Publications

Journal article

Chalmers JD, Mall MA, McShane PJ, Nielsen KG, Shteinberg M, Sullivan SD, Chotirmall SHet al., 2024,

A systematic literature review of the clinical and socioeconomic burden of bronchiectasis.

, Eur Respir Rev, Vol: 33

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). Journal articles and congress abstracts reporting on observational studies, randomised controlled trials and registry studies were included. Editorials, narrative reviews and systematic literature reviews were included to identify primary studies. PRISMA guidelines were followed. RESULTS: 1585 unique publications were identified, of which 587 full texts were screened and 149 were included. A further 189 citations were included from reference lists of editorials and reviews, resulting in 338 total publications. Commonly reported symptoms and complications included dyspnoea, cough, wheezing, sputum production, haemoptysis and exacerbations. Disease severity across several indices and increased mortality compared with the general population was reported. Bronchiectasis impacted quality of life across several patient-reported outcomes, with patients experiencing fatigue, anxiety and depression. Healthcare resource utilisation was considerable and substantial medical costs related to hospitalisations, treatments and emergency department and outpatient visits were accrued. Indirect costs included sick pay and lost income. CONCLUSIONS: Bronchiectasis causes significant clinical and socioeconomic burden. Disease-modifying therapies that reduce symptoms, improve quality of life and reduce both healthcare resource utilisation and overall costs are needed. Further systematic analyses of specific aetiologies and paediatric disease may provide more insight into unmet therapeutic needs.

Journal article

Arendrup MC, Armstrong-James D, Borman AM, Denning DW, Fisher MC, Gorton R, Maertens J, Martin-Loeches I, Mehra V, Mercier T, Price J, Rautemaa-Richardson R, Wake R, Andrews N, White PLet al., 2024,

The Impact of the Fungal Priority Pathogens List on Medical Mycology: A Northern European Perspective.

, Open Forum Infect Dis, Vol: 11, ISSN: 2328-8957

Fungal diseases represent a considerable global health concern, affecting >1 billion people annually. In response to this growing challenge, the World Health Organization introduced the pivotal fungal priority pathogens list (FPPL) in late 2022. The FPPL highlights the challenges in estimating the global burden of fungal diseases and antifungal resistance (AFR), as well as limited surveillance capabilities and lack of routine AFR testing. Furthermore, training programs should incorporate sufficient information on fungal diseases, necessitating global advocacy to educate health care professionals and scientists. Established international guidelines and the FPPL are vital in strengthening local guidance on tackling fungal diseases. Future iterations of the FPPL have the potential to refine the list further, addressing its limitations and advancing our collective ability to combat fungal diseases effectively. Napp Pharmaceuticals Limited (Mundipharma UK) organized a workshop with key experts from Northern Europe to discuss the impact of the FPPL on regional clinical practice.

Journal article

Choi H, Xu J-F, Chotirmall SH, Chalmers JD, Morgan LC, Dhar Ret al., 2024,

Bronchiectasis in Asia: a review of current status and challenges.

, Eur Respir Rev, Vol: 33

Recent bronchiectasis studies from large-scale multinational, multicentre registries have demonstrated that the characteristics of the disease vary according to geographic region. However, most perspectives on bronchiectasis are dominated by data from Western countries. This review intends to provide an Asian perspective on the disease, focusing on the established registries in India, Korea and China. Asian patients with bronchiectasis are less likely to show female predominance and experience exacerbations, are more likely to be younger, have milder disease, and have fewer options for guideline-recommended treatment than those living in other global regions. Furthermore, Asian bronchiectasis patients demonstrate different comorbidities, microbiological profiles and unique endophenotypes, including post-tuberculosis and dry bronchiectasis. Notably, each Asian region reveals further geographic variations and inter-patient differences. Future studies are warranted to better characterise Asian patients with bronchiectasis.

Journal article

Mac Aogáin M, Dicker AJ, Mertsch P, Chotirmall SHet al., 2024,

Infection and the microbiome in bronchiectasis.

, Eur Respir Rev, Vol: 33

Bronchiectasis is marked by bronchial dilatation, recurrent infections and significant morbidity, underpinned by a complex interplay between microbial dysbiosis and immune dysregulation. The identification of distinct endophenotypes have refined our understanding of its pathogenesis, including its heterogeneous disease mechanisms that influence treatment and prognosis responses. Next-generation sequencing (NGS) has revolutionised the way we view airway microbiology, allowing insights into the "unculturable". Understanding the bronchiectasis microbiome through targeted amplicon sequencing and/or shotgun metagenomics has provided key information on the interplay of the microbiome and host immunity, a central feature of disease progression. The rapid increase in translational and clinical studies in bronchiectasis now provides scope for the application of precision medicine and a better understanding of the efficacy of interventions aimed at restoring microbial balance and/or modulating immune responses. Holistic integration of these insights is driving an evolving paradigm shift in our understanding of bronchiectasis, which includes the critical role of the microbiome and its unique interplay with clinical, inflammatory, immunological and metabolic factors. Here, we review the current state of infection and the microbiome in bronchiectasis and provide views on the future directions in this field.

Journal article

Mall MA, Davies JC, Donaldson SH, Jain R, Chalmers JD, Shteinberg Met al., 2024,

Neutrophil serine proteases in cystic fibrosis: role in disease pathogenesis and rationale as a therapeutic target.

, Eur Respir Rev, Vol: 33

Chronic airway inflammation is a central feature in the pathogenesis of bronchiectasis (BE), which can be caused by cystic fibrosis (CFBE; hereafter referred to as CF lung disease) and non-CF-related conditions (NCFBE). Inflammation in both CF lung disease and NCFBE is predominantly driven by neutrophils, which release proinflammatory cytokines and granule proteins, including neutrophil serine proteases (NSPs). NSPs include neutrophil elastase, proteinase 3 and cathepsin G. An imbalance between NSPs and their antiproteases has been observed in people with CF lung disease and people with NCFBE. While the role of the protease/antiprotease imbalance is well established in both CF lung disease and NCFBE, effective therapies targeting NSPs are lacking. In recent years, the introduction of CF transmembrane conductance regulator (CFTR) modulator therapy has immensely improved outcomes in many people with CF (pwCF). Despite this, evidence suggests that airway inflammation persists, even in pwCF treated with CFTR modulator therapy. In this review, we summarise current data on neutrophilic inflammation in CF lung disease to assess whether neutrophilic inflammation and high, uncontrolled NSP levels play similar roles in CF lung disease and in NCFBE. We discuss similarities between the neutrophilic inflammatory profiles of people with CF lung disease and NCFBE, potentially supporting a similar therapeutic approach. Additionally, we present evidence suggesting that neutrophilic inflammation persists in pwCF treated with CFTR modulator therapy, at levels similar to those in people with NCFBE. Collectively, these findings highlight the ongoing need for new treatment strategies targeting neutrophilic inflammation in CF lung disease.

Journal article

Aslam S, Cowger J, Shah P, Stosor V, Copeland H, Reed A, Morales D, Giblin G, Mathew J, Morrissey O, Morejon P, Nicoara A, Molina Eet al., 2024,

The International Society for Heart and Lung Transplantation (ISHLT): 2024 infection definitions for durable and acute mechanical circulatory support devices.

, J Heart Lung Transplant, Vol: 43, Pages: 1039-1050

Infections remain a significant concern in patients receiving mechanical circulatory support (MCS), encompassing both durable and acute devices. This consensus manuscript provides updated definitions for infections associated with durable MCS devices and new definitions for infections in acute MCS, integrating a comprehensive review of existing literature and collaborative discussions among multidisciplinary specialists. By establishing consensus definitions, we seek to enhance clinical care, facilitate consistent reporting in research studies, and ultimately improve outcomes for patients receiving MCS.

Journal article

Koreshkov M, Antreich SJ, Bismarck A, Fritz I, Reimhult E, Takatsuna Y, Zirbs Ret al., 2024,

Sustainable food packaging using modified SiO<inf>2</inf> nanofillers in biodegradable polymers

, Materials Chemistry Frontiers, Vol: 8, Pages: 2754-2763

The need to switch to bio-based, biodegradable and/or fully recyclable polymers is becoming increasingly clear, especially in the area of food packaging, which is a major contributor to plastic pollution. To meet this challenge, biodegradable polymers must not only be economically viable, but also have properties that match or better those of conventional fossil-based polymers, such as robust mechanical strength and efficient gas barrier properties. One promising route is the production of composite materials from biodegradable polymers and SiO2 nanoparticles. However, the high surface energy of SiO2 often leads to agglomeration of the filler in the hydrophobic polymer matrix, which compromises the integrity of the composite. Here we present an innovative approach in which the surface of silica nanoparticles is modified with l-lactic acid oligomers (OLLA), effectively reducing the agglomeration of the filler and improving processability. Using conventional polymer processing methods that comply with industry standards, we prepared PLLA and PHBV nanocomposites and evaluated the effectiveness of the modification using a novel SBF-SEM technique. Our results show that modified silica achieves better dispersion in the polymer matrix and yields 70% more independent particles in the nanocomposite. The introduction of OLLA-g-SiO2 increases the oxygen barrier of PLLA by 38% while accelerating the biodegradation rate and improving the toughness of the eco-friendly nanocomposites. This innovative approach offers a sustainable solution that is set to revolutionise the landscape of green food packaging.

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Journal article

Collins ASP, Kurt H, Duggan C, Cotur Y, Coatsworth P, Naik A, Kaisti M, Bozkurt T, Güder Fet al., 2024,

Parallel, continuous monitoring and quantification of programmed cell death in plant tissue

, Advanced Science, Vol: 11, ISSN: 2198-3844

Accurate quantification of hypersensitive response (HR) programmed cell death is imperative for understanding plant defense mechanisms and developing disease-resistant crop varieties. Here, a phenotyping platform for rapid, continuous-time, and quantitative assessment of HR is demonstrated: Parallel Automated Spectroscopy Tool for Electrolyte Leakage (PASTEL). Compared to traditional HR assays, PASTEL significantly improves temporal resolution and has high sensitivity, facilitating detection of microscopic levels of cell death. Validation is performed by transiently expressing the effector protein AVRblb2 in transgenic Nicotiana benthamiana (expressing the corresponding resistance protein Rpi-blb2) to reliably induce HR. Detection of cell death is achieved at microscopic intensities, where leaf tissue appears healthy to the naked eye one week after infiltration. PASTEL produces large amounts of frequency domain impedance data captured continuously. This data is used to develop supervised machine-learning (ML) models for classification of HR. Input data (inclusive of the entire tested concentration range) is classified as HR-positive or negative with 84.1% mean accuracy (F1 score = 0.75) at 1 h and with 87.8% mean accuracy (F1 score = 0.81) at 22 h. With PASTEL and the ML models produced in this work, it is possible to phenotype disease resistance in plants in hours instead of days to weeks.

Journal article

Tung NWH, Edmondson C, Westrupp N, Rosenthal M, Davies JCet al., 2024,

Neutrophil-to-lymphocyte ratio as a biomarker of acute pulmonary exacerbations in children with cystic fibrosis: a retrospective cohort study

, ARCHIVES OF DISEASE IN CHILDHOOD, ISSN: 0003-9888

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Journal article

Hai D, Li J, Jiang D, Cheng J, Fu Y, Xiao X, Yin H, Lin Y, Chen T, Li B, Yu X, Cai Q, Chen W, Kotta-Loizou I, Xie Jet al., 2024,

Plants interfere with non-self recognition of a phytopathogenic fungus via proline accumulation to facilitate mycovirus transmission

, Nature Communications, Vol: 15, ISSN: 2041-1723

Non-self recognition is a fundamental aspect of life, serving as a crucial mechanism for mitigating proliferation of molecular parasites within fungal populations. However, studies investigating the potential interference of plants with fungal non-self recognition mechanisms are limited. Here, we demonstrate a pronounced increase in the efficiency of horizontal mycovirus transmission between vegetatively incompatible Sclerotinia sclerotiorum strains in planta as compared to in vitro. This increased efficiency is associated with elevated proline concentration in plants following S. sclerotiorum infection. This surge in proline levels attenuates the non-self recognition reaction among fungi by inhibition of cell death, thereby facilitating mycovirus transmission. Furthermore, our field experiments reveal that the combined deployment of hypovirulent S. sclerotiorum strains harboring hypovirulence-associated mycoviruses (HAVs) together with exogenous proline confers substantial protection to oilseed rape plants against virulent S. sclerotiorum. This unprecedented discovery illuminates a novel pathway by which plants can counteract S. sclerotiorum infection, leveraging the weakening of fungal non-self recognition and promotion of HAVs spread. These promising insights provide an avenue to explore for developing innovative biological control strategies aimed at mitigating fungal diseases in plants by enhancing the efficacy of horizontal HAV transmission.

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