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  • Journal article
    Noakes FF, Smitten KL, Maple LEC, Bernardino de la Serna J, Robertson CC, Pritchard D, Fairbanks SD, Weinstein JA, Smythe CGW, Thomas JAet al., 2024,

    Phenazine cations as anticancer theranostics

    , Journal of the American Chemical Society, Vol: 146, Pages: 12836-12849, ISSN: 0002-7863

    The biological properties of two water-soluble organic cations based on polypyridyl structures commonly used as ligands for photoactive transition metal complexes designed to interact with biomolecules are investigated. A cytotoxicity screen employing a small panel of cell lines reveals that both cations show cytotoxicity toward cancer cells but show reduced cytotoxicity to noncancerous HEK293 cells with the more extended system being notably more active. Although it is not a singlet oxygen sensitizer, the more active cation also displayed enhanced potency on irradiation with visible light, making it active at nanomolar concentrations. Using the intrinsic luminescence of the cations, their cellular uptake was investigated in more detail, revealing that the active compound is more readily internalized than its less lipophilic analogue. Colocalization studies with established cell probes reveal that the active cation predominantly localizes within lysosomes and that irradiation leads to the disruption of mitochondrial structure and function. Stimulated emission depletion (STED) nanoscopy and transmission electron microscopy (TEM) imaging reveal that treatment results in distinct lysosomal swelling and extensive cellular vacuolization. Further imaging-based studies confirm that treatment with the active cation induces lysosomal membrane permeabilization, which triggers lysosome-dependent cell-death due to both necrosis and caspase-dependent apoptosis. A preliminary toxicity screen in the Galleria melonella animal model was carried out on both cations and revealed no detectable toxicity up to concentrations of 80 mg/kg. Taken together, these studies indicate that this class of synthetically easy-to-access photoactive compounds offers potential as novel therapeutic leads.
  • Journal article
    Philip K, Buttery S, Bowen S, Lewis A, Jeffery E, Alghamdi SM, Williams PJ, Alasmari AM, Alsulayyim A, Orton CM, Conway F, Chan L, Vijayakumar B, Tana A, Tonkin J, Perkins A, Garner J, Srikanthan K, Sadaka A, Pavitt M, Banya W, Lound A, Elkin S, Polkey MI, Man W, Lewis K, Cave P, Fancourt D, Hopkinson NSet al., 2024,

    Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery

    , BMJ Open Respiratory Research, Vol: 11, ISSN: 2052-4439

    Background Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach.Methods We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores.Results We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62–74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3–4), forced expiratory volume in 1 s % predicted 49 (35–63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI −1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403).Discussion and conclusion A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful.Trial registration number NCT04034212.
  • Conference paper
    Doffman S, Dosanjh D, Sadiq M, Asimus S, Cooper J, Zhou X-H, Seth H, Pandya HC, Saralaya D, Beier J, Forsman H, Brown MN, Matsunaga Y, Belvisi MG, Molfino NAet al., 2024,

    Phase 1 Safety and Efficacy of AZD8630/AMG 104 Inhaled Anti-TSLP in Healthy Volunteers and Patients With Asthma on Medium-High Dose Inhaled Corticosteroid (ICS) and Long-Acting Beta-agonist (LABA) With Elevated Baseline Fractional Exhaled Nitric Oxide (FeNO)

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Owen CA, Zhou X, Sobande O, Ferrari N, Hezaveh K, Nemes S, Sosnowski M, Ringqvist KE E L, Mo J, Gottfridsson C, Platt A, Brohawn Z, Gochuico B, Wall G, Williams ML, Belvisi MG, Keen C, Prothon S, Goldwater R, Hornberg Eet al., 2024,

    A First-in-human Study in Healthy Volunteers Investigating the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD5055, A Novel Oral Porcupine Inhibitor Under Development as a Treatment for Pulmonary Fibrosis

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Small P, Rudd M, Chung KF, 2024,

    Cough-omics: Quantifying the Variability and Predictability of Daily Cough Countsin Persistent Coughers

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Khalaf Z, Saglani S, Bloom CI, 2024,

    The Impact of Routine Asthma Reviews: A UK Population-based Cohort

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Journal article
    Bloom CI, 2024,

    Reply: Asthma and cardiovascular disease: the strength of triangulation

    , EUROPEAN RESPIRATORY JOURNAL, Vol: 63, ISSN: 0903-1936
  • Conference paper
    Dixey P, Kermani NZ, Raby K, Bhavsar PK, Chung Ket al., 2024,

    Enose - Derived Response Clusters in Severe Asthmatics Treated With Anti-IL5/5R Biologics

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Raby K, Dixey P, Versi A, Koranteng JB, Chung K, Bhavsar PKet al., 2024,

    Mechanisms of Nasal Epithelial Cell Permeability in Eosinophilic Severe Asthma: Effect of Anti-IL5R Therapy

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Ritchie AI, Hoffman EA, Allinson JP, Bloom CI, Bolton CE, Choudhury G, Gerard SE, Guo J, Alves-Moreira L, Mcgarvey L, Sapey E, Stockley RA, Vestbo J, Singh D, Yip KP, Wilkinson T, Mullerova H, Ostridge K, Mezzi K, Jons O, Bucchioni E, Calverley PM, Compton C, Jones PW, Wedzicha JAet al., 2024,

    Structural Predictors of Lung Function Decline in the British Early COPD Network (BEACON) Cohort

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Bloom CI, Sundaram V, Hubbard RB, Wedzicha JAet al., 2024,

    Association of Cardiovascular Disease, Pulmonary Embolism, and Pneumonia With Inhaled Corticosteroid Use in Asthma: A UK Cohort Study

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Fiorenzo E, Kumar K, Kebadze T, Mallia P, Singanayagam A, Edwards MR, Johnston SLet al., 2024,

    Clinically relevant β2-agonists induce and augment rhinovirus-induction of asthma- relevant pro-inflammatory mediators in human bronchial epithelial cells

    , International Conference of the American-Thoracic-Society (ATS), Publisher: American Thoracic Society, ISSN: 1073-449X
  • Conference paper
    Raby K, Koranteng JB, Dixey P, Adcock I, Gow ANM, Howarth P, Chung K, Bhavsar PKet al., 2024,

    Mepolizumab Depleted Blood Eosinophils Display a Reduced Adhesion Phenotype

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Kimura H, Kermani NZ, Adcock IM, Chung K, Kraft Met al., 2024,

    Association of CC16 Expression in the Airways With Signature Expression of Multi-omics Data

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Pyle CJ, Patel ND, Edwards MR, Shaw S, Johnston SLet al., 2024,

    A Rhinovirus VP0 Vaccine Induces Cross-reactive Type 1 Immunity and Promotes Lymphocyte Activation and Maturation

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Choy D, Nazarova E, Grimbaldeston M, Dugger D, Mar J, Chen H, Cheung DS, Johnston SL, Edwards MR, Morgan C, Park S, Trujillo-Torralbo M, Mallia P, Kon OM, Wilson M, Lafkas D, Chang Det al., 2024,

    A Stop-gain in FUT2 Associates With Several COPD Related Phenotypes and Clinical Outcomes

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Mar J, Dugger D, Chen H, Cheung DS, Morgan C, Park S, Trujillo-Torralbo M, Mallia P, Kon OM, Edwards MR, Johnston SL, Grimbaldeston M, Choy DFet al., 2024,

    Longitudinal Effects of Experimental Rhinovirus Challenge on Airway Phenotype in Chronic Obstructive Pulmonary Disease

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Conference paper
    Bell J, Graul E, Nordon C, Kallis C, Whittaker HR, Janson C, Wilkinson AJK, Usmani OS, Quint JKet al., 2024,

    EXACOS CARBON: Describing the Greenhouse Gas Emissions of Healthcare Resource Utilization by Frequency and Severity of COPD Exacerbation in England

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X
  • Journal article
    Cass SP, Nicolau DV, Baker JR, Mwasuku C, Ramakrishnan S, Mahdi M, Barnes PJ, Donnelly LE, Martinez-Nunez RT, Russell REK, Bafadhel Met al., 2024,

    Coordinated nasal mucosa-mediated immunity accelerates recovery from COVID-19

    , ERJ OPEN RESEARCH, Vol: 10
  • Conference paper
    Thillai M, Oldham J, Ruggiero A, Kanavati F, McLellan TR, Saini G, Johnson S, Fahy W, Ble F-X, Azim A, Ostridge K, Platt A, Belvisi MG, Maher TM, Molyneaux PLet al., 2024,

    Deep Learning-based Segmentation of CT Scans Predicts Disease Progression and Mortality in IPF

    , International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

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