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Research outputs from the Respiratory Medicine department at the RD&E.


Recent Submissions

Now showing 1 - 5 of 137
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    Treatable traits: a comprehensive precision medicine approach in interstitial lung disease
    (European Respiratory Society, 2023-07-01) Khor, Y. H.; Cottin, V.; Holland, A. E.; Inoue, Y.; McDonald, V. M.; Oldham, J.; Renzoni, E. A.; Russell, A. M.; Strek, M. E.; Ryerson, C. J.
    Interstitial lung disease (ILD) is a diverse group of inflammatory and fibrotic lung conditions causing significant morbidity and mortality. A multitude of factors beyond the lungs influence symptoms, health-related quality of life, disease progression and survival in patients with ILD. Despite an increasing emphasis on multidisciplinary management in ILD, the absence of a framework for assessment and delivery of comprehensive patient care poses challenges in clinical practice. The treatable traits approach is a precision medicine care model that operates on the premise of individualised multidimensional assessment for distinct traits that can be targeted by specific interventions. The potential utility of this approach has been described in airway diseases, but has not been adequately considered in ILD. Given the similar disease heterogeneity and complexity between ILD and airway diseases, we explore the concept and potential application of the treatable traits approach in ILD. A framework of aetiological, pulmonary, extrapulmonary and behavioural and lifestyle treatable traits relevant to clinical care and outcomes for patients with ILD is proposed. We further describe key research directions to evaluate the application of the treatable traits approach towards advancing patient care and health outcomes in ILD.
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    Treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs: British Society for Rheumatology guideline scope
    (Oxford University Press, 2023-05-15) Zhao, S. S.; Harrison, S. R.; Chan, A.; Clarke, N.; Davis, C.; Eddison, J.; Gregory, W. J.; Jones, G. T.; Marzo-Ortega, H.; Murphy, D. J.; Sandhu, V.; Sengupta, R.; Siebert, S.; Thompson, B.; Webb, D.; Yates, M.; Gaffney, K.
    Pharmacological management has advanced considerably since the 2015 British Society for Rheumatology axial spondyloarthritis (axSpA) guideline to incorporate new classes of biologic DMARDs (bDMARDs, including biosimilars), targeted synthetic DMARDs (tsDMARDs) and treatment strategies such as drug tapering. The aim of this guideline is to provide an evidence-based update on pharmacological management of adults with axSpA (including AS and non-radiographic axSpA) using b/tsDMARDs. This guideline is aimed at health-care professionals in the UK who care directly for people with axSpA, including rheumatologists, rheumatology specialist nurses, allied health professionals, rheumatology specialty trainees and pharmacists; people living with axSpA; and other stakeholders, such as patient organizations and charities.
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    Moving forward together: collaborative landscapes of research in idiopathic inflammatory myopathies and calcinosis
    (Oxford University Press, 2023-07-01) Saketkoo, L. A.; Valenzuela, A.; Kim, S.; McCann, L. J.; Lood, C.; Wahezi, D. M.; Werth, V. P.; Yi, B.; Alexanderson, H.; Maillard, S.; Pilkington, C.; Fligelstone, K.; Limbach, B.; Orandi, A. B.; Regardt, M.; Russell, A. M.; Davuluri, S.; deGroot, I.; Ernste, F.; Paik, J. J.; von Muhlen, C. A.; Dimachkie, M. M.; Machado, P. M.; Naddaf, E.; Zulian, F.; Chung, L.
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    Interstitial Lung Disease and Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: A Review
    (Elsevier, 2023-05-01) Steward, M.; Thould, H.; Myat Noe Khin, A.; Gibbons, M. A.
    Interstitial lung disease is a common complication of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). It is seen most commonly in microscopic polyangiitis owing to the pathogenic effect of myeloperoxidase in the lung. Oxidative stress, neutrophil elastase release, and expression of inflammatory proteins by neutrophil extracellular traps result in fibroblast proliferation and differentiation and therefore fibrosis. Usually, interstitial pneumonia pattern fibrosis is common and associated with poor survival. Treatment for patients with AAV and interstitial lung disease lacks evidence, and those with vasculitis are treated with immunosuppression, whereas those with progressive fibrosis may well benefit from antifibrotic therapy.
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    Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis
    (European Respiratory Society, 2023-04-03) Kroes, J. A.; Alfonso-Cristancho, R.; Bansal, A. T.; Berret, E.; Bieksiene, K.; Bourdin, A.; Brussino, L.; Canhoto, D.; Cardini, C.; Celik, G.; Csoma, Z.; Dahlén, B.; Damadoglu, E.; Eger, K.; Gauquelin, L.; Gemicioglu, B.; Goksel, O.; Graff, S.; Heffler, E.; Hofstee, H. B.; Howarth, P.; Jakes, R. W.; Jaun, F.; Kalinauskaite-Zukauske, V.; Kopač, P.; Kwon, N.; Loureiro, C. C.; Lozoya García, V.; Masoli, M.; Rezelj, M. P.; Pérez De Llano, L.; Popović-Grle, S.; Ramos-Barbón, D.; A, Sà Sousa; Samitas, K.; Schleich, F.; Sirena, C.; Skrgat, S.; Zervas, E.; Zichnalis, G.; Bel, E. H.; Sont, J. K.; Hashimoto, S.; Ten Brinke, A.
    BACKGROUND: An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. METHODS: In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. RESULTS: In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg·day(-1), 95% CI -5.24-2.62 mg·day(-1)) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. CONCLUSIONS: By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.