Ideas and methods of in vitro model establishment for cell microenvironment in COPD / 中国药理学通报

Chronic obstructive pulmonary disease ( COPD ) major chronic disease threatening public health with complex pathological mechanisms. The change of the cell microenvironment of the lung is an important part of the pathophysiology of COPD. Cell culture technology is an important method to investigate the pathological mechanism of COPD and evaluate the pharmacological effect of medicine. Here we introduce the composition of the cell microenvironment of the lung, the change of the cell microenvironment in the pathological process of COPD, and summarize the application of in vitro model mimics cell microenvironment of COPD in the study of mechanism. In addition, we aim to put forward the ideas of the in vitro model establishment of cell microenvironment of COPD.

Prognosis and risk factors of lung cancer with acute exacerbation of COPD in Tongchuan City / 公共卫生与预防医学

Objective To analyse the prognosis and risk factors of lung cancer with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Tongchuan City, and to provide a theoretical basis for improving the prognosis of patients with lung cancer complicated with AECOPD. Methods A total of 280 patients with lung cancer combined with AECOPD admitted to Tongchuan People's Hospital from January 2021 to August 2022 were selected and divided into survival group and death group according to whether the patients survived during hospitalization. Serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA 21-1) and other tumor markers were compared between the two groups. Lung function was measured by lung function instruments, and the levels of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1/FVC and other lung function indicators were compared between the two groups. The patients' clinical data were collected from the medical record system, and univariate analysis and logistic regression were used to analyze the independent risk factors affecting the prognosis of patients with lung cancer complicated with AECOP. Results The values of FEV1, FVC and FEV1/FVC in the death group were significantly lower than those in the survival group (P<0.05). Serum CEA and CYFRA 21-1 levels in the death group were significantly higher than those in the survival group (P<0.05). Multiple logistic regression analysis showed that albumin level <35 g/L (OR=2.728), TNM stage III to IV (OR=2.416), multidrug-resistant bacterial infection (OR=2.982), and GOLD grade III to IV (OR=3.417) were independent risk factors for death in patients with lung cancer complicated with AECOPD in Tongchuan City (P<0.05). Conclusion Patients with lung cancer complicated with AECOPD in Tongchuan City have a high risk of death during hospitalization, especially patients with TNM stage III to IV and GOLD grade III to IV. Multi-drug resistant bacteria infection should be actively controlled to improve the albumin level of patients, which is conducive to the prognosis of patients.

Pathogenesis of Airway Mucus Hypersecretion in Chronic Obstructive Pulmonary Disease and Intervention of Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Chronic obstructive pulmonary disease （COPD） is one of the most common chronic diseases of the respiratory system in the clinic. The disease has a long course and is difficult to cure， which seriously threatens human health. Airway mucus hypersecretion （AMH） is an independent risk factor for COPD and has a significant impact on the development and prognosis of the disease. The review finds that the abnormal proliferation of goblet cells and the excessive secretion of mucin are the direct causes of AMH. The pathogenesis of AMH may be closely related to the inhalation of heterogeneous particles， airway inflammation， the imbalance of mucin/water salt ratio， and the regulation of related signaling pathways. Traditional Chinese medicine （TCM） believes that AMH of COPD belongs to the category of lung distension with phlegm-fluid retention syndrome， and the disease is mainly treated from phlegm on the basis of lung distension. This article summarizes the relevant research in the field of TCM in recent years and finds that the single TCM that effectively intervened AMH of COPD is mainly phlegm-resolving TCM， and the main active ingredients of TCM are flavonoids， terpenoids， phenols， and alkaloids. The main TCM compounds are mainly designed to remove heat-phlegm， warmly resolve cold-phlegm， dry dampness to eliminate phlegm， invigorate Qi， promote blood circulation and dispel phlegm， and invigorate lung， spleen， and kidney. Its mechanism of action may be direct inhibition or indirect inhibition of airway epithelial goblet cell metaplasia and mucin expression by inhibiting airway inflammation， regulating aquaporins to correct the imbalance of mucin/water salt ratio， and regulating signaling pathways， so as to reduce mucus oversecretion in COPD. However， there are still some problems. For example， the research mainly focuses on TCM compounds instead of the single TCM or its effective components. The research on the mechanism of action is not thorough enough， and the research results are not interoperable. The clinical transformation rate of basic research is insufficient. This article systematically reviews the research status of AMH in the treatment of COPD with TCM and puts forward some thoughts on the existing problems， so as to provide a reference for clinical rational medication and in-depth research.

Videofluoroscopic measures of swallowing in people with stable COPD compared to healthy aging

ABSTRACT Purpose Swallowing impairment is a serious extra-pulmonary manifestation of Chronic Obstructive Pulmonary Disease (COPD). Previous studies suggest that individuals with stable COPD show atypical values for several videofluoroscopy measures of swallowing, compared to healthy adults under age 60. However, it is unclear to what degree these changes are attributable to healthy aging. In this study, we aimed to clarify how swallowing in people with stable COPD differs from age-matched healthy controls. Methods We performed a retrospective analysis of videofluoroscopy data from two previously-collected datasets: a) a sample of 28 adults with stable COPD (18 male); b) a sample of 76 healthy adults, from which 28 adults were selected, matched for sex and age to participants in the COPD cohort. In both prior studies, participants swallowed 20% w/v liquid barium prepared in different consistencies (thin; mildly, moderately, and extremely thick). Blinded duplicate ratings were performed according to a standard procedure, yielding measures of laryngeal vestibule closure (LVC) integrity and timing, swallow timing, upper esophageal sphincter (UES) opening, pharyngeal constriction and pharyngeal residue. Mann-Whitney U tests and odds ratios were performed to determine significant group differences (p<.05). Results Across the consistencies tested, participants with COPD showed significantly shorter durations of LVC, earlier onsets and shorter durations of UES opening, and reduced pharyngeal constriction. No significant differences were seen in other measures. Conclusion These results point to features of swallowing in people with stable COPD that differ from changes seen with healthy aging, and which represent risks for potential aspiration.

Risk factors and determinants of pulmonary function impairments in chronic respiratory diseases in Ethiopia: A hospital-based cross-sectional study

Introduction: Chronic respiratory diseases (CRDs) are diseases of the lung airways and parenchyma. Globally, they are the leading causes of morbidity and mortality. This study aimed to characterize the common CRDs, along with their lung function and possible determinants in symptomatic patients attending Bishoftu General Hospital, Ethiopia. Methods: A cross-sessional study was conducted at the outpatient of Bishoftu Hospital, Ethiopia from June 2019 to March 2020. Consecutive adult patients aged 18 and above with CRDs (≥8 weeks) were recruited. Questionnaires were used to collect data on demographics, symptoms, diagnoses, and putative risk factors. Lung function was measured by spirometry. Result: A total of 170 participants were recruited, the majority 102(60.0%) were female. The mean age was 49 years (SD=16). The most common symptoms were wheezing in the last twelve months 156 (91.8%), cough 138 (81.2%), and severe exertional breathlessness 137 (80.6%). Thirty-nine (22.9%) were either active or passive smokers. Half of the patients (50.3%) were exposed daily to vapors, dust, gases, or fumes and 58 (34.3%) were exposed to biomass smoke. In total, 138 (81.2%) had a positive allergen skin prick test. Chronic bronchitis (49.1%) and asthma (36.1%) were the most common clinical diagnoses. Classification of lung function revealed 23 (15%) normal, 29 (19%) obstructive, 36(23.5%) restrictive and 61(39.9%) mixed patterns. Airflow obstruction was independently associated with increasing age (p<0.05), exertional breathlessness (p<0.001), previous history of asthma (p<0.05), BMI (p<0.05), and doctor-diagnosed chronic obstructive pulmonary disease (p<0.001) and asthma (p<0.05). Conclusion: This study shows a high burden of abnormal lung function in patients attending clinics because of CRDs symptoms. These findings support the critical need for spirometry services to determine lung abnormality in patients with chronic respiratory symptoms.

Corticoides inhalados como factor de riesgo de neumonía adquirida en la comunidad en enfermedad pulmonar obstructiva crónica

Objetivo: Determinar si el uso de corticoides inhalados es factor de riesgo de neumonía adquirida en la comunidad en pacientes con enfermedad pulmonar obstructiva crónica en el Hospital Víctor Lazarte Echegaray durante el período 2017-2020. Métodos: El estudio fue analítico, observacional, retrospectivo de casos y controles no emparejados a razón de 4:1, con una población de 405 sujetos; se seleccionaron 81 casos y 324 controles, quienes cumplieron los criterios de selección. Se realizó un muestro no probabilístico. Se incluyeron las variables, uso de corticoides inhalados, pacientes con neumonía adquirida en la comunidad, edad, sexo, desnutrición y tabaquismo. La medida de asociación se hizo utilizando la prueba no paramétrica Chi Cuadrado de Pearson y la prueba exacta de Fisher en frecuencias menores de 5. El análisis bivariado y multivariado se realizó mediante regresión logística múltiple con significancia estadística (valor p 0,05). Conclusión: El uso de corticoides inhalados no es factor de riesgo de neumonía adquirida en la comunidad en pacientes con enfermedad pulmonar obstructiva crónica.

Objective: To determine if the use of inhaled corticosteroids is a risk factor for community-acquired pneumonia in patients with Chronic Obstructive Pulmonary Disease at the Víctor Lazarte Echegaray Hospital during the period 2017-2020. Methods: The study was analytical, observational, retrospective of cases and unmatched controls in a ratio of 4:, with a population of 405 subjects from whom 81 cases and 324 controls were selected, who met the selection criteria. A non-probabilistic sampling was carried out. The variables, use of inhaled corticosteroids, patients with community-acquired pneumonia, age, sex, malnutrition and smoking were included. The association was measured using Pearson's non-parametric Chi-square test and Fisher's exact test at lower frequencies less than 5. The bivariate and multivariate analysis was performed using multiple logistic regression with statistical significance (p value 0.05). Conclusion: The use of inhaled corticosteroids is not a risk factor for community-acquired pneumonia in patients with chronic obstructive pulmonary disease.

Female sexual dysfunction in chronic obstructive pulmonary disease

Background: Sexual life of women with chronic obstructive pulmonary disease (COPD) can be affected by breathing difficulties, a decrease in functional status, depressive mood and fatigue. Objetive: To evaluate the sexual dysfunction in female COPD patients and the possible explanatory mechanisms or correlations between these conditions. Methods: The study included 70 female patients with COPD aged between 36-65 and 70 age-matched controls. All the subjects completed questionnaires for the Female Sexual Functional Index (FSFI), BECK depression inventory and, spirometry. Results: Statistically significant sexual dysfunction was noted in COPD patients compared to the non-COPD group (p0.005). In linear regression analysis determining depression, no statistically significant factor was found among age, number of comorbidities, and FEV1/ forced vital capacity (FVC) % predicted (p>0.05). In multivariable analysis, only fatigue during intercourse was found to be a statistically significant factor in predicting sexual dysfunction among factors like age, presence of comorbidities, duration of the disease, smoking status, FEV1%, m MRCpoints, 6-minutes walk test, BECK depression scores (p=0.008). Conclusion: Sexual dysfunction is reported in many COPD females and seems to be related not to spirometric measures or exercise capacity but to fatigue. Depression is also a common comorbidity, of which both disorders are often neglected.

Antecedentes: La vida sexual en mujeres con enfermedad pulmonar obstructiva crónica (EPOC) es afectada por dificultades respiratorias, disminución del estado funcional, estado de ánimo depresivo y fatiga. Objetive: Evaluar la disfunción sexual en mujeres con EPOC y posibles mecanismos explicativos de esas dos condiciones Métodos: Participaron 70 pacientes mujeres con EPOC, rango edad 36-65 años y 70 controles emparejados por edad. Todos los sujetos respondieron un cuestionario para el índice funcional sexual femenino e inventario de depresión de BECK, mas una espirometría. Resultados: Se observó disfunción sexual significativa en las pacientes con EPOC comparado con el grupo sin EPOC. Las puntuaciones del inventario de depresión BECK fueron significativamente inferiores a las del grupo control. No hubo correlación entre las puntuaciones del FSFI y la depresión BECK con las características de las "mujeres" (r=-0.055). No se encontraron diferencias significativas en edad, FEV1% y antecedentes de exacerbación del año anterior según la gravedad de la depresión. En la regresión lineal para determinar la depresión, no hubo ningún factor estadísticamente significativo entre edad, número de comorbilidades y FEV1/FVC% predicho. En el multivariado, sólo la fatiga durante el coito resultó ser un factor significativo para predecir la disfunción sexual entre factores como edad, presencia de comorbilidades, duración de la enfermedad, hábito tabáquico, FEV1%, m MRCpoints, prueba de la marcha de 6 minutos y puntuaciones de depresión de BECK. Conclusiones: La disfunción sexual parece no estar relacionada con las medidas espirométricas o la capacidad de ejercicio, pero si con la fatiga. La depresión es una comorbilidad frecuente, de la que a menudo se descuidan ambos trastornos.

Noncommunicable and Communicable Diseases: Finding Common Ground

As the world grapples with unprecedented health challenges, such as coronavirus disease 2019 (COVID-19) and now monkeypox, the focus on traditional concerns, like maternal and child health, and relatively newer pandemics, e.g., diabetes and obesity tend to get diluted. This is especially concerning in countries which face a dual challenge of both communicable and noncommunicable diseases (NCDs). In this article, we list the factors that are common to both communicable disease and NCDs, and suggest measures to integrate procedures for their screening, management and prevention.

Six-minute walk test for assessment of work capability in patients with chronic obstructive pulmonary disease: A cross-sectional comparative study

Background: Chronic obstructive pulmonary disease (COPD) is a systemic disorder causing morbidity, disability, and mortality throughout the world. Although, spirometry parameters have been used for decades to diagnose COPD as well as to grade the severity of this disease, others factors such as the BMI, degree of inflation, and exercise capacity have become important outcome measures for extra-pulmonary manifestations. The 6-min walk test (6MWT) is considered as a simple test to assess the functional capacity of COPD patients. The aim of our study was to implement 6MWT in patients of COPD in our setup to predict morbidity. Aims and Objectives: The objective of our study was to implement 6MWT in patients of COPD in our setup to predict morbidity. Materials and Methods: A cross-sectional comparative study was conducted on thirty COPD patients and thirty control subjects. All the subjects were investigated through history taking, clinical examination, spirometry, and 6MWT in the Department of Physiology, R.G. Kar Medical College and Hospital, Kolkata. Statistical analysis was done by SPSS version-21. Results: The values of the spirometry parameters were significantly reduced in cases than in the controls (P < 0.05). The values of 6-min walk distance as well as 6-min work (6MWORK) were also significantly reduced in cases than in the controls (P = 0.0023 and P = 0.0028, respectively). A strong positive correlation was found between forced vital capacity and 6MWORK (r = 0.556), BMI, and 6MWORK (r = 0.84) in patients of COPD. Conclusion: Our study substantiates that 6MWT can be implemented in our set up to assess the work capability and thus to predict morbidity in patients of COPD.

Factores de riesgo de mortalidad en pacientes con enfermedad pulmonar obstructiva crónica exacerbada

Introducción: La enfermedad pulmonar obstructiva crónica es un problema de salud; constituye la tercera causa de muerte en el mundo, la exacerbación de esta enfermedad es responsable del fallecimiento de un elevado porcentaje de pacientes. Objetivo: Identificar factores de riesgo de mortalidad en pacientes hospitalizados con enfermedad pulmonar obstructiva crónica exacerbada. Métodos: Se realizó una investigación transversal, analítica, en el Hospital General Provincial "Camilo Cienfuegos" de Sancti Spíritus, durante dos años. Se incluyeron 335 pacientes. Se estudiaron variables sociodemográficas y clínicas. Para la identificación de factores de riesgo se elaboró un modelo de regresión logística binaria mediante el método hacia delante de Wald. Resultados: En el modelo de regresión logística el índice de porcentaje global que mostró la relación entre lo pronosticado respecto a lo observado fue de un 94,6 %. Los predictores utilizados explicaron el 86,3 % de la variabilidad de la variable dependiente. El análisis estadístico permitió identificar factores de riesgo de mortalidad: insuficiencia respiratoria aguda, diagnóstico de neumonía, tromboembolismo pulmonar, edad mayor de 60 años y adicción tabáquica. Conclusiones: La identificación de cinco factores de riesgo de mortalidad en pacientes hospitalizados por enfermedad pulmonar obstructiva crónica exacerbada, con el empleo de un modelo predictivo para el cálculo de la probabilidad de fallecimiento; contribuyó al perfeccionamiento de la atención médica individualizada, en función de minimizar la ocurrencia de eventos fatales en estos pacientes.

Introduction: Chronic obstructive pulmonary disease is a health problem; It is the third cause of death in the world, the exacerbation of this disease is responsible for the death of a high percentage of patients. Objective: To identify risk factors for mortality in hospitalized patients with exacerbated chronic obstructive pulmonary disease. Methods: A cross-sectional, analytical investigation was carried out, based on the epidemiological design of correlational studies, at the "Camilo Cienfuegos" Provincial General Hospital of Sancti Spíritus, for two years. 335 patients were included. Sociodemographic and clinical variables were studied. To identify risk factors, a binary logistic regression model was developed using the Wald forward method. Mortality during hospitalization for exacerbated COPD was considered the dependent variable. Results: In the logistic regression model, the global percentage index that showed the relationship between what was predicted with respect to what was observed was 94, 6 %. The predictors used explained 86, 3 % of the variability of the dependent variable. Statistical analysis allowed us to identify the following risk factors for mortality: acute respiratory failure, diagnosis of pneumonia, pulmonary thromboembolism, age over 60 years, and smoking addiction. Conclusions: The identification of five mortality risk factors in patients hospitalized for exacerbated COPD, with the use of a predictive model to calculate the probability of death; contributes to the improvement of individualized medical care, in order to minimize the occurrence of fatal events in these patients.

Does cryptogenic organizing pneumonia change seasonal?

SUMMARY BACKGROUND AND AIM: Meteorological factors affect the respiratory system, and the most important factor is the change in ambient temperature and humidity. We aimed to investigate the seasonal characteristics of patients diagnosed with cryptogenic organizing pneumonia. METHODS: The study included 84 cryptogenic organizing pneumonia, 55 chronic obstructive pulmonary disease, and 42 asthma patients. To determine the characteristics of the disease according to the seasons, the number of attacks and admissions was grouped according to the seasonal characteristics and analyzed for three groups. RESULTS: Among cryptogenic organizing pneumonia and chronic obstructive pulmonary disease patients, males significantly predominated (p<0.001). The hospitalization rate was highest in chronic obstructive pulmonary disease patients but similar to cryptogenic organizing pneumonia and asthma patients (p<0.001). The highest admission rate in cryptogenic organizing pneumonia patients was observed in spring (39.3% in spring, 26.2% in fall, 22.6% in winter, and 11.9% in summer). In winter, cryptogenic organizing pneumonia patients were admitted less frequently than chronic obstructive pulmonary disease and asthma patients. The neutrophil-to-lymphocyte ratio was higher in cryptogenic organizing pneumonia patients than in asthma patients and similar to chronic obstructive pulmonary disease patients. CONCLUSION: As a result of our study, the high rate of diagnosis and admission in the spring in cryptogenic organizing pneumonia suggested that the effect of allergens on the formation of cryptogenic organizing pneumonia should be investigated. In contrast, it should be kept in mind that cryptogenic organizing pneumonia may develop as a prolonged finding of involvement that may occur in the lung parenchyma due to lung infections and/or cold weather triggering during the winter months. In this regard, further studies can be conducted in which allergens and/or the history of infection in patients and meteorological variables are also evaluated.

Prevalence of oral candidiasis in asthma and COPD patients using inhaled corticosteroids in the Philippine General Hospital Department of out-patient services

Background and Objectives@#Oral candidiasis (OC) is a well-known local side effect of inhaled corticosteroid (ICS) therapy in patients with asthma and chronic obstructive pulmonary disease (COPD). This study aimed to determine the prevalence of OC and its association with ICS-related factors in out-patient asthma and COPD patients of the Departments of Pulmonology and Pediatric Pulmonology of the Philippine General Hospital (PGH).@*Methods@#This is a cross-sectional study conducted from October 2019 to January 2020. Data was collected through a two-part questionnaire accomplished by doctors and patients with asthma or COPD. Results. A total of 67 patients were included in the study. Oral candidiasis was observed in 4 (5.97%) ICS users, and the prevalence was 1.65% to 14.59% (95% CI, SE: 0.028946).@*Conclusion@#This study determined the prevalence of oral candidiasis in asthma and COPD patients and its association with ICS-related factors, including the dosage, medication, device, and duration of therapy. The prevalence of OC in ICS users in PGH cannot be interpreted as high or low due to the small number of respondents, but is consistent with OC prevalence found in related literature. Increased prevalence was observed in adult females with asthma under low dose ICS therapy with Fluticasone/Salmeterol DPI for more than a year. There was no statistically significant correlation among OC prevalence, age, sex, and components of ICS-therapy including dosage, medication, device, frequency, and duration of therapy. A large-scale study is recommended for more accurate assessment of OC prevalence in the population and to determine statistically significant associations among the factors. It is also recommended to quantifiably measure patient compliance, inhalation technique and instruction, and its association to OC prevalence. Findings may be used to strengthen patient education, preventive measures, and disease management to facilitate improved compliance and effective treatment outcomes.

Correlation between tumor necrosis factor-α and interleukin-1β in exhaled breath condensate and pulmonary function in chronic obstructive pulmonary disease / 中国热带医学

@#Abstract: Objective To explore the correlation between lung function in patients with chronic obstructive pulmonary disease (COPD) and tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels in exhaled breath condensate (EBC), and to provide a convenient methodological basis for the diagnosis and treatment of COPD and the determination of its efficacy. Methods A total of 81 COPD patients and 40 healthy controls were selected from the respiratory department of the Fourth Affiliated Hospital of Guangzhou Medical University from August 2020 to February 2022 as the research subjects. The COPD patients were divided into 41 cases in the acute exacerbation group and 40 cases in the remission group according to their status. All participants underwent lung function detection, venous blood and EBC collection, and the levels of TNF-α and IL-1β in EBC and venous blood were analyzed by enzyme-linked immunosorbent assay (ELISA), and correlation analysis was performed by Pearson correlation analysis method. Results The levels of TNF-α and IL-1β in EBC of in the acute exacerbation group, the healthy control group, the remission group were (5.16±0.18) pg/μL and (7.75±0.27) pg/μL, (2.66±0.31) pg/μL and (2.41±0.24） pg/μL, (3.61±0.29) pg/μL and (3.17±0.38) pg/μL, respectively. Compared with the healthy control group, the levels of TNF-α and IL-1β in EBC in the COPD acute exacerbation group were significantly higher than those in the healthy control group and the COPD remission group (F=9.451, 8.217, P<0.001). Serum tests were consistent with this result. Correlation analysis showed that the levels of TNF-α and IL-1β in EBC were significantly positively correlated with the level of serum inflammation levels (P<0.001), while significantly negatively correlated with lung function (P<0.001).  Conclusions TNF-α and IL-1β in EBC are potential biomarkers of inflammation in patients with COPD, and their detection can be used to effectively assess lung function in patients with COPD. 

Modified Erchentang Alleviates Inflammation in Chronic Obstructive Pulmonary Disease via Midkine/Notch2/Hey1 Signaling Pathway in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the molecular mechanism of the anti-inflammatory effect of Erchentang in the lung tissue of the rat model of chronic obstructive pulmonary disease （COPD） via the heparin-binding factor （Midkine）/transmembrane receptor protein （Notch2）/Hey1 signaling pathway. MethodSixty SD rats were randomized into normal group， model group， modified Erchentang （5， 10， 20 g·kg-1·d-1） groups， and Notch1 pathway inhibitor （γ-secretase inhibitor， DAPT， 0.02 g·kg-1） group， with 10 rats in each group. The rat model of COPD was established by cigarette smoke combined with lipopolysaccharide （LPS）. After the modeling， the rats were administrated with corresponding drugs by gavage， and those in the normal and model groups were administrated with normal saline by gavage for 21 days. The levels of Midkine， cytokine-induced neutrophil chemoattractant-1 （CINC-1）， macrophage-derived chemokine （MDC）， chemokine ligand 5 （CXCL5）， neutrophil elastase （NE）， and nuclear factor-kappa B （NF-κB） p65 in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and immunohistochemistry were respectively employed to determine the mRNA and protein levels of Midkine， Notch2， and Hey1 in the lung tissue. ResultCompared with the normal group， the modeling increased the levels of Midkine， CINC-1， MDC， CXCL5， NE， and NF-κB p65 in BALF （P<0.01） and up-regulated the mRNA and protein levels of Midkine， Notch2， and Hey1 in the lung tissue （P<0.01）. Compared with the model group， medium- and high-dose modified Erchentang and DAPT lowered the levels of Midkine， CINC-1， MDC， CXCL5， and NF-κB p65 in BALF （P<0.01） and down-regulated the mRNA levels of Midkine， Notch2， and Hey1 （P<0.01）. ConclusionModified Erchentang may inhibit the inflammation in COPD rats by down-regulating the expression of Midkine， Notch2， and Hey1 and reducing the content of Midkine， CINC-1， MDC， and CXCL5.

Analysis on Material Basis of Anti-COPD Effect of Euphorbia helioscopia Based on Serum Pharmacochemistry and Network Pharmacology / 中国实验方剂学杂志

ObjectiveTo analyze the migrating components absorbed into blood of the aqueous extract of Euphorbia helioscopia， and to explore the pharmacodynamic material basis of the aqueous extract of E. helioscopia against chronic obstructive pulmonary disease（COPD）. MethodUltra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detecte the migrating components absorbed into blood of rats after intragastric administration of aqueous extract of E. helioscopia. An Agilent RRHD SB-C18 column（3 mm×100 mm， 1.8 μm） was used with 0.1% formic acid aqueous solution（A）-acetonitrile（B） as the mobile phase for gradient elution（0-15 min， 5%-30%B； 15-20 min， 30%-50%B； 20-30 min， 50%-95%B； 30-35 min， 95%-5%B）， and the detection wavelength of 190-800 nm， column temperature of 40 ℃， flow rate of 0.3 mL∙min-1 and injection volume of 4 μL. The electrospray ionization（ESI） was used in positive and negative ion modes， and the detection range was m/z 50-1 250. Network pharmacology was used to screen out the key components and the key targets of COPD through the interaction analysis. Metascape database was used to predict the molecular function， biological process， cellular composition and signal pathways mainly involved in the anti-COPD effect of E. helioscopia. Molecular docking technique was used to determine the affinity of key targets with key components. ResultA total of 29 migrating components absorbed into blood of rats were identified after intragastric administration of aqueous extract of E. helioscopia， 9 of which were prototype components and 20 were metabolites. Network pharmacological analysis showed that luteolin， quercetin， apigenin， naringenin and helioscopinolide C were the key components of E. helioscopia against COPD， and vascular endothelial growth factor A（VEGFA）， albumin（ALB）， protein kinase B1（Akt1）， tumor necrosis factor（TNF） and interleukin-6（IL-6） were the key targets. Molecular docking results showed that one diterpene lactone（helioscopinolide C） and three flavonoids（naringenin， luteolin， apigenin） in the migrating components absorbed into blood all had strong binding activity to the key targets of E. helioscopia against COPD. ConclusionNaringenin， helioscopinolide C， luteolin and apigenin may be the main anti-COPD active substances of E. helioscopia.

In-hospital Mortality and Hospital Outcomes among Adults Hospitalized for Exacerbations of Asthma and COPD in Southern Thailand (2017-2021): A Population-Based Study / 中国医学科学杂志(英文版)

Background Hospitalizations for asthma and chronic obstructive pulmonary disease (COPD) exacerbations frequently occur in Thailand. National trends in hospital outcomes are essential for planning preventive strategies within the healthcare system. We examined temporal trends in in-hospital outcomes, including mortality rate, length of stay (LOS), and expenses for reimbursement in adults hospitalized for asthma and COPD exacerbations in southern Thailand.Methods A retrospective, population-based study on adults hospitalized for exacerbations of asthma and COPD was carried out using data from the National Health Security Office in southern Thailand. Baseline demographic and in-hospital outcome assessments were conducted on 19,459 and 66,457 hospitalizations for asthma and COPD, respectively, between 2017 and 2021.Results Significant reductions in hospital admissions for exacerbations of asthma and COPD were observed over time, particularly in 2020/2021. From 2017 to 2021, the in-hospital mortality rate for asthma rose from 3.2 to 3.7 deaths per 1,000 admissions (P<0.05). The rates for COPD admissions, on the other hand, reduced from 20.3 to 16.4 deaths per 1,000 admissions between 2017 and 2020, but subsequently increased to 21.8 in 2021 (P<0.05). The prominent contributor to the higher mortality rate was found to be increasing age. Nonetheless, the average LOS for both asthma and COPD decreased slightly over the study period. The total expenses for reimbursing exacerbations of asthma and COPD per hospitalisation have risen significantly each year, with a particularly notable increase in 2020/2021.Conclusion During 2017-2021, exacerbations of asthma and COPD in Thailand continued to account for significant in-hospital mortality rates and reimbursement expenses, despite the overall decrease in hospitalizations and slight fluctuations in the LOS.

Compound Tinglizi Decoction intervenes COPD-associated pulmonary hypertension through regulation of HMGB1-mediated pyroptosis and immune imbalance / 中国中药杂志

This paper aimed to investigate the effects of high mobility group box 1(HMGB1)-mediated pulmonary artery smooth muscle cell pyroptosis and immune imbalance on chronic obstructive pulmonary disease-associated pulmonary hypertension(COPD-PH) in rats and the intervening mechanism of Compound Tinglizi Decoction. Ninety rats were randomly divided into a normal group, a model group, low-dose, medium-dose, and high-dose Compound Tinglizi Decoction groups, and a simvastatin group. The rat model of COPD-PH was established by fumigation combined with lipopolysaccharide(LPS) intravascular infusion, which lasted 60 days. Rats in the low, medium, and high-dose Compound Tinglizi Decoction groups were given 4.93, 9.87, and 19.74 g·kg~(-1) Compound Tinglizi Decoction by gavage, respectively. Rats in the simvastatin group were given 1.50 mg·kg~(-1) simvastatin by gavage. After 14 days, the lung function, mean pulmonary artery pressure, and arterial blood gas of rats were analyzed. Lung tissues of rats were collected for hematoxylin-eosin(HE) staining to observe the pathological changes. Real-time fluorescent quantitative polymerase chain reaction(qRT-PCR) was used to determine the expression of related mRNA in lung tissues, Western blot(WB) was used to determine the expression of related proteins in lung tissues, and enzyme linked immunosorbent assay(ELISA) was used to determine the levels of inflammatory factors in the lung tissues of rats. The ultrastructure of lung cells was observed by transmission electron microscope. The forced vital capacity(FVC), forced expiratory volume in 0.3 second(FEV_(0.3)), FEV_(0.3)/FVC, peek expiratory flow(PEF), respiratory dynamic compliance(Cdyn), arterial partial pressure of oxygen(PaO_2), and arterial oxygen saturation(SaO_2) were increased, and resistance of expiration(Re), mean pulmonary arterial pressure(mPAP), right ventricular hypertrophy index(RVHI), and arterial partial pressure of carbon dioxide(PaCO_2) were decreased by Compound Tinglizi Decoction in rats with COPD-PH. Compound Tinglizi Decoction inhibited the protein expression of HMGB1, receptor for advanced glycation end products(RAGE), pro caspase-8, cleaved caspase-8, and gasdermin D(GSDMD) in lung tissues of rats with COPD-PH, as well as the mRNA expression of HMGB1, RAGE, and caspase-8. Pulmonary artery smooth muscle cell pyroptosis was inhibited by Compound Tinglizi Decoction. Interferon-γ(IFN-γ) and interleukin-17(IL-17) were reduced, and interleukin-4(IL-4) and interleukin-10(IL-10) were incresead by Compound Tinglizi Decoction in lung tissues of rats with COPD-PH. In addition, the lesion degree of trachea, alveoli, and pulmonary artery in lung tissues of rats with COPD-PH was improved by Compound Tinglizi Decoction. Compound Tinglizi Decoction had dose-dependent effects. The lung function, pulmonary artery pressure, arterial blood gas, inflammation, trachea, alveoli, and pulmonary artery disease have been improved by Compound Tinglizi Decoction, and its mechanism is related to HMGB1-mediated pulmonary artery smooth muscle cell pyroptosis and helper T cell 1(Th1)/helper T cell 2(Th2), helper T cell 17(Th17)/regulatory T cell(Treg) imbalance.

Enfermedad pulmonar obstructiva crónica (EPOC): no siempre relacionada con tabaquismo / Chronic Obstructive Pulmonary Disease (COPD): Not Always Related to Smoking

Existen un número importante de riesgos no relacionados al tabaco pasible de provocar la EPOC, por lo que la carga de la EPOC no tabáquica es mucho mayor de lo pensado. En los países del tercer mundo, existen importantes agentes de peligro no relacionados al tabaco pasibles de provocar la EPOC. No está aclarada la patogenia de la EPOC y su relación con la exposición laboral a polvos, gases y humos. Son necesarias más investigaciones experimentales y epidemiológicas de mayor magnitud para confirmar la relación entre estas dos variables. Aproximadamente el 15 % de la EPOC relacionada con el trabajo está agravada por el tabaquismo y continúan publicándose nuevos agentes que causan EPOC. Las mujeres presentan una manifestación clínica diferente de la EPOC y son -ante exposiciones semejantes- más propensas a desarrollar la enfermedad que los hombres. La protección personal de los trabajadores es de importancia, ya que es dificultoso valorar la naturaleza del polvo, humo o gases, su concentración ambiente y el tiempo de exposición.

There are a lot of risks unrelated to tobacco that can cause COPD, so the burden of non-smoking COPD is much greater than previously thought. In the Third World countries, there is a significant number of non-tobacco-related risk agents capable of causing COPD. The pathogenesis of COPD and its relationship with occupational exposure to dust, gases, and fumes is not fully understood. Further experimental and epidemiological research on a larger scale is needed to confirm the relationship between these two variables. Approximately 15 % of COPD is related to work, and aggravated by smoking. New agents causing COPD continue to be reported and published. Women exhibit a different clinical manifestation of COPD and, under similar exposures, are more prone to developing the disease compared to men. Personal protection for workers is of particular importance since it is challenging to as sess the nature of dust, smoke, or gases, their ambient concentration, and the duration of the exposure.

Association between erectile dysfunction and the severity of obstruction to airflow in patients with chronic obstructive pulmonary disease / Asociación entre disfunción eréctil y la severidad de la obstrucción al flujo aéreo en pacientes con enfermedad pulmonar obstructiva crónica

Objectives: The objective of this study was to explore a possible association between ED and the severity of airflow obstruction in patients with COPD. Materials and methods: A cross-sectional study was conducted using the International Index Erectile Function (IIEF), a scale validated and translated to Spanish. Bivariate analyses between subgroups were made for quantitative variables using a t-test for means and Mann­Whitney U for medians; qualitative variables were compared using the χ2 test or Fisher's test, depending on distribution. Confusion bias in the association between ED and airflow obstruction was controlled using a logistic regression model. Results: The Spanish version of the IIEF-15 scale was valid and applicable to the Colombian population. The prevalence of ED in COPD patients living at high altitudes was similar to that found at sea level. Such prevalence is higher than in general population. Beta-blockers increased 7 times the risk of ED, but we found no association between the degree of airflow obstruction and ED. Conclusion: Although the severity of COPD is not associated with ED, the prevalence of ED in COPD is higher than in general population. Therefore, ED screening in COPD patients using the IIEF could be justified. The strong association between beta-blockers and ED had not been previously described in patients with COPD but must be considered in their clinical management.

Objetivos: Explorar una posible asociación entre DE y severidad de la obstrucción al flujo aéreo en pacientes con EPOC. Materiales y métodos: Estudio de corte transversal aplicando el Índice Internacional de Función Eréctil (IIFE), validado y traducido al español. Se realizó análisis bivariado para variables cuantitativas usando prueba-t para medias y U de Mann Whitney para medianas; las variables cualitativas fueron comparadas usando prueba de Chi2 o test de Fisher, según distribución. Los sesgos de confusión en la asociación entre DE y obstrucción al flujo aéreo fueron controlados usando un modelo de regresión logística. Resultados: La versión en español de la escala IIFE-15 fue aplicable en población colombiana. La prevalencia de DE en pacientes con EPOC viviendo a gran altura fue similar a lo encontrado a nivel del mar. Esta prevalencia es mayor que en población general. El uso de beta-bloqueadores aumentó hasta siete veces el riesgo de DE, pero no se encontró asociación entre el grado de obstrucción y la DE. Conclusiones: Aunque la severidad de la EPOC no está asociada con DE, la prevalencia de DE en EPOC es mayor que en población general. Está justificada la realización de tamizaje usando el IIFE. La asociación fuerte entre beta-bloqueadores y DE no se ha descrito previamente en pacientes con EPOC, pero debe considerarse en su manejo.

Effects of atorvastatin in suppressing pulmonary vascular remodeling in rats with chronic obstructive pulmonary disease

Abstract Objective To investigate the effects of atorvastatin calcium on pulmonary vascular remodeling, the authors explored the regulatory mechanism of Histone Deacetylation Enzyme-2 (HDAC2) in rats with Chronic Obstructive Pulmonary Disease (COPD), and provided a new direction for drug treatment in the progression of vascular remodeling. Methods Eighteen female SD rats were randomly divided into control (Group S1), COPD (Group S2), and atorvastatin calcium + COPD (Group S3) groups. A COPD rat model was established by passive smoking and intratracheal injection of Lipopolysaccharide (LPS). Haematoxylin and eosin staining and Victoria Blue + Van Gibson staining were used to observe pathological changes in the lung tissue. The pulmonary vascular inflammation score was calculated, and the degree of pulmonary vascular remodeling was evaluated. The ratio of Muscular Arteries in lung tissue (MA%), the ratio of the vessel Wall Area to the vessel total area (WA%), and the ratio of the vessel Wall Thickness to the vascular outer diameter (WT%) were measured using imaging software. The expression of HDAC2 was measured using western blotting, ELISA (Enzyme-Linked Immunosorbent Assay), and qPCR (Real-time PCR). Results Compared with the control group, the degree of pulmonary vascular inflammation and pulmonary vascular remodeling increased in rats with COPD. The WT%, WA%, and lung inflammation scores increased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissue decreased, and the level of Vascular Endothelial Growth Factor (VEGF) in the lung tissues increased (p< 0.05). Compared with the COPD group, the lung tissues from rats in the atorvastatin group had fewer inflammatory cells, and the vascular pathological changes were significantly relieved. The WT%, WA%, and lung inflammation scores decreased significantly; the expression of HDAC2 and HDAC2mRNA in the serum and lung tissues increased, and the level of VEGF in the lung tissues decreased (p< 0.05). Conclusion The present study revealed that atorvastatin calcium could regulate the contents and expression of HDAC2 in serum and lung tissues and inhibit the production of VEGF, thereby regulating pulmonary vascular remodeling in a rat model with COPD.