Effect of inhaled corticosteroids on blood eosinophil count in steroid-naive patients with COPD.
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ABSTRACT:
SUBMITTER: Kreindler JL
PROVIDER: S-EPMC5020662 | biostudies-literature | 2016
REPOSITORIES: biostudies-literature
Publications
Effect of inhaled corticosteroids on blood eosinophil count in steroid-naïve patients with COPD.
Kreindler James L JL Watkins Michael L ML Lettis Sally S Tal-Singer Ruth R Locantore Nicholas N
BMJ open respiratory research 20160908 1
<h4>Introduction</h4>Sputum and blood eosinophil counts have attracted attention as potential biomarkers in chronic obstructive pulmonary disease (COPD). One question regarding the use of blood eosinophils as a biomarker in COPD is whether their levels are affected by the use of inhaled corticosteroids (ICS), which are commonly prescribed for COPD.<h4>Methods</h4>We performed a retrospective analysis of peripheral blood leucocytes from a previously completed clinical trial that examined effects ...[more]
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Project description:BackgroundGrowing 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.MethodsThe studies assessed ICS/long-acting β2 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).ResultsIn 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.ConclusionHigher 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:BackgroundWhether the clinical or pathophysiologic significance of the "treatable trait" high blood eosinophil count in COPD is the same as for asthma remains controversial. We sought to determine the relationship between the blood eosinophil count, clinical characteristics and gene expression from bronchial brushings in COPD and asthma.MethodsSubjects were recruited into a COPD (emphysema versus airway disease [EvA]) or asthma cohort (Unbiased BIOmarkers in PREDiction of respiratory disease outcomes, U-BIOPRED). We determined gene expression using RNAseq in EvA (n = 283) and Affymetrix microarrays in U-BIOPRED (n = 85). We ran linear regression analysis of the bronchial brushings transcriptional signal versus blood eosinophil counts as well as differential expression using a blood eosinophil > 200 cells/μL as a cut-off. The false discovery rate was controlled at 1% (with continuous values) and 5% (with dichotomized values).ResultsThere were no differences in age, gender, lung function, exercise capacity and quantitative computed tomography between eosinophilic versus noneosinophilic COPD cases. Total serum IgE was increased in eosinophilic asthma and COPD. In EvA, there were 12 genes with a statistically significant positive association with the linear blood eosinophil count, whereas in U-BIOPRED, 1197 genes showed significant associations (266 positive and 931 negative). The transcriptome showed little overlap between genes and pathways associated with blood eosinophil counts in asthma versus COPD. Only CST1 was common to eosinophilic asthma and COPD and was replicated in independent cohorts.ConclusionDespite shared "treatable traits" between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different.
| S-EPMC7064968 | biostudies-literature
Project description:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder encompassing different phenotypes with different responses to treatment. The present 1-year, two-center hospital-based study investigated whether the plasma immunoglobulin E (IgE) level and/or eosinophil cell count could be used as biomarkers to stratify patients with COPD according to predicted responses to inhaled corticosteroids (ICS)-based therapy.A hospital-data based cohort study of COPD patients treated at two territory hospital centers was conducted for 1 year. Allergic biomarkers, including blood eosinophil counts and IgE levels, were assessed at baseline. Lung function parameters, including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and the COPD Assessment Test (CAT), were also evaluated. The frequencies of acute exacerbation (AE) and pneumonia were also measured. Eosinophilia and a high IgE level were defined as >3% and 173 IU/mL, respectively.A total of 304 patients were included. Among patients with eosinophilia and high IgE levels, ICS-based therapy was associated with significant improvements in FEV1, FVC, and CAT scores, compared with bronchodilator (BD) therapy (P≤0.042). ICS-based therapy was also associated with a significantly lower incidence of AE vs BD-based therapy (11.7% vs 24.1%; P<0.008). Among patients with only eosinophilia, ICS-based therapy yielded significantly better CAT score results vs BD-based treatment (7 vs 13; P=0.032). A receiver operating characteristic curve analysis found that the combination of a high plasma IgE level and eosinophilia most sensitively and specifically identified patients who would benefit from the addition of ICS to BD therapy.Our findings support the use of blood eosinophil cell counts plus IgE levels as predictive biomarkers of the ICS response in certain patients with COPD. Both biomarkers could potentially be used to stratify COPD patients regarding ICS-based therapy.
| S-EPMC5546185 | biostudies-other
Project description:BackgroundThe Global Initiative for Chronic Obstructive Lung Disease (GOLD) considers blood eosinophil counts < 100 cells/μL (BEC≤100) in people with COPD to predict poor inhaled corticosteroid (ICS) responsiveness. However, the BEC≤100 phenotype is inadequately characterized, especially in advanced COPD.Research questionAre there differences between GOLD group D patients with high BEC and those with low BEC regarding baseline characteristics and longitudinal outcomes?Study design and methodsWe used multivariable mixed models and logistic regression to contrast clinical characteristics and outcomes of BEC≤100 vs BEC > 100 (BEC100+) in all subjects with COPD (n = 1,414) and GOLD group D subjects (n = 185) not receiving ICS.ResultsWe identified n = 485 with BEC≤100 (n = 61 GOLD group D) and n = 929 people with BEC100+ (n = 124 GOLD group D). BEC≤100 status was stable at 6 weeks and approximately 52 weeks (intraclass correlations of 0.78 and 0.71, respectively). Compared with BEC100+, BEC≤100 comprised more women, with greater current smoking, and less frequent childhood asthma. Among all analyzed participants, the two BEC-defined subsets showed similar rates of lung function decline (mean slope, BEC≤100 vs BEC100+, -50 vs -39 mL/y; P = .140), exacerbations (0.40 vs 0.36/y; P = .098), subsequent ICS initiation (2.5% vs 4.4%; P = .071), and mortality (7.8% vs 8.4%; P = .715). However, in GOLD group D, people with BEC≤100 showed higher exacerbation rates within 365 days of enrollment (0.62 vs 0.33/y; P = .002) and total follow-up (1.16 vs 0.83/y; P = .014). They also had greater lung function decline (mean slope of -68 mL/y vs -23 mL/y; P = .036) and had greater emphysema at baseline (voxels < 950 Hounsfield units at total lung capacity of 7.46% vs 4.61%; P = .029).InterpretationIn non-ICS-treated GOLD group D COPD, people with BEC≤100 had more baseline emphysema, prospective exacerbations, and lung function decline. Our analysis has identified a particularly vulnerable subpopulation of people with COPD, suggesting the need for studies focused specifically on their therapeutic treatment.Clinical trial registrationClinicalTrials.gov; No.: NCT01969344; URL: www.Clinicaltrialsgov.
| S-EPMC10083128 | biostudies-literature
Project description:BackgroundBlood eosinophil count has been proposed as a predictor of response to inhaled corticosteroid (ICS) in the prevention of acute exacerbations of COPD. An optimal threshold of blood eosinophil count for prescribing ICS has not been agreed. Doubt has been cast on the role by observational studies. The role of inhaled corticosteroids in this relationship, independent of long-acting bronchodilators, has not been examined.MethodsWe conducted a systematic review of post-hoc analyses of randomised controlled trials (RCTs) and observational studies examining three blood eosinophil thresholds and the independent role of ICS. Included studies were categorised by the form (relative or absolute count) and cut point of eosinophil threshold used. Thresholds assessed were relative eosinophil count of 2%, and absolute counts of 150 cells/μL and 300 cells/μL. Three meta-analyses of the effect of ICS use in post-hoc analyses of RCTs based on these counts were carried out. Initial analysis included all studies of ICS vs. any non-ICS regimen. Further analysis examined the effect of ICS, independent of the effect of long-acting bronchodilators.ResultsSixteen studies examined the association between blood eosinophil count and response of exacerbation risk to ICS, in COPD patients. Eleven studies (25,881 patients) were post-hoc analyses of RCTs. Five studies (109,704 patients) were retrospective observational studies. The independent effect of ICS on the reduction of exacerbation risk was 20% at ≥2% blood eosinophil threshold (RR, 0.80; 95% CI, 0.74-0.85), 35% at ≥150 cells/μL blood eosinophil threshold (RR, 0.65; 0.52-0.79), and 39% at ≥300 cells/μL blood eosinophil threshold (RR, 0.61; 0.44-0.78). No association was found in four out of five observational studies.ConclusionThis is the first systematic review to assess, in post-hoc analyses of RCTs, the independent effect of ICS in reducing the risk of COPD exacerbation across a range of blood eosinophil thresholds. Association between ICS prescription and reduced exacerbation risk at these thresholds was confirmed. The lack of association found in the observational studies questions the relevance of these observations to a "real world" COPD population. To clarify the clinical utility of this biomarker, the association should be tested in prospective effectiveness studies.
| S-EPMC6942335 | biostudies-literature
Project description:Inhaled corticosteroid (ICS) therapy is widely prescribed without a history of exacerbations and consensus guidelines suggest withdrawal of ICS in these patients would reduce the risk of side effects and promote cost-effective prescribing. The study describes the prescribing behaviour in the United Kingdom (UK) in relation to ICS withdrawal and identifies clinical outcomes following withdrawal using primary and secondary care electronic health records between January 2012 and December 2017. Patients with a history ≥12 months' exposure who withdrew ICS for ≥6 months were identified into two cohorts; those prescribed a long-acting bronchodilator maintenance therapy and those that were not prescribed any maintenance therapy. The duration of withdrawal, predictors of restarting ICS, and clinical outcomes were compared between both patient cohorts. Among 76,808 patients that had ≥1 prescription of ICS in the study period, 11,093 patients (14%) withdrew ICS therapy at least once during the study period. The median time without ICS was 9 months (IQR 7-14), with the majority (71%) receiving subsequent ICS prescriptions after withdrawal. Patients receiving maintenance therapy with a COPD review at withdrawal were 28% less likely to restart ICS (HR: 0.72, 95% CI 0.61, 0.85). Overall, 69% and 89% of patients that withdrew ICS had no recorded exacerbation event or COPD hospitalisation, respectively, during the withdrawal. This study provides evidence that most patients withdrawing from ICS do not experience COPD exacerbations and withdrawal success can be achieved by carefully planning routine COPD reviews whilst optimising the use of available maintenance therapies.
| S-EPMC9300648 | biostudies-literature
Project description:Various phenotypes exist in asthma and Chronic Obstructive Pulmonary Disease (COPD). These are important to identify in order to guide treatment decisions. We aim to investigate the prevalence and clinical characteristics of obstructive airway diseases in the middle-aged population. We estimated the prevalence of COPD and/or asthma in the Asklepios cohort study (Belgium), using information from the third European Community Respiratory Health Survey (ECRHS3), medical records, and spirometry. Respiratory symptoms, respiratory medication, and current disease status distinguished clinical from sub-clinical cases. In addition, we compared the blood eosinophil count/µL (median [IQR]) between cases and controls. Of the 2221 participants (mean age 56.1 ± 5.9 years; 48.7% males), 138 (6.2%) participants had clinical current asthma, 22 (1.0%) participants had sub-clinical ever asthma, 102 (4.6%) had sub-clinical spirometry-defined COPD, 104 (4.6%) participants had clinical spirometry-confirmed COPD, and 11 (0.5%) had asthma and COPD overlap (ACO). Clinical current asthma (160.0 [110.0-250.0]), sub-clinical ever asthma (170.0 [110.0-230.0]), and clinical COPD (160.0 [110.0-220.0])-but less sub-clinical COPD (140.0 [90.0-210.0])-had higher eosinophil counts, compared to controls (130.0 [80.0-200.0]). We conclude that obstructive airway diseases are prevalent in the middle-aged Asklepios cohort. Moreover, the systemic eosinophil count is increased in clinical COPD cases, and in asthma cases regardless of clinical remission.
| S-EPMC6723474 | biostudies-literature
Project description:Introduction:The biomarker soluble urokinase plasminogen activator receptor (suPAR) has been associated with increased mortality in chronic obstructive pulmonary disease (COPD), while elevated blood eosinophils have been associated with better survival. We hypothesized that suPAR and blood eosinophil count are independent risk factors for readmission and mortality after an acute admission in patients with COPD. Methods:This retrospective cohort study comprised 4022 patients with prevalent COPD acutely admitted to Hvidovre Hospital, Denmark. Irrespective of cause of admission, suPAR and blood eosinophils were measured, and patients were followed up to 365 days. Associations with 365-day respiratory readmission, all-cause readmission and all-cause mortality were investigated by Cox regression analyses adjusted for age, sex, Charlson score and C-reactive protein. Results:suPAR was significantly elevated in patients who later experienced readmission or died. At 365 days, hazard ratios (HRs) for all-cause readmission and mortality reached 1.61 (95% CI 1.40-1.85; p<0.0001) and 3.40 (95% CI 2.64-4.39; p<0.0001), respectively, for COPD patients in the fourth suPAR quartile compared to patients in the first suPAR quartile. High blood eosinophils (>300 cells/?L) were associated with lower risk of mortality (HR 0.49, 95% CI 0.39-0.62; p<0.0001) compared with patients with <150 cells/?L. When stratifying patients by suPAR quartiles and blood eosinophil counts, the highest relative mortality rate was found in patients belonging to both the fourth suPAR quartile and the low blood eosinophil (<150 cells/?L) group. Conclusion:In this cohort of COPD patients acutely admitted to a hospital, elevated suPAR concentrations were associated with both higher risk of all-cause readmission and mortality, whereas higher blood eosinophil count was associated with lower risk of mortality.
| S-EPMC7147624 | biostudies-literature
Project description: Not available
| S-EPMC7328335 | biostudies-literature
Project description:ImportanceChronic obstructive pulmonary disease (COPD) is a major global health issue and theophylline is used extensively. Preclinical investigations have demonstrated that low plasma concentrations (1-5 mg/L) of theophylline enhance antiinflammatory effects of corticosteroids in COPD.ObjectiveTo investigate the effectiveness of adding low-dose theophylline to inhaled corticosteroids in COPD.Design, setting, and participantsThe TWICS (theophylline with inhaled corticosteroids) trial was a pragmatic, double-blind, placebo-controlled, randomized clinical trial that enrolled patients with COPD between February 6, 2014, and August 31, 2016. Final follow-up ended on August 31, 2017. Participants had a ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 0.7 with at least 2 exacerbations (treated with antibiotics, oral corticosteroids, or both) in the previous year and were using an inhaled corticosteroid. This study included 1578 participants in 121 UK primary and secondary care sites.InterventionsParticipants were randomized to receive low-dose theophylline (200 mg once or twice per day) to provide plasma concentrations of 1 to 5 mg/L (determined by ideal body weight and smoking status) (n = 791) or placebo (n = 787).Main outcomes and measuresThe number of participant-reported moderate or severe exacerbations treated with antibiotics, oral corticosteroids, or both over the 1-year treatment period.ResultsOf the 1567 participants analyzed, mean (SD) age was 68.4 (8.4) years and 54% (843) were men. Data for evaluation of the primary outcome were available for 1536 participants (98%) (772 in the theophylline group; 764 in the placebo group). In total, there were 3430 exacerbations: 1727 in the theophylline group (mean, 2.24 [95% CI, 2.10-2.38] exacerbations per year) vs 1703 in the placebo group (mean, 2.23 [95% CI, 2.09-2.37] exacerbations per year); unadjusted mean difference, 0.01 (95% CI, -0.19 to 0.21) and adjusted incidence rate ratio, 0.99 (95% CI, 0.91-1.08). Serious adverse events in the theophylline and placebo groups included cardiac, 2.4% vs 3.4%; gastrointestinal, 2.7% vs 1.3%; and adverse reactions such as nausea (10.9% vs 7.9%) and headaches (9.0% vs 7.9%).Conclusions and relevanceAmong adults with COPD at high risk of exacerbation treated with inhaled corticosteroids, the addition of low-dose theophylline, compared with placebo, did not reduce the number COPD exacerbations over a 1-year period. The findings do not support the use of low-dose theophylline as adjunctive therapy to inhaled corticosteroids for the prevention of COPD exacerbations.Trial registrationisrctn.org Identifier: ISRCTN27066620.
| S-EPMC6233797 | biostudies-literature