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Background:  Accumulating evidence on the role of blood eosinophils as a biomarker prompted the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee to refine the existing treatment algorithm by incorporating eosinophil counts into treatment recommendations. However, there is a lack of data on when, why and how frequently such blood tests and other measures are being performed by German private respiratory specialists., Methods:  A questionnaire evaluating doctors' opinions on the use of diagnostic measures at initial diagnosis and during follow-up, including blood eosinophil count in patients with COPD, was completed by 27 respiratory specialists. Medical records from the past 12 months of 251 patients treated by the same physicians were reviewed retrospectively to investigate the use of these measures., Results:  Body plethysmography (100 % of doctors) and chest X-ray (96.3 %) were the most commonly used measures according to the doctor's questionnaire; other measures were COPD assessment test (CAT; 85.2 %) and blood eosinophil count (81.5 %). The evaluation of patients' medical records revealed that body plethysmography was performed in 72.7 %, the CAT in 61.8 % and chest X-ray in 40.6 % of patients. Blood eosinophil count was measured in 7.2 %., Conclusions:  In line with the GOLD recommendations, these results confirm that lung function, imaging and patient-reported outcome questionnaires play a crucial role in managing COPD. Our analyses reveal that measurement of the blood eosinophil count gained importance due to physicians' increased awareness of these cells as a useful biomarker. However, this test seems to be performed mainly for initial diagnosis and not on a regular basis., Competing Interests: Timm Greulich reports personal fees for advisory board meetings and lectures from AstraZeneca, Berlin-Chemie, Boehringer-Ingelheim, Chiesi, CSL-Behring, GlaxoSmithKline, Novartis and grants from Grifols and the German centre for Lung Research (DZL), Marburg, Germany, outside the submitted work.Volker Töpfer has no conflict of interest to declare.Michael Hennig, Christina C. Orehounig, Klaus Ams and Cordula D. Mohrlang are employed at GlaxoSmithKline GmbH & Co, Munich, the sponsor.Peter H. Killian was a full-time employee of GSK until 31st of March 2020, which included conduction of the study and the preparation of the manuscript.Peter Kardos reports personal fees for advisory board meetings and lectures from Astra Zeneca, Berlin-Chemie, Bionorica, Chiesi, Engelhardt, GlaxoSmithKline GmbH & Co, Klosterfrau Health Care Club, Novartis, MSD, Schwabe Pharma Italia, conference participation was reimbursed by AstraZeneca and he is an investigator in a phase 3 MSD study, outside the submitted work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: In COPD, the course of the disease including morbidity and mortality is strongly associated with severe exacerbations. The current GOLD recommendations emphasize blood eosinophil counts as a marker for responsiveness to inhaled corticosteroids (ICS). Retrospective analyses from randomized clinical trials indicate a favorable response to systemic corticosteroids in exacerbated COPD patients with blood eosinophils > 2%, however data outside clinical trials are scarce., Patients and Methods: We retrospectively evaluated data from 1007 cases of patients who were admitted to the University Medical Center Marburg between 01/2013 and 12/2018. All patients had been diagnosed with an acute exacerbation of COPD (ICD-10 J44.0/J44.1). Our analysis was based on a subgroup of 417 patients in whom a full blood cell count was obtained at the day of admission. Patients were predominantly male (63.3%), had a median age of 74 years (IQR 65 years - 83 years) and a median FEV1 of 1.03 l (42.6% predicted). We compared the hospital length of stay and other outcome parameters using established thresholds for the eosinophil blood cell count (100 and 300 eosinophils/μl and 2%)., Results: Patients with low eosinophils (< 2%, <100 cells/μl) had a longer median time in hospital (length of hospital stay - LOS) as compared to patients with high eosinophils (< 2%: 9.31 vs. ≥2%:7 days, and < 100/μl: 10 vs. 100-300/μl: 8 vs. > 300/μl: 7 days). The median CRP was higher in patients with low eosinophils as compared to the other groups (< 2%: 22.7 vs. ≥2%: 9 mg/dl and < 100: 25 vs. 100-300: 13.5 vs. > 300: 7.1 mg/dl). Time to re-hospitalization or time to death did not differ between strata of eosinophils. Sensitivity analysis in a subgroup of patients in which pneumonia was excluded by chest x-ray did not significantly alter the results., Conclusion: The results support the hypothesis that patients with severe COPD exacerbations and elevated blood eosinophil counts respond better to systemic corticosteroid treatment than patients with a non-eosinophilic exacerbation.

Background: Whether 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., Methods: Subjects 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)., Results: There 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., Conclusion: Despite shared "treatable traits" between asthma and COPD, the molecular mechanisms underlying these clinical entities are predominately different., (© 2019 The Authors. Allergy published by John Wiley & Sons Ltd.)

Background: A subset of COPD-patients presents with eosinophilic airway inflammation. While treatment of asthmatic patients with the GATA3-specific DNAzyme SB010 attenuated sputum eosinophilia after allergen challenge, this specific treatment has not been evaluated in patients with COPD. Our objective was to evaluate the feasibility and safety of inhaled SB010 in COPD patients with sputum eosinophilia., Methods: We conducted a randomized, double-blind, placebo-controlled, multicentre clinical trial in COPD-patients with sputum eosinophilia (≥2.5% non-squamous cells). Patients inhaled 10 mg SB010 bid or matching placebo via the controlled inhalation system AKITA2 APIXNEB for 28 days. Endpoints included the feasibility of the study (primary), patient's safety, sputum eosinophils, F E NO, lung function, symptoms, and biomarkers. The study was registered in the German Clinical Trials Register: DRKS00006087., Results: One hundred thirty patients were screened, 23 patients were randomized (FEV 1 49.4 ± 11.5%; sputum eosinophils 8.0 ± 8.4%) and 19 patients completed the study (10 placebo, 9 SB010. After 28 days, SB010 decreased the relative sputum eosinophil count (p = 0.004) as compared to no changes in placebo-treated patients. F E NO, lung function, and symptoms were not affected significantly. We found an increase in blood IFN-γ (p = 0.02) and a trend to lower IL-5 levels in patients treated with SB010. SB010 was safe and well tolerated. Thirty five AEs (22 SB010, 13 placebo including 1 SAE) were observed with 3 AEs in each group judged to be possibly treatment-related., Conclusion: In patients with eosinophilic COPD, sputum eosinophils could be reduced by inhalation of SB010. Long-term studies are needed to demonstrate clinical efficacy.