Airway IL-1β is related to disease severity and mucociliary function in bronchiectasis.

Rationale: The inflammasome is a key regulatory complex of the inflammatory response leading to interleukin-1β (IL-1β) release and activation. IL-1β amplifies inflammatory responses and induces mucus secretion and hyperconcentration in other diseases. The role of IL-1β in bronchiectasis has not been investigated.

Endotypes of Exacerbation in Bronchiectasis: An Observational Cohort Study.

Bronchiectasis is characterized by acute exacerbations, but the biological mechanisms underlying these events are poorly characterized. To investigate the inflammatory and microbial characteristics of exacerbations of bronchiectasis. A total of 120 patients with bronchiectasis were enrolled and presented with acute exacerbations within 12 months.

Sputum metagenomics of people with bronchiectasis.

Background: The microbiota in the sputum of people with bronchiectasis has repeatedly been investigated in cohorts of different geographic origin, but so far has not been studied to the species level in comparison to control populations including healthy adults and smokers without lung disease.

Methods: The microbial metagenome from sputa of 101 European Bronchiectasis Registry (EMBARC) study participants was examined by using whole-genome shotgun sequencing.

Results: Our analysis of the metagenome of people with bronchiectasis revealed four clusters characterised by a predominance of , or polymicrobial communities with varying compositions of nonpathogenic commensals and opportunistic pathogens.

Airway "Resistotypes" and Clinical Outcomes in Bronchiectasis.

Chronic infection and inflammation shapes the airway microbiome in bronchiectasis. Utilizing whole-genome shotgun metagenomics to analyze the airway resistome provides insight into interplay between microbes, resistance genes, and clinical outcomes. To apply whole-genome shotgun metagenomics to the airway microbiome in bronchiectasis to highlight a diverse pool of antimicrobial resistance genes: the "resistome," the clinical significance of which remains unclear.

Bronchiectasis with Chronic Rhinosinusitis Is Associated with Eosinophilic Airway Inflammation and Is Distinct from Asthma.

Bronchiectasis is an airway inflammatory disease that is frequently associated with chronic rhinosinusitis (CRS). An eosinophilic endotype of bronchiectasis has recently been described, but detailed testing to differentiate eosinophilic bronchiectasis from asthma has not been performed. This prospective observational study aimed to test the hypotheses that bronchiectasis with CRS is enriched for the eosinophilic phenotype in comparison with bronchiectasis alone and that the eosinophilic bronchiectasis phenotype exists as a separate entity from bronchiectasis associated with asthma.

Extensive acute and sustained changes to neutrophil proteomes post-SARS-CoV-2 infection.

Background: Neutrophils are important in the pathophysiology of coronavirus disease 2019 (COVID-19), but the molecular changes contributing to altered neutrophil phenotypes following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not fully understood. We used quantitative mass spectrometry-based proteomics to explore neutrophil phenotypes immediately following acute SARS-CoV-2 infection and during recovery.

Methods: Prospective observational study of hospitalised patients with PCR-confirmed SARS-CoV-2 infection (May to December 2020).

Inflammatory Molecular Endotypes in Bronchiectasis: A European Multicenter Cohort Study.

Although inflammation and infection are key disease drivers in bronchiectasis, few studies have integrated host inflammatory and microbiome data to guide precision medicine. To identify clusters among patients with bronchiectasis on the basis of inflammatory markers and to assess the association between inflammatory endotypes, microbiome characteristics, and exacerbation risk. Patients with stable bronchiectasis were enrolled at three European centers, and cluster analysis was used to stratify the patients according to the levels of 33 sputum and serum inflammatory markers.

Dipeptidyl peptidase-1 inhibition in patients hospitalised with COVID-19: a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial.

Background: Neutrophil serine proteases are involved in the pathogenesis of COVID-19 and increased serine protease activity has been reported in severe and fatal infection. We investigated whether brensocatib, an inhibitor of dipeptidyl peptidase-1 (DPP-1; an enzyme responsible for the activation of neutrophil serine proteases), would improve outcomes in patients hospitalised with COVID-19.

Methods: In a multicentre, double-blind, randomised, parallel-group, placebo-controlled trial, across 14 hospitals in the UK, patients aged 16 years and older who were hospitalised with COVID-19 and had at least one risk factor for severe disease were randomly assigned 1:1, within 96 h of hospital admission, to once-daily brensocatib 25 mg or placebo orally for 28 days.

Characterization of Eosinophilic Bronchiectasis: A European Multicohort Study.

Bronchiectasis is classically considered a neutrophilic disorder, but eosinophilic subtypes have recently been described. To use multiple datasets available through the European Multicentre Bronchiectasis Audit and Research Collaboration to characterize eosinophilic bronchiectasis as a clinical entity focusing on the impact of eosinophils on bronchiectasis exacerbations. Patients were included from five countries to examine the relationships between blood eosinophil counts and clinical phenotypes after excluding coexisting asthma.

Multicentre evaluation of two multiplex PCR platforms for the rapid microbiological investigation of nosocomial pneumonia in UK ICUs: the INHALE WP1 study.

Background: Culture-based microbiological investigation of hospital-acquired or ventilator-associated pneumonia (HAP or VAP) is insensitive, with aetiological agents often unidentified. This can lead to excess antimicrobial treatment of patients with susceptible pathogens, while those with resistant bacteria are treated inadequately for prolonged periods. Using PCR to seek pathogens and their resistance genes directly from clinical samples may improve therapy and stewardship.

Exhaled volatile organic compounds and lung microbiome in COPD: a pilot randomised controlled trial.

Background: Breath analysis is a burgeoning field, with interest in volatile organic compounds (VOCs) as a noninvasive diagnostic tool or an outcome measure, but no randomised controlled trials (RCTs) have yet evaluated this technology in a clinical trial longitudinally. In a pilot RCT, our exploratory objectives were feasibility of measuring VOCs multiple techniques, assessing relationships between VOCs and colonisation and whether CXCR2 antagonism with danirixin altered lung microbiome composition in individuals with COPD.

Method: 43 participants had VOCs and sputum biomarkers evaluated.

CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin.

https://bit.ly/32SeisO.

Metagenomic analysis of planktonic riverine microbial consortia using nanopore sequencing reveals insight into river microbe taxonomy and function.

Background: Riverine ecosystems are biogeochemical powerhouses driven largely by microbial communities that inhabit water columns and sediments. Because rivers are used extensively for anthropogenic purposes (drinking water, recreation, agriculture, and industry), it is essential to understand how these activities affect the composition of river microbial consortia. Recent studies have shown that river metagenomes vary considerably, suggesting that microbial community data should be included in broad-scale river ecosystem models.

The microbiome in bronchiectasis.

Bronchiectasis is increasing in prevalence worldwide, yet current treatments available are limited to those alleviating symptoms and reducing exacerbations. The pathogenesis of the disease and the inflammatory, infective and molecular drivers of disease progression are not fully understood, making the development of novel treatments challenging. Understanding the role bacteria play in disease progression has been enhanced by the use of next-generation sequencing techniques such as 16S rRNA sequencing.

Presence of Subspecies Monitored Over Varying Temporal and Spatial Scales in River Catchments: Persistent Routes for Human Exposure.

subspecies () was monitored by quantitative PCR over a range of temporal and spatial scales in the River Tywi catchment. This study shows the persistence of over a 10-year period with little change, which correlates with the recognised levels of Johne's disease in British herds over that period (aim 1). was quantified within the river at up to 10 cell equivalents L and was shown to be consistently present when monitored over finer timescales (aim 4).

Leprosy at the edge of Europe-Biomolecular, isotopic and osteoarchaeological findings from medieval Ireland.

Relatively little is known of leprosy in Medieval Ireland; as an island located at the far west of Europe it has the potential to provide interesting insights in relation to the historical epidemiology of the disease. To this end the study focuses on five cases of probable leprosy identified in human skeletal remains excavated from inhumation burials. Three of the individuals derived from the cemetery of St Michael Le Pole, Golden Lane, Dublin, while single examples were also identified from Ardreigh, Co.

Nanopore sequencing and assembly of a human genome with ultra-long reads.

We report the sequencing and assembly of a reference genome for the human GM12878 Utah/Ceph cell line using the MinION (Oxford Nanopore Technologies) nanopore sequencer. 91.2 Gb of sequence data, representing ∼30× theoretical coverage, were produced.

Mycobacterium avium Subspecies paratuberculosis: Human Exposure through Environmental and Domestic Aerosols.

Mycobacterium avium subspecies paratuberculosis (Map) causes Johne's disease in animals and is significantly associated with Crohn's disease (CD) in humans. Our previous studies have shown Map to be present in U.K.