validation approach was employed. Additionally, the hyperparameters were optimized using grid-search on each ML model. For best performance assessment, accuracy, F1-score, precision, and recall metrics were computed. Afterward, we further examined the best classifier by utilizing the Area Under the Curve (AUC), Average Precision (AP), and SHapley Additive exPlanations (SHAP) feature-importance measures. RESULTS: The classifiers RF, SVM, and CB achieved a maximum accuracy of 77 %, 69 %, and 78 % on the test set and 93 %, 78 % and 97 % on the validation set, respectively. The CB classifier outperformed RF and SVM. After further investigation of the best-performing classifier, CB demonstrated the highest performance, producing an AUC of 82 % and AP of 76 %. In addition to age and gender, the mean values of baseline acoustic and MFCC features demonstrate high importance and deterministic characteristics for classification performance in both test and validation sets, though in varied order. CONCLUSION: This study concludes that the utterance of vowel "a" recordings contain information that can be captured by the CatBoost classifier with high accuracy for the classification of COPD. Additionally, baseline acoustic and MFCC features, in conjunction with age and gender information, can be employed for classification purposes and benefit healthcare for decision support in COPD diagnosis. CLINICAL TRIAL REGISTRATION NUMBER: NCT05897944.
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Aprendizaje Automático , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/clasificación , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Voz/fisiología , Máquina de Vectores de SoporteRESUMEN
Although the recombinant zoster vaccine (RZV) has demonstrated efficacy in reducing the risk of herpes zoster (HZ) for individuals aged 50 years and older, its effectiveness in patients with chronic obstructive pulmonary disease (COPD) remains uncertain. This study was conducted to assess the effect of RZV on the risk of HZ in COPD patients. A multi-institutional propensity score-matched retrospective cohort study was conducted using the TriNetX Research network, including individuals aged 40 years or older with COPD from January 1, 2018, to December 31, 2022. Patients with a history of HZ or prior zoster vaccination were excluded. The primary outcome was HZ occurrence, with secondary outcomes including severe and nonsevere HZ. After propensity score matching, each 17 431 patients receiving RZV and unvaccinated patients were included. The vaccinated group had a significantly lower risk of HZ compared to the unvaccinated group (HR, 0.62; [95% confidence intervals] 95% CI, 0.51-0.75, p < 0.01). Similar risk reductions were observed for nonsevere HZ (HR, 0.61; 95% CI, 049-0.75, p < 0.01) and severe HZ (HR, 0.53; 95% CI, 0.38-0.73, p < 0.01). Further subgroup analyses demonstrated consistent risk reductions across age (50-59, 60-69, 70-79, and ≥80 years), sex, and comorbidities, except for individual aged 40-49 years. This study confirms the effectiveness of RZV in reducing HZ risk in patients with COPD aged 50 years and older, supporting its administration in this population. However, vaccination rates remain low, highlighting the need for improved vaccination strategies in this high-risk group. Efforts to enhance vaccine uptake are warranted to reduce HZ morbidity.
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Vacuna contra el Herpes Zóster , Herpes Zóster , Puntaje de Propensión , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Masculino , Femenino , Anciano , Herpes Zóster/prevención & control , Estudios Retrospectivos , Persona de Mediana Edad , Vacuna contra el Herpes Zóster/inmunología , Vacuna contra el Herpes Zóster/administración & dosificación , Vacunas Sintéticas/inmunología , Vacunas Sintéticas/administración & dosificación , Anciano de 80 o más Años , Adulto , VacunaciónRESUMEN
Objectives: This study aimed to investigate the dynamic patterns of perception and expectations among COPD patients. Methods: Conducted at the Heart-Respiratory Rehabilitation Unit, IRCCS Fondazione Don Carlo Gnocchi, in Milan, Italy, the research involved 28 participants (16 males; mean age 72.8 ± 9.9) in face-to-face interviews. Utilizing a Grounded Theory approach, complemented by clinical data, recorded, and transcribed interviews underwent enhancement through the integration of two pictorial tools. Results: The central theme that emerged was a profound sense of responsibility toward their condition, perceived as a significant threat to life. Key symptoms, such as shortness of breath, coupled with negative expectations about their condition, contributed to depressive mood and avoidance behaviors. A notable proportion (N = 17; 60.71%) of participants struggled to envision a positive future, expressing a pervasive sense of hopelessness, which significantly influenced their health behaviors and adherence to medical recommendations. Conversely, individuals who felt supported and optimistic about treatment efficacy exhibited more positive expectations and adopted proactive coping strategies. Discussion: Recognizing the dynamic nature of patients' perceptions and negative illness expectations is essential to create personalized therapeutic interventions and meet the specific needs of COPD patients, ultimately improving the overall effectiveness of their care journey.
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Adaptación Psicológica , Teoría Fundamentada , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/psicología , Enfermedad Pulmonar Obstructiva Crónica/terapia , Masculino , Femenino , Anciano , Persona de Mediana Edad , Depresión/psicología , Depresión/etiología , Anciano de 80 o más Años , Disnea/psicología , Disnea/etiología , Disnea/terapia , Investigación Cualitativa , Medicina de Precisión/métodos , Actitud Frente a la Salud , Conductas Relacionadas con la Salud , Percepción , Entrevistas como AsuntoRESUMEN
BACKGROUND: Studies have identified individual blood biomarkers associated with chronic obstructive pulmonary disease (COPD) and related phenotypes. However, complex diseases such as COPD typically involve changes in multiple molecules with interconnections that may not be captured when considering single molecular features. METHODS: Leveraging proteomic data from 3,173 COPDGene Non-Hispanic White (NHW) and African American (AA) participants, we applied sparse multiple canonical correlation network analysis (SmCCNet) to 4,776 proteins assayed on the SomaScan v4.0 platform to derive sparse networks of proteins associated with current vs. former smoking status, airflow obstruction, and emphysema quantitated from high-resolution computed tomography scans. We then used NetSHy, a dimension reduction technique leveraging network topology, to produce summary scores of each proteomic network, referred to as NetSHy scores. We next performed a genome-wide association study (GWAS) to identify variants associated with the NetSHy scores, or network quantitative trait loci (nQTLs). Finally, we evaluated the replicability of the networks in an independent cohort, SPIROMICS. RESULTS: We identified networks of 13 to 104 proteins for each phenotype and exposure in NHW and AA, and the derived NetSHy scores significantly associated with the variable of interests. Networks included known (sRAGE, ALPP, MIP1) and novel molecules (CA10, CPB1, HIS3, PXDN) and interactions involved in COPD pathogenesis. We observed 7 nQTL loci associated with NetSHy scores, 4 of which remained after conditional analysis. Networks for smoking status and emphysema, but not airflow obstruction, demonstrated a high degree of replicability across race groups and cohorts. CONCLUSIONS: In this work, we apply state-of-the-art molecular network generation and summarization approaches to proteomic data from COPDGene participants to uncover protein networks associated with COPD phenotypes. We further identify genetic associations with networks. This work discovers protein networks containing known and novel proteins and protein interactions associated with clinically relevant COPD phenotypes across race groups and cohorts.
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Estudio de Asociación del Genoma Completo , Proteómica , Enfermedad Pulmonar Obstructiva Crónica , Fumar , Humanos , Enfermedad Pulmonar Obstructiva Crónica/genética , Fumar/genética , Masculino , Femenino , Persona de Mediana Edad , Anciano , Sitios de Carácter Cuantitativo , Fenotipo , Polimorfismo de Nucleótido Simple , Variación GenéticaRESUMEN
Objective To identify the risk factors of patients with frequent acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and construct a prediction model based on the clinical data,providing a theoretical basis for the clinical prevention and treatment. Methods A total of 25 638 COPD patients admitted to the Department of Respiratory and Critical Care Medicine,the Third People's Hospital of Chengdu from January 1,2013 to May 1,2023 were selected.Among them,11 315 patients were included according to the inclusion and exclusion criteria,and their clinical characteristics were analyzed.Multivariate Logistic regression was carried out to identify the risk factors for frequent AECOPD.A nomogram model was utilized to quantify the risk of acute exacerbation,and the performance of the prediction model was assessed based on the area under the receiver operating characteristic (ROC) curve. Results In the patients with frequent AECOPD,male percentage (P<0.001),age (P<0.001),urban residence (P<0.001),smoking (P<0.001),length of stay (P<0.001),total cost (P<0.001),antibiotic cost (P<0.001),diabetes (P=0.003),respiratory failure (P<0.001),heart disease (P<0.001),application of systemic glucocorticoids (P<0.001),white blood cell count (P<0.001),neutrophil percentage (P<0.001),C-reactive protein (P<0.001),total cholesterol (P<0.001),and brain natriuretic peptide (BNP) (P<0.001) were all higher than those in the patients with infrequent AECOPD.Multivariate Logistic regression analysis revealed that age,urban residence,smoking,diabetes,heart disease,Pseudomonas aeruginosa infection,application of systemic glucocorticoids,antibiotics,respiratory failure,and elevated white blood cell count,total cholesterol,and BNP were independent risk factors for hospitalization due to frequent AECOPD.A nomogram model of hospitalization due to frequent AECOPD was constructed according to risk factors.The ROC curve was established to evaluate the performance of the model,which showed the area under the ROC curve of 0.899 (95%CI=0.892-0.905),the sensitivity of 85.30%,and the specificity of 79.80%. Conclusion Frequent AECOPD is associated with smoking,heart disease,application of systemic glucocorticoids,Pseudomonas aeruginosa infection,age,low body mass index,and elevated BNP.Predicting the risks of hospitalization due to frequent AECOPD by the established model can provide theoretical support for the treatment and risk factor management of the patients.
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Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Masculino , Femenino , Factores de Riesgo , Anciano , Persona de Mediana Edad , Modelos Logísticos , Nomogramas , Anciano de 80 o más AñosRESUMEN
OBJECTIVE: To explore the correlation between serum nitric oxide synthase (NOS) levels and readmission due to acute exacerbation within 30 days in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: A prospective cohort study was conducted. The AECOPD patients admitted to the First Affiliated Hospital of Hebei North University from January 2020 to December 2022 were enrolled as the research subjects. The general data such as gender, age, body mass index (BMI), chronic obstructive pulmonary disease (COPD) course, smoking history, and basic diseases were collected. The laboratory indicators, serum NOS level [inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS)] and acute physiology and chronic health evaluation II (APACHE II) score within 24 hours after admission and total length of hospital stay were also collected, and whether patients were readmitted due to acute exacerbation within 30 days after discharge were recorded. The differences in the above clinical indexes between the readmitted and non-readmitted patients within 30 days were compared. Multivariate Logistic regression analysis was used to screen the influencing factors of readmission within 30 days after discharge in AECOPD patients. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of various influencing factors on readmission. RESULTS: A total of 168 patients were enrolled, 38 patients were readmitted due to acute aggravation within 30 days after discharge, and 130 were not readmitted. Compared with the non-readmission group, the levels of white blood cell count (WBC), C-reactive protein (CRP), APACHE II score, and serum iNOS and eNOS levels within 24 hours after admission in the readmission group were significantly increased [WBC (×109/L): 14.19 (12.88, 16.12) vs. 11.81 (10.63, 14.11), CRP (mg/L): 51.41±12.35 vs. 40.12±7.79, APACHE II score: 22.0 (19.0, 25.0) vs. 18.0 (14.0,20.5), iNOS (µg/L): 5.87±1.36 vs. 4.52±0.89, eNOS (µg/L): 4.40±1.00 vs. 3.51±1.08, all P < 0.01], and the levels of hemoglobin (Hb) and albumin (Alb) were significantly decreased [Hb (g/L): 108.82±22.06 vs. 123.98±24.26, Alb (g/L): 30.28±3.27 vs. 33.68±2.76, both P < 0.01]. There were no significant differences in gender, age, BMI, COPD course, smoking history, basic diseases, total length of hospital stay and serum nNOS level between the two groups. Multivariate Logistic regression analysis showed that CRP [odds ratio (OR) = 1.201, 95% confidence interval (95%CI) was 1.075-1.341], APACHE II score (OR = 1.335, 95%CI was 1.120-1.590), and serum iNOS (OR = 5.496, 95%CI was 2.143-14.095) and eNOS (OR = 3.366, 95%CI was 1.272-8.090) were the independent risk factors for readmission within 30 days after discharge in AECOPD patients (all P < 0.05), and Hb (OR = 0.965, 95%CI was 0.933-0.997) and Alb (OR = 0.551, 95%CI was 0.380-0.799) were protective factors (both P < 0.05). ROC curve analysis showed that serum iNOS and eNOS levels had predictive value for readmission within 30 days after discharge in AECOPD patients, and the area under the ROC curve (AUC) was 0.791 (95%CI was 0.694-0.887) and 0.742 (95%CI was 0.660-0.823), respectively. When the optimal cut-off value was 5.22 µg/L and 3.82 µg/L, the sensitivity was 81.54% and 69.23%, and the specificity was 71.05% and 81.58%, respectively. The AUC of serum iNOS and eNOS levels combined with Hb, Alb, CRP and APACHE II score for predicting the readmission was 0.979 (95%CI was 0.958-1.000), the sensitivity was 91.54%, and the specificity was 97.37%. CONCLUSIONS: The increased serum iNOS and eNOS levels of AECOPD patients correlate with the readmission due to acute exacerbation within 30 days after discharge. Combined detection of Hb, Alb, CRP, serum iNOS and eNOS levels, and evaluation of APACHE II score within 24 hours after admission can effectively predict readmission.
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Readmisión del Paciente , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/sangre , Readmisión del Paciente/estadística & datos numéricos , Estudios Prospectivos , Masculino , Femenino , APACHE , Óxido Nítrico Sintasa/sangre , Tiempo de Internación , Óxido Nítrico Sintasa de Tipo III/sangre , Óxido Nítrico Sintasa de Tipo II/sangre , Modelos Logísticos , Anciano , Proteína C-Reactiva/análisis , Persona de Mediana Edad , Progresión de la EnfermedadRESUMEN
Introduction: Lung function constraints and comorbidities such as coronary heart disease, sarcopenia, and mood disorders make chronic obstructive pulmonary disease (COPD) patients avoid physical activity (PA). However, PA represents an important pillar of COPD management and is explicitly recommended by professional associations to enhance physical functioning and positively modulate disease progression. Methods: In this monocentric, prospective, observational feasibility study, it was our primary objective to investigate the association between PA and the evolution of the COPD assessment test (CAT) and the occurrence of acute exacerbations of COPD (AECOPD), respectively. To this end, we equipped 42 COPD patients with an activity tracking wearable and telemonitored their daily PA levels over one year using a dedicated web-based interface. Patients additionally provided weekly CAT scores using the same telehealth platform and came in for 3 study visits to assess functional parameters and biochemical markers related to nutrition and inflammation. Results: A principal study finding was that PA was inversely associated with CAT score (drop of 0.21 points associated with an increase of 1000 daily steps, p = 0.004), and that the 50% of patients with higher PA levels showed less CAT score progression over time (0.42 points per year) than the 50% of patients with lower PA levels (3.26 points per year) (p < 0.001). In addition, higher PA levels were significantly associated with a lower likelihood of experiencing a moderate-to-severe AECOPD (31% risk reduction associated with an increase of 1000 daily steps, p = 0.0097). Discussion: Our study demonstrates the relevance of PA for key COPD outcome metrics in a real-world setting and underpins the importance of PA for COPD self-management in everyday life. Our study paves the way for future intervention trials to prospectively identify medically relevant PA thresholds and establish training recommendations for different patient subgroups.
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Actigrafía , Progresión de la Enfermedad , Ejercicio Físico , Estudios de Factibilidad , Monitores de Ejercicio , Pulmón , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/terapia , Estudios Prospectivos , Femenino , Masculino , Anciano , Persona de Mediana Edad , Factores de Tiempo , Pulmón/fisiopatología , Actigrafía/instrumentación , Telemedicina , Valor Predictivo de las PruebasRESUMEN
Purpose: COPD affects more than 300 million people worldwide, requiring inhalation treatment. Novel triple formulations of ICS, LABAs and LAMAs are becoming the mainstay of treatment, however there is still a lack of clinical evidence for personalized therapy. Patients and Methods: RATIONALE was a non-interventional, prospective, 52 week study, assessing the effectiveness of beclometasone/formoterol/glycopyrronium-bromide (BDP/FF/G), in symptomatic COPD patients, with moderate airflow obstruction. The study included 4 visits, where data on demographic parameters, exacerbations, symptoms, quality of life (based on the EQ-5D-3L questionnaire) and lung function were collected. Data on adherence to treatment, based on prescriptions filled was collected from the database of the National Health Insurance Fund, with the patients' consent. The primary objective was the change of adherence to treatment during the study, compared to baseline. Results: Altogether 613 patients had been enrolled. Their average age was 64.56 years and 50.5% were female. The average CAT score was 20.86, and most patients had suffered minimum one exacerbation (82.2%). Average FEV1 was 59.6%. Most patients had some limitation in one or more dimensions of EQ-5D-3L, with an average visual analogue scale score (VAS) of 60.31. After 12 months of treatment, adherence improved significantly - proportion of patients in the highest adherence group increased from 29.8% to 69.7% (p<0.001). The average CAT score improved by 7.02 points (95% CI 5.82-8.21, p<0.001). There was a significant improvement in all dimensions of EQ-5D-3L, with an average increase of 17.91 (95% CI 16.51-19.31, p< 0.001) points in the VAS score. Exacerbation frequency also decreased significantly. Conclusion: Although limitations of observational studies are present, we observed that early introduction of fixed triple combination results in a marked improvement in adherence to treatment, symptom scores, exacerbation frequency and quality of life. The optimal choice of treatment is crucial for reaching the highest possible adherence.
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Agonistas de Receptores Adrenérgicos beta 2 , Beclometasona , Broncodilatadores , Combinación de Medicamentos , Fumarato de Formoterol , Glicopirrolato , Pulmón , Cumplimiento de la Medicación , Antagonistas Muscarínicos , Enfermedad Pulmonar Obstructiva Crónica , Calidad de Vida , Humanos , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Femenino , Masculino , Persona de Mediana Edad , Administración por Inhalación , Estudios Prospectivos , Anciano , Resultado del Tratamiento , Broncodilatadores/administración & dosificación , Glicopirrolato/administración & dosificación , Agonistas de Receptores Adrenérgicos beta 2/administración & dosificación , Pulmón/fisiopatología , Pulmón/efectos de los fármacos , Antagonistas Muscarínicos/administración & dosificación , Antagonistas Muscarínicos/efectos adversos , Beclometasona/administración & dosificación , Factores de Tiempo , Fumarato de Formoterol/administración & dosificación , Volumen Espiratorio Forzado , Índice de Severidad de la Enfermedad , Recuperación de la Función , Progresión de la Enfermedad , Glucocorticoides/administración & dosificaciónRESUMEN
Purpose: Sedentary time (ST) is associated with mortality independent of moderate-to-vigorous physical activity in patients with COPD. The proper processing methods for the measurement data and factors related to ST are still unknown. We investigated several conditions for determining the proper processing of ST accelerometric data and created a reference equation for ST using ST-related factors. Patients and Methods: In Study 1, we evaluated the minimum required number of days to obtain repeatability at different measurement times and assessed the effects of rainy days or weekend days on ST in patients with COPD. In Study 2, we detected the ST-related factors among 28 parameters and created a reference equation for ST using the detected factors. Results: In Study 1, 38 patients with stable COPD were analyzed. The minimum number of days required for repeatability was 3 for 8-h wearing and 2 for 10-h wearing. The ST was significantly prolonged on rainy days, but not on weekends. In Study 2, 216 patients with stable COPD were analyzed. BMI, FEV1%pred, 6MWD, and mMRC were detected as ST-related factors, and a reference equation could be created using these four factors. The equation was validated for patients whose ST was ≥ 6 h. Conclusion: By using properly processed measurement data of ST, we created a reference equation for assessing ST that is expected to be useful for providing individual guidance on the shortening of ST to patients with COPD.
When measuring sedentary time (ST) objectively, we should recognize that the minimum required number of days is three and that ST is prolonged on rainy days. The reference equation for ST could be created using four ST-related factors. It might serve as a guide for shortening ST in COPD.
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Pulmón , Valor Predictivo de las Pruebas , Enfermedad Pulmonar Obstructiva Crónica , Conducta Sedentaria , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Masculino , Femenino , Anciano , Factores de Tiempo , Reproducibilidad de los Resultados , Persona de Mediana Edad , Pulmón/fisiopatología , Volumen Espiratorio Forzado , Actigrafía/instrumentación , Monitores de Ejercicio , Ejercicio Físico , Prueba de Paso , Índice de Masa CorporalRESUMEN
It is estimated that there are 544.9 million people suffering from chronic respiratory diseases in the world, which is the third largest chronic disease. Although there are various clinical treatment methods, there is no specific drug for chronic pulmonary diseases, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF). Therefore, it is urgent to clarify the pathological mechanism and medication development. Single-cell transcriptome data of human and mouse from GEO database were integrated by "Harmony" algorithm. The data was standardized and normalized by using "Seurat" package, and "SingleR" algorithm was used for cell grouping annotation. The "Findmarker" function is used to find differentially expressed genes (DEGs), which were enriched and analyzed by using "clusterProfiler", and a protein interaction network was constructed for DEGs, and four algorithms are used to find the hub genes. The expression of hub genes were analyzed in independent human and mouse single-cell transcriptome data. Bulk RNA data were used to integrate by the "SVA" function, verify the expression levels of hub genes and build a diagnostic model. The L1000FWD platform was used to screen potential drugs. Through exploring the similarities and differences by integrated single-cell atlas, we found that the lung parenchymal cells showed abnormal oxidative stress, cell matrix adhesion and ubiquitination in COPD, corona virus disease 2019 (COVID-19), ILD and IPF. Meanwhile, the lung resident immune cells showed abnormal Toll-like receptor signals, interferon signals and ubiquitination. However, unlike acute pneumonia (COVID-19), chronic pulmonary disease shows enhanced ubiquitination. This phenomenon was confirmed in independent external human single-cell atlas, but unfortunately, it was not confirmed in mouse single-cell atlas of bleomycin-induced pulmonary fibrosis model and influenza virus-infected mouse model, which means that the model needs to be optimized. In addition, the bulk RNA-Seq data of COVID-19, ILD and IPF was integrated, and we found that the immune infiltration of lung tissue was enhanced, consistent with the single-cell level, UBA52, UBB and UBC were low expressed in COVID-19 and high expressed in ILD, and had a strong correlation with the expression of cell matrix adhesion genes. UBA52 and UBB have good diagnostic efficacy, and salermide and SSR-69071 can be used as their candidate drugs. Our study found that the disorder of protein ubiquitination in chronic pulmonary diseases is an important cause of pathological phenotype of pulmonary fibrosis by integrating scRNA-Seq and bulk RNA-Seq, which provides a new horizons for clinicopathology, diagnosis and treatment.
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RNA-Seq , Ubiquitina , Humanos , Animales , Ratones , Ubiquitina/metabolismo , Ubiquitina/genética , Análisis de la Célula Individual/métodos , Transcriptoma , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/patología , COVID-19/genética , COVID-19/metabolismo , COVID-19/virología , Perfilación de la Expresión Génica , Mapas de Interacción de Proteínas , Enfermedad Crónica , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/metabolismo , SARS-CoV-2/genética , Enfermedad Pulmonar Obstructiva Crónica/genética , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Análisis de Expresión Génica de una Sola CélulaRESUMEN
The WHO recently published a Tobacco Knowledge Summary (TKS) synthesizing current evidence on tobacco and COPD, aiming to raise awareness among a broad audience of health care professionals. Furthermore, it can be used as an advocacy tool in the fight for tobacco control and prevention of tobacco-related disease. This article builds on the evidence presented in the TKS, with a greater level of detail intended for a lung-specialist audience. Pulmonologists have a vital role to play in advocating for the health of their patients and the wider population by sharing five key messages: (1) Smoking is the leading cause of COPD in high-income countries, contributing to approximately 70% of cases. Quitting tobacco is an essential step toward better lung health. (2) People with COPD face a significantly higher risk of developing lung cancer. Smoking cessation is a powerful measure to reduce cancer risk. (3) Cardiovascular disease, lung cancer and type-2 diabetes are common comorbidities in people with COPD. Quitting smoking not only improves COPD management, but also reduces the risk of developing these coexisting conditions. (4) Tobacco smoke also significantly impacts children's lung growth and development, increasing the risk of respiratory infections, asthma and up to ten other conditions, and COPD later in life. Governments should implement effective tobacco control measures to protect vulnerable populations. (5) The tobacco industry's aggressive strategies in the marketing of nicotine delivery systems and all tobacco products specifically target children, adolescents, and young adults. Protecting our youth from these harmful tactics is a top priority.
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Enfermedad Pulmonar Obstructiva Crónica , Organización Mundial de la Salud , Humanos , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/prevención & control , Cese del Hábito de Fumar , Conocimientos, Actitudes y Práctica en Salud , Fumar/efectos adversos , Fumar/epidemiologíaRESUMEN
Current treatments for chronic obstructive pulmonary disease (COPD) are relatively limited and cannot meet the needs of all patients. Ensifentrine (development code RPL554), a representative drug of cyclic nucleotide phosphodiesterase 3/4 (PDE 3/4) inhibitors, has shown promising developments in the treatment of COPD in recent years, which need to be summarized. This article reviews the mechanism and clinical research progress of ensifentrine, focusing on its chemical structure, pharmacokinetics, pathophysiological mechanism, efficacy, and safety. Additionally, we provide clinical application suggestions and future research prospects.