Publications by authors named "P M McShane"

Background: Guideline-based therapy (GBT) for Mycobacterium abscessus (Mab) lung disease achieves sputum culture conversion rates (SCC) of 35%. This poor GBT efficacy is mirrored in the hollow fiber system model of Mab (HFS-Mab). While imipenem is part of GBT, biological effect with or without β-lactamase inhibitors, is unproven.

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Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis. Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase (NE), cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur.

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Article Synopsis
  • Bronchiectasis is caused by high levels of neutrophil serine protease (NSP) activity, and inhibiting Cathepsin C (CatC) may help decrease lung damage caused by neutrophils.
  • A Phase II trial tested a new CatC inhibitor (BI 1291583) in 322 adults with bronchiectasis, comparing different doses (1, 2.5, 5 mg) to a placebo over 24 to 48 weeks.
  • Results showed that higher doses of BI 1291583 significantly delayed the onset of pulmonary exacerbations, with the 2.5 mg dose being the most effective, while the safety profile was comparable to that of the placebo. *
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Background: The overall burden of bronchiectasis on patients and healthcare systems has not been comprehensively described. Here, we present the findings of a systematic literature review that assessed the clinical and socioeconomic burden of bronchiectasis with subanalyses by aetiology (PROSPERO registration: CRD42023404162).

Methods: Embase, MEDLINE and the Cochrane Library were searched for publications relating to bronchiectasis disease burden (December 2017-December 2022).

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