Elevated blood eosinophils in acute COPD exacerbations: better short- and long-term prognosis.
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ABSTRACT:
SUBMITTER: Jabarkhil A
PROVIDER: S-EPMC7241534 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundBlood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting ?2-agonist and long-acting muscarinic antagonist).MethodsIn a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.ResultsOf the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included. Among patients with ?2 exacerbations and available eosinophil counts in the baseline period (CPRD, n =?3089 and Optum, n =?13414), 17.0 and 13.3% respectively had eosinophil counts ?400 cells/?L. Patients with ?2 exacerbations or eosinophil count ?400 cells/?L during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ?300 cells/?L (76.8% vs 76.5%), respectively in the follow-up year. In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/?L; patients with eosinophil count <?150 cells/?L had the lowest variability. Approximately 10% patients had both ?2 exacerbations and eosinophil count ?300 cells/?L across the databases.ConclusionA high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions. A small proportion of COPD patients had frequent exacerbations and eosinophil count ?300 cells/?L.
| S-EPMC6686508 | biostudies-literature
Project description:IntroductionContinuing inhaled corticosteroid (ICS) use does not benefit all patients with COPD, yet it is difficult to determine which patients may safely sustain ICS withdrawal. Although eosinophil levels can facilitate this decision, better biomarkers could improve personalised treatment decisions.MethodsWe performed transcriptional profiling of sputum to explore the molecular biology and compared the predictive value of an unbiased gene signature versus sputum eosinophils for exacerbations after ICS withdrawal in COPD patients. RNA-sequencing data of induced sputum samples from 43 COPD patients were associated with the time to exacerbation after ICS withdrawal. Expression profiles of differentially expressed genes were summarised to create gene signatures. In addition, we built a Bayesian network model to determine coregulatory networks related to the onset of COPD exacerbations after ICS withdrawal.ResultsIn multivariate analyses, we identified a gene signature (LGALS12, ALOX15, CLC, IL1RL1, CD24, EMR4P) associated with the time to first exacerbation after ICS withdrawal. The addition of this gene signature to a multiple Cox regression model explained more variance of time to exacerbations compared to a model using sputum eosinophils. The gene signature correlated with sputum eosinophil as well as macrophage cell counts. The Bayesian network model identified three coregulatory gene networks as well as sex to be related to an early versus late/nonexacerbation phenotype.ConclusionWe identified a sputum gene expression signature that exhibited a higher predictive value for predicting COPD exacerbations after ICS withdrawal than sputum eosinophilia. Future studies should investigate the utility of this signature, which might enhance personalised ICS treatment in COPD patients.
| S-EPMC8255541 | biostudies-literature
Project description:BackgroundThere is no clinically useful score to predict chronic obstructive pulmonary disease (COPD) exacerbations. We aimed to derive this by analyzing data from three existing COPD clinical trials of budesonide/formoterol, formoterol, or placebo in patients with moderate-to-very-severe COPD and a history of exacerbations in the previous year.MethodsPredictive variables were selected using Cox regression for time to first severe COPD exacerbation. We determined absolute risk estimates for an exacerbation by identifying variables in a binomial model, adjusting for observation time, study, and treatment. The model was further reduced to clinically useful variables and the final regression coefficients scaled to obtain risk scores of 0-100 to predict an exacerbation within 6 months. Receiver operating characteristic (ROC) curves and the corresponding C-index were used to investigate the discriminatory properties of predictive variables.ResultsThe best predictors of an exacerbation in the next 6 months were more COPD maintenance medications prior to the trial, higher mean daily reliever use, more exacerbations during the previous year, lower forced expiratory volume in 1 second/forced vital capacity ratio, and female sex. Using these risk variables, we developed a score to predict short-term (6-month) risk of COPD exacerbations (SCOPEX). Budesonide/formoterol reduced future exacerbation risk more than formoterol or as-needed short-acting ?2-agonist (salbutamol).ConclusionSCOPEX incorporates easily identifiable patient characteristics and can be readily applied in clinical practice to target therapy to reduce COPD exacerbations in patients at the highest risk.
| S-EPMC4315304 | biostudies-literature
Project description:BACKGROUND:Exacerbations of COPD (ECOPD) are a frequent cause of emergency room (ER) visits. Predictors of early outcome could help clinicians in orientation decisions. In the current study, we investigated whether mid-regional pro-adrenomedullin (MR-proADM) and copeptin, in addition to clinical evaluation, could predict short-term outcomes. PATIENTS AND METHODS:This prospective blinded observational study was conducted in 20 French centers. Patients admitted to the ER for an ECOPD were considered for inclusion. A clinical risk score was calculated, and MR-proADM and copeptin levels were determined from a venous blood sample. The composite primary end point comprised 30-day death or transfer to the intensive care unit or a new ER visit. RESULTS:A total of 379 patients were enrolled in the study, of whom 277 were eventually investigated for the primary end point that occurred in 66 (24%) patients. In those patients, the median (interquartile range [IQR]) MR-proADM level was 1.02 nmol/L (0.77-1.48) versus 0.83 nmol/L (0.63-1.07) in patients who did not meet the primary end point (P=0.0009). In contrast, copeptin levels were similar in patients who met or did not meet the primary end point (P=0.23). MR-proADM levels increased with increasing clinical risk score category: 0.74 nmol/L (0.57-0.89), 0.83 nmol/L (0.62-1.12) and 0.95 nmol/L (0.75-1.29) for the low-, intermediate- and high-risk categories, respectively (P<0.001). MR-proADM was independently associated with the primary end point (odds ratio, 1.65; 95% confidence interval [CI], 1.10-2.48; P=0.015). MR-proADM predicted the occurrence of primary end point with a sensitivity of 46% (95% CI, 33%-58%) and a specificity of 79% (95% CI, 74-84). CONCLUSION:MR-proADM but not copeptin was significantly associated with outcomes at 30 days, even after adjustment for clinical risk category. Overall, MR-proADM, alone or combined with the clinical risk score, was a moderate strong predictor of short-term outcomes.
| S-EPMC5383071 | biostudies-literature
Project description:OBJECTIVE:We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting ?2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ?2% were associated with a greater reduction in exacerbation rates with ICS therapy. METHODS:Three studies of ?1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ?2%). At baseline, 57-75% of patients had ?2% blood eosinophils. Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. RESULTS:For patients with ?2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. DISCUSSION:Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations.
| S-EPMC4752631 | biostudies-other
Project description:BackgroundTechnology-based physical activity (PA) interventions have been shown to improve daily step counts and health-related quality of life, but their effect on long-term clinical outcomes like acute exacerbations (AEs) is unknown in persons with COPD.MethodsU.S. Veterans with stable COPD were randomized (1:1) to either pedometer alone (control) or pedometer plus a website with feedback, goal-setting, disease education, and a community forum (intervention) for 3 months. AEs were assessed every 3 months over a follow-up period of approximately 15 months. Pedometer-assessed daily step counts, health-related quality-of-life (HRQL), and self-efficacy were assessed at baseline, end-of-intervention at 3 months, and during follow-up approximately 6 and 12 months after enrollment. Zero-inflated Poisson models assessed the effect of the intervention on risk for AEs, compared to controls. Generalized linear mixed-effects models for repeated measures examined between-group and within-group changes in daily step count, HRQL, and self-efficacy.ResultsThere were no significant differences in age, FEV1% predicted, baseline daily step count, AEs the year prior to enrollment, or duration of follow-up between the intervention (n = 57) and control (n = 52) groups. The intervention group had a significantly reduced risk of AEs (rate ratio = 0.51, [95%CI 0.31-0.85]), compared to the control group. There were no significant between-group differences in change in average daily step count, HRQL, or self-efficacy at 6 and 12 months after enrollment.ConclusionsA 3-month internet-mediated, pedometer-based PA intervention was associated with reduced risk for AEs of COPD over 12-15 months of follow-up. ClinicalTrials.gov identifier: NCT01772082.
| S-EPMC7269114 | biostudies-literature
Project description:BACKGROUND:Chronic obstructive pulmonary disease (COPD) is characterized by varying trajectories of decline. Information regarding the prognostic value of preventing short-term clinically important deterioration (CID) in lung function, health status, or first moderate/severe exacerbation as a composite endpoint of worsening is needed. We evaluated post hoc the link between early CID and long-term adverse outcomes. METHODS:CID was defined as ?100 mL decrease in forced expiratory volume in 1 s (FEV1), ?4-unit increase in St George's Respiratory Questionnaire (SGRQ) score from baseline, and/or a moderate/severe exacerbation during enrollment in two 3-year studies. Presence of CID was assessed at 6 months for the principal analysis (TORCH) and 12 months for the confirmatory analysis (ECLIPSE). Association between presence (+) or absence (-) of CID and long-term deterioration in FEV1, SGRQ, future risk of exacerbations, and all-cause mortality was assessed. RESULTS:In total, 2870 (54%; TORCH) and 1442 (73%; ECLIPSE) patients were CID+. At 36 months, in TORCH, CID+ patients (vs CID-) had sustained clinically significant worsening of FEV1 (-?117 mL; 95% confidence interval [CI]: -?134, -?100 mL; P?<?0.001) and SGRQ score (+?6.42 units; 95% CI: 5.40, 7.45; P?<?0.001), and had higher risk of exacerbations (hazard ratio [HR]: 1.61 [95% CI: 1.50, 1.72]; P?<?0.001) and all-cause mortality (HR: 1.41 [95% CI: 1.15, 1.72]; P?<?0.001). Similar risks post-CID were observed in ECLIPSE. CONCLUSIONS:A CID within 6-12 months of follow-up was consistently associated with increased long-term risk of exacerbations and all-cause mortality, and predicted sustained meaningful loss in FEV1 and health status amongst survivors. TRIAL REGISTRATION:NCT00268216 ; NCT00292552 .
| S-EPMC6245880 | biostudies-literature
Project description:Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are caused by a variety of different etiologic agents. Our aim was to phenotype COPD exacerbations using imaging (chest X-ray [CXR] and computed tomography [CT]) and to determine the possible role of the blood tests (C-reactive protein [CRP], the N-terminal prohormone brain natriuretic peptide [NT-proBNP]) as diagnostic biomarkers.Subjects who were hospitalized with a primary diagnosis of AECOPD and who had had CXRs, CT scans, and blood collection for CRP and NT-proBNP were assessed in this study. Radiologist blinded to the clinical and laboratory characteristics of the subjects interpreted their CXRs and CT images. ANOVA and Spearman's correlation were performed to test for associations between these imaging parameters and the blood-based biomarkers NT-proBNP and CRP; logistic regression models were used to assess the performance of these biomarkers in predicting the radiological parameters.A total of 309 subjects were examined for this study. Subjects had a mean age of 65.6±11.1 years, 66.7% of them were males, and 62.4% were current smokers, with a mean FEV1 54.4%±21.5% of predicted. Blood NT-proBNP concentrations were associated with cardiac enlargement (area under the curve [AUC] =0.72, P<0.001), pulmonary edema (AUC =0.63, P=0.009), and pleural effusion on CXR (AUC =0.64, P=0.01); whereas on CT images, NT-proBNP concentrations were associated with pleural effusion (AUC =0.71, P=0.002). Serum CRP concentrations, on the other hand, were associated with consolidation on CT images (AUC =0.75, P<0.001), ground glass opacities (AUC =0.64, P=0.028), and pleural effusion (AUC =0.72, P<0.001) on CT images. A serum CRP sensitivity-oriented cutoff point of 11.5 mg/L was selected for the presence of consolidation on CT images in subjects admitted as cases of AECOPD, which has a sensitivity of 91% and a specificity of 53% (P<0.001).Elevated CRP may indicate the presence of pneumonia, while elevated NT-proBNP may indicate cardiac dysfunction. These readily available blood-based biomarkers may provide more accurate phenotyping of AECOPD and enable the discovery of more precise therapies.
| S-EPMC5764289 | biostudies-literature
Project description:Background:Growing evidence suggests that blood eosinophil count is associated with patient responsiveness to inhaled corticosteroids (ICS). We performed post hoc predictive modeling on data from the FORWARD study and two replicate studies by Dransfield, to evaluate the relationships between baseline eosinophil count and the effect of ICS on exacerbations and lung function in patients with COPD. Methods:The studies assessed ICS/long-acting ?2 agonist (LABA) combinations vs LABA alone. Using data from each study, we modeled COPD exacerbation rates, predose FEV1, and St George's Respiratory Questionnaire score ([FORWARD only]) over a continuous range of eosinophils (0-1,000 eosinophils/µL in FORWARD, 0-993 eosinophils/µL in Dransfield). Results:In all studies, ICS/LABA reduced exacerbations versus LABA alone across all eosinophil levels, with progressively greater reductions at increasing baseline blood eosinophil counts. In FORWARD, annual exacerbation rates ranged from 0.78 to 0.83 per year between 0 and 1,000 eosinophils/µL in the ICS/LABA arm, and from 0.81 to 1.54 per year in the LABA-only arm. In the Dransfield studies, exacerbation rates ranged from 0.54 to 1.02 per year in the ICS/LABA arm between 0 and 993 eosinophils/µL, and from 0.56 to 1.75 per year in the LABA-only arm. Change in FEV1 was not associated with eosinophil count in ICS-treated patients in FORWARD, whereas an increased treatment benefit in terms of FEV1 was observed at higher eosinophil levels in the Dransfield studies. ICS/LABA led to greater improvements in St George's Respiratory Questionnaire total scores compared to LABA alone in patients in FORWARD with ?67 eosinophils/µL. Conclusion:Higher blood eosinophil count in patients with COPD is associated with an increased beneficial effect from ICS in terms of exacerbation reduction. Further prospective data are required to assess the role of blood eosinophils as a biomarker for therapeutic recommendations.
| S-EPMC6225850 | biostudies-literature
Project description:ObjectiveSleep apnea and elevated plasma glucose associates with inflammation which associates with the risk of COPD exacerbations. We investigated the risk of exacerbations in individuals with COPD, witnessed sleep apneas, and elevated plasma glucose.MethodsFrom the Copenhagen City Heart Study cohort, we identified 564 individuals with COPD (forced expiratory volume in 1 sec divided by forced vital capacity, FEV1/FVC<0.70), no asthma, above 40 years of age, and more than 10 pack-years of smoking history, with information on witnessed apneas and levels of plasma glucose. We prospectively recorded hospital admissions with COPD exacerbations during maximum available follow-up (26.3 years; mean 10.7 years). Cox-regression analyses were used to analyze the risk of COPD exacerbations.ResultsWe identified 74 (13%) individuals with sleep apnea without elevated plasma glucose, 70 (12%) had elevated plasma glucose (above 6.9 mM (>125 mg/dL)) without sleep apnea and 11 individuals had the presence of both conditions. In univariable analysis, witnessed apneas together with elevated plasma glucose had a high risk of exacerbations, hazard ratio (HR) = 5.81 (2.34-14.4, p = 0.0001) compared to those without sleep apnea and without elevated plasma glucose. Multivariable analysis, adjusting for several risk factors of exacerbations, showed a similar result, HR = 3.45 (1.13-10.5, p = 0.03). Both presence of sleep apnea without elevated plasma glucose and the presence of elevated plasma glucose without sleep apnea showed no associations with the risk of exacerbations.ConclusionsWitnessed sleep apneas in COPD are associated with increased risk of exacerbations, but only among those with elevated plasma glucose.
| S-EPMC7655047 | biostudies-literature