Blood Eosinophil Counts in Clinical Trials for Chronic Obstructive Pulmonary Disease.
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ABSTRACT:
SUBMITTER: Singh D
PROVIDER: S-EPMC7462391 | biostudies-literature | 2020 Sep
REPOSITORIES: biostudies-literature
Publications
Blood Eosinophil Counts in Clinical Trials for Chronic Obstructive Pulmonary Disease.
Singh Dave D Bafadhel Mona M Brightling Christopher E CE Sciurba Frank C FC Curtis Jeffrey L JL Martinez Fernando J FJ Pasquale Cara B CB Merrill Debora D DD Metzdorf Norbert N Petruzzelli Stefano S Tal-Singer Ruth R Compton Christopher C Rennard Stephen S Martin Ubaldo J UJ
American journal of respiratory and critical care medicine 20200901 5
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Project description:BackgroundEosinophilic airway inflammation in patients with chronic obstructive pulmonary disease (COPD) is associated with exacerbations and responsivity to steroids, suggesting potential shared mechanisms with eosinophilic asthma. However, there is no consistent blood eosinophil count that has been used to define the increased exacerbation risk.ObjectiveWe sought to investigate blood eosinophil counts associated with exacerbation risk in patients with COPD.MethodsBlood eosinophil counts and exacerbation risk were analyzed in patients with moderate-to-severe COPD by using 2 independent studies of former and current smokers with longitudinal data. The Genetic Epidemiology of COPD (COPDGene) study was analyzed for discovery (n = 1,553), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was analyzed for validation (n = 1,895). A subset of the ECLIPSE study subjects were used to assess the stability of blood eosinophil counts over time.ResultsCOPD exacerbation risk increased with higher eosinophil counts. An eosinophil count threshold of 300 cells/μL or greater showed adjusted incidence rate ratios for exacerbations of 1.32 in the COPDGene study (95% CI, 1.10-1.63). The cutoff of 300 cells/μL or greater was validated for prospective risk of exacerbation in the ECLIPSE study, with adjusted incidence rate ratios of 1.22 (95% CI, 1.06-1.41) using 3-year follow-up data. Stratified analysis confirmed that the increased exacerbation risk associated with an eosinophil count of 300 cells/μL or greater was driven by subjects with a history of frequent exacerbations in both the COPDGene and ECLIPSE studies.ConclusionsPatients with moderate-to-severe COPD and blood eosinophil counts of 300 cells/μL or greater had an increased risk exacerbations in the COPDGene study, which was prospectively validated in the ECLIPSE study.
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Project description:Treating patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (COPD) usually involves administering systemic corticosteroids. The many unwanted side effects associated with this treatment have led to increased interest in minimising the accumulated corticosteroid dose necessary to treat exacerbations. Studies have shown that short-term treatment with corticosteroids is preferred, and recent trials have shown that biomarkers can be used to further reduce exposure to corticosteroids. Interestingly, high eosinophil counts in patients with acute exacerbations of COPD are indicative of an eosinophilic phenotype with a distinct response to treatment with corticosteroids. In addition, post-hoc analysis of randomised control trials have shown that higher blood eosinophil counts at the start of the study predict a greater response to inhaled corticosteroids in stable COPD. In this review, we examine the studies on this topic, describe how blood eosinophil cell count may be used as a biomarker to guide treatment with corticosteroids, and identify some relevant challenges.
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Project description:Telehealth (TH) interventions with Chronic Obstructive Pulmonary Disease (COPD) management were introduced in the literature more than 20 years ago with different labeling, but there was no summary for the overall acceptance and dropout rates as well as associated variables. This review aims to summarize the acceptance and dropout rates used in TH interventions and identify to what extent clinical settings, sociodemographic factors, and intervention factors might impact the overall acceptance and completion rates of TH interventions. We conducted a systematic search up to April 2021 on CINAHL, PubMed, MEDLINE (Ovid), Cochrane, Web of Sciences, and Embase to retrieve randomized and non-randomized control trials that provide TH interventions alone or accompanied with other interventions to individuals with COPD. Twenty-seven studies met the inclusion criteria. Overall, the unweighted average of acceptance and dropout rates for all included studies were 80% and 19%, respectively. A meta-analysis on the pooled difference between the acceptance rates and dropout rates (weighted by the sample size) revealed a significant difference in acceptance and dropout rates among all TH interventions 51% (95% CI 49% to 52; p < 0.001) and 63% (95% CI 60% to 67; p < 0.001), respectively. Analysis revealed that acceptance and dropout rates can be impacted by trial-related, sociodemographic, and intervention-related variables. The most common reasons for dropouts were technical difficulties (33%), followed by complicated system (31%). Current TH COPD interventions have a pooled acceptance rate of 51%, but this is accompanied by a high dropout rate of 63%. Acceptance and dropout levels in TH clinical trials can be affected by sociodemographic and intervention-related factors. This knowledge enlightens designs for well-accepted future TH clinical trials. PROSPERO registration number CRD4201707854.
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Project description:Diaphragm muscles in Chronic Obstructive Pulmonary Disease (COPD) patients undergo an adaptive fast to slow transformation that includes cellular adaptations. This project studies the signaling mechanisms responsible for this transformation. Keywords: other
2003-07-16 | GSE475 | GEO
Project description:BackgroundThe distribution and determinants of blood eosinophil counts in the general population are unclear. Furthermore, whether elevated blood eosinophil counts increase risk for cardiovascular disease (CVD) and other chronic diseases, other than atopic conditions, remains uncertain.ObjectiveWe sought to describe the distribution of eosinophil counts in the general population and determine the association of eosinophil count with prevalent chronic disease and incident CVD.MethodsA population-based adult cohort was followed from January 1, 2006, to December 31, 2020. Electronic health record data regarding demographic characteristics, prevalent clinical characteristics, and incident CVD were extracted. Associations between blood eosinophil counts and demographic characteristics, chronic diseases, laboratory values, and risks of incident CVD were assessed using chi-square test, ANOVA, and Cox proportional hazards regression.ResultsBlood eosinophil counts increased with age, body mass index, and reported smoking and tobacco use. The prevalence of chronic obstructive pulmonary disease, hypertension, cardiac arrhythmias, hyperlipidemia, diabetes mellitus, chronic kidney disease, and cancer increased as eosinophil counts increased. Eosinophil counts were significantly associated with coronary heart disease (hazard ratio [HR], 1.44; 95% CI, 1.12-1.84) and heart failure (HR, 1.62; 95% CI, 1.30-2.01) in fully adjusted models and with stroke/transient ischemic attack (HR, 1.37; 95% CI, 1.16-1.61) and CVD death (HR, 1.49; 95% CI, 1.10-2.00) in a model adjusting for age, sex, race, and ethnicity.ConclusionsBlood eosinophil counts differ by demographic and clinical characteristics as well as by prevalent chronic disease. Moreover, elevated eosinophil counts are associated with risk of CVD. Further prospective investigations are needed to determine the utility of eosinophil counts as a biomarker for CVD risk.
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Project description:IntroductionChronic obstructive pulmonary disease (COPD) is the third leading cause of death, and COPD exacerbation worsens the prognosis. Eosinophilic airway inflammation is a COPD phenotype that causes COPD exacerbation and is correlated with peripheral blood eosinophil count. We analyzed real-world data of COPD patients to assess the risk factors of COPD exacerbation focusing on blood eosinophils.Materials and methodsPatients with COPD who visited our hospital between January 1, 2018, and December 31, 2018, were recruited, and their background information, spirometry data, laboratory test results, and moderate-to-severe exacerbation events during the one-year follow-up period were collected from the electronic medical records and analyzed. The COPD exacerbation risk factors were assessed using univariate and multivariate logistic regression analyses.ResultsTwenty-two of 271 (8.1%) patients experienced moderate-to-severe exacerbation. Patients with exacerbation showed worse pulmonary function, and we found that a high blood eosinophil count (≥350 cells/μL; p=0.014), low % FEV1 (<50%; p=0.002), increase in white blood cell (≥9000 cells/μL; p=0.039), and use of home oxygen therapy (p=0.005) were risk factors for future exacerbations. We also found a strong correlation between eosinophil count cut-offs and exacerbation risk (r = 0.89, p < 0.001). On the other hand, there was no relation between exacerbation risk and inhalation therapy for COPD.ConclusionIn a real-world setting, peripheral blood eosinophil count could be a predictor of future COPD exacerbation.
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Project description:BackgroundChest computed tomography (CT) is a widely used method to assess morphological and dynamic abnormalities in chronic obstructive pulmonary disease (COPD). The small pulmonary vascular cross-section (CSA), quantitatively extracted from volumetric CT, is a reliable indicator for predicting pulmonary vascular changes. CSA is associated with the severity of symptoms, pulmonary function tests (PFT) and emphysema and in COPD patients the severity increases over time. We analyzed the correlation longitudinal changes in pulmonary vascular parameters with clinical parameters in COPD patients.Materials and methodsA total of 288 subjects with COPD were investigated during follow up period up to 6 years. CT images were classified into five subtypes from normal to severe emphysema according to percentage of low-attenuation areas less than -950 and -856 Hounsfield units (HU) on inspiratory and expiratory CT (LAA-950, LAA-856exp). Total number of vessels (Ntotal) and total number of vessels with area less than 5 mm2 (N<5 mm) per 1 cm2 of lung surface area (LSA) were measured at 6 mm from the pleural surface.ResultsNtotal/LSA and N<5 mm/LSA changed from 1.16 ± 0.27 to 0.87 ± 0.2 and from 1.02 ± 0.22 to 0.78 ± 0.22, respectively, during Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage progression. Both parameters changed from normal to severe emphysema according to CT subtype from 1.39 ± 0.21 to 0.74 ± 0.17 and from 1.18 ± 0.19 to 0.67 ± 0.15, respectively. LAA-950 and LAA-856exp were negatively correlated with Ntotal/LSA (r = - 0.738, - 0.529) and N<5 mm /LSA (r = - 0.729, -- .497). On the other hand, pulmonary function test (PFT) results showed a weak correlation with Ntotal/LSA and N<5 mm/LSA (r = 0.205, 0.210). The depth in CT subtypes for longitudinal change both Ntotal/LSA and N<5 mm/LSA was (- 0.032, - 0.023) and (- 0.027) in normal and SAD, respectively.ConclusionsQuantitative computed tomography features faithfully reflected pulmonary vessel alterations, showing in particular that pulmonary vascular alteration started.
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2014-08-14 | E-GEOD-60399 | biostudies-arrayexpress
Project description:ObjectiveOur goal is to determine short-term intraindividual biologic and measurement variability in spirometry of patients with a wide range of stable chronic obstructive pulmonary disease severity, using datasets from the National Emphysema Treatment Trial (NETT) and the Lung Health Study (LHS). This may be applied to determine criteria that can be used to assess a clinically meaningful change in spirometry.MethodsA total of 5,886 participants from the LHS and 1,215 participants from the NETT performed prebronchodilator spirometry during two baseline sessions. We analyzed varying criteria for absolute and percent change of FEV(1) and FVC to determine which criterion was met by 90% of the participants.ResultsThe mean +/- SD FEV(1) for the initial session was 2.64 +/- 0.60 L (75.1 +/- 8.8% predicted) for the LHS and 0.68 +/- 0.22 L (23.7 +/- 6.5% predicted) for the NETT. The mean +/- SD number of days between test sessions was 24.9 +/- 17.1 for the LHS and 85.7 +/- 21.7 for the NETT. As the degree of obstruction increased, the intersession percent difference of FEV(1) increased. However, the absolute difference between tests remained relatively constant despite the severity of obstruction (0.106 +/- 0.10 L). Over 90% of participants had an intersession FEV(1) difference of less than 225 ml irrespective of the severity of obstruction.ConclusionsAbsolute changes in FEV(1) rather than percent change should be used to determine whether patients with chronic obstructive pulmonary disease have improved or worsened between test sessions.
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