Neutrophil extracellular traps in chronic lung disease:implications for pathogenesis and therapy

Neutrophilic inflammation has a key role in the pathophysiology of multiple chronic lung diseases. The formation of neutrophil extracellular traps (NETs) has emerged as a key mechanism of disease in neutrophilic lung diseases including asthma, COPD, cystic fibrosis and, most recently, bronchiectasis. NETs are large, web-like structures composed of DNA and anti-microbial proteins that are able to bind pathogens, prevent microbial dissemination and degrade bacterial virulence factors. The release of excess concentrations of proteases, antimicrobial proteins, DNA and histones, however, also leads to tissue damage, impaired mucociliary clearance, impaired bacterial killing and increased inflammation. A number of studies have linked airway NET formation with greater disease severity, increased exacerbations and overall worse disease outcomes across the spectrum of airway diseases. Treating neutrophilic inflammation has been challenging in chronic lung disease because of the delicate balance between reducing inflammation and increasing the risk of infections through immunosuppression. Novel approaches to suppressing NET formation or the associated inflammation are in development and represent an important therapeutic target. This review will discuss the relationship between NETs and the pathophysiology of cystic fibrosis, asthma, COPD and bronchiectasis, and explore the current and future development of NET-targeting therapies

Inhaled corticosteroids and the lung microbiome in copd

The Global Initiative for Chronic Obstructive Lung Disease 2021 Report recommends inhaled corticosteroid (ICS)-containing regimens as part of pharmacological treatment in patients with chronic obstructive lung disease (COPD) and frequent exacerbations, particularly with eosinophilic inflammation. However, real-world studies reveal overprescription of ICS in COPD, irrespective of disease presentation and inflammatory endotype, leading to increased risk of side effects, mainly respiratory infections. The optimal use of ICS in COPD therefore remains an area of intensive research, and additional biomarkers of benefit and risk are needed. Although the interplay between inflammation and infection in COPD is widely acknowledged, the role of the microbiome in shaping lower airway inflammation has only recently been explored. Next-generation sequencing has revealed that COPD disease progression and exacerbation frequency are associated with changes in the composition of the lung microbiome, and that the immunosuppressive effects of ICS can contribute to potentially deleterious airway microbiota changes by increasing bacterial load and the abundance of potentially pathogenic taxa such as Streptococcus and Haemophilus. Here, we explore the relationship between microbiome, inflammation, ICS use and disease phenotype. This relationship may inform the benefit:risk assessment of ICS use in patients with COPD and lead to more personalised pharmacological management

ERS International Congress 2020:highlights from the Respiratory Infections assembly

In the coronavirus disease 2019 (COVID-19) pandemic year 2020, the 30th European Respiratory Society (ERS) International Congress took place for the first time in a fully virtual format. Despite the challenging nature of the task to create and deliver an online event of this size and scope, it turned out to be a great success, welcoming over 33 000 delegates to the specially designed online platform and offering more than 450 scientific and educational sessions. Somewhat predictably, this year's ERS International Congress dedicated a full day to the topic of COVID-19, highlighting that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory disease that is particularly important this year. In this article, the Early Career Members of the Assembly 10 (Respiratory Infections and Tuberculosis) review some of the most interesting sessions including presentations and posters on respiratory infections and tuberculosis that were deemed as important

Pronouns Are as Sensitive to Structural Constraints as Reflexives in Early Processing: Evidence From Visual World Paradigm Eye-Tracking

A number of studies in the extant literature report findings that suggest asymmetry in the way reflexive and pronoun anaphors are interpreted in the early stages of processing: that pronouns are less sensitive to structural constraints, as formulated by Binding Theory, than reflexives, in the initial antecedent retrieval process. However, in previous visual world paradigm eye-tracking studies, these conclusions were based on sentences that placed the critical anaphors within picture noun phrases or prepositional phrases, which have independently been shown not to neatly conform to the Binding Theory principles. We present results from a visual world paradigm eye-tracking experiment that show that when critical anaphors are placed in the indirect object position immediately following a verb as a recipient argument, pronoun and reflexive processing are equally sensitive to structural constraints

Antimicrobial peptides, disease severity and exacerbations in bronchiectasis

Rationale: Recently a frequent exacerbator phenotype has been described in bronchiectasis, but the underlying biological mechanisms are unknown. Antimicrobial peptides (AMPs) are important in host defence against microbes but can be proinflammatory in chronic lung disease. Objectives: To determine pulmonary and systemic levels of AMP and their relationship with disease severity and future risk of exacerbations in bronchiectasis. Methods: A total of 135 adults with bronchiectasis were prospectively enrolled at three European centres. Levels of cathelicidin LL-37, lactoferrin, lysozyme and secretory leucocyte protease inhibitor (SLPI) in serum and sputum were determined at baseline by ELISA. Patients were followed up for 12 months. We examined the ability of sputum AMP to predict future exacerbation risk. Measurements and main results: AMP levels were higher in sputum than in serum, suggesting local AMP release. Patients with more severe disease at baseline had dysregulation of airway AMP. Higher LL-37 and lower SLPI levels were associated with Bronchiectasis Severity Index, lower FEV1 (forced expiratory volume in 1 s) and Pseudomonas aeruginosa infection. Low SLPI levels were also associated with the exacerbation frequency at baseline. During follow-up, higher LL-37 and lower SLPI levels were associated with a shorter time to the next exacerbation, whereas LL-37 alone predicted exacerbation frequency over the next 12 months. Conclusions: Patients with bronchiectasis showed dysregulated sputum AMP levels, characterised by elevated LL-37 and reduced SLPI levels in the frequent exacerbator phenotype. Elevated LL-37 and reduced SLPI levels are associated with Pseudomonas aeruginosa infection and can predict future risk of exacerbations in bronchiectasis

Highlights of the ERS Lung Science Conference 2022

This article presents the highlights of the ERS Lung Science Conference 2022, including a session organised by the Early Career Member Committee (ECMC) dedicated to career development https://bit.ly/3tarCXc Every year, the European Respiratory Society (ERS) organises the Lung Science Conference (LSC), in Estoril, to discuss basic and translational science. The topic of the 20th LSC was “Mucosal immunology of the lung: balancing protective immunity and chronic inflammation”. This was the first time that the LSC was organised as a hybrid congress with both in person and online attendance. In addition to an outstanding scientific programme, the LSC provides excellent opportunities for career development and inclusion of early career members (ECMs). All scientific and poster sessions are chaired by an ECM who is paired with a senior faculty to allow ECMs to become acquainted with session chairing, and there is a session organised by the Early Career Member Committee (ECMC) dedicated to career development. Moreover, travel bursaries are made available to abstract authors, and all bursary recipients and first-time attendees are invited to take part in a mentorship lunch. In this article, we provide the names of the ECM awardees and describe the scientific highlights of the LSC 2022 for those who could not attend.info:eu-repo/semantics/publishedVersio