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      Patients with Chronic Obstructive Pulmonary Disease harbour a variation of Haemophilus species

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          Abstract

          H. haemolyticus is often misidentified as NTHi due to their close phylogenetic relationship. Differentiating between the two is important for correct identification and appropriate treatment of infective organism and to ensure any role of H. haemolyticus in disease is not being overlooked. Speciation however is not completely reliable by culture and PCR methods due to the loss of haemolysis by H. haemolyticus and the heterogeneity of NTHi. Haemophilus isolates from COPD as part of the AERIS study (ClinicalTrials - NCT01360398) were speciated by analysing sequence data for the presence of molecular markers. Further investigation into the genomic relationship was carried out using average nucleotide identity and phylogeny of allelic and genome alignments. Only 6.3% were identified as H. haemolyticus. Multiple in silico methods were able to distinguish H. haemolyticus from NTHi. However, no single gene target was found to be 100% accurate. A group of omp2 negative NTHi were observed to be phylogenetically divergent from H. haemolyticus and remaining NTHi. The presence of an atypical group from a geographically and disease limited set of isolates supports the theory that the heterogeneity of NTHi may provide a genetic continuum between NTHi and H. haemolyticus.

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          Microreact: visualizing and sharing data for genomic epidemiology and phylogeography

          Visualization is frequently used to aid our interpretation of complex datasets. Within microbial genomics, visualizing the relationships between multiple genomes as a tree provides a framework onto which associated data (geographical, temporal, phenotypic and epidemiological) are added to generate hypotheses and to explore the dynamics of the system under investigation. Selected static images are then used within publications to highlight the key findings to a wider audience. However, these images are a very inadequate way of exploring and interpreting the richness of the data. There is, therefore, a need for flexible, interactive software that presents the population genomic outputs and associated data in a user-friendly manner for a wide range of end users, from trained bioinformaticians to front-line epidemiologists and health workers. Here, we present Microreact, a web application for the easy visualization of datasets consisting of any combination of trees, geographical, temporal and associated metadata. Data files can be uploaded to Microreact directly via the web browser or by linking to their location (e.g. from Google Drive/Dropbox or via API), and an integrated visualization via trees, maps, timelines and tables provides interactive querying of the data. The visualization can be shared as a permanent web link among collaborators, or embedded within publications to enable readers to explore and download the data. Microreact can act as an end point for any tool or bioinformatic pipeline that ultimately generates a tree, and provides a simple, yet powerful, visualization method that will aid research and discovery and the open sharing of datasets.
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            Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction.

            Chronic obstructive pulmonary disease is a leading global cause of morbidity and mortality that is characterised by inexorable deterioration of small airways obstruction with emphysema associated with cellular inflammation and structural remodelling. Other features include apoptosis as well as proliferation of cells, and both tissue repair and lack of tissue repair. Metalloprotease release, together with that of apoptotic factors, may underlie the emphysema, and, conversely, fibrosis of the small airways may be accounted for by the effects of growth factor activation. In advanced disease, influential factors include the development of autoimmunity, with activation of dendritic cells and T-helper cells of both type 1 and 2, and the senescence response. An inability of macrophages to ingest apoptosed cells and bacteria may exacerbate inflammatory responses. Systemic inflammation with concomitant cardiovascular disease and metabolic syndrome may reflect the effect of cigarette smoke on nonpulmonary cells. Corticosteroid resistance may be secondary to oxidative stress mechanisms, such as inactivation of histone deacetylases. The mechanisms of chronic obstructive pulmonary disease may be heterogeneous, according to severity, and clinical phenotypes need to be correlated with cellular and pathological processes. Treatments may be targeted to patients with specific mechanisms.
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              Effect of Interactions Between Lower Airway Bacterial and Rhinoviral Infection in Exacerbations of COPD

              Study objectives The inflammatory responses and associated clinical severity of COPD exacerbations are greatly variable, and the determinants of these factors are poorly understood. We examined the hypothesis that bacteria and viruses may modulate this heterogeneity and that interactions between bacterial and viral infection may affect changes in airway bacterial load and the clinical features and inflammatory responses of exacerbations in patients with COPD. Design Prospective cohort study. Setting Outpatient Department, London Chest Hospital, London, UK. Patients Thirty-nine patients with COPD. Measurements We prospectively studied 56 COPD exacerbations, obtaining clinical data and paired sputum and serum samples at baseline and exacerbation. Qualitative and quantitative microbiology, polymerase chain reaction detection for rhinovirus, and estimation of cytokine levels by enzyme-linked immunosorbent assay were performed. Results A total of 69.6% of exacerbations were associated with a bacterial pathogen, most commonly Haemophilus influenzae. Rhinovirus was identified in 19.6% of exacerbations. The rise in bacterial load at exacerbation correlated with the rise in sputum interleukin (IL)-8 (r = 0.37, p = 0.022) and fall in FEV1 (r = 0.35, p = 0.048). Exacerbations with both rhinovirus and H influenzae had higher bacterial loads (108.56 cfu/mL vs 108.05cfu/mL, p = 0.018) and serum IL-6 (13.75 pg/mL vs 6.29 pg/mL, p = 0.028) than exacerbations without both pathogens. In exacerbations with both cold symptoms (a marker of putative viral infection) and a bacterial pathogen, the FEV1 fall was greater (20.3% vs 3.6%, p = 0.026) and symptom count was higher (p = 0.019) than those with a bacterial pathogen alone. Conclusions The clinical severity and inflammatory responses in COPD exacerbations are modulated by the nature of the infecting organism: bacterial and viral pathogens interact to cause additional rises in inflammatory markers and greater exacerbation severity.
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                Author and article information

                Contributors
                S.C.Clarke@soton.ac.uk
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                3 October 2018
                3 October 2018
                2018
                : 8
                : 14734
                Affiliations
                [1 ]ISNI 0000 0004 1936 9297, GRID grid.5491.9, Clinical and Experimental Sciences, Faculty of Medicine, , University of Southampton, ; Southampton, Hants SO16 6YD UK
                [2 ]GRID grid.425090.a, GlaxoSmithKline Pharmaceuticals, ; Wavre, Belgium
                [3 ]GRID grid.454385.b, NIHR Southampton Respiratory Biomedical Research Unit, ; Southampton, United Kingdom
                [4 ]ISNI 0000 0004 1936 9297, GRID grid.5491.9, NIHR Biomedical Research Centre, , University of Southampton, ; Southampton, United Kingdom
                [5 ]ISNI 0000 0004 1936 9297, GRID grid.5491.9, Wessex Investigational Sciences Hub, , University of Southampton, ; Southampton, United Kingdom
                [6 ]ISNI 0000 0004 1936 9297, GRID grid.5491.9, Institute for Life Sciences, , University of Southampton, ; Southampton, United Kingdom
                [7 ]ISNI 0000 0004 1936 9297, GRID grid.5491.9, Global Health Research Institute, , University of Southampton, ; Southampton, United Kingdom
                [8 ]ISNI 0000 0001 2260 0793, GRID grid.417993.1, Present Address: Merck Exploratory Science Center, , Merck Research Laboratories, ; Cambridge, MA USA
                Article
                32973
                10.1038/s41598-018-32973-3
                6170463
                30282975
                7cd33ade-547c-474d-87d8-745e3eb03fcf
                © The Author(s) 2018

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 12 June 2018
                : 19 September 2018
                Funding
                Funded by: FundRef https://doi.org/10.13039/100004330, GlaxoSmithKline (GlaxoSmithKline Plc.);
                Award ID: NCT01360398
                Award ID: NCT01360398
                Award ID: NCT01360398
                Award ID: NCT01360398
                Award ID: NCT01360398
                Award ID: NCT01360398
                Award ID: NCT01360398
                Award Recipient :
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