Comorbidities in COPD have a complex relationship with disease severity, requiring a comprehensive therapy approach.

BackgroundA 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.MethodsWe 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, FENO, lung function, symptoms, and biomarkers. The study was registered in the German Clinical Trials Register: DRKS00006087.ResultsOne hundred thirty patients were screened, 23 patients were randomized (FEV1 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. FENO, 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.ConclusionIn patients with eosinophilic COPD, sputum eosinophils could be reduced by inhalation of SB010. Long-term studies are needed to demonstrate clinical efficacy.Electronic supplementary materialThe online version of this article (10.1186/s12931-018-0751-x) contains supplementary material, which is available to authorized users.

Lower respiratory infections, such as community-acquired pneumonia (cAp), and chronic obstructive pulmonary disease (copD) rank among the most frequent causes of death worldwide. improved diagnostics and profound pathophysiological insights are urgent clinical needs. in our cohort, we analysed transcriptional networks of peripheral blood mononuclear cells (pBMcs) to identify central regulators and potential biomarkers. We investigated the mRnA-and miRnA-transcriptome of pBMcs of healthy subjects and patients suffering from CAP or AECOPD by microarray and Taqman Low Density Array. Genes that correlated with PBMC composition were eliminated, and remaining differentially expressed genes were grouped into modules. One selected module (120 genes) was particularly suitable to discriminate AECOPD and CAP and most notably contained a subset of five biologically relevant mRNAs that differentiated between CAP and AECOPD with an AUC of 86.1%. Likewise, we identified several microRNAs, e.g. miR-545-3p and miR-519c-3p, which separated AECOPD and CAP. We furthermore retrieved an integrated network of differentially regulated mRNAs and microRNAs and identified HNF4A, MCC and MUC1 as central network regulators or most important discriminatory markers. in summary, transcriptional analysis retrieved potential biomarkers and central molecular features of cAp and AecopD. Community acquired pneumonia (CAP) is clinically defined by a sudden onset of severe illness that is accompanied by signs of lower respiratory tract infection, fever, cough and dyspnoea 1. When left untreated, severe secondary effects such as organ damage and occurrence of bacteria in the blood (bacteremia) can ensue. While subject to variance due to region, season and population characteristics, the incidence of CAP is estimated to lie between 1.5 and 14 cases per 1,000 persons per year, with children under 5 years of age and the elderly of more than 65 years being most strongly affected 2. Immunocompromised persons also bear a higher risk of CAP contraction. The leading underlying cause of CAP is infection with the gram-positive bacterium Streptococcus pneumoniae, accounting for 30-35% of CAP cases worldwide 3. The initial colonization of the nasopharynx and the upper respiratory tract often remains asymptomatic. Aspiration into the alveoli can cause severe respiratory or systemic disease, depending on the host immune status and the pneumococcal serotype 1. As CAP is a multifaceted disease with a host of potential causative agents, the robust identification of microR-NAs that are functionally involved in pneumonia depends on the pathogen. In severe Influenza A Virus (H1N1)

PurposeAlpha-1-antitrypsin deficiency (AATD) is a rare hereditary condition resulting from the mutations in the SERPINA1 (serine protease inhibitor) gene and is characterized by low circulating levels of the alpha-1 antitrypsin (AAT) protein. The traditional algorithm for laboratory testing of AATD involves the analysis of AAT concentrations (nephelometry), phenotyping (isoelectric focusing, IEF), and genotyping (polymerase chain reaction, PCR); in selected cases, full sequencing of the SERPINA1 gene can be undertaken. New technologies arise that may make diagnosis easier and faster.MethodsWe developed and evaluated a new diagnostic algorithm based on Luminex xMAP (multi-analyte profiling) technology using Progenika A1AT Genotyping Test. In an initial learning phase, 1979 samples from individuals suspected of having AATD were examined by both, a traditional and a “new” algorithm. In a second phase, 1133 samples were analyzed with the Luminex xMAP only.ResultsBy introducing a Luminex xMAP based algorithm, we were able to simultaneously identify 14 mutations in SERPINA1 gene (instead of two- S and Z-by using our old algorithm). Although the quantity of IEF assays remained unchanged, the nephelometric measurements and sequencing were reduced by 79% and 63.4%, respectively.ConclusionThe new method is convenient, fast and user-friendly. The application of the Luminex xMAP technology can simplify and shorten the diagnostic workup of patients with suspected AATD.