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  1. Article ; Online: Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease

    Aran Singanayagam / Joseph Footitt / Matthias Marczynski / Giorgia Radicioni / Michael T. Cross / Lydia J. Finney / Maria-Belen Trujillo-Torralbo / Maria Calderazzo / Jie Zhu / Julia Aniscenko / Thomas B. Clarke / Philip L. Molyneaux / Nathan W. Bartlett / Miriam F. Moffatt / William O. Cookson / Jadwiga Wedzicha / Christopher M. Evans / Richard C. Boucher / Mehmet Kesimer /
    Oliver Lieleg / Patrick Mallia / Sebastian L. Johnston

    The Journal of Clinical Investigation, Vol 132, Iss

    2022  Volume 8

    Abstract: The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases, but the relationship between mucus and ... ...

    Abstract The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases, but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway mucin 5AC (MUC5AC) and MUC5B concentrations during spontaneous and experimentally induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with viral load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation, as Muc5ac-deficient (Muc5ac–/–) mice had attenuated RV-induced (RV-induced) airway inflammation, and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased the release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of RV-induced inflammation in mice. Therapeutic suppression of mucin production using an EGFR antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B expression suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identified a proinflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.
    Keywords Pulmonology ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher American Society for Clinical Investigation
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Use of the oral beta blocker bisoprolol to reduce the rate of exacerbation in people with chronic obstructive pulmonary disease (COPD)

    Seonaidh Cotton / Graham Devereux / Hassan Abbas / Andrew Briggs / Karen Campbell / Rekha Chaudhuri / Gourab Choudhury / Dana Dawson / Anthony De Soyza / Shona Fielding / Simon Gompertz / John Haughney / Chim C. Lang / Amanda J. Lee / Graeme MacLennan / William MacNee / Kirsty McCormack / Nicola McMeekin / Nicholas L. Mills /
    Alyn Morice / John Norrie / Mark C. Petrie / David Price / Philip Short / Jorgen Vestbo / Paul Walker / Jadwiga Wedzicha / Andrew Wilson / Brian J. Lipworth

    Trials, Vol 23, Iss 1, Pp 1-

    a randomised controlled trial (BICS)

    2022  Volume 16

    Abstract: Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies ... ...

    Abstract Abstract Background Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity, mortality and healthcare costs. Beta blockers are well-established drugs widely used to treat cardiovascular conditions. Observational studies consistently report that beta blocker use in people with COPD is associated with a reduced risk of COPD exacerbations. The bisoprolol in COPD study (BICS) investigates whether adding bisoprolol to routine COPD treatment has clinical and cost-effective benefits. A sub-study will risk stratify participants for heart failure to investigate whether any beneficial effect of bisoprolol is restricted to those with unrecognised heart disease. Methods BICS is a pragmatic randomised parallel group double-blind placebo-controlled trial conducted in UK primary and secondary care sites. The major inclusion criteria are an established predominant respiratory diagnosis of COPD (post-bronchodilator FEV1 < 80% predicted, FEV1/FVC < 0.7), a self-reported history of ≥ 2 exacerbations requiring treatment with antibiotics and/or oral corticosteroids in a 12-month period since March 2019, age ≥ 40 years and a smoking history ≥ 10 pack years. A computerised randomisation system will allocate 1574 participants with equal probability to intervention or control groups, stratified by centre and recruitment in primary/secondary care. The intervention is bisoprolol (1.25 mg tablets) or identical placebo. The dose of bisoprolol/placebo is titrated up to a maximum of 4 tablets a day (5 mg bisoprolol) over 4–7 weeks depending on tolerance to up-dosing of bisoprolol/placebo—these titration assessments are completed by telephone or video call. Participants complete the remainder of the 52-week treatment period on the final titrated dose (1, 2, 3, 4 tablets) and during that time are followed up at 26 and 52 weeks by telephone or video call. The primary outcome is the total number of participant reported COPD exacerbations requiring oral corticosteroids and/or antibiotics during the 52-week ...
    Keywords COPD ; Exacerbation ; Randomised controlled trial ; Bisoprolol ; Beta blocker ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2022-04-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    Full text online

    More links

    Kategorien

    Inter-library loan at ZB MED

    Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

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