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  • Journal article
    Abubakar-Waziri H, Edwards DA, Bhandu Bhatta D, Hull JH, Rudd M, Small P, Chung KFet al., 2024,

    Inhaled alkaline hypertonic divalent salts reduce refractory chronic cough frequency

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

    Background. Treatment of chronic cough remains a challenge. We hypothesized that inhaled alkaline hypertonic divalent salts (alkaline HDS) might provide relief for refractory chronic cough by laryngeal and tracheal hydration.Methods. We conducted an exploratory, single-blinded, nasal-saline-controlled study in 12 refractory chronic cough patients to examine cough-suppression efficacy of an alkaline HDS composition (SC001) at pH 8 or pH 9 administered by nasal inhalation. As control, we used nasal saline with the same hand-held pump spray aerosol device. Each subject was monitored continuously using a digital cough monitor watch for one week of baseline, one week of control treatment, and one week of active treatment.Results. Baseline daily cough rates ranged from 4 to 34 coughs/hour with mean visual analog score 65±17 pre- and post-baseline testing. Control-adjusted efficacy of cough rate reduction ranged from 15% (p=0.015) (from Day 1) to 23% (p=0.002) (from Day 3). Control-adjusted efficacy was highest with SC001 pH 9 (n=5), ranging from 25% (p=0.03) (from Day 1) to 35% (p=0.02) (from Day 3), and lowest for SC001 pH 8 (n=7), ranging from 9% (p=0.08) (from Day 1) to 16% (p=0.02) (from Day 3). Hourly cough counts and VAS correlated for baseline (r=0.254, p-value=0.02) and control (r=0.299, p-value=0.007) monitoring weeks. Treatment improved this correlation (r=0.434, p-value=0.00006). No adverse events were reported.Conclusions. Alkaline (pH 9) HDS aerosol is a promising treatment for refractory chronic cough and should be further evaluated.
  • Journal article
    Cheng SL, Hedges M, Keski-Rahkonen P, Chatziioannou AC, Scalbert A, Chung KF, Sinharay R, Green DC, de Kok TMCM, Vlaanderen J, Kyrtopoulos SA, Kelly F, Portengen L, Vineis P, Vermeulen RCH, Chadeau-Hyam M, Dagnino Set al., 2024,

    Correction to "Multiomic signatures of traffic-related air pollution in London reveal potential short-term perturbations in gut microbiome-related pathways"

    , Environmental Science and Technology (Washington), Vol: 58, Pages: 17520-17521, ISSN: 0013-936X

    This randomized crossover study investigated the metabolic and mRNA alterations associated with exposure to high and low traffic-related air pollution (TRAP) in 50 participants who were either healthy or were diagnosed with chronic pulmonary obstructive disease (COPD) or ischemic heart disease (IHD). For the first time, this study combined transcriptomics and serum metabolomics measured in the same participants over multiple time points (2 h before, and 2 and 24 h after exposure) and over two contrasted exposure regimes to identify potential multiomic modifications linked to TRAP exposure. With a multivariate normal model, we identified 78 metabolic features and 53 mRNA features associated with at least one TRAP exposure. Nitrogen dioxide (NO2) emerged as the dominant pollutant, with 67 unique associated metabolomic features. Pathway analysis and annotation of metabolic features consistently indicated perturbations in the tryptophan metabolism associated with NO2 exposure, particularly in the gut-microbiome-associated indole pathway. Conditional multiomics networks revealed complex and intricate mechanisms associated with TRAP exposure, with some effects persisting 24 h after exposure. Our findings indicate that exposure to TRAP can alter important physiological mechanisms even after a short-term exposure of a 2 h walk. We describe for the first time a potential link between NO2 exposure and perturbation of the microbiome-related pathways.
  • Journal article
    Rupani H, Busse WW, Howarth PH, Bardin PG, Adcock IM, Konno S, Jackson DJet al., 2024,

    Therapeutic relevance of eosinophilic inflammation and airway viral interactions in severe asthma

    , ALLERGY, Vol: 79, Pages: 2589-2604, ISSN: 0105-4538
  • Journal article
    Ribeiro C, Pamplona P, Simonds AK, 2024,

    Advance care planning in patients with respiratory failure

    , EUROPEAN RESPIRATORY REVIEW, Vol: 33, ISSN: 0905-9180
  • Journal article
    Chung KF, Chaccour C, Jover L, Galvosas M, Song W-J, Rudd M, Small Pet al., 2024,

    Longitudinal Cough Frequency Monitoring in Persistent Coughers: Daily Variability and Predictability

    , LUNG, Vol: 202, Pages: 561-568, ISSN: 0341-2040
  • Journal article
    Cooles F, Vidal-Pedrola G, Naamane N, Pratt A, Barron-Millar B, Anderson A, Hilkens C, Casement J, Bondet V, Duffy D, Zhang F, Shukla R, Isaacs J, Little M, Payne M, Coupe N, Fairfax B, Taylor CA, Mackay S, Milotay G, Bos S, Hunter B, Mcdonald D, Merces G, Sheldon G, Pradere P, Majo J, Pulle J, Vanstapel A, Vanaudenaerde BM, Vos R, Filby AJ, Fisher AJ, Collier J, Lambton J, Suomi F, Prigent M, Guissart C, Erskine D, Rozanska A, Mccorvie T, Trimouille A, Imam A, Hobson E, Mccullagh H, Frengen E, Misceo D, Bjerre A, Smeland M, Klingenberg C, Alkuraya F, Mcfarland R, Alston C, Yue W, Legouis R, Koenig M, Lako M, Mcwilliams T, Olahova M, Taylor R, Newman W, Harkness R, McDermott J, Metcalfe K, Khan N, Macken W, Pitceathly R, Record C, Maroofian R, Sabir A, Santra S, Urquhart J, Demain L, Byers H, Beaman G, Yue W, Taylor R, Durmusalioglu E, Atik T, Isik E, Cogulu O, Reunert J, Marquardt T, Ryba L, Buchert-Lo R, Haack T, Lassuthova P, Polavarapu K, Lochmuller H, Horvath R, Jamieson P, Reilly M, O'Keefe R, Boggan R, Ng YS, Franklin I, Alston C, Blakely E, Buechner B, Bugiardini E, Colclough K, Feeney C, Hanna M, Hattersley A, Klopstock T, Kornblum C, Mancuso M, Patel K, Pitceathly R, Pizzamiglio C, Prokisch H, Schaefer J, Schaefer A, Shepherd M, Thaele A, Thomas R, Turnbull D, Gorman G, Woodward C, McFarland R, Taylor R, Cordell H, Pickett S, Tsilifis C, Pearce M, Gennery A, Daly A, Darlay R, Zatorska M, Worthington S, Anstee Q, Cordell H, Reeves H, Nizami S, Mauricio-Muir J, McCain M, Singh R, Wordsworth J, Kadharusman M, Watson R, Masson S, McPherson S, Burt A, Tiniakos D, Littler P, Nsengimana J, Zhang S, Mann D, Jamieson D, Leslie J, Shukla R, Wilson C, Betts J, Croall I, Hoggard N, Bennett J, Naamane N, Hollingsworth KG, Pratt AG, Egail M, Feeney C, Di Leo V, Taylor RW, Dodds R, Anderson AE, Sayer AA, Isaacs JD, McCracken C, Condurache D-G, Szabo L, Elghazaly H, Walter F, Meade A, Chakraverty R, Harvey N, Manisty C, Petersen S, Neubauer S, Raisi-Estabragh Z, Allen Let al., 2024,

    ASSOCIATION OF PHYSICIANS OF GREAT BRITAIN AND IRELAND 117th Annual Meeting 23-24 May 2024 Frederick Douglass Centre, Newcastle Abstracts

    , QJM-AN INTERNATIONAL JOURNAL OF MEDICINE, ISSN: 1460-2725
  • Journal article
    Oqua AI, Chao K, El Eid L, Casteller L, Miguéns A, Barg S, Jones B, de la Serna JB, Rouse SL, Tomas Aet al., 2024,

    Molecular mapping and functional validation of GLP-1R cholesterol binding sites in pancreatic beta cells

    , eLife, ISSN: 2050-084X

    G protein-coupled receptors (GPCRs) are integral membrane proteins which closely interact with their plasma membrane lipid microenvironment. Cholesterol is a plasma membrane enriched lipid with pivotal roles in the control of membrane fluidity and maintenance of membrane microarchitecture, directly impacting on GPCR stability, dynamics and function. Cholesterol extraction from pancreatic beta cells has previously been shown to disrupt the internalisation, clustering and cAMP responses of the glucagon-like peptide-1 receptor (GLP 1R), a class B1 GPCR with key roles in the control of blood glucose levels via the potentiation of insulin secretion in beta cells and weight reduction via the modulation of brain appetite control centres. Here, we unveil the detrimental effect of a high cholesterol diet on GLP-1R dependent glucoregulation in vivo, and the improvement in GLP-1R function that a reductionin cholesterol synthesis using simvastatin exerts in pancreatic islets. We next identify and mapsites of cholesterol high occupancy and residence time on active versus inactive GLP-1Rsusing coarse-grained molecular dynamics (cgMD) simulations, followed by a screen of key residues selected from these sites and detailed analyses of the effects of mutating one of these residues, Val229, to alanine on GLP-1R interactions with cholesterol, plasma membrane behaviours, clustering, trafficking and signalling in pancreatic beta cells and primary islets, unveiling an improved insulin secretion profile for the V229A mutant receptor. This study 1) highlights the role of cholesterol in regulating GLP-1R responses in vivo; 2) provides a detailed map of GLP-1R - cholesterol binding sites in model membranes; 3) validates their functional relevance in beta cells; and 4) highlights their potential as locations for the rational design of novel allosteric modulators with the capacity to fine-tune GLP-1R responses.
  • Journal article
    Mortaz E, Roofchayee ND, Jamaati H, Tabarsi P, Ahmadi S, Shahi H, Varahram M, Mogadam KB, Sajadi MM, Adcock IMet al., 2024,

    Characterization of QuantiFERON Severe Acute Respiratory Syndrome Coronavirus 2 and Anti-severe Acute Respiratory Syndrome Coronavirus 2 Nucleocapsid and S1 Spike Protein Antibodies in Vaccinated and Unvaccinated Coronavirus Disease 2019 Patients

    , BIOMEDICAL AND BIOTECHNOLOGY RESEARCH JOURNAL, Vol: 8, Pages: 393-402, ISSN: 2588-9834
  • Journal article
    McKee M, Greenhalgh T, Qasim A, Hopkinson NS, Nicholl Det al., 2024,

    Independent inquiry finds serious governance failures at the Royal College of Physicians of London

    , BMJ: British Medical Journal, Vol: 386, Pages: q1983-q1983, ISSN: 0959-535X
  • Journal article
    Jarjour NN, Winders T, Hansen AM, Akuthota P, Chung KF, Durrington H, Fowler SJ, Gaston B, Mendonca EA, Siddiqui S, Walker S, Zein J, Djukanovic Ret al., 2024,

    Asthma innovations from the second International Collaborative Asthma Network (ICAN) forum

    , JOURNAL OF ASTHMA, ISSN: 0277-0903
  • Journal article
    Yildirim AO, Conlon TM, Adcock IM, Gosens R, Lehmann M, Kapellos TS, Tesfaigzi Y, Polverino F, Sauler M, Wasnick R, Neptune ERet al., 2024,

    COPD-iNET: a call to the lung community for action to combat the of COPD

    , EUROPEAN RESPIRATORY JOURNAL, Vol: 64, ISSN: 0903-1936
  • Journal article
    Hopkinson NS, Bush A, Allinson JP, Faner R, Zar HJ, Agusti Aet al., 2024,

    Early Life Exposures and the Development of Chronic Obstructive Pulmonary Disease across the Life Course

    , AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 210, Pages: 572-580, ISSN: 1073-449X
  • Conference paper
    Waziri H, Edwards DA, Bhatta DB, Hull J, Rudd M, Small P, Chung KFet al., 2024,

    Inhaled alkaline hypertonic divalent salts reduce refractory chronic cough frequency

    , Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
  • Conference paper
    Guo Y, Fenwick P, Viola P, Al-Sahaf M, Barnes PJ, Donnelly LEet al., 2024,

    Navitoclax inhibits senescence in human alveolar type 2 cells from COPD patients

    , European-Respiratory-Society Congress (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
  • Conference paper
    Valencia-Hernandez C, Wong E, Bloom C, 2024,

    Influence of pregnancy on asthma exacerbation patterns: a UK population-based cohort

    , European-Respiratory-Society Congress (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
  • Conference paper
    Ritchie A, Donaldson G, Hoffman E, Allinson J, Bloom C, Smith B, Bolton C, Choudhury G, Gerard S, Guo J, Alves-Moreira L, Mcgarvey L, Sapey E, Stockley R, Yip K, Singh D, Wilkinson T, Mullerova H, Ostridge K, Joens O, Bucchioni E, Compton C, Jones P, Mezzi K, Vestbo J, Calverley P, Wedzicha Jet al., 2024,

    Association of Dysanapsis with FEV1 Decline in Early COPD: The BEACON Cohort

    , Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
  • Conference paper
    Ou C, Xia T, Deng Z, Liu Y, Shi G, Qiu M, Wei X, Gu W, Zhao J, Liu X, Sun S, Tang H, He B, Cai S, Chen P, Chen P, Xie L, Chung KF, Jin M, Lu S, Zhang Qet al., 2024,

    Asthma clusters from quantitative computed tomographic measurements in the lungs in CBIOPRED cohort

    , European-Respiratory-Society Congress (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
  • Conference paper
    Delgado Ortiz L, Buekers J, Chynkiamis N, Demeyer H, Frei A, Gimeno-Santos E, Hansen C, Hausdorff J, Hopkinson N, Jansen C-P, Koch S, Maetzler W, Megaritis D, Puhan M, Singleton D, Thoemmes G, Vogiatzis I, Watz H, Del Din S, Cauffield B, Becker C, Rochester L, Troosters T, Garcia-Aymerich Jet al., 2024,

    Real-world walking of people with COPD

    , European-Respiratory-Society Congress (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
  • Conference paper
    Philip KEJ, Burton A, Lewis A, Buttery SC, Williams PJ, Polkey M, Fancourt D, Hopkinson Net al., 2024,

    Participant experience of Scottish Ballet's online dance based long COVID support programme: A mixed methods study

    , Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
  • Conference paper
    Blondeel A, Demeyer H, Alcaraz-Serrano V, Buttery S, Buekers J, Chynkiamis N, Cullere AJ, Delgado-Ortiz L, Frei A, Glorie L, Gimeno-Santos E, Hopkinson N, Hume E, Jansen C-P, Kirsten A, Koch S, Megaritis D, Mellaerts P, Puhan M, Vogiatzis I, Watz H, Wuyts M, Garcia-Aymerich J, Troosters Tet al., 2024,

    Validation of the Late-Life Function and Disability Instrument in people with COPD

    , European-Respiratory-Society Congress (ERS), Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

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