Chronic Obstructive Pulmonary Disease Research Research Articles

CRISPR/Cas13a-triggered entropy-driven amplification for colorimetric and fluorescent dual-mode detection of microRNA

MicroRNAs (miRNAs) are crucial biomarkers for the early detection and monitoring of disease progression of chronic obstructive pulmonary disease (COPD). Herein, we have devised a method for detecting miRNA using a combination of colorimetric and graphene oxide-based fluorescent techniques. The target miRNA in our design could precisely activate the trans-cleavage activity of the CRISPR-Cas13a system. The activated Cas13a enzyme cuts the “rUrU” section in the P1 probe, generating a nicking site to induce entropy-driven amplification (EDA). One of the available EDA products has the capability to unfold the hairpin probe, thereby initiating the catalytic hairpin assembly, exposing the G-quadruplex structure, facilitating the subsequent color response. The fuel strand labeled with Cy3 successfully established a double-stranded DNA structure with DNA3, and consequently the Cy3 would not be quenched by graphene oxide (GO). The implementation of the dual-mode technique in this method yields greater benefits in terms of improving the precision and consistency of the miRNA measurements. The developed method has the capability to fluorescently measure miRNA-21 levels down to a concentration of 5.8 fM. In addition, the analysis of miRNA targets from clinical samples using this method demonstrates its promising utility in the fields of biomedical research of COPD.

Protease-armed, Pathogenic Extracellular Vesicles Link Smoking and Chronic Obstructive Pulmonary Disease.

Rationale: Mounting evidence demonstrates a role for extracellular vesicles (EVs) in driving lung disorders, such as chronic obstructive pulmonary disease (COPD). Although cigarette smoke (CS) is the primary risk factor for COPD, a link between CS and the EVs that could lead to COPD is unknown. Objective: To ascertain whether exposure to CS elicits a proteolytic EV signature capable of driving disease pathogenesis. Methods: Protease expression and enzymatic activity were measured in EVs harvested from the BAL fluid of smoke-exposed mice and otherwise healthy human smokers. Pathogenicity of EVs was examined using pathological tissue scoring after EV transfer into naive recipient mice. Measurements and Main Results: The analyses revealed a unique EV profile defined by neutrophil- and macrophage-derived EVs. These EVs are characterized by abundant surface expression of neutrophil elastase (NE) and matrix metalloproteinase 12 (MMP12), respectively. CS-induced mouse or human-derived airway EVs had a robust capacity to elicit rapid lung damage in naive recipient mice, with an additive effect of NE- and MMP12-expressing EVs. Conclusions: These studies demonstrate the capacity of CS to drive the generation of unique EV populations containing NE and MMP12. The coordinated action of these EVs is completely sufficient to drive emphysematous disease, and their presence could operate as a prognostic indicator for COPD development. Furthermore, given the robust capacity of these EVs to elicit emphysema in naive mice, they provide a novel model to facilitate preclinical COPD research. Indeed, the development of this model has led to the discovery of a previously unrecognized CS-induced protective mechanism against EV-mediated damage.

Knowledge of Chronic Obstructive Pulmonary Diseases among Healthcare Workers: Nigerian COPD Research Project (NICORP)

Background: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic inflammatory lung disease that often causes obstruction to airflow in the lungs. The main risk factor in Nigeria is long term exposure to indoor pollution from cooking with firewood and fossil fuel in poorly ventilated spaces. Aims/ objectives: The aim was to evaluate the level of COPD knowledge among healthcare workers (HCWs) in the southwestern state of Nigeria.Materials/ methods: Self-administered online BCKQ which is made up of 65 stem questions was used to evaluate the level of knowledge of HCWs. The overall score of individual participants was represented in percentages and frequencies. Tests of statistical significance like the Chi-square test are applied to find out the statistical significance of the difference in percentages. Univariate analysis was done using respondent knowledge about COPD as the dependent variable and the socio-demographic were identified as independent variables. A p-value of <0.05 was taken as statistically significant in the calculations of variables. Results: Four hundred and five healthcare workers were involved in this study, 53.3% of whom were females. The mean age of the study cohort was 48.7±0.55 years, significant majority (75.6%) of whom were <40 years. (p< 0.001). Majority of cohorts (39.3%) were doctors, while 32.0% were nurses. Only 11.7% had PhD or Fellowship as their highest educational qualification. The overall mean total score of cohorts on the Bristol COPD questionnaire was 51.9±21.9 %, with 40.4% having good scores and only 11.3% had excellent score. Mean knowledge scores were high among doctors (69.9±02.4), HCWs with medical fellowships /PhD (69.9±02.4) and had worked for <10 years. A positive correlation was demonstrated between age, level of education and knowledge score (p<0.05). Conclusion: This study examined knowledge of COPD among healthcare workers in the southwestern part of Nigeria and confirmed that the knowledge of COPD among healthcare workers was essentially good but there were serious gaps in knowledge observed in areas of vaccination, inhalational therapy, and use of inhaled and oral steroid.

FEV1/FVC Severity Stages for Chronic Obstructive Pulmonary Disease.

The diagnosis of COPD is based on low ratio of the forced expiratory volume in one second to the forced vital capacity (FEV1/FVC) but its severity is classified using percentage predicted FEV1 (ppFEV1). To test a new severity classification scheme for COPD using FEV1/FVC, a more robust measure of airflow obstruction than ppFEV1. In COPDGene (n=10,132), the severity of airflow obstruction was categorized by GOLD Stages I-IV (ppFEV1 ≥80, ≥50-80, ≥30-50, and <30). A new severity classification (STaging of Airflow obstruction by Ratio, STAR) was tested in COPDGene: FEV1/FVC ≥0.60 to <0.70, ≥0.50 to <0.60, ≥0.40 to <0.50, and <0.40, respectively for stages I-IV, and applied to the combined Pittsburgh SCCOR and Pittsburgh Emphysema registry cohorts for replication (n=2017). Agreement (weighted Bangdiwala B) between GOLD and new FEV1/FVC severity stages was 0.89 in COPDGene and 0.88 in the Pittsburgh cohort. In both COPDGene and the Pittsburgh cohort, in comparison to GOLD staging, STAR provided significant discrimination between the absence of airflow obstruction and Stage I for all-cause mortality, respiratory-quality of life, dyspnea, airway wall thickness, exacerbations and lung function decline. No difference was noted for emphysema, small airways disease, and 6-minute walk distance. The STAR classification system identified a greater number of adults with Stage III-IV disease who would be eligible for lung transplantation and lung volume reduction evaluations. The new severity classification scheme STAR provides discrimination for mortality similar to the GOLD classification but with a more uniform gradation of disease truncated.

Bibliometric Analysis of Exercise and Chronic Obstructive Pulmonary Disease.

Chronic Obstructive Pulmonary Disease (COPD) is the leading cause of death in the world. Pulmonary rehabilitation includes, but is not limited to, exercise training and education, which aim to improve the physical and psychological conditions of patients with chronic respiratory diseases through self-management interventions. The aim of this study was to perform a bibliometric analysis of studies on exercise and COPD published from 2000 to 2021 using VOSviewer and CiteSpace. All included literature was obtained from the Web of Science core collection. VOSviewer was used to analyze country or region, institution, major co-cited journals, and keywords. CiteSpace was used to analyze centrality, author and co-cited authors, journals, the strongest citation bursts of references, and keywords. A total of 1889 articles meeting the criteria were obtained. The United States has the largest number of publications. The American Journal of Respiratory and Critical Care Medicine is the most influential in this field, and the most published research institution is Queen's University. Denis E. O'Donnell has made significant contributions to exercise and COPD research. Association, impact, and statement are hot spots of research in this field. A bibliometric analysis of exercise interventions for COPD over the past 22 years provides direction for future research.

Chronic Obstructive Pulmonary Disease – Recent Updates

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of death and disability globally as well as in Bangladesh. Continuing research is essential to combat the threat posed by rising prevalence of COPD. Here we present recent updates in the field of COPD research. The revised definition of COPD emphasizes COPD as a heterogeneous disease affecting the bronchi, bronchioles, alveoli and pulmonary vasculature. The traditional view of COPD as a smoker’s disease with a late onset has been replaced by the new concept of COPD etiotypes, which recognizes the contribution of developmental, genetic, environmental, infective and idiopathic contributions to COPD. Vaping has also been proposed as a risk factor for COPD. Two precursors to COPD – pre-COPD and PRISm – have also been proposed to highlight the opportunity of early detection and management. Clinical classification of COPD has been updated to the simplified ABE approach. New recommendations for treatment prioritize the initial use of a fixed dose LABA+LAMA combination. A more judicious use of ICS in COPD patients is recommended, in those with specific indications (exacerbation-prone, high eosinophil counts, or concomitant asthma). In this population, single-inhaler triple-therapy of LABALAMA- ICS has replaced previous recommendations of LABA-ICS. A strong emphasis has been placed on appropriate, individualized choice of inhaler device and training on technique for each patient. Interventional pulmonology and minimally invasive surgery also have a growing role in management of selected patients. Small airways disease is a key cause of morbidity in COPD. Newer diagnostic techniques, such as impulse oscillometry, and novel drug formulations (extra-fine particles, cosuspension forms, soft mist inhalers) are under study. The monoclonal antibody dupilumab has also shown promise in reducing COPD exacerbation. Finally, COPD is a multisystem disease and any management plan must include steps to identify and treat associated co-morbidities. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 197

A bibliometric analysis of chronic obstructive pulmonary disease and COVID-19.

The coronavirus disease 2019 (COVID-19) outbreak became the worst epidemic in decades. Since its inception, COVID-19 has had a dramatic impact on chronic obstructive pulmonary disease (COPD) patients. This study explores explore the current status, hot spots, and research frontiers of COVID-19 and COPD based on a bibliometric approach. The Web of Science Core Collection was used to search the literature related to COPD and COVID-19, and VOSviewer and CiteSpace software were applied to analyze the distribution characteristics, research hotspots, and research frontiers of literature in related fields and to map the scientific knowledge domains. A total of 816 valid publications were included, among which USA, China, and England are the core countries/regions publishing related literature, and the research institutions are concentrated in Huazhong University of Science and Technology (18 papers), University College London (17 papers), and Imperial College London (16 papers). Guan WJ is the most prolific author with the most articles. The journals with the most publications are PLOS ONE, JOURNAL OF CLINICAL MEDICINE, and FRONTIERS IN MEDICINE. The main research hotspots in this field are clinical features, disease management, and mechanism research. By constructing COPD and COVID-19 research network diagrams, we reveal the hot spots, frontiers, and development trends of relevant research fields, which provide a reference for subsequent researchers to quickly grasp the current status of related research fields.

A proteomics approach to identify COPD-related changes in lung fibroblasts.

Lung fibroblasts are implicated in abnormal tissue repair in chronic obstructive pulmonary disease (COPD). The exact mechanisms are unknown and comprehensive analysis comparing COPD- and control fibroblasts is lacking. The aim of this study is to gain insight into the role of lung fibroblasts in COPD pathology using unbiased proteomic and transcriptomic analysis. Protein and RNA were isolated from cultured parenchymal lung fibroblasts of 17 patients with stage IV COPD and 16 non-COPD controls. Proteins were analyzed using LC-MS/MS and RNA through RNA sequencing. Differential protein and gene expression in COPD was assessed via linear regression, followed by pathway enrichment, correlation analysis, and immunohistological staining in lung tissue. Proteomic and transcriptomic data were compared to investigate the overlap and correlation between both levels of data. We identified 40 differentially expressed (DE) proteins and zero DE genes between COPD and control fibroblasts. The most significant DE proteins were HNRNPA2B1 and FHL1. Thirteen of the 40 proteins were previously associated with COPD, including FHL1 and GSTP1. Six of the 40 proteins were related to telomere maintenance pathways, and were positively correlated with the senescence marker LMNB1. No significant correlation between gene and protein expression was observed for the 40 proteins. We hereby describe 40 DE proteins in COPD fibroblasts including previously described COPD proteins (FHL1, GSTP1) and new COPD research targets like HNRNPA2B1. Lack of overlap and correlation between gene and protein data supports the use of unbiased proteomics analysis and indicates that different types of information are generated with both methods.

Development of a real-world database for asthma and COPD: The SingHealth-Duke-NUS-GSK COPD and Asthma Real-World Evidence (SDG-CARE) collaboration

PurposeThe SingHealth-Duke-GlaxoSmithKline COPD and Asthma Real-world Evidence (SDG-CARE) collaboration was formed to accelerate the use of Singaporean real-world evidence in research and clinical care. A centerpiece of the collaboration was to develop a near real-time database from clinical and operational data sources to inform healthcare decision making and research studies on asthma and chronic obstructive pulmonary disease (COPD).MethodsOur multidisciplinary team, including clinicians, epidemiologists, data scientists, medical informaticians and IT engineers, adopted the hybrid waterfall-agile project management methodology to develop the SingHealth COPD and Asthma Data Mart (SCDM). The SCDM was developed within the organizational data warehouse. It pulls and maps data from various information systems using extract, transform and load (ETL) pipelines. Robust user testing and data verification was also performed to ensure that the business requirements were met and that the ETL pipelines were valid.ResultsThe SCDM includes 199 data elements relevant to asthma and COPD. Data verification was performed and found the SCDM to be reliable. As of December 31, 2019, the SCDM contained 36,407 unique patients with asthma and COPD across the spectrum from primary to tertiary care in our healthcare system. The database updates weekly to add new data of existing patients and to include new patients who fulfil the inclusion criteria.ConclusionsThe SCDM was systematically developed and tested to support the use RWD for clinical and health services research in asthma and COPD. This can serve as a platform to provide research and operational insights to improve the care delivered to our patients.

The Current Landscape of COPD-Related Clinical Trials Registered on the World Health Organization's International Clinical Trials Registry Platform: A Comprehensive Analysis of Study Characteristics and Publication Status.

Despite studies investigating the publication rates and factors influencing publication outcomes of clinical trials in some disease fields, there is a notable lack of research focusing on chronic obstructive pulmonary disease (COPD) clinical trials. This study aims to explore the characteristics of COPD-related clinical trials and identify factors associated with publication status and publication time. A systematic search was conducted on the World Health Organization International Clinical Trials Registry Platform on April 28, 2022, to identify completed interventional clinical trials related to COPD. Various trial features were analyzed, and factors influencing publication status and time were examined. A total of 2577 completed interventional clinical trials focusing on COPD were identified. A total of 42.76% of trials enrolled ≤50 participants. The majority of trials were randomized (81.72%), blind (57.39%), parallel-assignment (59.14%), single-center (51.30%), multi-arm (83.86%), nonindustry funded (52.00%), and conducted for therapeutic purposes (73.11%). The 2-year cumulative publication rate was found to be 27.9%. The median time of study duration, dissemination lag, and publication lag were 17.27, 21.07, and 24.70 months, respectively. Multivariate analysis revealed that sample size, blind design, and study phase significantly influenced the likelihood of publication, while intervention model, primary purpose, study phase, funder, and study duration were significant factors affecting publication time. The findings highlight the inadequacy of large multi-center interventional clinical trials for COPD and indicate a low 2-year cumulative publication rate. Strengthening collaboration among investigators and adopting scientifically robust designs for larger phase 3 clinical trials are crucial to advancing COPD research and enhancing publication outcomes.

Disease-related knowledge in people with chronic obstructive pulmonary disease and their informal caregivers: A multilevel modelling analysis.

To assess the level of chronic obstructive pulmonary disease (COPD)-related knowledge within patient and informal caregiver dyads, and to identify factors influencing the knowledge level considering the interdependence within the dyads. Patients with COPD and their informal caregivers present poor disease knowledge and different characteristics are associated with their level of knowledge. Disease knowledge and related characteristics have been assessed separately in patients and informal caregivers, without considering possible influence within the dyads. Cross-sectional study. A convenience sample of dyads was recruited in outpatient and inpatient settings in Central and South Italy. The Bristol COPD Knowledge Questionnaire was used to measure disease knowledge. Sociodemographic, clinical and caregiving characteristics, self-efficacy and depression were measured in patients and caregivers. Multilevel modelling was used to analyse COPD knowledge at the level of the dyad to control for interdependency between patients and informal caregivers. The STROBE guidelines for cross-sectional studies were followed for study reporting. We recruited 133 dyads. The total level of correct knowledge shared by dyads was 32.89%. Dyads presented higher levels of correct knowledge about disease symptoms, smoking cessation and vaccination, and lower about COPD treatment. Younger patients with greater self-efficacy, who attended pulmonary rehabilitation and were cared for by a spouse/partner with low levels of depression, and informal caregivers who were patients' spouse/partner were more likely to have higher levels of disease-related knowledge. Our study advances dyadic research in COPD. Future studies should investigate the effects of shared knowledge and incongruent knowledge (where one member knows more than the other) on patient self-care and caregiver contribution to patient self-care. Our study shows what knowledge nurses should provide in educational programmes directed at patients and caregivers, and which dyads have greater knowledge deficits, to whom offer targeted educational interventions.

Improving Physiological, Physical, and Psychological Health Outcomes: A Narrative Review in US Veterans with COPD.

The Veterans Health Administration (VHA) is the largest integrated healthcare system in the United States (US) providing healthcare to an increasing number of middle-aged and older adults who remain at greater risk for chronic obstructive pulmonary disease (COPD) compared to their civilian counterparts. The VHA has obligated research funds, drafted clinical guidelines, and built programmatic infrastructure to support the diagnosis, treatment, and care management of Veterans with COPD. Despite these efforts, COPD remains a leading cause of morbidity and mortality in Veterans. This paper provides a narrative review of research conducted with US Veteran samples targeting improvement in COPD outcomes. We review key physiological, physical, and psychological health outcomes and intervention research that included US Veteran samples. We conclude with a discussion of directions for future research to continue advancing the treatment of COPD in Veterans and inform advancements in COPD research within and outside the VHA.

Photon-counting CT versus conventional CT for COPD quantifications: intra-scanner optimization and inter-scanner assessments using virtual imaging trials.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease and a major cause of death and disability worldwide. Quantitative CT is a powerful tool to better understand the heterogeneity and severity of this disease. Quantitative CT is being increasingly used in COPD research, and the recent advancements in CT technology have made it even more encouraging. One recent advancement has been the development of photon-counting detectors, offering higher spatial resolution, higher image contrast, and lower noise levels in the images. However, the quantification performance of this new technology compared to conventional scanners remains unknown. Additionally, different protocol settings (e.g., different dose levels, slice thicknesses, reconstruction kernels and algorithms) affect quantifications in an unsimilar fashion. This study investigates the potential advantages of photon-counting CT (PCCT) against conventional energy-integrating detector (EID) CT and explores the effects of protocol settings on lung density quantifications in COPD patients. This study was made possible using a virtual imaging platform, taking advantage of anthropomorphic phantoms with COPD (COPD-XCAT) and a scanner-specific CT simulator (DukeSim). Having the physical and geometrical properties of three Siemens commercial scanners (Flash, Force for EID and NAEOTOM Alpha for PCCT) modeled, we simulated CT images of ten COPD-XCAT phantoms at 0.63 and 3.17 mGy dose levels and reconstructed at three levels of kernel sharpness. The simulated CT images were quantified in terms of "Lung mean absolute error (MAE)," "LAA -950," "Perc 15," "Lung mass" imaging biomarkers and compared against the ground truth values of the phantoms. The intra-scanner assessment demonstrated the superior qualitative and quantitative performance of the PCCT scanner over the conventional scanners (21.01% and 22.74% mean lung MAE improvement, and 53.97% and 68.13% mean LAA -950 error improvement compared to Flash and Force). The results also showed that higher mAs, thinner slices, smoother kernels, and iterative reconstruction could lead to more accurate and precise quantification scores. This study underscored the qualitative and quantitative benefits of PCCT against conventional EID scanners as well as the importance of optimal protocol choice within scanners for more accurate quantifications.

Potential Natural Small Molecular Compounds for the Treatment of Chronic Obstructive Pulmonary Disease: An Overview.

Chronic obstructive pulmonary disease (COPD) is one of the major diseases threatening human life and health. According to the report released by the World Health Organization (WHO) in 2020, COPD has become the third leading cause of death in the world, featuring a sustainable growth of incidence rate as well as population age. The purpose of this review focuses on the advancement of bioactive natural compounds, such as baicalin, quercetin, resveratrol, and curcumin, which demonstrate promising therapeutic/interventional effects on CODP in vitro and in vivo. Information emphasizing on COPD was systematically collected from several authoritative internet databases including Web of Science, PubMed, Elsevier, Wiley Online Library, and Europe PMC, with a combination of keywords containing “COPD” and “natural small molecular compounds”. The new evidence indicated that these valuable molecules featured unique functions in the treatment of COPD through various biological processes such as anti-inflammatory, anti-oxidant, anti-apoptosis, and anti-airway fibrosis. Moreover, we found that the promising effects of these natural compounds on COPD were mainly achieved through JAK3/STAT3/NF-κB and MAPK inflammatory signaling pathways, Nrf2 oxidative stress signaling pathway, and TGF-β1/Smad 2/3 fibrosis signaling pathway, which referenced to multiple targets like TNF-α, IL-6, IL-8, TIMP-1, MMP, AKT, JAK3, IKK, PI3K, HO-1, MAPK, P38, ERK, etc. Current challenges and future directions in this promising field are also discussed at the end of this review. For the convenience of the readers, this review is divided into ten parts according to the structures of potential natural small molecular compounds. We hope that this review brings a quick look and provides some inspiration for the research of COPD.

Disparities in Hospitalized Chronic Obstructive Pulmonary Disease Exacerbations Between American Indians and Non-Hispanic Whites.

The prevalence of chronic obstructive pulmonary disease (COPD) is high in American Indian (AI) populations, as are diabetes and obesity, which are common COPD comorbidities. However, COPD research among AI populations is limited. We conducted a retrospective study to investigate potential health disparities and risk factors among AI and non-Hispanic White (NHW) patients with COPD exacerbations hospitalized at the University of Oklahoma Medical Center between July 2001 and June 2020. Demographics, clinical variables, and outcomes were collected. A total of 76 AI patients and 304 NHW patients were included. AI patients had more comorbidities than did NHW patients (4.3 versus.3.1, p<0.001). In multiple variable analyses, AI race was associated with higher odds of needing intensive care unit (ICU) care ( odds ratio [OR], 2.37, 95% confidence interval [CI], 1.36--4.16, p=0.002) and invasive mechanical ventilator use (OR, 2.75, 95% CI, 1.42-5.29, p=0.002). AI race was also associated with longer ICU stays compared with NHWs (OR, 1.43, 95% CI, 1.18--1.73, p<0.001). The average number of days on mechanical ventilator support increased by 137.3% for an AI patient compared to an NHW patient (p<0.001). AI race was not associated with discharge to other health facilities (OR, 0.98, 95% CI, 0.52-1.83, p=0.944). AI patients were more likely than NHW patients to need ICU care and ventilator support, have longer ICU stays, and more days on mechanical ventilator support. More studies are needed to identify reasons for these disparities and effective interventions to reduce them.

Developing a patient-driven chronic obstructive pulmonary disease (COPD) research agenda in the U.S.

BackgroundTo document a generalizable process for developing a patient-prioritized chronic obstructive pulmonary disease (COPD) research agenda and to provide an overview of domains that were developed in response to people living with COPD and caregivers’ suggestions for research.MethodsAdults with COPD and caregivers who are members of the COPD Patient-Powered Research Network (PPRN) provided suggestions for COPD-related research through a self-administered, online survey. These responses were analyzed with a content analysis approach: domains for categorizing all survey responses were created, then all responses were categorized independently by a group of researchers, then these categorizations were adjudicated, and finally a density map was created that represented the number of responses in each of the domains.ResultsAt the time of analysis, 6157 adults had fully completed the baseline survey. Survey responses were categorized across seven domains as follows: 22.5% of all responses fell into the domain family/social/community research, 20.8% of all responses fell into the domain well-being, 15% of all responses fell into the domain curative research, 14.6% of all responses fell into the domain biomedical therapies, 10.5% of all responses fell into the domain policy concerns, 6% of all responses fell into the domain holistic therapies and 10.7% of all responses fell into the domain ambiguous comments that could not be translated into concrete research topics.ConclusionUsing qualitative open-ended survey responses from the COPD PPRN registrants, we were able to identify six key domains of research about COPD that are considered most important by patients. These domains differ in content from prior scientist-led efforts to develop priorities for COPD research, demonstrating the ongoing importance of involving patients and their caregivers in determining research priorities. The results suggest the field can more closely align research efforts to patient priorities by considering the identified domains.

Research priorities to address the global burden of chronic obstructive pulmonary disease (COPD) in the next decade.

BackgroundThe global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD.MethodsWe adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities.Results62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity.ConclusionsThe experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD.

An independently validated, portable algorithm for the rapid identification of COPD patients using electronic health records

Electronic health records (EHR) provide an unprecedented opportunity to conduct large, cost-efficient, population-based studies. However, the studies of heterogeneous diseases, such as chronic obstructive pulmonary disease (COPD), often require labor-intensive clinical review and testing, limiting widespread use of these important resources. To develop a generalizable and efficient method for accurate identification of large COPD cohorts in EHRs, a COPD datamart was developed from 3420 participants meeting inclusion criteria in the Mass General Brigham Biobank. Training and test sets were selected and labeled with gold-standard COPD classifications obtained from chart review by pulmonologists. Multiple classes of algorithms were built utilizing both structured (e.g. ICD codes) and unstructured (e.g. medical notes) data via elastic net regression. Models explicitly including and excluding spirometry features were compared. External validation of the final algorithm was conducted in an independent biobank with a different EHR system. The final COPD classification model demonstrated excellent positive predictive value (PPV; 91.7%), sensitivity (71.7%), and specificity (94.4%). This algorithm performed well not only within the MGBB, but also demonstrated similar or improved classification performance in an independent biobank (PPV 93.5%, sensitivity 61.4%, specificity 90%). Ancillary comparisons showed that the classification model built including a binary feature for FEV1/FVC produced substantially higher sensitivity than those excluding. This study fills a gap in COPD research involving population-based EHRs, providing an important resource for the rapid, automated classification of COPD cases that is both cost-efficient and requires minimal information from unstructured medical records.

Artificial intelligence in COPD: Possible applications and future prospects.

Artificial intelligence in COPD: Possible applications and future prospects.

Inhaled nitric oxide improves ventilatory efficiency and exercise capacity in patients with mild COPD: A randomized-control cross-over trial.

Patients with mild chronic obstructive pulmonary disease (COPD) have an elevated ventilatory equivalent to CO2 production ( / ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. Despite emerging evidence that mild COPD is associated with pulmonary microvascular dysfunction, limited research has focused on experimentally modulating the pulmonary microvasculature during exercise in mild COPD. The present study sought to examine the effect of inhaled nitric oxide (iNO), a selective pulmonary vasodilator, on / , dyspnoea and exercise capacity in patients with mild COPD. Experimental iNO increased peak oxygen uptake in mild COPD, secondary to reduced / and dyspnoea. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD. Patients with mild chronic obstructive pulmonary disease (COPD) have an exaggerated ventilatory response to exercise, contributing to dyspnoea and exercise intolerance. Previous research in mild COPD has demonstrated an elevated ventilatory equivalent to CO2 production ( / ) during exercise, secondary to increased dead space ventilation. The reason for the increased dead space is unclear, although pulmonary microvascular dysfunction and the corresponding capillary hypoperfusion is a potential mechanism. The present study tested the hypothesis that inhaled nitric oxide (iNO), a selective pulmonary vasodilator, would lower / and dyspnoea, and improve exercise capacity in patients with mild COPD. In this multigroup randomized-control cross-over study, 15 patients with mild COPD (FEV1 = 89±11% predicted) and 15 healthy controls completed symptom-limited cardiopulmonary exercise tests while breathing normoxic gas or 40ppm iNO. Compared with placebo, iNO significantly increased peak oxygen uptake (1.80±0.14 vs. 1.53±0.10 L·min-1 , P<0.001) in COPD, whereas no effect was observed in controls. At an equivalent work rate of 60W, iNO reduced / by 3.8±4.2units (P=0.002) and dyspnoea by 1.1±1.2Borg units (P<0.001) in COPD, whereas no effect was observed in controls. Operating lung volumes and oxygen saturation were unaffected by iNO in both groups. iNO increased peak oxygen uptake in COPD, secondary to reduced / and dyspnoea. These data suggest that mild COPD patients demonstrate pulmonary microvascular dysfunction that contributes to increased / , dyspnoea and exercise intolerance. This is the first study to demonstrate that experimental manipulation of the pulmonary circulation alone, can positively impact dyspnoea and exercise capacity in mild COPD.