Search

RATIONALE: Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. OBJECTIVE: Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. METHODS: We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). RESULTS: Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohens Kappa = 0.47 ± 0.07; P

• The incidence of COPD exacerbation was lower in patients on SGLT2i medication. • Any hospitalization post-COPD exacerbation was significantly lower in the SGLT-2i group. • There was a non-significant trend for lower ICU admissions and intubations in participants with SGLT-2i. Sodium Glucose Transporter 2 inhibitor (SGLT-2i) medications reduce inflammation, improve glycemic control, and impart weight loss, all of which may play a role in chronic obstructive pulmonary disease (COPD) pathophysiology. The primary objective of our study was to explore the incidence of COPD exacerbation in patients with diabetes and COPD on SGLT-2i medications. The secondary objective was to assess the impact of SGLT-2i medications on COPD exacerbations needing hospitalization, ICU admission, and mechanical ventilation. This was a retrospective cohort analysis of COPD patients with diabetes enrolled in the COPD registry at a Mid-west Tertiary care teaching hospital from January 1, 2022, to December 31, 2022. We used Slicer-Dicer, a self-service cohort exploration tool embedded in EPIC for data extraction. We had 31,411 patients registered with the COPD registry during the study period. Of these, 18,713 had diabetes, and 1295 patients were on SGLT-2i medication. The incidence of COPD exacerbation, including severe COPD exacerbation needing hospitalization, was significantly lower in the SGLT-2i medication group (3.16% vs 18.3%, p < 0.05; 1.2% vs 5.04%, p < 0.05). Also, there was a non-significant trend suggesting that the incidence of COPD exacerbation needing intensive care unit admission and intubation was lower in the SGLT-2i medication group (0.07% vs 3.4%; 0 vs 0.04%). SGLT-2i medication use was associated with reduced incidence of COPD exacerbation irrespective of underlying control of diabetes. Our study suggests possible role of SGLT-2i in preventing COPD exacerbation. Randomized trials are needed in the future to confirm or refute these findings. [ABSTRACT FROM AUTHOR]

Point of Care ultrasound (POCUS) of the lungs, also known as lung ultrasound (LUS), has emerged as a technique that allows for the diagnosis of many respiratory pathologies with greater accuracy and speed compared to conventional techniques such as chest x-ray and auscultation. The goal of this narrative review is to provide a simple and practical approach to LUS for critical care, pulmonary, and anesthesia providers, as well as respiratory therapists and other health care providers to be able to implement this technique into their clinical practice. In this review, we will discuss the basic physics of LUS, provide a hands-on scanning technique, describe LUS findings seen in normal and pathological conditions (such as mainstem intubation, pneumothorax, atelectasis, pneumonia, aspiration, COPD exacerbation, cardiogenic pulmonary edema, ARDS, and pleural effusion) and also review the training necessary to achieve competence in LUS. [ABSTRACT FROM AUTHOR]

BACKGROUND: The ratio of oxygen saturation index (ROX index; or .../.../breathing frequency) has been shown to predict risk of intubation after high-flow nasal cannula (HFNC) support among adults with acute hypoxemic respiratory failure primarily due to pneumonia. However, its predictive value for other subtypes of respiratory failure is unknown. This study investigated whether the ROX index predicts liberation from HFNC or noninvasive ventilation (NIV), intubation with mechanical ventilation, or death in adults admitted for respiratory failure due to an exacerbation of COPD. METHODS: We performed a retrospective study of 260 adults hospitalized with a COPD exacerbation and treated with HFNC and/or NIV (continuous or bi-level). ROX index scores were collected at treatment initiation and predefined time intervals throughout HFNC and/or NIV treatment or until the subject was intubated or died. A ROX index score of ≥ 4.88 was applied to the cohort to determine if the same score would perform similarly in this different cohort. Accuracy of the ROX index was determined by calculating the area under the receiver operator curve. RESULTS: A total of 47 subjects (18%) required invasive mechanical ventilation or died while on HFNC/NIV. The ROX index at treatment initiation, 1 h, and 6 h demonstrated the best prediction accuracy for avoidance of invasive mechanical ventilation or death (area under the receiver operator curve 0.73 [95% CI 0.66-0.80], 0.72 [95% CI 0.65-0.79], and 0.72 [95% CI 0.63-0.82], respectively). The optimal cutoff value for sensitivity (Sn) and specificity (Sp) was a ROX index score > 6.88 (sensitivity 62%, specificity 57%). CONCLUSIONS: The ROX index applied to adults with COPD exacerbations treated with HFNC and/or NIV required higher scores to achieve similar prediction of low risk of treatment failure when compared to subjects with hypoxemic respiratory failure/pneumonia. ROX scores < 4.88 did not accurately predict intubation or death. [ABSTRACT FROM AUTHOR]

Abstract Rationale Research studies typically quantify acute respiratory exacerbation episodes (AECOPD) among people with chronic obstructive pulmonary disease (COPD) based on self-report elicited by survey questionnaire. However, AECOPD quantification by self-report could be inaccurate, potentially rendering it an imprecise tool for identification of those with exacerbation tendency. Objective Determine the agreement between self-reported and health records-documented quantification of AECOPD and their association with airway inflammation. Methods We administered a questionnaire to elicit the incidence and severity of respiratory exacerbations in the three years preceding the survey among current or former heavy smokers with or without diagnosis of COPD. We then examined electronic health records (EHR) of those with COPD and those without (tobacco-exposed persons with preserved spirometry or TEPS) to determine whether the documentation of the three-year incidence of moderate to very severe respiratory exacerbations was consistent with self-report using Kappa Interrater statistic. A subgroup of participants also underwent bronchoalveolar lavage (BAL) to quantify their airway inflammatory cells. We further used multivariable regressions analysis to estimate the association between respiratory exacerbations and BAL inflammatory cell composition with adjustment for covariates including age, sex, height, weight, smoking status (current versus former) and burden (pack-years). Results Overall, a total of 511 participants completed the questionnaire, from whom 487 had EHR available for review. Among the 222 participants with COPD (70 ± 7 years-old; 96% male; 70 ± 38 pack-years smoking; 42% current smoking), 57 (26%) reported having any moderate to very severe AECOPD (m/s-AECOPD) while 66 (30%) had EHR documentation of m/s-AECOPD. However, 42% of those with EHR-identified m/s-AECOPD had none by self-report, and 33% of those who reported m/s-AECOPD had none by EHR, suggesting only moderate agreement (Cohen’s Kappa = 0.47 ± 0.07; P

Fernando J Martinez,1 Alberto Papi,2 Tobias Welte3,4 ,† Dave Singh,5 Dmitry V Galkin,6 Alessandro Guasconi,7 Stefania Pirondi,7 George Georges,7 Joseph Imperato,8 Ruben Hermans9 1Weill Cornell Medicine, New York–Presbyterian Hospital, New York, NY, USA; 2Research Center on Asthma and COPD, Department of Medical Sciences, University of Ferrara, Ferrara, Italy; 3Pneumonology and Infectiology, Member of the German Center of Lung Research, Hannover Medical School, Hannover, Germany; 4Biomedical Research in End Stage and Obstructive Lung Disease, German Center for Lung Research, Hannover Medical School, Hannover, Germany; 5Medicines Evaluations Unit, University of Manchester, Manchester University Foundation Hospitals Trust, Manchester, UK; 6Global Clinical Development, Chiesi USA, Cary, NC, USA; 7Global Clinical Development, Chiesi Farmaceutici, S.p.A, Parma, Italy; 8Medical Affairs, IQVIA Inc, New York, NY, USA; 9Medical Affairs, IQVIA Inc, London, UK†Prof. Tobias We 50% in 2020 compared with 2019. The proportions of patients with an exacerbation increased in most countries in 2021. Across each country, seasonal exacerbation increases seen during autumn and winter in pre-pandemic years were absent during the first year of the pandemic. The percentage of patients filling COPD prescriptions across each country increased by 4.53– 22.13% in 2019 to 9.94– 34.17% in 2021.Conclusion: Early, steep declines in exacerbation rates occurred in 2020 versus 2019 across all five countries and were accompanied by a loss of the seasonal pattern of exacerbation.Keywords: COPD exacerbation, chronic obstructive pulmonary disease, COVID-19, electronic health records, real-world study

Abstract While studies have suggested increased risks of severe COVID-19 infection in chronic obstructive pulmonary disease (COPD), the persistent and delayed consequences of COVID-19 infection on patients with COPD upon recovery remain unknown. A prospective clinical study was conducted in Hong Kong to investigate the persistent and delayed outcomes of patients with COPD who had COVID-19 infection of different severity (mild-moderate COVID-19 and severe COVID-19), compared with those who did not. Chinese patients with COPD ≥ 40 years old were recruited from March to September 2021. They were prospectively followed up for 24.9 ± 5.0 months until 31st August 2023. The primary outcome was the deterioration in COPD control defined as the change in mMRC dyspnea scale. The secondary outcomes included the change in exacerbation frequency and non-COVID-19 respiratory mortality (including death from COPD exacerbation or bacterial pneumonia). 328 patients were included in the analysis. Patients with mild-moderate and severe COVID-19 infection had statistically significant increased risks of worsening of mMRC dyspnoea scale by increase in 1 score from baseline to follow-up with adjusted odds ratios of 4.44 (95% CI = 1.95–10.15, p

To test the hypothesis that they serve as systemic biomarkers of chronic obstructive pulmonary disease (COPD), we profiled the mRNA expression of enzymes connected to systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs). These were taken from patients displaying acute exacerbation of COPD (AE-COPD) and stable COPD, and also from non-obstructive smokers and non-smokers. The expression of poly(ADP-ribose) polymerase-1 was increased, but that of histone deacetylase 2 was decreased in association with AE-COPD. The expression of modulatory subunit of glutamyl–cysteine ligase was higher and that of its catalytic subunit, together with the expression of dipeptidyl peptidase 4, was lower in COPD patients compared with non-obstructive smokers and non-smokers. Leukotriene A4 hydrolase saw increased expression in patients with COPD according to disease severity compared to non-obstructive individuals, whereas the expression of GSH peroxidase increased in non-obstructive smokers and COPD patients with the growing number of pack-years smoked. The results corroborate COPD and its acute exacerbation as a complex systemic disorder demonstrating distinct associations with the expression of enzymes linked to inflammation and the regulation of GSH metabolism. [ABSTRACT FROM AUTHOR]

COPD is a common and lethal chronic condition, recognized as a leading cause of death worldwide. COPD is associated with significant morbidity and disability, particularly among older adults. The disease course is marked by periods of stability and disease exacerbations defined by worsening respiratory status resulting in a high burden of health care utilization and an increased risk of mortality. Treatment is focused on pharmacologic therapies, but these are not completely effective. Pulmonary rehabilitation (PR) represents a key medical intervention for patients with chronic respiratory diseases, including COPD. PR provides individualized and progressive exercise training, education, and self-management strategies through a comprehensive and multidisciplinary program. PR has been associated with improvement in exercise capacity, health-related quality of life, and dyspnea in patients living with COPD. Moreover, PR has been associated with improvements in hospital readmission and 1-y survival. In addition to the clinical benefits, PR is estimated to be a cost-effective medical intervention. Despite these benefits, participation in PR remains low. We will review the evidence for PR in each of these benefit domains among patients with stable COPD and in those recovering from a COPD exacerbation. [ABSTRACT FROM AUTHOR]

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPDs) are associated with a significant disease burden. Blood immune phenotyping may improve our understanding of a COPD endotype at increased risk of exacerbations. Objective: To determine the relationship between the transcriptome of circulating leukocytes and COPD exacerbations. Methods: Blood RNA sequencing data (n = 3,618) from the COPDGene (Genetic Epidemiology of COPD) study were analyzed. Blood microarray data (n = 646) from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study were used for validation. We tested the association between blood gene expression and AE-COPDs. We imputed the abundance of leukocyte subtypes and tested their association with prospective AE-COPDs. Flow cytometry was performed on blood in SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study) (n = 127), and activation markers for T cells were tested for association with prospective AE-COPDs. Measurements and Main Results: Exacerbations were reported 4,030 and 2,368 times during follow-up in COPDGene (5.3 ± 1.7 yr) and ECLIPSE (3 yr), respectively. We identified 890, 675, and 3,217 genes associated with a history of AE-COPDs, persistent exacerbations (at least one exacerbation per year), and prospective exacerbation rate, respectively. In COPDGene, the number of prospective exacerbations in patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage ⩾2) was negatively associated with circulating CD8+ T cells, CD4+ T cells, and resting natural killer cells. The negative association with naive CD4+ T cells was replicated in ECLIPSE. In the flow-cytometry study, an increase in CTLA4 on CD4+ T cells was positively associated with AE-COPDs. Conclusions: Individuals with COPD with lower circulating lymphocyte counts, particularly decreased CD4+ T cells, are more susceptible to AE-COPDs, including persistent exacerbations.

This article is an editorial published in Frontiers in Immunology titled "The chemokine system in epithelial immunity." The editorial discusses the role of chemokines in epithelial immunity in various contexts, including healthy, infected, or inflamed tissues. It highlights specific research topics such as the influence of cytokines on lung microenvironment during COPD exacerbations, the potential therapeutic use of a glycosaminoglycan-binding chemokine fragment in managing severe pulmonary viral infections, the stabilization of the chemokine SDF-1/ CXCL12 using a macromolecular compound for enhanced wound healing, and the involvement of chemokines in lymphocyte homing in Sjögren's syndrome. The article emphasizes the importance of understanding chemokine signaling pathways for developing targeted therapies and improving treatment outcomes in various diseases. [Extracted from the article]

Abstract Chronic obstructive pulmonary disease (COPD) has a high prevalence and a major impact on health-related quality of life (HRQL). COPD exacerbations are an important cause of morbidity and mortality, affecting cardiovascular risk, and are associated with poorer health status. The aim of this study was to assess the association between cardiovascular risk (CVR) and HRQL, according to exacerbator or non-exacerbator phenotype. We undertook a cross-sectional, observational, descriptive study of 107 patients with COPD. Patients with two or more moderate exacerbations or one severe exacerbation in the previous year were considered as exacerbators. The CVR was calculated with the Framingham scale and SCORE (Systematic Coronary Risk Evaluation) and the HRQL was assessed with the generic questionnaire Short Form-36 Health Survey (SF-36), the St George Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT). Statistical analysis was done with SPSS version 26.0 for Windows. The SF-36 and the SGRQ showed lower values for the exacerbator phenotype, indicating a poorer quality of life. The CAT questionnaire showed values above 10 for the exacerbator phenotype, and lower values in the non-exacerbator group. After categorizing the sample according to their median age (65 years), we found a greater deterioration in HRQL in patients under 65 years of age according to the SF-36, the SGRQ and the CAT. We also detected differences in HRQL between non-exacerbator patients with a high CVR according to the Framingham (≥ 20%) and SCORE (≥ 5%) scales compared to those without this risk. A tendency towards worse HRQL was observed in non-exacerbator patients with a high CVR, which was statistically significant for the SGRQ impact domain on the SCORE scale. The CAT also showed a worse quality of life in non-exacerbator patients with a high CVR, which was significant in the Framingham model (Framingham high risk 8.41 vs non-high risk 6.05, p

Mengjiao Yang,1,2,&ast; Yang Liu,1,&ast; Yangyang Zhao,3,&ast; Ziwei Wang,4 Jie He,5 Yali Wang,2 Tokie Anme6 1Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan; 2Department of Cardiovascular Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan Province, People’s Republic of China; 3Department of Blood Transfusion, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan Province, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan Province, People’s Republic of China; 5Department of Nursing, Affiliated Hospital of North Sichuan Medical College, Nanchong City, Sichuan Province, People’s Republic of China; 6Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan&ast;These authors contributed equally to this workCorrespondence: Tokie Anme, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 3058577, Japan, Tel\Fax +81-29-853-3436, Email tokieanme@gmail.comPurpose: This study aimed to explore the correlation of frailty status with disease characteristics and patient-reported outcomes (PROs) in patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and determine the sensitivity and specificity of modified COPD PRO scale (mCOPD-PRO) for detecting frailty.Patients and Methods: This cross-sectional study surveyed 315 inpatients with AECOPD from a tertiary hospital in China from August 2022 to June 2023. Patient frailty and PROs were assessed using the validated FRAIL scale and mCOPD-PRO, respectively. Spearman’s ρ was used to assess the relevance of lung disease indicators commonly used in clinical practice, and ordinal logistic regression analyses were used to identify the variables associated with frailty status. The validity of mCOPD-PRO in discriminating frail or non-frail individuals was determined using the receiver operating characteristic curve.Results: The participants (N=302, mean age 72.4± 9.1 years) were predominantly males (73.2%). Among them, 43 (14.3%) patients were not frail, whereas 123 (40.7%) and 136 (45.0%) patients were pre-frail and frail, respectively. The FRAIL scale was moderately correlated with the mCOPD-PRO scores (Spearman’s rank correlation coefficient [Rs]=0.52, P< 0.01) for all dimensions (Rs=0.43– 0.49, P< 0.01). Patients residing in rural areas (odds ratio [OR], 1.67; 95% confidence interval [95% CI], 1.01– 2.76) and with higher mCOPD-PRO scores (OR, 4.78; 95% CI, 2.75– 8.32) were more likely to be frail. Physically active patients (OR, 0.42; 95% CI, 0.21– 0.84) were less likely to be frail. In addition, mCOPD-PRO had good discriminate validity for detecting frailty (area under the curve=0.78), with a sensitivity and specificity of 84.6% and 60.8%, respectively. The optimal probability threshold for mCOPD-PRO was ≥ 1.52 points.Conclusion: In patients with AECOPD, frailty is closely related to PROs and disease characteristics. Additionally, the mCOPD-PRO score can distinguish well between frail and non-frail patients. Our findings provide support for interventions targeting frail populations with AECOPD.Plain Language Summary: Patients with chronic obstructive pulmonary disease often have concomitant frailty that may lead to disease deterioration such as acute exacerbations, hospital readmissions, disability, and premature death. Patient-reported outcomes are often used in clinical practice to measure patients’ disease characteristics and overall status. Whether patients’ frailty state is associated with patient-reported outcomes and if so, which factors are associated with frailty remain unclear. This study, conducted in China, examined their relationship as well as identified factors associated with frailty states. 302 hospitalized patients with acute exacerbations of chronic obstructive pulmonary disease completed a questionnaire answering questions about disease severity, frailty state, anxiety, and depression. The findings suggest that people who live in rural areas, self-reported more severe overall conditions, and are physically inactive are more likely to be frail. Patient-reported outcomes can distinguish between frail and non-frail patients. Therefore, patient-reported outcomes can be used to assess the extent of frailty; early screening of AECOPD combined frailty population and implementation of interventions can help mitigate the adverse effects of frailty.Keywords: frailty, COPD, COPD exacerbation, patient-report outcome, aging

Abstract The mucosa of the respiratory system is an essential site for local vitamin D synthesis, degradation, and signaling. It modulates the inflammatory and immune response by saving the integrity of the mucosal barrier and killing the invading pathogen through the induction of antimicrobial peptides. The proper functioning of the immune system within the respiratory system is influenced by the complex interactions of numerous immune pathways, including the gut-lung axis. Recent research has indicated that the gut microbiota is vital in developing and progressing chronic inflammatory chest conditions, such as asthma and chronic obstructive pulmonary disease (COPD). Furthermore, the immune-modulating function of vitamin D operates through the gut mucosa; hence, the vitamin D receptor is expressed to regulate the antimicrobial peptide. The potential protective role of vitamin D and its correlation with COPD has garnered significant interest. It is currently under exploration as a possible adjuvant therapy to aid in managing frequent exacerbation of COPD. In this review, we explored the connection between vitamin D and the immune system, as well as its relationship with microbiota. We also summarized some novel mechanisms of action of vitamin D supplementation that can impact disease exacerbation.

AbstractBackground Type 2 diabetes is a frequent comorbidity in chronic obstructive pulmonary disease (COPD) patients, with the GOLD treatment recommendations asserting that the presence of diabetes be disregarded in the choice of treatment.Methods In a cohort of COPD patients with frequent exacerbations, initiators of single-inhaler triple therapy or dual bronchodilators were compared on the incidence of COPD exacerbation and pneumonia over one year, adjusted by propensity score weighting and stratified by type 2 diabetes.Results The COPD cohort included 1,114 initiators of triple inhalers and 4,233 of dual bronchodilators (28% with type 2 diabetes). The adjusted hazard ratio (HR) of exacerbation with triple therapy was 1.04 (95% CI: 0.86–1.25) among COPD patients with type 2 diabetes and 0.74 (0.65–0.85) in those without. The incidence of severe pneumonia was elevated with triple therapy among patients with type 2 diabetes (HR 1.77; 1.14–2.75).Conclusion Triple therapy in COPD is effective among those without, but not those with, type 2 diabetes. Future therapeutic trials in COPD should consider diabetes comorbidity.

Chronic obstructive pulmonary disease (COPD) has a high prevalence and a major impact on health-related quality of life (HRQL). COPD exacerbations are an important cause of morbidity and mortality, affecting cardiovascular risk, and are associated with poorer health status. The aim of this study was to assess the association between cardiovascular risk (CVR) and HRQL, according to exacerbator or non-exacerbator phenotype. We undertook a cross-sectional, observational, descriptive study of 107 patients with COPD. Patients with two or more moderate exacerbations or one severe exacerbation in the previous year were considered as exacerbators. The CVR was calculated with the Framingham scale and SCORE (Systematic Coronary Risk Evaluation) and the HRQL was assessed with the generic questionnaire Short Form-36 Health Survey (SF-36), the St George Respiratory Questionnaire (SGRQ) and the COPD Assessment Test (CAT). Statistical analysis was done with SPSS version 26.0 for Windows. The SF-36 and the SGRQ showed lower values for the exacerbator phenotype, indicating a poorer quality of life. The CAT questionnaire showed values above 10 for the exacerbator phenotype, and lower values in the non-exacerbator group. After categorizing the sample according to their median age (65 years), we found a greater deterioration in HRQL in patients under 65 years of age according to the SF-36, the SGRQ and the CAT. We also detected differences in HRQL between non-exacerbator patients with a high CVR according to the Framingham (≥ 20%) and SCORE (≥ 5%) scales compared to those without this risk. A tendency towards worse HRQL was observed in non-exacerbator patients with a high CVR, which was statistically significant for the SGRQ impact domain on the SCORE scale. The CAT also showed a worse quality of life in non-exacerbator patients with a high CVR, which was significant in the Framingham model (Framingham high risk 8.41 vs non-high risk 6.05, p < 0.01). These differences were not observed in exacerbator patients. Our findings confirm that a high CVR influences HRQL in patients with COPD, especially in non-exacerbator patients with a high CVR, measured according to the SGRQ and the CAT. [ABSTRACT FROM AUTHOR]

Introduction: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the United States, and one in five COPD hospitalizations result in a readmission within 30 days. Pharmacists have been identified as key members of interdisciplinary teams to improve transitions of care. Objective: The objective of this study was to develop, implement, and evaluate outcomes for a pharmacist‐driven COPD transitions of care bundle at an academic medical center. Methods: A COPD care bundle was implemented for patients presenting with a COPD exacerbation from December 1, 2021 to February 28, 2022. A historical control group was created from patients who were discharged between December 1, 2020 and February 28, 2021. Patient characteristics, pharmacist‐driven interventions, and time required for the intervention were assessed descriptively. Inhaler technique was assessed before and after pharmacist education utilizing standardized rubrics. The percentage change in inhaler scores was assessed with a Wilcoxon signed‐rank test. Readmission outcomes were analyzed using a chi‐squared test. Results: There were 30 patients in the intervention group and 46 in the control group. There were 104 interventions requiring provider collaboration, of which 84 (81%) were accepted. A median (interquartile range, IQR) of 46 (37–55) min was spent per patient in the intervention group. At baseline, patients scored a median of 84.6% (75–100) of steps correctly across all inhaler device types. After pharmacist education, patient scores increased to a median of 100% [92.3–100] (p < 0.0001). There were eight (26.7%) 30‐day all‐cause readmission rates in the intervention group and 15 (32.6%) in the control group (p = 0.58). Conclusion: Most pharmacist recommendations were accepted by providers. Medication education led to improved understanding of inhaler technique, but there was no difference in 30‐day readmission rates. Further development of this service is warranted based on these findings. [ABSTRACT FROM AUTHOR]

The mucosa of the respiratory system is an essential site for local vitamin D synthesis, degradation, and signaling. It modulates the inflammatory and immune response by saving the integrity of the mucosal barrier and killing the invading pathogen through the induction of antimicrobial peptides. The proper functioning of the immune system within the respiratory system is influenced by the complex interactions of numerous immune pathways, including the gut-lung axis. Recent research has indicated that the gut microbiota is vital in developing and progressing chronic inflammatory chest conditions, such as asthma and chronic obstructive pulmonary disease (COPD). Furthermore, the immune-modulating function of vitamin D operates through the gut mucosa; hence, the vitamin D receptor is expressed to regulate the antimicrobial peptide. The potential protective role of vitamin D and its correlation with COPD has garnered significant interest. It is currently under exploration as a possible adjuvant therapy to aid in managing frequent exacerbation of COPD. In this review, we explored the connection between vitamin D and the immune system, as well as its relationship with microbiota. We also summarized some novel mechanisms of action of vitamin D supplementation that can impact disease exacerbation. [ABSTRACT FROM AUTHOR]

RationaleLong-acting muscarinic antagonists (LAMAs) reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), usually taken once daily in the morning. However, the circadian activity of autonomic regulation suggests that the highest need for anticholinergic therapy may be in the late night/early morning. This is supported by evidence that AECOPD most often begins in the morning. Furthermore, the trough spirometry effect of LAMA is lower than the peak effect, which further argues that evening dosing may be more optimal than morning dosing. This trial aims to determine whether evening administration of LAMA reduces hospitalization-requiring AECOPD or death from all causes within 1 year as compared to morning administration of the same LAMA.MethodsRandomized controlled open-label trial. Persons aged 30 years or older with a once-daily LAMA prescription and a confirmed COPD diagnosis were recruited. Participants were randomized in a 1:1 ratio to either morning or evening LAMA administration. Complete follow-up for the primary outcome, hospitalization-requiring AECOPD, or death from all causes within 1 year was captured from the Danish National Health Register, as were patient-reported outcome assessments at 6 and 12 months.ResultsA total of 10,013 participants were randomized, and the recruitment process started on 9 March 2023. Secondary outcomes include (i) moderate COPD exacerbations; (ii) all-cause hospitalization; (iii) ICU admission; (iv) need for non-invasive ventilation; and (v) all-cause mortality, among others. All outcomes will be evaluated 12 months after recruitment.Clinical trial registration:ClinicalTrials.gov, NCT05563675.

Background Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow‐up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study. Methods and Results The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack‐years of smoking history. Cox proportional hazards models and Kaplan‐Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47–2.22]; with CVD: HR, 1.92 [95% CI, 1.51–2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events. Conclusions COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00608764.

Decisions to admit or refuse admission to intensive care for acute exacerbations of COPD (AECOPD) can be difficult, due to an uncertainty about prognosis. Few studies have evaluated outcomes after intensive care for AECOPD in patients with chronic respiratory failure requiring long-term oxygen therapy (LTOT). In this nationwide observational cohort study, we investigated survival after first-time admission for AECOPD in all patients aged ≥40 years admitted to Swedish intensive care units between January 2008 and December 2015, comparing patients with and without LTOT. Among the 4,648 patients enrolled in the study, 450 were on LTOT prior to inclusion. Respiratory support data was available for 2,631 patients; 73% of these were treated with noninvasive ventilation (NIV) only, 17% were treated with immediate invasive ventilation, and 10% were intubated after failed attempt with NIV. Compared to patients without LTOT, patients with LTOT had higher 30-day mortality (38% vs. 25%; p

Background: Smartwatches have gained tremendous attention in recent years and have become widely accepted by patients, despite not being intended for medical diagnosis. Objective: This study aimed to determine the accuracy of Apple Watch oxygen saturation measurement in patients with acute exacerbation of COPD by comparing it with medical-grade pulse oximetry and ABG. Method: This single-center, prospective, cross-sectional study involved 167 patients. Patients presenting with cardiac arrest, life-threatening symptoms, severe hypoxia, or obvious jaundice were excluded. Additionally, patients whose SpO2 measurements with the Apple Watch took more than 2 min or required eight attempts were also excluded. Vital signs were measured simultaneously using the IntelliVue MX500 monitor with the Masimo Rainbow Set pulse oximeter and the Apple Watch. Concurrently, arterial blood gas (ABG) samples were drawn. Results: A strong correlation between the Apple Watch 6 and medical-grade pulse oximetry (r = 0.89, ICC = 0.940) was noted. The Bland-Altman analysis revealed a mean error of 0.458% between the Apple Watch 6 and ABG (SD: 2.78, level of agreement: − 5.912 to 4.996). The mean error between pulse oximetry and ABG (SD: 5.086, level of agreement; − 10.983 to 8.953) was 1.015%. There was a correlation between respiratory rate and the number of attempts to measure SpO2 with the Apple Watch 6 (r = 0.75, p < 0.05). Conclusion: Apple Watch 6 is an accurate and reliable method for measuring SpO2 levels in emergency patients who presented with acute exacerbation of COPD. However, tachypneic patients may encounter challenges due to the potential need for multiple attempts to measure their oxygen saturation. [ABSTRACT FROM AUTHOR]

The purpose of this mixed methods feasibility study was to gain insights into unmet clinical needs, stakeholder preferences and potential barriers and enablers to adoption for planning the implementation of point-of-care testing for earlier detection and guided treatment of chronic obstructive pulmonary disease (COPD) acute exacerbation in the NHS in England. Exacerbations of COPD cause considerable mortality and morbidity. Earlier identification of exacerbations and guided treatment would lead to reduced exacerbation duration, reduced hospitalizations and mortality, improve health-related quality of life, reduce unnecessary treatments (including inappropriate antibiotic prescribing) which could save the NHS over £400 per patient. During the early stages of product design, we took a multi-disciplinary approach to evidence generation, gaining insights from key stakeholders to test the product concept and inform evidence-based implementation planning. Primary data was collected from 11 health care and service professionals involved in the management of acute COPD exacerbations. Overall, participants agreed that by earlier differentiation of acute exacerbation from stable COPD, patients could be started on appropriate treatment. To implement point-of-care testing into clinical practice, evidence is required to demonstrate the accuracy of differentiating between exacerbation etiologies and to provide information on the beneficial impact to the system in terms of optimized management, reduced long-term side effects, admission avoidance, and cost-effectiveness. This research provides an evidence base for future implementation planning of point-of-care testing for earlier detection and guided treatment of COPD acute exacerbation. Moreover, the technology developers can decide whether to refine the product design and value proposition thereby de-risking product development. [ABSTRACT FROM AUTHOR]

IntroductionPatients suffering from chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations (AECOPD) or community acquired pneumonia (CAP), both posing severe risk of morbidity and mortality. There is no available biomarker that correctly separates AECOPD from COPD. However, because CAP and AECOPD differ in aetiology, treatment and prognosis, their discrimination would be important.MethodsThis study analysed the ability of selected candidate transcripts from peripheral blood mononuclear cells (PBMCs) to differentiate between patients with AECOPD, COPD & CAP, and CAP without pre-existing COPD.ResultsIn a previous study, we identified differentially regulated genes between CAP and AECOPD in PBMCs. In the present new cohort, we tested the potential of selected candidate PBMC transcripts to differentiate at early time points AECOPD, CAP+COPD, and CAP without pre-existing COPD. Expression of YWHAG, E2F1 and TDRD9 held predictive power: This gene set predicted diseases markedly better (model accuracy up to 100%) than classical clinical markers like CRP, lymphocyte count and neutrophil count (model accuracy up to 82%).DiscussionIn summary, in our cohort expression levels of YWHAG, E2F1 and TDRD9 differentiated with high accuracy between COPD patients suffering from acute exacerbation or CAP.

To test the hypothesis that they serve as systemic biomarkers of chronic obstructive pulmonary disease (COPD), we profiled the mRNA expression of enzymes connected to systemic inflammation and GSH metabolism in peripheral blood mononuclear cells (PBMCs). These were taken from patients displaying acute exacerbation of COPD (AE-COPD) and stable COPD, and also from non-obstructive smokers and non-smokers. The expression of poly(ADP-ribose) polymerase-1 was increased, but that of histone deacetylase 2 was decreased in association with AE-COPD. The expression of modulatory subunit of glutamyl–cysteine ligase was higher and that of its catalytic subunit, together with the expression of dipeptidyl peptidase 4, was lower in COPD patients compared with non-obstructive smokers and non-smokers. Leukotriene A4 hydrolase saw increased expression in patients with COPD according to disease severity compared to non-obstructive individuals, whereas the expression of GSH peroxidase increased in non-obstructive smokers and COPD patients with the growing number of pack-years smoked. The results corroborate COPD and its acute exacerbation as a complex systemic disorder demonstrating distinct associations with the expression of enzymes linked to inflammation and the regulation of GSH metabolism.

BackgroundIn chronic obstructive pulmonary disease (COPD) patients with exacerbations despite optimized bronchodilator therapy, roflumilast and chronic azithromycin are recommended options. Roflumilast is recommended in severe COPD patients with chronic bronchitis, whereas chronic azithromycin is more broadly indicated. The comparative effectiveness between these 2 treatments to reduce exacerbation rate remains unclear.ObjectivesOur objective was analysis of the Veterans Health Administration (VHA) database (medication and claims data without lung function or presence of chronic bronchitis or tobacco use) to compare the effectiveness of roflumilast and azithromycin on hospitalizations and mortality.MethodsThe primary outcome of the study was cumulative incidences of first COPD-related and all-cause hospitalization. Sensitivity analysis on hospitalizations was conducted for VHA patients who also had Medicare.ResultsIn 1302 roflumilast and 2573 azithromycin patients, the all-cause mortality rates at 1 year were 19% and 15%, respectively. The median times-to-all-cause death were 47 months (interquartile range [IQR] 16-81) for the roflumilast and 48 months (IQR 20-83) for the azithromycin groups. Roflumilast was associated with higher mortality (hazard ratio [HR] 1.16; 95% confidence interval [CI], 1.04-1.29). Roflumilast showed no significant association for COPD-related hospitalization (subdistribution HR [SHR]=1.14, 95% CI, 1.00-1.29) and all-cause hospitalization (HR 1.07, 95% CI, 0.97-1.18). For patients with Medicare (N=2030), roflumilast was associated with higher COPD-related (SHR 1.21; 95% CI, 1.05-1.41) and all-cause (SHR 1.23; 95% CI, 1.09-1.38) hospitalizations.ConclusionsRoflumilast was associated with higher hazard ratios for death, COPD-related hospitalizations, and all-cause hospitalizations in COPD patients only after adjustment for VHA and external Medicare events. Prospective clinical trials are needed to directly compare the relative efficacy of these therapies.

Wang Chun Kwok,1 Chi Hung Chau,2 Terence Chi Chun Tam,1 Fai Man Lam,1 James Chung Man Ho1 1Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong Special Administrative Region, People’s Republic of China; 2Tuberculosis and Chest Unit, Grantham Hospital, Hong Kong Special Administrative Region, People’s Republic of ChinaCorrespondence: James Chung Man Ho, Department of Medicine, Queen Mary Hospital, 4/F, Professorial Block, 102 Pokfulam Road, Hong Kong Special Administrative Region, People’s Republic of China, Tel +852 2255 4542, Fax +852 2816-2863, Email jhocm@hku.hkBackground: Chronic obstructive pulmonary disease (COPD) phenotyping using stable-state blood eosinophil level was shown to have prognostic implication in terms of exacerbation risk. However, using a single cut-off of blood eosinophil level to predict clinical outcome has been challenged. There have been suggestions that variability of blood eosinophil count at stable-state could provide additional information on exacerbation risk.Methods: A retrospective cohort study was conducted in a major regional hospital and a tertiary respiratory referral centre in Hong Kong, including 275 Chinese patients with COPD, to investigate the possible role of variability of blood eosinophil count at stable-state to predict COPD exacerbation risk in one year.Results: Higher variability of baseline eosinophil count, which is defined as the difference of the minimal and maximal eosinophil count at stable-state, was associated with increased risk of COPD exacerbation in the follow-up period with adjusted OR (aOR) of 1.001 (95% CI = 1.000– 1.003, p-value = 0.050) for 1 unit (cells/μL) increase in variability of baseline eosinophil count, aOR of 1.72 (95% CI = 1.00– 3.58, p-value = 0.050) for 1 SD increase in variability of baseline eosinophil count and aOR of 1.06 (95% CI = 1.00– 1.13) for 50 cells/μL increase in variability of baseline eosinophil count. The AUC by ROC analysis was 0.862 (95% CI = 0.817– 0.907, p-value < 0.001). The cut-off for variability of baseline eosinophil count identified was 50 cells/μL, with sensitivity of 82.9% and specificity of 79.3%. Similar findings were also shown in the subgroup with stable-state baseline eosinophil count below 300 cells/μL.Conclusion: Variability of baseline eosinophil count at stable-state might predict the exacerbation risk of COPD, exclusively among patients with baseline eosinophil count below 300 cells/μL. The cut-off value for variability was 50 cells/μValidation of the study findings in large scale prospective study would be meaningful.Keywords: COPD, eosinophil, phenotype, COPD exacerbation

The purpose of this mixed methods feasibility study was to gain insights into unmet clinical needs, stakeholder preferences and potential barriers and enablers to adoption for planning the implementation of point-of-care testing for earlier detection and guided treatment of chronic obstructive pulmonary disease (COPD) acute exacerbation in the NHS in England. Exacerbations of COPD cause considerable mortality and morbidity. Earlier identification of exacerbations and guided treatment would lead to reduced exacerbation duration, reduced hospitalizations and mortality, improve health-related quality of life, reduce unnecessary treatments (including inappropriate antibiotic prescribing) which could save the NHS over £400 per patient. During the early stages of product design, we took a multi-disciplinary approach to evidence generation, gaining insights from key stakeholders to test the product concept and inform evidence-based implementation planning. Primary data was collected from 11 health care and service professionals involved in the management of acute COPD exacerbations. Overall, participants agreed that by earlier differentiation of acute exacerbation from stable COPD, patients could be started on appropriate treatment. To implement point-of-care testing into clinical practice, evidence is required to demonstrate the accuracy of differentiating between exacerbation etiologies and to provide information on the beneficial impact to the system in terms of optimized management, reduced long-term side effects, admission avoidance, and cost-effectiveness. This research provides an evidence base for future implementation planning of point-of-care testing for earlier detection and guided treatment of COPD acute exacerbation. Moreover, the technology developers can decide whether to refine the product design and value proposition thereby de-risking product development.

Introduction: Clinical studies demonstrate an accelerated decline in lung function in patients with moderate chronic obstructive pulmonary disease (COPD) (Global Initiative for Chronic Obstructive Lung Disease [GOLD] grade 2) versus severe and very severe COPD (GOLD grades 3 and 4). This predictive modelling study assessed the impact of initiating pharmacotherapy earlier versus later on long-term disease progression in COPD. Methods: The modelling approach used data on decline in forced expiratory volume in 1 s (FEV1) extracted from published studies to develop a longitudinal non-parametric superposition model of lung function decline with progressive impact of exacerbations from 0 per year to 3 per year and no ongoing pharmacotherapy. The model simulated decline in FEV1 and annual exacerbation rates from age 40 to 75 years in COPD with initiation of long-acting anti-muscarinic antagonist (LAMA)/long-acting beta2-agonist (LABA) (umeclidinium (UMEC)/vilanterol (VI)) or triple (inhaled corticosteroid (ICS)/LAMA/LABA; fluticasone furoate (FF)/UMEC/VI) therapy at 40, 55 or 65 years of age. Results: Model-predicted decline in FEV1 showed that, compared with 'no ongoing' therapy, initiation of triple or LAMA/LABA therapy at age 40, 55 or 65 years preserved an additional 469.7 mL or 236.0 mL, 327.5 mL or 203.3 mL, or 213.5 mL or 137.5 mL of lung function, respectively, by the age of 75. The corresponding average annual exacerbation rates were reduced from 1.57 to 0.91, 1.06 or 1.23 with triple therapy or to 1.2, 1.26 and 1.4 with LAMA/LABA therapy when initiated at 40, 55 or 65 years of age, respectively. Conclusions: This modelling study suggests that earlier initiation of LAMA/LABA or triple therapy may have positive benefits in slowing disease progression in patients with COPD. Greater benefits were demonstrated with early initiation therapy with triple versus LAMA/LABA. [ABSTRACT FROM AUTHOR]

Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a complication of COPD that typically necessitates intensified treatment and hospitalization. It is linked to higher morbidity, mortality and healthcare spending. Assessment of therapy response for AECOPD is difficult due to the variability of symptoms and limitations in current measures. Hence, there is a need for new biomarkers to aid in the management of AECOPD in acute care settings. Fifteen hospitalized AECOPD patients (GOLD 3–4) were enrolled in this study. Treatment response was assessed daily through clinical evaluations and by monitoring tidal breathing biomarkers (respiratory rate [RR], expiratory time [T ex ], inspiratory time [T in ], expiratory pause [T rst ], total breath time [T tot ]), using a novel, wearable nanosensor-based device (SenseGuard™). Patients who showed significant clinical improvement had substantial changes in ΔT ex /T tot (+14%), ΔT rst /T tot (−18%), and ΔT in /T ex (+0.09), whereas patients who showed mild or no clinical improvement had smaller changes (+5%, +3%, and −0.03, respectively). Linear regression between change in physician's assessment score and the median change in tidal breathing parameters was significant for T in /T ex (R2 ​= ​0.449, ∗p ​= ​0.017), T ex /T tot (R2 ​= ​0.556, ∗p ​= ​0.005) and T rst /T tot (R2 ​= ​0.446, ∗p ​= ​0.018), while no significant regression was observed for RR, T in /(T rst ​+ ​T ex) and T in /T tot. Our study demonstrates the potential of the SenseGuard™ to monitor treatment response in AECOPD patients by measuring changes in tidal breathing biomarkers, which were shown to be associated with significant changes in the patients' respiratory condition as evaluated by physicians. However, further large-scale clinical studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Computational models have been used extensively to assess diseases and disabilities effects on musculoskeletal system dysfunction. In the current study, we developed a two degree-of-freedom subject-specific second-order task-specific arm model for characterizing upper-extremity function (UEF) to assess muscle dysfunction due to chronic obstructive pulmonary disease (COPD). Older adults (65 years or older) with and without COPD and healthy young control participants (18 to 30 years) were recruited. First, we evaluated the musculoskeletal arm model using electromyography (EMG) data. Second, we compared the computational musculoskeletal arm model parameters along with EMG-based time lag and kinematics parameters (such as elbow angular velocity) between participants. The developed model showed strong cross-correlation with EMG data for biceps (0.905, 0.915) and moderate cross-correlation for triceps (0.717, 0.672) within both fast and normal pace tasks among older adults with COPD. We also showed that parameters obtained from the musculoskeletal model were significantly different between COPD and healthy participants. On average, higher effect sizes were achieved for parameters obtained from the musculoskeletal model, especially for co-contraction measures (effect size = 1.650 ± 0.606, p < 0.001), which was the only parameter that showed significant differences between all pairwise comparisons across the three groups. These findings suggest that studying the muscle performance and co-contraction, may provide better information regarding neuromuscular deficiencies compared to kinematics data. The presented model has potential for assessing functional capacity and studying longitudinal outcomes in COPD. [ABSTRACT FROM AUTHOR]

In this study, we aimed to examine the correlation between current prognostic scores and the integrated pulmonary index (IPI) in patients admitted to the emergency department (ED) with exacerbation of chronic obstructive pulmonary disease (COPD), and the diagnostic value of using the IPI in combination with other scores in determining patients who can be discharged safely. This study was conducted as a multicenter and prospective observational study between August 2021 and June 2022. Patients diagnosed with COPD exacerbation (eCOPD) at the ED were included in the study and they were grouped according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The CURB-65 (Confusion, Urea, Respiratory rate, Blood pressure, and age older than 65 years), BAP-65 (Blood urea nitrogen, Altered mental status, Pulse rate, and age older than 65 years), and DECAF (Dyspnea, Eosinopenia, Consolidation, Academia, and atrial Fibrillation) scores and IPI values of the patients were recorded. The correlation between the IPI and the other scores and its diagnostic value in detecting mild eCOPD were examined. The diagnostic value of CURB-IPI, a new score created by the combination of CURB-65 and IPI, in mild eCOPD was examined. The study was carried out with 110 patients (49 female and 61 male), mean age of 67 (min/max: 40/97). The IPI and CURB-65 had better predictive value in detecting mild exacerbations than DECAF and BAP-65 scores [Area under curves (AUC) were 0.893, 0.795, 0.735, 0.541 respectively]. The CURB-IPI score, on the other hand, had the best predictive value for detecting mild exacerbations (AUC 0.909). We found that the IPI has good predictive value in the detection of mild COPD exacerbations, and its predictive value increases when used in combination with CURB-65. We think that the CURB-IPI score can be a guide when deciding whether patients with exacerbation of COPD can be discharged. [ABSTRACT FROM AUTHOR]

Introduction:The aging of the communities and higher pollution levels increases chronic obstructive pulmonary disease (COPD) burden and are projected to rise in the number of the patients with COPD and its exacerbations. There is little evidence for short-term outcomes of COPD exacerbations of the biomarkers that are easily available. Biomarker-based hematological phenotype classification is useful and effective for outcome predictions. This study evaluates the relationship between the phenotypes of patients with COPD who presented in the emergency department due to COPD exacerbation and admitted to the hospital have been evaluated.Methods:All hospitalized patients older than 18 years old who presented to the emergency department due to the COPD exacerbation between July 2018 and July 2020 were included in the study. The patient data evaluated retrospectively for vital parameters, biomarker results, and mortality rates. The primary outcome measure of the study was determined as the thirty-day mortality rates of the groups. Secondary outcome measures were determined by comparing the differences between the trophilic and eosinophilic groups.Results:One hundred forty-three patients were included in the study. The mean age of the patients was 74.8±10.6. One hundred and two of the patients (71.3%) were male. The neutrophilic and eosinophilic groups had a statistically significant difference in body temperature and heart rate (p=0.018 and p=0.001, respectively). In contrast, no significant difference was observed for systolic blood pressure, diastolic blood pressure, and sPO2 (p=0.400, p=0.564, p=0.248, respectively). One month mortality of the neutrophilic and eosinophilic groups were 15.9% and 3.2%, respectively. Blood neutrophil count levels have been assigned in 3 different groups for mortality and compared which had no significant difference for 1,3 and 12-month mortality (p=0.142, 0.280, 0.351 respectively).Conclusion:The patients admitted to the hospital via the emergency department had no mortality difference between different neutrophil levels or hematologic phenotypes. Further studies are required to assess cutoff values of blood neutrophil counts as an independent biomarker.

Khadiga SM Salama,1 Eman M Moazen,1 Sawsan B Elsawy,1 Sanaa F Kotb,1 Eid M Mohammed,2 Sara A Tahoun,3 Marwa A A Ramadan,3 Samar M Abd Elhamid,3 Rania H M Bahi,4 Etemad A Mohammad5 1Chest Diseases Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 2Chest Diseases Department Faculty of Medicine for Men’s, Al-Azhar University, Cairo, Egypt; 3Clinical Pathology Department Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt; 4Chest Diseases Department Faculty of Medicine, Zagazig University, Zagazig, Egypt; 5Chest Diseases Department Faculty of Medicine, Benha University, Benha, EgyptCorrespondence: Sawsan B Elsawy, Chest Diseases Department, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt, Email Sawsan.bakr79@gmail.comBackground and Aim: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) has profound effects on disease progression and patients’ quality of life. Emerging evidence suggests an association between alterations in the respiratory microbiome flora species and airway inflammation in patients with AECOPD. The present study aimed to describe the inflammatory cells and bacterial microbiome distributions in respiratory tract in Egyptian patients with AECOPD.Subjects and Methods: The present cross-sectional study included 208 patients with AECOPD. Sputum and broncho-alveolar lavage samples from the studied patients were submitted to microbial cultures using appropriate media. Total and differential leukocytic counts and were done via automated cell counter.Results: The present study included 208 AECOPD patients. They comprised 167 males (80.3%) and 41 females (19.7%) with an age of 57.9 ± 4.9 years. AECOPD was categorized as mild, moderate and severe in 30.8%, 43.3% and 26%, respectively. Sputum samples had significantly higher TLC, neutrophil percent and eosinophil percent when compared with BAL samples. In contrast, lymphocyte percent was significantly higher in BAL samples. Sputum specimens had significantly lower frequency of positive growths (70.2% versus 86.5%, p = 0.001). Among the identified organisms, sputum specimens had significantly lower frequency of Strept. pneumoniae (14.4% versus 30.3%, p = 0.001), Klebsiella pneumoniae (19.7% versus 31.7%, p = 0.024), Haemophilus influenzae (12.5% versus 26.9%, p = 0.011), Pseudomonas aeruginosa (2.9% versus 10%, p = 0.019) and Acinetobacter spp. (1.9% versus 7.2%, p = 0.012) growths when compared with BAL samples.Conclusion: The present study could identify a distinctive pattern of inflammatory cell distribution in sputum and BAL samples of AECOPD patients. The most commonly isolated organisms were Klebsiella pneumoniae and Strept. pneumoniae.Keywords: chronic obstructive pulmonary disease, COPD exacerbation, inflammatory cells, bacterial microbiome, sputum culture, bronchoalveolar culture

BackgroundSlow heart rate recovery (HRR) after exercise is associated with autonomic dysfunction and increased mortality. What HRR criterion at 1-minute after a 6-minute walk test (6MWT) best defines pulmonary impairment?.Study design and methodsA total of 5008 phase 2 COPDGene (NCT00608764) participants with smoking history were included. A total of 2127 had COPD and, of these, 385 were followed-up 5-years later. Lung surgery, transplant, bronchiectasis, atrial fibrillation, heart failure and pacemakers were exclusionary. HR was measured from pulse oximetry at end-walk and after 1-min seated recovery. A receiver operator characteristic (ROC) identified optimal HRR cut-off. Generalized linear regression determined HRR association with spirometry, chest CT, symptoms and exacerbations.ResultsHRR after 6MWT (bt/min) was categorized in quintiles: ≤5 (23.0% of participants), 6-10 (20.7%), 11-15 (18.9%), 16-22 (18.5%) and ≥23 (18.9%). Compared to HRR≤5, HRR≥11 was associated with (p

Rationale: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPDs) are associated with a significant disease burden. Blood immune phenotyping may improve our understanding of a COPD endotype at increased risk of exacerbations. Objective: To determine the relationship between the transcriptome of circulating leukocytes and COPD exacerbations. Methods: Blood RNA sequencing data (n = 3,618) from the COPDGene (Genetic Epidemiology of COPD) study were analyzed. Blood microarray data (n = 646) from the ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) study were used for validation. We tested the association between blood gene expression and AE-COPDs. We imputed the abundance of leukocyte subtypes and tested their association with prospective AE-COPDs. Flow cytometry was performed on blood in SPIROMICS (Subpopulations and Intermediate Outcomes in COPD Study) (n = 127), and activation markers for T cells were tested for association with prospective AE-COPDs. Measurements and Main Results: Exacerbations were reported 4,030 and 2,368 times during follow-up in COPDGene (5.3 ± 1.7 yr) and ECLIPSE (3 yr), respectively. We identified 890, 675, and 3,217 genes associated with a history of AE-COPDs, persistent exacerbations (at least one exacerbation per year), and prospective exacerbation rate, respectively. In COPDGene, the number of prospective exacerbations in patients with COPD (Global Initiative for Chronic Obstructive Lung Disease stage ⩾2) was negatively associated with circulating CD8+ T cells, CD4+ T cells, and resting natural killer cells. The negative association with naive CD4+ T cells was replicated in ECLIPSE. In the flow-cytometry study, an increase in CTLA4 on CD4+ T cells was positively associated with AE-COPDs. Conclusions: Individuals with COPD with lower circulating lymphocyte counts, particularly decreased CD4+ T cells, are more susceptible to AE-COPDs, including persistent exacerbations. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is considered one of the leading causes of mortality. Cardiovascular comorbidities are diagnosed often in COPD patients, not only because of the common risk factors these two diseases share, but also because of the systemic inflammation which characterizes COPD and has deleterious effects in the cardiovascular system. The comorbid cardiovascular diseases in COPD result in several difficulties in the holistic treatment of these patients and affect outcomes such as morbidity and mortality. Several studies have reported that mortality from cardiovascular causes is common among COPD patients, while the risk for acute cardiovascular events increases during COPD exacerbations and remains high for a long time even after recovery. In this review, we focus on the prevalence of cardiovascular comorbidities in COPD patients, presenting the evidence regarding the interaction of the pathophysiological pathways which characterize each disease. Furthermore, we summarize information regarding the effects of cardiovascular treatment on COPD outcomes and vice versa. Finally, we present the current evidence regarding the impact of cardiovascular comorbidities on exacerbations, quality of life and survival of COPD patients. [ABSTRACT FROM AUTHOR]

Anna Leenders,1 Esther Sportel,1 Elise Poppink,1 Wendy van Beurden,2 Paul van der Valk,2 Marjolein Brusse-Keizer3,4 1Department of Clinical Pharmacy, Medisch Spectrum Twente, Enschede, the Netherlands; 2Department of Pulmonary Medicine, Medisch Spectrum Twente, Enschede, the Netherlands; 3Health Technology and Services Research, Faculty of Behavioural, Management and Social Sciences, Technical Medical Centre, University of Twente, Enschede, the Netherlands; 4Medical School Twente, Medisch Spectrum Twente, Enschede, the NetherlandsCorrespondence: Marjolein Brusse-Keizer, Medisch Spectrum Twente, PO Box 50000, Enschede, 7500 KA, the Netherlands, Tel +31 53 487 20 00, Email m.brusse-keizer@mst.nlPurpose: Chronic obstructive pulmonary disease (COPD) is a highly prevalent chronic disease partly characterised by the occurrence of acute exacerbations (AECOPD). The need for hospital admissions for COPD exacerbations could theoretically be decreased through timely and appropriate outpatient care or self-management. The aim of this study is to explore and compare patients’ and health care providers’ (HCP) perspectives on the potential preventability of COPD hospitalisations and to identify strategies to prevent unnecessary hospitalisations.Patients and Methods: Semi-structured interviews were conducted with patients admitted for an AECOPD (N = 11), HCPs on the respiratory ward (N = 11), and treating pulmonologists (N = 10). Interviews were transcribed verbatim and analysed using thematic content analysis.Results: Patient and HCP perspectives on the potential preventability of hospital admissions for AECOPD often conflict. The kappa coefficients were − 0.18 [95% CI: − 0.46– 0.11] for patients and pulmonologists and − 0.28 [95% CI: − 0.80– 0.21] for patients and HCPs, which indicates poor agreement. The kappa coefficient for pulmonologists and HCPs was 0.14 [95% CI: − 0.13– 0.41], which indicates slight agreement. Patient and HCP factors that could potentially prevent hospitalisation for AECOPD were identified, including timely calling for help, recognizing and acting on symptoms, and receiving instruction about COPD, including treatment and action plans.Conclusion: Patients and their HCPs have different beliefs about the potential preventability of AECOPD hospitalisations. Most patients and HCPs mentioned factors that potentially could have led to a different outcome for the current AECOPD or that could impact the patient’s health status and treatment of AECOPDs in the future. The factors identified in this study indicate that shared decision making is crucial to center the patient’s perspective and individual needs and to provide timely treatment or prevention of AECOPD, thereby potentially decreasing hospital admission rates.Keywords: patient and provider preferences, hospitalisation, COPD exacerbation, prevention

Introduction: Increased red blood cell distribution width (RDW) has been reported to be related to underlying chronic inflammation. Our aim is to investigate the relationship of different complete blood count (CBC) parameters such as hemoglobin level, mean corpuscular volume (MCV), mean platelet volume (MPV) or RDW with COPD exacerbation severity. Methods: In the present retrospective analysis, consecutive patients admitted with the diagnosis of "COPD Exacerbation" between 1 January 2012 and 31 December 2015 were evaluated. Results: The study population included 804 patients with COPD exacerbation. The maximal partial pressure of carbon dioxide in the arterial blood (PaCO2) during hospital stay was significantly higher in patients with high MCV (p < 0.001), and in patients with a high RDW (p < 0.001). The hospitalization duration was significantly longer in patients with high RDW (p < 0.001) and in patients with elevated C-reactive protein (CRP) levels (p < 0.001). CRP levels strongly correlated to RDW (p = 0.001). Conclusions: Our study demonstrated that different CBC parameters, such as MCV and RDW, are in correlation with the severity of acute exacerbation of COPD reflected by the PaCO2 level and the duration of hospitalization. Furthermore, we also found a positive correlation between RDW and CRP levels. This finding supports the hypothesis that RDW is a good biomarker of acute inflammation. [ABSTRACT FROM AUTHOR]

SUMMARY OF KEY POINTS: International respiratory organizations now recommend using lower limit of normal and standardized residuals to diagnose airflow obstruction and COPD though using a fixed ratio <0.7 is simpler and robustly predicts important clinical outcomes.The most common COPD comorbidities are coronary artery calcification, emphysema and bronchiectasis. COPD patients with psychological (high anxiety and depression) and cachectic (underweight and osteoporotic) comorbidity have higher mortality and exacerbate more.Serum eosinophil count remains an important COPD biomarker and we have greater clarity about normal eosinophil levels in COPD and the wider population.Criteria for entry into COPD clinical trials continue to exclude many patients, in particular those at greater risk of exacerbation and death.The effect of hyperinflation on cardiac function impacts COPD mortality and is an important target for successful lung volume reduction procedures. [ABSTRACT FROM AUTHOR]

Background and Objective: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are heterogeneous in aetiology and accelerate disease progression. Here, we aimed to investigate the association of fractional exhaled nitric oxide (FeNO) and its variability with AECOPD of different aetiology. Methods: FeNO was determined in 2157 visits (1697 stable, 133 AECOPD and 327 follow‐up) of 421 COPD patients from the PREVENT study, an investigator‐initiated, longitudinal and interventional study, who were on daily treatment with inhaled corticosteroids/long‐acting β2‐agonists. Results: Longitudinal measurements of FeNO revealed an intra‐subject variability of FeNO that was significantly higher in exacerbators compared to non‐exacerbators (p < 0.001) and positively associated with the number of AECOPD. As FeNO variability increased, the probability of patients to remain AECOPD‐free decreased. In patients included in the highest FeNO variability quartile (≥15.0 ppb) the probability to remain free of AECOPD was only 35% as compared to 80% for patients included in the lowest FeNO variability quartile (0.50–4.39 ppb). The change of FeNO from the last stable visit to AECOPD was positively associated with the probability of viral infections and this association was stronger in current smokers than ex‐smokers. In contrast, the change in FeNO from the last stable visit to an AECOPD visit was inversely associated with the probability of bacterial infections in ex‐smokers but not in current smokers. Conclusion: FeNO variability was associated with the risk and aetiology of AECOPD differentially in current and ex‐smokers. Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) affect disease progression and are associated with considerable morbidity and mortality. Longitudinal measurements of FeNO revealed an association with future exacerbations. There is a differential increase of FeNO at exacerbations according to the aetiology and smoking status. See relatedEditorial [ABSTRACT FROM AUTHOR]

Introduction: The aging of the communities and higher pollution levels increases chronic obstructive pulmonary disease (COPD) burden and are projected to rise in the number of the patients with COPD and its exacerbations. There is little evidence for short-term outcomes of COPD exacerbations of the biomarkers that are easily available. Biomarker-based hematological phenotype classification is useful and effective for outcome predictions. This study evaluates the relationship between the phenotypes of patients with COPD who presented in the emergency department due to COPD exacerbation and admitted to the hospital have been evaluated. Methods: All hospitalized patients older than 18 years old who presented to the emergency department due to the COPD exacerbation between July 2018 and July 2020 were included in the study. The patient data evaluated retrospectively for vital parameters, biomarker results, and mortality rates. The primary outcome measure of the study was determined as the thirty-day mortality rates of the groups. Secondary outcome measures were determined by comparing the differences between the trophilic and eosinophilic groups. Results: One hundred forty-three patients were included in the study. The mean age of the patients was 74.8±10.6. One hundred and two of the patients (71.3%) were male. The neutrophilic and eosinophilic groups had a statistically significant difference in body temperature and heart rate (p=0.018 and p=0.001, respectively). In contrast, no significant difference was observed for systolic blood pressure, diastolic blood pressure, and sPO2 (p=0.400, p=0.564, p=0.248, respectively). One month mortality of the neutrophilic and eosinophilic groups were 15.9% and 3.2%, respectively. Blood neutrophil count levels have been assigned in 3 different groups for mortality and compared which had no significant difference for 1,3 and 12-month mortality (p=0.142, 0.280, 0.351 respectively). Conclusion: The patients admitted to the hospital via the emergency department had no mortality difference between different neutrophil levels or hematologic phenotypes. Further studies are required to assess cutoff values of blood neutrophil counts as an independent biomarker. [ABSTRACT FROM AUTHOR]

Background and Objective: Physical activity worsens during exacerbations of chronic obstructive pulmonary disease (COPD) and notably after hospitalizations. Pedometer‐based interventions are useful to increase physical activity in stable patients with COPD. However, there is little information concerning the implementation of such programs following severe exacerbation. This study assessed the efficacy of a physical activity program after hospitalization for a COPD exacerbation. Methods: We performed a prospective, 12‐week, parallel group, assessor‐blinded, randomized control trial in COPD patients hospitalized for an exacerbation. After discharge, physical activity and other secondary variables were assessed. Patients were allocated (1:1) to a physical activity promotion program (intervention group, IG) or usual care (control group, CG). Based on a motivational interview and accelerometer physical activity assessment, a patient‐tailored, pedometer‐based, progressive and target‐driven program was designed. Linear mixed effect models were used to analyse between‐group differences. Results: Forty‐six out of 61 patients recruited were randomized and 43 (IG = 20, CG = 23) completed the study. In‐hospital and baseline characteristics were similar in both groups. After 12 weeks of intervention, the mean steps difference between groups was 2093 steps/day, p = 0.018, 95% CI 376–4012, favouring the IG. Only the IG significantly increased the number of steps/day compared to baseline (mean difference [95% CI] 2932 [1069–4795] steps; p = 0.004). There were no other between‐group differences. Conclusion: After hospitalization for a COPD exacerbation, a patient‐tailored physical activity program based on a motivational interview and the use of pedometers, with progressive and customized targets, improved the number of steps/day. [ABSTRACT FROM AUTHOR]

Background: Noninvasive mechanical ventilation (NIV) decreases the need for endotracheal intubation (ETI) and also decreases mortality in severe acute exacerbation of COPD (AECOPD). Objective: The aim of the current study is to assess determinants of NIV effectiveness in patients with COPD exacerbation. Patients and methods: Our study was a cross-sectional comparative study. A total 100 patients with AECOPD were included in this study. Patients were admitted to the Respiratory Intensive Care Unit (RICU) in Minia Cardiothoracic University Hospital. All patients were evaluated at the time of admission, at the start of NIV, after 1 hour (hr) of NIV and at the end of NIV. This evaluation included heart rate, respiratory rate, systolic blood pressure, diastolic blood pressure, and arterial blood gases (ABG) which include PaO2, PaCO2, PH, HCO3, as well as PaO2/FiO2 ratio. Results: Patients were divided into 2 groups; 85 (85%) patients improved with NIV (success group, Group I) and 15 (15%) patients failed NIV and were intubated (Group II). PH, PO2, as well as PCO2 revealed significant improvement after 1 hr, which persisted till the end of the study in the success group. Clinical data including heart rate, respiratory rate, systolic blood pressure, and diastolic blood pressure showed significant difference between the two groups at time of hospital admission and the initiation of NIV. After 1 hr, these variables showed significant improvement in the success group that continued till the and at the end of the study. Also, PaO2/FiO2 ratio showed a significant improvement in the success group after 1 hr of NIV. Multivariate analysis showed PH <7.26 and RR = 35 (at hospital admission) are predictors of failure of NIV. Conclusion: Clinical parameters including HR, RR and blood pressure, as well as ABG, could predict success of NIV in patients with AECOPD. Improvement in these parameters within 1 hr of NIV could be a good predictor of success. [ABSTRACT FROM AUTHOR]