Exacerbation Of Chronic Obstructive Pulmonary Disease Research Articles

Ivacaftor for Chronic Obstructive Pulmonary Disease - Results from a Phase 2, Randomized Controlled Trial.

Patients with chronic obstructive pulmonary disease (COPD) exhibit acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. CFTR modulators may improve outcomes in patients with COPD, although recent data regarding magnitude of benefit have been inconclusive and effects on mucociliary clearance are unknown. We conducted a phase 2, randomized, double blind placebo control trial to determine safety and tolerability, and explore the potential mechanism of ivacaftor for the treatment of COPD. We randomized 40 patients with moderate to severe COPD and symptoms of chronic bronchitis to ivacaftor (N=30) or placebo (N=10) 150mg BID for 12 weeks. Primary endpoints included evaluation of safety of ivacaftor and pharmacokinetics (PK). Secondary endpoints included measures of CFTR activity and clinical outcomes. Ivacaftor was safe and tolerable with similar rates of adverse events rates between groups. Most common adverse event was diarrhea in the ivacaftor group and acute COPD exacerbation in the placebo group. PK analysis found the mean area under the curve over 12 hours (AUC12) to be 72% of the previously reported AUC12 in cystic fibrosis (CF). Treatment with ivacaftor did not improve sweat chloride, whole lung mucociliary clearance, lung function or respiratory symptoms. Ivacaftor was safe and well tolerated, but did not improve measures of CFTR activity or mucus clearance. As serum concentrations achieved were lower than observed in CF at the same dose, and modulation of wild type CFTR differs from G551D, further dose determination studies are needed to better understand treatment efficacy of CFTR potentiators in COPD. Clinical trial registration available at www. gov, ID: NCT03085485.

Use of Sodium-glucose cotransporter 2 (SGLT 2) inhibitor is associated with reduced emergency room visits and hospitalizations in patients with Chronic obstructive pulmonary disease (COPD) and type 2 Diabetes Mellitus

BackgroundThe Sodium-Glucose Cotransporter 2 inhibitors (SGLT2i) are a class of anti-diabetic medications that confer cardio-renal-metabolic (CRM) benefits. Emerging evidence also suggests that these agents provide better benefits for chronic pulmonary conditions, especially chronic obstructive pulmonary disease (COPD). Research questionWe aimed to assess the association between SGLT2i use and outcomes in patients with COPD and concomitant Type 2 Diabetes Mellitus (T2DM). Study design and methodsWe conducted a retrospective cohort study on adults with T2DM and COPD in a primary care clinic from January 01, 2019 to 01/01//2023. Patients were categorized into two groups based on SGLT2i use. We collected demographic information and outcomes such as emergency room (ER) visits, hospitalizations secondary to COPD exacerbation over the period of four years and time to hospitalization and ER visits. Chi-square analysis was used for categorical variables, whereas an unpaired t-test was used for continuous variables. Cox regression was performed to identify significant prognostic factors of hospitalization and ER visits. A Kaplan-Meir analysis was used to visualize the probability of non-hospitalization and the probability of not visiting the ER. Statistical significance was set at p-value <0.05. ResultsOf the 220 patients screened, 94 met the inclusion criteria, of which 20 patients (21.3 %) had SGLT2i use at admission, and 74 (78.7 %) did not. Baseline demographic information were well-matched between the two groups. SGLT2i use was associated with a significant reduction in ER visits (70 % vs. 97.3 %, p-0.001) and the number of hospitalizations (55 % vs 87.8 %, p-0.001). Further multivariate analysis showed lower hazards of hospitalization (adjusted HR-0.156; CI:0.073 to 0.331) and ER visits (HR)-0.232; CI:0.118 to 0.453) in patients on SGLT2i. InterpretationIn patients with T2DM with COPD, SGLT2i use was associated with reduced ER visits and hospitalizations related to COPD. This protective effect of SGLT2i could be explained by reduced systemic proinflammatory markers and increased anti-inflammatory markers via inhibition of Node like receptor protein 3(NLRP3) inflammasome activation in multiple tissues, including the lungs.

Frequency of Asymptomatic Deep Vein Thrombosis in Hospitalized Patients With Acute Exacerbation of Chronic Obstructive Pulmonary Disease (COPD).

Acute exacerbations of chronic obstructive pulmonary disease (COPD) are always associated with high mortality. Because of the presence of some concomitant risk factors such as immobilization and bronchial superinfection, patients who are admitted for acute exacerbations of COPD are generally considered to be at moderate risk for the development of venous thromboembolism. Thromboembolism is a cause of unexplained dyspnea, exacerbations, and mortality in COPD. This study aims to determine the frequency of asymptomatic deep vein thrombosis (DVT) in patients with acute exacerbations of COPD presented at a tertiary care hospital. This is a descriptive cross-sectional study conducted at the Department of Chest Medicine, Jinnah Postgraduate Medical Center (JPMC), Karachi. A duplex ultrasound study of both lower limbs was performed by a sonologist to assess asymptomatic DVT in patients with acute exacerbations of COPD. The mean age of the sample was 59.64 ± 9.711 years. Out of 106 patients, 95 (90%) were male and 11 (10%) were female. Asymptomatic DVT was found in 16 (15%) patients with acute exacerbations of COPD. Male patients exhibited a higher incidence of DVT, with 12 cases versus four in females, a statistically significant finding (p=0.03). Additionally, DVT was significantly more prevalent among patients with restricted mobility, with all 16 cases occurring in this group (p=0.006). Age did not show a statistically significant difference in DVT occurrence between patients above and below 59 years. Deep venous thrombosis is a common occurrence in COPD exacerbations. It is a risk factor for pulmonary embolism that carries a high mortality. All patients with COPD exacerbations may need to be assessed for thromboembolic events. COPD morbidity and mortality are continually rising despite efforts to recognize new phenotypes and treatments. The cause may be the association of unrecognized and untreated thromboembolism. Prompt diagnosis and treatment with anticoagulants in COPD patients may lead to a better prognosis.

Predictive value of neutrophil-to-lymphocyte ratio for adverse outcomes in hospitalized patients with acute exacerbation of chronic obstructive pulmonary disease: A retrospective study.

Chronic obstructive pulmonary disease (COPD) stands as one of the leading causes of mortality worldwide. Acute exacerbations of COPD (AECOPD) lead to rapid respiratory function decline and worsened disease status. Despite recent studies, the ability of the neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in patients with COPD remains controversial. We investigated the predictive value of NLR for adverse outcomes in hospitalized patients with AECOPD. A retrospective study was conducted at the Department of Pulmonary Medicine, Cho Ray Hospital (Vietnam) from November 2019 to November 2021. The study extracted data from patients diagnosed with AECOPD at discharge and met the inclusion criteria. NLR is calculated by dividing the number of neutrophils by the number of lymphocytes in the peripheral blood test. Adverse outcomes are defined as invasive mechanical ventilation, admission to intensive care unit, or in-hospital mortality. Multivariable regression analysis was conducted to identify variables predicting adverse outcomes. The cutoff, sensitivity, specificity, area under the curve, and receiver operating characteristic of NLR were determined for predicting adverse outcomes. Two hundred eighty-seven patients with AECOPD were included in the final analysis, with a mean age of 70.9, and males comprising 92.7%. The rate of adverse outcomes was 15.7%. Multivariable logistic regression identified reduced consciousness at admission (adjusted odds ratio = 0.08, 95% confidence interval [CI]: 0.02-0.38, P = .001) and high NLR (adjusted odds ratio = 1.17, 95% CI: 1.10-1.24, P < .001) as predictors of adverse outcomes. The receiver operating characteristic of NLR's predictive value yielded an area under the curve of 0.877 (95% CI: 0.83-0.93). An NLR cutoff of 11.0 predicted adverse outcomes with a sensitivity of 80.0%, specificity of 77.7%, and an odds ratio of 13.9 (95% CI: 6.3-30.7), P < .001. NLR is a simple, routine, and cost-effective tool for predicting adverse outcomes in hospitalized patients with AECOPD. Future studies should evaluate the kinetics of NLR in predicting treatment response in patients with AECOPD.

Medication adherence to inhalation therapy and the risk of COPD exacerbations: a systematic review with meta-analysis

BackgroundAssessing medication adherence is crucial in chronic obstructive pulmonary disease (COPD) management to prevent exacerbations. However, it is unclear whether this association between adherence and exacerbations is influenced by the...

In-depth comparative pathogenome, virulome, and resistome analysis of an extensive drug resistant Ralstonia mannitolilytica strain isolated from blood

IntroductionRalstonia mannitolilytica is an global opportunistic pathogen responsible for various diseases. In this study, we reported the genome of a R. mannitolilytica isolate responsible for bacteremia in an acute exacerbation of chronic obstructive pulmonary disease (AECOPD). MethodsBacterial identification was performed with a Vitek2™ Automated System and 16S rRNA sequencing with BLASTn against the Non-Redundant Protein Sequence (Nr) database. Genome sequencing and analysis were performed using PacBio RS II sequencer, Hierarchical Genome Assembly Process assembly, as well as multiple annotation databases to better understand the innate features. Antibiotic resistance genes and virulence factors were specifically identified through Antibiotic Resistance Genes database and Virulence Factors of Pathogenic Bacteria databases. ResultsThe complete genome sequence was assembled into two chromosomes with 3,495,817 bp and 1,342,871 bp in length and GC% of 65.37 % and 66.43 %, respectively. The two chromosomes were fully annotated. In chromosome 1 and 2, 19 and 14 antibiotic resistant genes and 48 and 55 virulence factors were predicted, respectively. Specifically, beta-lactam resistance genes blaOXA-443, blaOXA-444 were acquired. ConclusionsThis study aids in the understanding of the innate features of R. mannitolilytica in AECOPD.

Evaluating the mucolytic effectiveness of Ambroxol and N-Acetylcysteine in patients with Acute exacerbation of chronic obstructive pulmonary disease

IntroductionChronic obstructive pulmonary disease (COPD) is the third most fatal disease globally. Acute deterioration of the patient's respiratory symptoms is known as an acute exacerbation of COPD (AECOPD), that goes beyond usual variations and result in change in medications. Ambroxol (ABX) and N-acetylcysteine (NAC), are mainly used as mucolytics in the treatment of AECOPD. MethodologyThis prospective observational study examines effectiveness of ABX and NAC in COPD patients by assessing the quality of cough relief, peak expiratory flow rate (PEFR), length of hospital stay, quality of life (QOL) and reduction in symptoms of COPD. Leicester Cough Questionnaire (LCQ); Breathlessness, Cough and Sputum scale (BCSS)and St. George Respiratory Questionnaire (SGRQ) scales are used to evaluate patient condition before and after the treatment. ResultsThe mean duration of hospital stay for NAC and ABX were found to be 8 ± 3.6 and 9.9 ± 3.9 days, respectively. Lung function in both groups improved with a change in percentage mean score of PEFR. Reduction in symptoms of COPD was evident in both groups by decrease in mean BCSS score from admission to discharge. Our study also demonstrated better QOL in both groups using SGRQ. LCQ showed a mean increase in all domains: physical, psychological and social. ConclusionIt was concluded that both ABX and NAC leads to betterment in lung function, cough relief and control AECOPD. Hence, this study gives a signal to clinicians about these treatment options along with standard therapy of COPD for a better therapeutic outcome.

Disparities in Discharge Support Provided to Patients Leaving 'Before Medically Advised' from Hospitalization for COPD Exacerbation.

Disparities in Discharge Support Provided to Patients Leaving 'Before Medically Advised' from Hospitalization for COPD Exacerbation.

Predictive value of diaphragm ultrasound for mechanical ventilation outcome in patients with acute exacerbation of chronic obstructive pulmonary disease.

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is often combined with respiratory failure, which increases the patient's morbidity and mortality. Diaphragm ultrasound (DUS) has developed rapidly in the field of critical care in recent years. Studies with DUS monitoring diaphragm-related rapid shallow breathing index have demonstrated important results in guiding intensive care unit patients out of the ventilator. Early prediction of the indications for withdrawal of non-invasive ventilator and early evaluation of patients to avoid or reduce disease progression are very important. To explore the predictive value of DUS indexes for non-invasive ventilation outcome in patients with AECOPD. Ninety-four patients with AECOPD who received mechanical ventilation in our hospital from January 2022 to December 2023 were retrospectively analyzed, and they were divided into a successful ventilation group (68 cases) and a failed ventilation group (26 cases) according to the outcome of ventilation. The clinical data of patients with successful and failed noninvasive ventilation were compared, and the independent predictors of noninvasive ventilation outcomes in AECOPD patients were identified by multivariate logistic regression analysis. There were no significant differences in gender, age, body mass index, complications, systolic pressure, heart rate, mean arterial pressure, respiratory rate, oxygen saturation, partial pressure of oxygen, oxygenation index, or time of inspiration between patients with successful and failed mechanical ventilation (P > 0.05). The patients with successful noninvasive ventilation had shorter hospital stays and lower partial pressure of carbon dioxide (PaCO2) than those with failed treatment, while potential of hydrogen (pH), diaphragm thickening fraction (DTF), diaphragm activity, and diaphragm movement time were significantly higher than those with failed treatment (P < 0.05). pH [odds ratio (OR) = 0.005, P < 0.05], PaCO2 (OR = 0.430, P < 0.05), and DTF (OR = 0.570, P < 0.05) were identified to be independent factors influencing the outcome of mechanical ventilation in AECOPD patients. The DUS index DTF can better predict the outcome of non-invasive ventilation in AECOPD patients.

Effect of High-Intensity vs Low-Intensity Noninvasive Positive Pressure Ventilation on the Need for Endotracheal Intubation in Patients With an Acute Exacerbation of Chronic Obstructive Pulmonary Disease

The effect of high-intensity noninvasive positive pressure ventilation (NPPV) on the need for endotracheal intubation in patients with an acute exacerbation of chronic obstructive pulmonary disease (COPD) is unknown. To determine whether the use of high-intensity NPPV vs low-intensity NPPV reduces the need for endotracheal intubation in patients with an acute exacerbation of COPD and hypercapnia. Randomized clinical trial conducted at 30 general respiratory non-intensive care unit wards of Chinese hospitals from January 3, 2019, to January 31, 2022; the last 90-day follow-up was on April 22, 2022. The included patients had an acute exacerbation of COPD and a Paco2 level greater than 45 mm Hg after receiving 6 hours of low-intensity NPPV. Patients were randomized 1:1 to receive high-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume 10 mL/kg to 15 mL/kg of predicted body weight (n = 147) or to continue receiving low-intensity NPPV with inspiratory positive airway pressure that was adjusted to obtain a tidal volume of 6 mL/kg to 10 mL/kg of predicted body weight (n = 153). Patients in the low-intensity NPPV group who met the prespecified criteria for the need for endotracheal intubation were allowed to crossover to high-intensity NPPV. The primary outcome was the need for endotracheal intubation during hospitalization, which was defined by prespecified criteria. There were 15 prespecified secondary outcomes, including endotracheal intubation. The trial was terminated by the data and safety monitoring board and the trial steering committee after an interim analysis of the first 300 patients. Among the 300 patients who completed the trial (mean age, 73 years [SD, 10 years]; 68% were men), all were included in the analysis. The primary outcome of meeting prespecified criteria for the need for endotracheal intubation occurred in 7 of 147 patients (4.8%) in the high-intensity NPPV group vs 21 of 153 (13.7%) in the low-intensity NPPV group (absolute difference, -9.0% [95% CI, -15.4% to -2.5%], 1-sided P = .004). However, rates of endotracheal intubation did not significantly differ between groups (3.4% [5/147] in the high-intensity NPPV group vs 3.9% [6/153] in the low-intensity NPPV group; absolute difference, -0.5% [95% CI, -4.8% to 3.7%], P = .81). Abdominal distension occurred more frequently in the high-intensity NPPV group (37.4% [55/147]) compared with the low-intensity NPPV group (25.5% [39/153]). Patients with COPD and persistent hypercapnia in the high-intensity NPPV group (vs patients in the low-intensity NPPV group) were significantly less likely to meet criteria for the need for endotracheal intubation; however, patients in the low-intensity NPPV group were allowed to crossover to high-intensity NPPV, and the between-group rate of endotracheal intubation was not significantly different. ClinicalTrials.gov Identifier: NCT02985918.

Guidelines for peri-discharge management and follow-up of acute exacerbations of chronic obstructive pulmonary disease(2024 edition)

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are important events in the course of COPD, and its diagnosis, treatment and prevention are the focus of disease management. Optimizing the peri-discharge management of AECOPD will help improve care continuity, prevent recurrence of acute events in short time, and improve long-term prognosis. In recent years, the evidence on the peri-discharge period and the cluster management of AECOPD has been accumulating, and the benefit of early follow-up and management after discharge has been confirmed. By reviewing available evidence, this guideline aims to standardize discharge management and follow-up pathways for AECOPD patients. This guideline applies to physicians and nursing staff involved in the clinical practice of COPD.

Prevalence of and factors associated with cognitive frailty in elderly patients with chronic obstructive pulmonary disease: A cross-sectional study.

The status of cognitive frailty in elderly patients with chronic obstructive pulmonary disease (COPD) and its influencing factors in China remains unclear. This study aimed to investigate the prevalence of and factors associated with cognitive frailty in elderly patients with COPD. This cross-sectional study enrolled elderly patients with stable COPD between May and November 2022 from the Respiratory Department of the First Affiliated Hospital of Zhengzhou University and the Fifth Affiliated Hospital of Zhengzhou University. Convenience sampling method was adopted. Frailty Phenotype scale, Montreal Cognitive Assessment scale, Geriatric Depression Scale, and Clinical Dementia Rating scale were used to assess the prevalence of cognitive frailty in elderly patients with COPD. Multivariable logistic regression analysis was used to explore the associated factors. A total of 406 valid questionnaires were collected, and 173 patients (35.6%) had cognitive frailty. Binary logistic regression analysis showed that sex (odds ratio [OR] = 0.009; 95%CI: 0.001-0.770; P = .038), depression (OR = 17.780; 95%CI: 1.092-289.478; P = .043), modified Medical Research Council grade 1-3 (OR = 28.394-4095.683; 95%CI: 1.086-4,592,652.211; P < .05), global initiative for chronic obstructive lung disease grade 2 and 3 (OR = 32.508-282.072; 95%CI: 1.101-12,516.874; P < .05), and frequencies of acute exacerbations of COPD and hospitalizations within 1 year of 2 times (OR = 21.907; 95%CI: 4.587-104.622; P < .001) were independently associated with cognitive frailty. The prevalence of cognitive frailty in elderly patients with stable COPD was high. Female, depression, modified Medical Research Council grade, global initiative for chronic obstructive lung disease grade, and frequencies of acute exacerbations of COPD and hospitalizations within 1 year might be the factors independently associated with cognitive frailty, educational level might be a protective associated factor for cognitive frailty.

Trends in COPD severe exacerbations, and all-cause and respiratory mortality, before and after implementation of newer long-acting bronchodilators in a large population-based cohort

BackgroundLittle is known about the trends in morbidity and mortality at the population level that followed the introduction of newer once-daily long-acting bronchodilators for COPD. The purpose of the study was to evaluate whether the availability of new bronchodilators was associated with changes in the temporal trends in severe COPD exacerbations and mortality between 2007 and 2018 in the older population with COPD; and whether this association was homogeneous across sex and socioeconomic status classes.MethodsWe used an interrupted time-series and three segments multivariate autoregressive models to evaluate the adjusted changes in slopes (i.e., trend effect) in monthly severe exacerbation and mortality rates after 03/2013 and 02/2015 compared to the tiotropium period (04/2007 to 02/2013). Cohorts of individuals > 65 years with COPD were created from the nationally representative database of the Quebec Integrated Chronic Disease Surveillance System in the province of Quebec, Canada. Whether these trends were similar for men and women and across different socioeconomic status classes was also assessed.ResultsThere were 130,750 hospitalizations for severe exacerbation and 104,460 deaths, including 24,457 (23.4%) respiratory-related deaths, over the study period (928,934 person-years). Significant changes in trends were seen after 03/2013 for all-cause mortality (-1.14%/month;95%CI -1.90% to -0.38%), which further decreased after 02/2015 (-1.78%/month;95%CI -2.70% to -0.38%). Decreases in respiratory-related mortality (-2.45%/month;95%CI -4.38% to -0.47%) and severe exacerbation (-1,90%/month;95%CI -3.04% to -0.75%) rates were only observed after 02/2015. These observations tended to be more pronounced in women than in men and in higher socioeconomic status groups (less deprived) than in lower socioeconomic status groups (more deprived).ConclusionsThe arrival of newer bronchodilators was chronologically associated with reduced trends in severe exacerbation, all-cause and respiratory-related mortality rates among people with COPD > 65 years. Our findings document population benefits on key patient-relevant outcomes in the years following the introduction of newer once-daily long-acting bronchodilators and their combinations, which were likely multifactorial. Public health efforts should focus on closing the gap between lower and higher socioeconomic status groups.

Peculiarities of granulocyte-macrophage and macrophage colony-stimulating factors receptors expression in subpopulations of peripheral blood monocytes of patients with chronic obstructive pulmonary disease

Introduction. To analyze of the severity of respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD), depending on the presence of an exacerbation or novel coronavirus infection (NCVI), taking into account the activity of acute phase blood parameters.Materials and methods. The medical documentation of 162 patients with COPD was studied, which were divided into 3 groups: group 1 (n=61) ‒ COPD and NCVI, group 2 (n=53) – stable COPD, group 3 (n=48) ‒ COPD exacerbation. The severity of respiratory symptoms was assessed using points. To assess the activity of inflammation the following biochemical indicators were used ‒ C-reactive protein (CRP) and fibrinogen (g/L).Results. According to the severity of cough and the intensity of dyspnea on the mMRC scale, the first, second and third groups did not differ statistically (p=0.07). Patients of the first group (82.5%) characterized by the absence of classical criteria for exacerbation of COPD. In terms of the severity of sputum production, the first, second and third groups are statistically different (p=0.0001). The first, second and third groups differ significantly in the level of serum CRP (p=0.0001) and fibrinogen (p=0.009). According to the results of the correlation analysis, some relationships found between respiratory symptoms and the level of CRP and fibrinogen.Conclusion. The clinical feature of the associated course of stable COPD and NCVI is the presence of severe dyspnea and the absence of classic criteria for exacerbation of COPD. Systemic inflammation in NCVI and stable COPD are more pronounced than in isolated stable COPD or exacerbation and correlates with cough and dyspnea. Practitioners for the differential diagnosis of NCVI in stable COPD can use the data obtained.

Development, evaluation and comparison of machine learning algorithms for predicting in-hospital patient charges for congestive heart failure exacerbations, chronic obstructive pulmonary disease exacerbations and diabetic ketoacidosis

BackgroundHospitalizations for exacerbations of congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD) and diabetic ketoacidosis (DKA) are costly in the United States. The purpose of this study was to predict in-hospital charges for each condition using machine learning (ML) models.ResultsWe conducted a retrospective cohort study on national discharge records of hospitalized adult patients from January 1st, 2016, to December 31st, 2019. We constructed six ML models (linear regression, ridge regression, support vector machine, random forest, gradient boosting and extreme gradient boosting) to predict total in-hospital cost for admission for each condition. Our models had good predictive performance, with testing R-squared values of 0.701-0.750 (mean of 0.713) for CHF; 0.694-0.724 (mean 0.709) for COPD; and 0.615-0.729 (mean 0.694) for DKA. We identified important key features driving costs, including patient age, length of stay, number of procedures, and elective/nonelective admission.ConclusionsML methods may be used to accurately predict costs and identify drivers of high cost for COPD exacerbations, CHF exacerbations and DKA. Overall, our findings may inform future studies that seek to decrease the underlying high patient costs for these conditions.

Imaging and Biomarkers: The Assesment of Pulmonary Embolism Risk and Early Mortality.

Background and Objectives: Pulmonary embolism (PE) incidence has been increasing in the last 10 years. Computed thoracic pulmonary angiography (CTPA) had a major role in PE diagnosis and prognosis. The main purpose of this study was as follows: the prognostic value of a CTPA parameter, pulmonary artery obstruction index (PAOI), in PE risk assessment and the predictive accuracy of biomarkers, D-dimer and cardiac Troponin T (c-TnT), in 7-day mortality. A second objective of the research was to investigate the relationship between imaging by PAOI and these biomarkers in different etiologies of PE. Materials and Methods: This study comprised 109 patients with PE, hospitalized and treated between February 2021 and August 2022. They had different etiologies of PE: deep vein thrombosis (DVT); persistent atrial fibrillation (AF); chronic obstructive pulmonary disease (COPD) exacerbation; COVID-19; and cancers. The investigations were as follows: clinical examination; D-dimer testing, as a mandatory method for PE suspicion (values ≥500 µg/L were highly suggestive for PE); c-TnT, as a marker of myocardial injury (values ≥14 ng/L were abnormal); CTPA, with right ventricle dysfunction (RVD) signs and PAOI. Treatments were according to PE risk: systemic thrombolysis in high-risk PE; low weight molecular heparins (LWMH) in high-risk PE, after systemic thrombolysis or from the beginning, when systemic thrombolysis was contraindicated; and direct oral anticoagulants (DOAC) in low- and intermediate-risk PE. Results: PAOI had a high predictive accuracy for high-risk PE (area under curve, AUC = 0.993). D-dimer and cTnT had a statistically significant relationship with 7-day mortality for the entire sample, p < 0.001, and for AF, p = 0.0036; COVID-19, p = 0.003; and cancer patients, p = 0.005. PAOI had statistical significance for 7-day mortality only in COVID-19, p = 0.045, and cancer patients, p = 0.038. The relationship PAOI-D-dimer and PAOI-c-TnT had very strong statistical correlation for the entire sample and for DVT, AF, COPD, and COVID-19 subgroups (Rho = 0.815-0.982). Conclusions: PAOI was an important tool for PE risk assessment. D-dimer and c-TnT were valuable predictors for 7-day mortality in PE. PAOI (imaging parameter for PE extent) and D-dimer (biomarker for PE severity) as well as PAOI and c-TnT (biomarker for myocardial injury) were strongly correlated for the entire PE sample and for DVT, AF, COPD, and COVID-19 patients.

Safety, Efficacy, and Feasibility of Nebulized Long-Acting Bronchodilators vs Short-Acting Bronchodilators in Hospitalized Patients With Acute Exacerbations of COPD: A Phase IV, Randomized, Parallel-Group Clinical Trial

BackgroundLong-acting bronchodilators are preferred over short-acting bronchodilators in patients with stable COPD, but prospective studies are needed to determine the safety and efficacy of nebulized long-acting bronchodilators in hospitalized patients with exacerbations of COPD (ECOPD). MethodsWe conducted a prospective, randomized, parallel-group study comparing a nebulized formoterol/revefenacin combination with an albuterol/ipratropium combination among n = 60 hospitalized patients (n = 30 in each group) with ECOPD who tested negative for COVID-19. Treatments were administered q12 to 24 hrs (formoterol/revefenacin), or q6 hrs (albuterol/ipratropium) by jet nebulizers for up to 7 days. Safety and efficacy assessments were recorded on days 1, 3, and 7, or at hospital discharge. Assessment of dyspnea by the Modified Borg dyspnea scale was the primary outcome. Data were analyzed with parametric or non-parametric statistical tests, and generalized estimating equations with an identity link function were used to analyze differences in the two groups. Statistical significance was assumed at an unadjusted two-sided alpha value of 0.05. ResultsParticipants’ mean age was 63.2 (SD 9.30) years, and 39 (65.0%) were current smokers. Patients' age, sex, race, smoking history, body mass index, Charlson Comorbidity Index, supplemental oxygen requirements, and length of hospital stay were similar in the two groups (p>0.05 for all). Patients receiving formoterol/revefenacin had similar Modified Borg dyspnea scores (p = 0.95) and required fewer total drug doses (P<0.001), but there was a non-significant trend for more frequent rescue treatments (p=0.08) compared to those receiving albuterol/ipratropium. There were no serious adverse events or treatment failures in either group. ConclusionIn non-ventilated hospitalized patients with ECOPD, the institution of nebulized formoterol/revefenacin in combination within 24 to 36 hours of hospital admission provided convenient dosing and required fewer drug doses to achieve comparable efficacy and safety with the standard short-acting nebulized albuterol/ipratropium combination.

Prediction Model of In-Hospital Death for Acute Exacerbation of Chronic Obstructive Pulmonary Disease Patients Admitted to Intensive Care Unit: The PD-ICU Score

Introduction: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care unit (ICU) are exposed to poor clinical outcomes, and no specific prognostic models are available among this population. We aimed to develop and validate a risk score for prognosis prediction for these patients. Methods: This was a multicenter observation study. AECOPD patients admitted to ICU were included for model derivation from a prospective, multicenter cohort study. Logistic regression analysis was applied to identify independent predictors for in-hospital death and establish the prognostic risk score. The risk score was further validated and compared with DECAF, BAP-65, CURB-65, and APACHE II score in another multicenter cohort. Results: Five variables were identified as independent predictors for in-hospital death in APCOPD patients admitted to ICU, and a corresponding risk score (PD-ICU score) was established, which was composed of procalcitonin >0.5 μg/L, diastolic blood pressure <60 mm Hg, need for invasive mechanical ventilation, disturbance of consciousness, and blood urea nitrogen >7.2 mmol/L. Patients were classified into three risk categories according to the PD-ICU score. The in-hospital mortality of low-risk, intermediate-risk, and high-risk patients was 0.3%, 7.3%, and 27.9%, respectively. PD-ICU score displayed excellent discrimination ability with an area under the receiver-operating characteristic curve (AUC) of 0.815 in the derivation cohort and 0.754 in the validation cohort which outperformed other prognostic models. Conclusion: We derived and validated a simple and clinician-friendly prediction model (PD-ICU score) for in-hospital mortality among AECOPD patients admitted to ICU. With good performance and clinical practicability, this model may facilitate early risk stratification and optimal decision-making among these patients.

Methodology for the selection and evaluation of outcomes for Chinese herbal injection in acute exacerbation of chronic obstructive pulmonary disease (AECOPD): a comprehensive study

Objective To develop a comprehensive framework for selecting outcomes in evaluating the clinical efficacy of Chinese herbal injections and to scientifically select outcomes for the clinical randomized controlled trial (RCT) of Tan-Re-Qing injection intervening AECOPD. Methods A comprehensive literature review and consensus methods, including focus groups and Delphi surveys, were utilized. Results Literature analysis identified 513 publications, encompassing regulatory guidance, guidelines, expert consensus, and RCTs. Initial dimensions include clinical efficacy, safety, and health economics. Primary outcomes should align with study objectives. Recommended evaluation domains include death, treatment outcome, future impact, quality of life, and safety. Commonly recommended outcomes comprise mortality, arterial blood gases, CAT, exacerbation frequency, adverse events, and lung function. Network meta-analysis identified specific therapeutic efficacy markers (white blood cell count, IL-6, IL-8). Quality of life assessment recommended SF-12, EQ-5D, or CAT. Emphasis on AECOPD frequency and lung function was noted. Delphi survey yielded 41 outcomes across various domains for evaluating Tan-Re-Qing in AECOPD. Conclusion The findings contribute to developing a robust and reliable trial design for Tan-Re-Qing injection in AECOPD. The methodology employed in this study ensures a systematic and comprehensive approach to the selection of outcomes for the clinical evaluation of future studies in this field.

Bacterial Profiles and Antibiotic Resistance in Chronic Obstructive Pulmonary Disease Patients with Exacerbation and Type 2 Respiratory Failure at Adam Malik General Hospital

Highlights:1. This study provides a comprehensive analysis of various factors such as age, sex, education, occupation, BMI, and comorbidities, and their relationship with bacterial infections in COPD patients experiencing exacerbation and type 2 respiratory failure.2. While the COPD patients experiencing exacerbation did not exhibit resistance to linezolid and vancomycin, they demonstrated specific antibiotic resistance patterns characterized by high resistance rates to commonly used antibiotics such as meropenem and amikacin.3. The findings enhance the understanding of the complex interplay of factors influencing infection patterns in this patient population. Abstract Chronic obstructive pulmonary disease (COPD) is a prevalent condition characterized by persistent respiratory symptoms and airflow limitation. Bacterial infections may trigger COPD exacerbations, leading to more severe symptoms as well as increased morbidity and mortality rates. This study aimed to investigate the bacterial profiles and antibiotic resistance in COPD patients who had experienced exacerbation and type 2 respiratory failure at Adam Malik Central General Hospital, Medan, Indonesia. This retrospective study utilized medical records spanning from January 1, 2020, to December 1, 2022. The sample included patients aged 40–90 years who had experienced COPD exacerbation and type 2 respiratory failure. The exclusion criteria were patients who had received antibiotic therapy within 48 hours before admission, were severely immunocompromised, and had severe malignancy. The analysis results were presented in the form of means, standard deviations, and frequency distributions. Additionally, an analysis of the relationship between the categorical variables was performed using the Chi-squared test (p&lt;0.05). The study analyzed 25 subjects with an average age of 63.6 years, primarily consisting of men (84%). It was shown that severe exacerbations were prevalent (92%), accompanied by the presence of common comorbidities including pneumonia (52%), diabetes mellitus (32%), and other non-communicable diseases (44%). Bacterial growth was observed in 76% of the subjects, predominantly involving Gram-negative bacteria (89.4%). Klebsiella pneumoniae (26.3%) and Pseudomonas aeruginosa (21.1%) were the most frequently isolated species. The antibiotic resistance patterns indicated that meropenem and amikacin had the highest resistance rates (100%). Cefepime, ertapenem, and gentamicin exhibited notable resistance rates of 66.7%, 66.7%, and 75.0%, respectively. This study highlights the high prevalence of Gram-negative bacteria and significant antibiotic resistance in COPD patients who exhibit exacerbation and type 2 respiratory failure.