Publications

Journal article

Chotirmall SH, Chalmers JD, 2024,

The Precision Medicine Era of Bronchiectasis.

, Am J Respir Crit Care Med, Vol: 210, Pages: 24-34

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

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

Patel S, Sylvester KP, Wu Z, Rhamie S, Dickel P, Maher TM, Molyneaux PL, Calverley PMA, Man WD-Cet al., 2024,

A comparison of respiratory oscillometry and spirometry in idiopathic pulmonary fibrosis: performance time, symptom burden and test-retest reliability.

, ERJ Open Res, Vol: 10, ISSN: 2312-0541

STUDY QUESTION: In large multinational patient surveys, spirometry (which requires repeated, reproducible maximal efforts) can be associated with cough, breathlessness and tiredness, particularly in those with idiopathic pulmonary fibrosis (IPF). Oscillometry is an effort-independent test of airways resistance and reactance. We hypothesised that oscillometry would take less time to perform and would be associated with reduced symptom burden than spirometry. PATIENTS AND METHODS: Spirometry and oscillometry were performed in 66 participants with IPF and repeated 2 weeks later. We compared time taken to perform tests, symptom burden and test-retest reliability with Bland-Altman plots and intraclass correlation coefficients (ICCs). RESULTS: Oscillometry took significantly less time to perform than spirometry (mean -4.5 (99% CI -6.0 to -3.0) min) and was associated with lower symptom burden scores for cough (-1.3, 99% CI -1.7 to -0.8), breathlessness (-1.0, 99% CI -1.4 to -0.5), and tiredness (-0.5, 99% CI -0.9 to -0.2). On Bland-Altman analysis, all measures showed good agreement, with narrow limits of agreement and the mean bias lying close to 0 in all cases. The ICCs for forced expiratory volume in 1 s and forced vital capacity were 0.94 and 0.89, respectively, and ranged between 0.70 and 0.90 for oscillometry measures. CONCLUSION: Oscillometry is quicker to perform and provokes less symptoms than spirometry in patients with IPF.

Journal article

Sewell TR, van Dorp L, Ghosh PN, Wierzbicki C, Caroe C, Lyakurwa JV, Tonelli E, Bowkett AE, Marsden S, Cunningham AA, Garner TWJ, Gilbert TP, Moyer D, Weldon C, Fisher MCet al., 2024,

Archival mitogenomes identify invasion by the Batrachochytrium dendrobatidis CAPE lineage caused an African amphibian extinction in the wild.

, Proc Biol Sci, Vol: 291

Outbreaks of emerging infectious diseases are influenced by local biotic and abiotic factors, with host declines occurring when conditions favour the pathogen. Deterioration in the population of the micro-endemic Tanzanian Kihansi spray toad (Nectophrynoides asperginis) occurred after the construction of a hydropower dam, implicating habitat modification in this species decline. Population recovery followed habitat augmentation; however, a subsequent outbreak of chytridiomycosis caused by Batrachochytrium dendrobatidis (Bd) led to the spray toad's extinction in the wild. We show using spatiotemporal surveillance and mitogenome assembly of Bd from archived toad mortalities that the outbreak was caused by invasion of the BdCAPE lineage and not the panzootic lineage BdGPL. Molecular dating reveals an emergence of BdCAPE across southern Africa overlapping with the timing of the spray toad's extinction. That our post-outbreak surveillance of co-occurring amphibian species in the Udzungwa Mountains shows widespread infection by BdCAPE yet no signs of ill-health or decline suggests these other species can tolerate Bd when environments are stable. We conclude that, despite transient success in mitigating the impact caused by dams' construction, invasion by BdCAPE caused the ultimate die-off that led to the extinction of the Kihansi spray toad.

Journal article

Lira-Junior R, Aogáin MM, Crncalo E, Ekberg NR, Chotirmall SH, Pettersson S, Gustafsson A, Brismar K, Bostanci Net al., 2024,

Effects of intermittent fasting on periodontal inflammation and subgingival microbiota.

, J Periodontol, Vol: 95, Pages: 640-649

BACKGROUND: Studies on the impact of intermittent fasting on periodontal health are still scarce. Thus, this study evaluated the effects of long-term intermittent fasting on periodontal health and the subgingival microbiota. METHODS: This pilot study was part of a nonrandomized controlled trial. Overweight/obese participants (n = 14) entered an intermittent fasting program, specifically the 5:2 diet, in which they restricted caloric intake to about a quarter of the normal total daily caloric expenditure for two nonconsecutive days/week. Subjects underwent a thorough clinical and laboratory examination, including an assessment of their periodontal condition, at baseline and 6 months after starting the diet. Additionally, subgingival microbiota was assessed by 16S rRNA gene sequencing. RESULTS: After 6 months of intermittent fasting, weight, body mass index, C-reactive protein, hemoglobin A1c (HbA1c), and the cholesterol profile improved significantly (p < 0.05). Moreover, significant reductions were observed in bleeding on probing (p = 0.01) and the presence of shallow periodontal pockets after fasting (p < 0.001), while no significant change was seen in plaque index (p = 0.14). While we did not observe significant changes in α- or β-diversity of the subgingival microbiota related to dietary intervention (p > 0.05), significant differences were seen in the abundances of several taxa among individuals exhibiting ≥60% reduction (good responders) in probing pocket depth of 4-5 mm compared to those with <60% reduction (bad responders). CONCLUSION: Intermittent fasting decreased systemic and periodontal inflammation. Although the subgingival microbiota was unaltered by this intervention, apparent taxonomic variability was observed between good and bad responders.

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

Wee LE, Tan JYJ, Chiew CJ, Abisheganaden JA, Chotirmall SH, Lye DCB, Tan KBet al., 2024,

A Nationwide Cohort Study of Delta and Omicron SARS-CoV-2 Outcomes in Vaccinated Individuals With Chronic Lung Disease.

, Chest

BACKGROUND: Individuals with chronic lung disease (CLD) are more susceptible to respiratory viral infections; however, significant heterogeneity exists in the literature on CLD and COVID-19 outcomes. Data are lacking on outcomes with newer variants (eg, Omicron) and in vaccinated and boosted populations. RESEARCH QUESTION: What are the outcomes of SARS-CoV-2 infection in individuals with CLD during Delta and Omicron transmission in a highly vaccinated and boosted population-based cohort? STUDY DESIGN AND METHODS: Outcomes of Delta and Omicron SARS-CoV-2 infection in a highly vaccinated and boosted cohort of adult Singaporeans with CLD (including asthma, COPD, bronchiectasis, and pulmonary fibrosis) were contrasted against matched population control participants. Calendar time-scale Cox regressions were used to compare risk of infection, COVID-19-related hospitalizations, and severe COVID-19 disease, adjusting for sociodemographic factors and comorbidities. RESULTS: Overall, 68,782 individual patients with CLD and 534,364 matched population control participants were included. By the end of the Omicron wave, 92.7% of patients with CLD were boosted. Compared with control participants, patients with CLD showed higher risk of SARS-CoV-2 infection, COVID-19-related hospitalization, and severe COVID-19 during both the Delta wave (infection: adjusted hazards ratio [aHR], 1.22 [95% CI, 1.17-1.28]; hospitalization: aHR, 1.76 [95% CI, 1.61-1.92]; severe COVID-19: aHR, 1.75 [95% CI, 1.50-2.05]) and Omicron wave (infection: aHR, 1.15 [95% CI, 1.14-1.17]; hospitalization: aHR, 1.82 [95% CI, 1.74-1.91]; severe COVID-19: aHR, 2.39 [95% CI, 2.18-2.63]). During Omicron, significantly higher risk of infection, hospitalization, and severe COVID-19 was observed among patients with asthma (severe COVID-19: aHR, 1.31 [95% CI, 1.10-1.55]) and COPD (severe COVID-19: aHR, 1.36 [95% CI, 1.12-1.66]) compared with control participants. Severe exacerb

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