Publications

Search or filter publications

Filter by type:

Filter by publication type

Filter by year:

to

Results

  • Showing results for:
  • Reset all filters

Search results

  • Journal article
    Wang M, Zhang Y, Xu M, Zhang H, Chen Y, Chung KF, Adcock IM, Li Fet al., 2019,

    Roles of TRPA1 and TRPV1 in cigarette smoke -induced airway epithelial cell injury model

    , Free Radical Biology and Medicine, Vol: 134, Pages: 229-238, ISSN: 0891-5849

    Transient receptor potential protein (TRP) ion channels TRPA1 and TRPV1 may be important in mediating airway tissue injury and inflammation. This study was designed to clarify the role of TRPA1 and TRPV1 channels in cigarette smoke extract (CSE)-induced damage to bronchial and alveolar epithelial cells. Alveolar epithelial (A549) cells and bronchial epithelial (Beas-2B) cells were treated with CSE in the presence and absence of a TRPA1 inhibitor (100 μM, A967079), a TRPV1 inhibitor (100 μM, AMG9810) or both. DCFH-DA and MitoSOX Red probes were used to assay intracellular and mitochondrial oxidative stress, respectively. The mRNA levels of inflammatory mediators (IL-1β, IL-8, IL-18, IL-33) and antioxidants (HO-1, NQO1, MnSOD, catalase) and the protein expression levels of mitochondrial and inflammasome factors (MFN2, OPA1, DRP1, MFF, NLRP3,caspase-1) were respectively detected by RT-PCR and Western Blot. The results were validated in TRPA1 shRNA and TRPV1 shRNA cells. In both cell types, 10% CSE increased intracellular and mitochondrial oxidative stress, induced Ca2+ influx, increased inflammatory gene expression, reduced antioxidant gene expression and inhibited the activities of mitochondrial respiratory chain (MRC) complexes. 10% CSE increased the expression of mitochondrial fission proteins (MFF and DRP1), Caspase-1 and NLRP3 protein expression and decreased that of mitochondrial fusion proteins (MFN2 and OPA1). Both inhibitors and gene-knockout of TRPA1 and TRPV1 reduced oxidative stress, blocked Ca2+ influx, and inhibited inflammatory and increased antioxidant gene expression. They also prevented the changes in mitochondrial fission and fusion proteins and in MRC complexes activities induced by CSE. Both TRPA1 and TRPV1 mediate CSE-induced damage of bronchial and alveolar epithelial cells via modulation of oxidative stress, inflammation and mitochondrial damage and their inhibition should be considered as potential therapy for COPD.
  • Journal article
    Dunne A, Kawamatawong T, Fenwick P, Davies C, Tullett H, Barnes P, Donnelly Let al., 2019,

    Direct inhibitory rffect of the phosphodiesterase-4 inhibitor, roflumilast, on neutrophil migration in COPD

    , American Journal of Respiratory Cell and Molecular Biology, Vol: 60, Pages: 445-453, ISSN: 1044-1549

    Neutrophilic inflammation is characteristic of COPD, yet there are no effective anti-inflammatory therapies. The phosphodiesterase (PDE)4 inhibitor, roflumilast is approved for use in COPD and suppresses sputum neutrophilia. The mechanism underlying this observation is unclear and therefore this study addressed whether roflumilast directly affected neutrophil migration. Blood-derived neutrophils were isolated from non-smokers, smokers and COPD patients and chemotaxis measured using Boyden chambers. Intracellular calcium ion concentration ([Ca2+]i) was measured by fluorimetry and shape change and CD11b expression by flow cytometry. Neutrophils from COPD patients showed enhanced chemotactic responses towards both CXCL1 and LTB4 compared with control cells. Chemotaxis was inhibited by both the active metabolite, roflumilast-N-oxide, and rolipram in a concentration-dependent manner with no difference in responsiveness between subjects. Roflumilast-N-oxide and rolipram were less efficacious against CXCL1 and LTB4-mediated [Ca2+]i suggesting that inhibition was not via this pathway. Both PDE4 inhibitors attenuated chemoattractant-mediated shape change and CD11b up-regulation suggesting common mechanisms. The stable cAMP analogue, 8-Br-cAMP, inhibited chemotaxis, as did the direct Epac1 activator 8-pCPT-2’-O-Me-cAMP but not the direct PKA activator, 6-Bnz-cAMP. These data suggest that roflumilast inhibits neutrophil chemotaxis directly via a cAMP-mediated mechanism requiring activation of Epac1, and that Epac1 activators could reduce COPD neutrophilic inflammation.
  • Journal article
    Ravanetti L, Dijkhuis A, Dekker T, Sabogal Pineros YS, Ravi A, Dierdorp BS, Erjefält JS, Mori M, Pavlidis S, Adcock IM, Rao NL, Lutter Ret al., 2019,

    IL-33 drives influenza-induced asthma exacerbations by halting innate and adaptive anti-viral immunity

    , Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 1355-1370, ISSN: 0091-6749

    BACKGROUND: Influenza virus triggers severe exacerbations of asthma for which no adequate treatment is available. It is known that IL-33 levels correlate with exacerbation severity, but its role in the immune-pathogenesis of exacerbations has remained elusive. OBJECTIVE: We hypothesized that IL-33 is necessary to drive asthma exacerbations. We intervened with the IL-33 cascade and sought to dissect its role, also in synergy with TSLP, in airway inflammation, anti-viral activity and lung function. We aimed to unveil the major source of IL-33 in the airways and IL-33-dependent mechanisms that underlie severe asthma exacerbation. METHODS: Mild asthmatic patients were experimentally infected with rhinovirus. Mice were chronically exposed to house dust mite (HDM) extract and then infected with influenza to resemble key features of exacerbations in humans. Interventions included anti-IL-33-receptor ST2 and/or anti-TSLP. RESULTS: We identified bronchial ciliated cells and Type-II alveolar cells as a major local source of IL-33 during virus-driven exacerbation in humans and mice, respectively. By blocking ST2 we demonstrated that IL-33 and not TSLP was necessary to drive exacerbations. IL-33 enhanced AHR and airway inflammation by suppressing innate and adaptive anti-viral responses and by instructing epithelial cells and dendritic cells (DCs) of HDM-sensitized mice to dampen IFN-β expression and prevent the Th1-promoting DCs phenotype. IL-33 also boosted luminal NETosis and halted cytolytic anti-viral activities, but did not affect the Th2-response. CONCLUSION: Interventions targeting the IL-33/ST2 axis could prove an effective acute, short-term therapy for virus-induced asthma exacerbation.
  • Journal article
    Potaczek DP, Unger SD, Zhang N, Taka S, Michel S, Akdag N, Lan F, Helfer M, Hudemann C, Eickmann M, Skevaki C, Megremis S, Sadewasser A, Alhamwe BA, Alhamdan F, Akdis M, Edwards MR, Johnston SL, Akdis CA, Becker S, Bachert C, Papadopoulos NG, Garn H, Renz Het al., 2019,

    Development and characterization of DNAzyme candidates demonstrating significant efficiency against human rhinoviruses

    , JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 143, Pages: 1403-1415, ISSN: 0091-6749
  • Journal article
    Bousquet J, Bedbrook A, Czarlewski W, Onorato GL, Arnavielhe S, Laune D, Mathieu-Dupas E, Fonseca J, Costa E, Lourenco O, Morais-Almeida M, Todo-Bom A, Illario M, Menditto E, Canonica GW, Cecchi L, Monti R, Napoli L, Ventura MT, De Feo G, Fokkens WJ, Chavannes NH, Reitsma S, Cruz AA, da Silva J, Serpa FS, Larenas-Linnemann D, Perez JMF, Huerta-Villalobos YR, Rivero-Yeverino D, Rodriguez-Zagal E, Valiulis A, Dubakiene R, Emuzyte R, Kvedariene V, Annesi-Maesano I, Blain H, Bonniaud P, Bosse I, Dauvilliers Y, Devillier P, Fontaine JF, Pepin JL, Pham-Thi N, Portejoie F, Picard R, Roche N, Rolland C, Schmidt-Grendelmeier P, Kuna P, Samolinski B, Anto JM, Cardona V, Mullol J, Pinnock H, Ryan D, Sheikh A, Walker S, Williams S, Becker S, Klimek L, Pfaar O, Bergmann KC, Mosges R, Zuberbier T, Roller-Wirnsberger RE, Tomazic PV, Haahtela T, Salimaki J, Toppila-Salmi S, Valovirta E, Vasankari T, Gemicioglu B, Yorgancioglu A, Papadopoulos NG, Prokopakis EP, Tsiligianni IG, Bosnic-Anticevich S, O'Hehir R, Ivancevich JC, Neffen H, Zernotti ME, Kull I, Melen E, Wickman M, Bachert C, Hellings PW, Brusselle G, Palkonen S, Bindslev-Jensen C, Eller E, Waserman S, Boulet LP, Bouchard J, Chu DK, Schunemann HJ, Sova M, De Vries G, van Eerd M, Agache I, Ansotegui IJ, Bewick M, Casale T, Dykewick M, Ebisawa M, Murray R, Naclerio R, Okamoto Y, Wallace DV, Bousquet J, Hellings PW, Aberer W, Agache I, Akdis CA, Akdis M, Aliberti MR, Almeida R, Amat F, Angles R, Annesi-Maesano I, Ansotegui IJ, Anto JM, Arnavielle S, Asayag E, Asarnoj A, Arshad H, Avolio F, Bacci E, Bachert C, Baiardini I, Barbara C, Barbagallo M, Baroni I, Barreto BA, Basagana X, Bateman ED, Bedolla-Barajas M, Bedbrook A, Bewick M, Beghe B, Bel EH, Bergmann KC, Bennoor KS, Benson M, Bertorello L, Bialoszewski AZ, Bieber T, Bialek S, Bindslev-Jensen C, Bjermer L, Blain H, Blasi F, Blua A, Marciniak MB, Bogus-Buczynska I, Boner AL, Bonini M, Bonini S, Bosnic-Anticevich CS, Bosse I, Bouchard J, Boulet LP, Bourret R, Bousquet PJ Bet al., 2019,

    Guidance to 2018 good practice: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma

    , CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 9, ISSN: 2045-7022

    AimsMobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases.MethodsMASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients.StakeholdersInclude patients, health care professionals (pharmacists and physicians), authorities, patient’s associations, private and public sectors.ResultsMASK is deployed in 23 countries and 17 languages. 26,000 users have registered.
  • Journal article
    Agusti A, Faner R, Donaldson G, Heuvelin E, Breyer-Kohansal R, Melén E, Maitland-van der Zee AH, Vestbo J, Allinson JP, Vanfleteren LEGW, van den Berge M, Adcock IM, Lahousse L, Brusselle G, Wedzicha JA, onbehalf of the CADSET Clinical Research Collaboration, Current members of the CADSET Clinical Research Collaborationet al., 2019,

    Chronic Airway Diseases Early Stratification (CADSET): a new ERS Clinical Research Collaboration

    , European Respiratory Journal, Vol: 53, ISSN: 0903-1936

    A recent editorial in the European Respiratory Journal highlighted the strategic importance of the Clinical Research Collaborations (CRCs) launched in 2013 by the European Respiratory Society (ERS) [1]. These have the aim of 1) promoting the exchange of research ideas among clinicians and affiliated scientists in Europe and/or globally; 2) building an infrastructure for prospective clinical research; 3) securing additional funding through national and European Union funding streams; and 4) facilitating the planning, implementation, evaluation and publication of clinical and translational studies at pan-European level and beyond. So far, there are currently 17 ongoing CRCs that cover eight major respiratory disease domains (airway diseases, interstitial lung diseases, pulmonary vascular diseases, sleep and breathing disorders, respiratory critical care, paediatric respiratory diseases, respiratory infections and thoracic oncology), all of them linked to one or more ERS assemblies [2–12]. CADSET, an acronym that stands for “Chronic Airway Diseases Early Stratification”, is the latest addition to the list of ongoing CRCs (www.ersnet.org/research/clinical-research-collaborations). This editorial presents the rationale, goals and research strategy for CADSET.
  • Journal article
    Wilkinson A, Hillman T, Hopkinson NS, Janson C, Smith J, Woodcock AAet al., 2019,

    Our patients and our planet-holistic considerations for inhaler choice

    , Lancet Respiratory Medicine, Vol: 7, Pages: e11-e11, ISSN: 2213-2600
  • Journal article
    Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, MOSAIC Investigators, Moffatt MF, O'Garra A, Openshaw PJMet al., 2019,

    Author Correction: Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza.

    , Nature Immunology, Vol: 20, Pages: 373-373, ISSN: 1529-2908

    In the version of this article initially published, a source of funding was not included in the Acknowledgements section. That section should include the following: P.J.M.O. was supported by EU FP7 PREPARE project 602525. The error has been corrected in the HTML and PDF version of the article.
  • Journal article
    Hakim A, Khan Y, Esteban I, Meah S, Miller-Larsson A, Barnes PJ, Usmani OSet al., 2019,

    Low-dose budesonide/formoterol counteracts airway inflammation and improves lung function in COPD

    , American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 662-664, ISSN: 1073-449X

    The latest Global Initiative for Chronic Obstructive Lung Disease (GOLD) document recommends new treatment algorithms, with inhaled corticosteroids (ICS) use only in moderate-to-severely symptomatic COPD patients with repeated exacerbations, where the emphasis is to review ICS use and to reduce ICS dosing (1). Indeed, safety concerns of pneumonia (2) with high-dose ICS has further concerted focus upon using appropriate doses of ICS. It is well-established that ICS in combination with long-acting β2-adrenoceptor agonist (LABA) can decrease exacerbations, improve symptomsand increase quality of life in patients with COPD (3-4), but nonetheless, the rationale to consider step-down of ICS is supported by several clinical studies (5). The Withdrawal of Inhaled Steroids during Optimized Bronchodilator Management (WISDOM) trial studied severe COPD patients on therapy with ICS, LAMA and LABA, where stepwise withdrawal of ICS did not lead to an increase in exacerbations compared to continued ICS use (6). Determining the optimal dose of ICS and LABA combination therapy is of great biological and clinical importance in order to address safety concerns associated with high-dose ICS use. There is in vitro evidence to support the clinical practice of using low-dose ICS. Low-dose ICS in combination with LABA enhances corticosteroid function by enhancing glucocorticoid receptor (GR) activity (7) and suppresses the release of inflammatory mediators (8). However, it is unknown whether this observation of enhanced corticosteroid function with low-dose ICS/LABA has a direct effect on airways inflammation and lung function. Our study investigated the cellular function that may be relevant and underpin the clinical approach to lowering the dose of ICS therapy in COPD patients. We compared the single administra
  • Journal article
    Bousquet J, Hellings PW, Agache I, Amat F, Annesi-Maesano I, Ansotegui IJ, Anto JM, Bachert C, Bateman ED, Bedbrook A, Bennoor K, Bewick M, Bindslev-Jensen C, Bosnic-Anticevich S, Bosse I, Brozek J, Brussino L, Canonica GW, Cardona V, Casale T, Sarabia AMC, Chavannes NH, Cecchi L, de Sousa JC, Costa E, Cruz AA, Czarlewski W, De Carlo G, De Feo G, Demoly P, Devillier P, Dykewicz MS, El-Gamal Y, Eller EE, Fonseca JA, Fontaine J-F, Fokkens WJ, Guzman M-A, Haahtela T, Illario M, Ivancevich J-C, Just J, Kaidashev I, Khaitov M, Kalayci O, Keil T, Klimek L, Kowalski ML, Kuna P, Kvedariene V, Larenas-Linnemann D, Laune D, Le LTT, Carlsen KL, Lourenco O, Mahboub B, Mair A, Menditto E, Milenkovic B, Morais-Almeida M, Mosges R, Mullol J, Murray R, Naclerio R, Namazova-Baranova L, Novellino E, O'Hehir RE, Ohta K, Okamoto Y, Okubo K, Onorato GL, Palkonen S, Panzner P, Papadopoulos NG, Park H-S, Paulino E, Pawankar R, Pfaar O, Plavec D, Popov TA, Potter P, Prokopakis EP, Rottem M, Ryan D, Salimaki J, Samolinski B, Sanchez-Borges M, Schunemann HJ, Sheikh A, Sisul J-C, Rajabian-Soderlund R, Sooronbaev T, Stellato C, To T, Todo-Bom A-M, Tomazic P-V, Toppila-Salmi S, Valero A, Valiulis A, Valovirta E, Ventura M-T, Wagenmann M, Wang DY, Wallace D, Waserman S, Wickman M, Yorgancioglu A, Zhang L, Zhong N, Zidarn M, Zuberbier T, Bousquet J, Hellings PW, Aberer W, Agache I, Akdis CA, Akdis M, Alberti MR, Almeida R, Amat F, Angles R, Annesi-Maesano I, Ansotegui IJ, Anto JM, Arnavielle S, Asayag E, Asarnoj A, Arshad H, Avolio F, Bacci E, Bachert C, Baiardini I, Barbara C, Barbagallo M, Baroni I, Barreto BA, Basagana X, Bateman ED, Bedolla-Barajas M, Bedbrook A, Bewick M, Beghe B, Bel EH, Bergmann KC, Bennoor KS, Benson M, Bertorello L, Biaoszewski AZ, Bieber T, Bialek S, Bindslev-Jensen C, Bjermer L, Blain H, Blasi F, Blua A, Marciniak MB, Bogus-Buczynska I, Boner AL, Bonini M, Bonini S, Bosnic-Anticevich CS, Bosse I, Bouchard J, Boulet LP, Bourret R, Bousquet PJ, Braido F, Briedis V, Brighet al., 2019,

    Allergic Rhinitis and its Impact on Asthma (ARIA) Phase 4 (2018): Change management in allergic rhinitis and asthma multimorbidity using mobile technology

    , Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 864-879, ISSN: 0091-6749

    Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline by using the best approach to integrated care pathways using mobile technology in patients with allergic rhinitis (AR) and asthma multimorbidity. The proposed next phase of ARIA is change management, with the aim of providing an active and healthy life to patients with rhinitis and to those with asthma multimorbidity across the lifecycle irrespective of their sex or socioeconomic status to reduce health and social inequities incurred by the disease. ARIA has followed the 8-step model of Kotter to assess and implement the effect of rhinitis on asthma multimorbidity and to propose multimorbid guidelines. A second change management strategy is proposed by ARIA Phase 4 to increase self-medication and shared decision making in rhinitis and asthma multimorbidity. An innovation of ARIA has been the development and validation of information technology evidence-based tools (Mobile Airways Sentinel Network [MASK]) that can inform patient decisions on the basis of a self-care plan proposed by the health care professional.
  • Journal article
    Pfeffer PE, Donaldson GC, Mackay AJ, Wedzicha JAet al., 2019,

    Increased COPD exacerbations of likely viral etiology follow elevated ambient nitrogen oxides

    , American Journal of Respiratory and Critical Care Medicine, Vol: 199, ISSN: 1073-449X

    RATIONALE: Epidemiological research strongly supports an association between air pollution and COPD exacerbations. Numerous mechanisms may underlie any association as pollutants are toxic to pulmonary cells and may increase susceptibility to respiratory infections. The relationship between ambient pollution and exacerbation etiology has not been studied. OBJECTIVES: To evaluate the characteristics of pollution-associated exacerbations and whether the association is specific to exacerbations of infective or non-infective etiology. METHODS: We analyzed the effect of preceding ambient PM10, NOx and O3 on characterized COPD exacerbations in a regression model adjusted for temperature, seasonality and long-term trend. We specifically examined associations with exacerbations of suspected viral and/or bacterial, or non-infective etiology. For the associations identified we further examined the characteristics of pollution-associated exacerbations. MEASUREMENTS AND MAIN RESULTS: 4173 exacerbations occurred over the 20 year study period. Higher ambient NOx was consistently associated with increased viral-type exacerbations at 2-4 days lag (p=0.010). Recovery for viral-type exacerbations following higher ambient NOx was significantly prolonged. These findings were consistent in the subset of 2841 exacerbations treated with oral corticosteroids or antibiotics, with recovery 1.29 (95% CI 1-17-1.42; P<0.001) times longer with 'viral-type' exacerbations of onset 3 days after above versus below median ambient NOx. A likely bimodal association of PM10 with infective exacerbations was also evident, and supported by a daily time-series analysis. CONCLUSIONS: Higher levels of ambient NOx are associated with prolonged exacerbations of likely viral etiology, supporting toxicological effects of air pollution that increase susceptibility to, and severity of, infection.
  • Journal article
    Ghosh B, Gaike AH, Pyasi K, Brashier B, Das VV, Londhe JD, Juvekar S, Shouche YS, Donnelly LE, Salvi SS, Barnes PJet al., 2019,

    Bacterial load and defective monocyte-derived macrophage bacterial phagocytosis in biomass-smoke COPD

    , European Respiratory Journal, Vol: 53, Pages: 1-14, ISSN: 0903-1936

    Lower airway colonisation with potentially pathogenic bacterial species (PPBs) is associated with defective bacterial phagocytosis, in monocyte-derived macrophages (MDMs) and alveolar macrophages, from tobacco-smoke associated COPD (S-COPD) subjects. In developing world, COPD among non-smokers is largely due to biomass-smoke (BMS) exposure. Yet, little is known about PPBs colonisation and its association with impaired innate immunity in these subjects.We investigated the PPBs load (Streptococcus pneumoniae, SP; Haemophilus influenzae, HI; Moraxella catarrhalis, MC; and Pseudomonas aeruginosa, PA) in BMS-exposed COPD (BMS-COPD) compared with S-COPD and spirometrically normal subjects. We also examined the association between load of PPBs with phagocytic activity of MDMs and lung function.Induced sputum and peripheral venous blood samples were collected from 18 healthy non-smokers, 15 smokers without COPD, 16 BMS-exposed healthy, 19 S-COPD and 23 BMS-COPD subjects. PPBs load in induced sputum and MDMs phagocytic activity were determined using qPCR and fluorimetry respectively.Higher bacterial load of SP, HI, and PA were observed in BMS-COPD. Increased PPBs load in BMS-exposed subjects was significantly negatively associated with defective phagocytosis in MDMs, and spirometric lung function indices (p<0.05).Increased load of PPBs in airways of BMS-COPD subjects is inversely associated with defective bacterial phagocytosis and lung function.
  • Journal article
    Jia M, Yan X, Jiang X, Wu Y, Xu J, Meng Y, Yang Y, Shan X, Zhang X, Mao S, Gu W, Pavlidis S, Barnes PJ, Adcock IM, Huang M, Yao Xet al., 2019,

    Ezrin, a membrane cytoskeleton cross-linker protein, as a marker of epithelial damage in asthma

    , American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 496-507, ISSN: 1073-449X

    RATIONALE: Bronchial epithelial cell damage occurs in patients with bronchial asthma. Ezrin, a membrane-cytoskeleton protein, maintains cellular morphology and intercellular adhesion and protects the barrier function of epithelial cells. OBJECTIVES: To study the role of ezrin in bronchial epithelial cells injury and correlate its expression with asthma severity. METHODS: Levels of ezrin were measured in exhaled breath condensate (EBC) and serum in asthma patients and bronchoalveolar lavage fluid (BALF) from a mouse model of asthma by ELISA. The regulation of IL-13 on ezrin protein levels was studied in primary bronchial epithelial cells (PBECs). Ezrin knockdown using shRNA was studied in human bronchial epithelial 16HBE cells. RESULTS: Ezrin levels were decreased in asthmatic EBC (392.7±34.99 vs 150.5±10.22 pg/ml, p<0.0001) and serum (700.7±55.59 vs 279.2±25.83pg/ml, p<0.0001) compared to normal subjects. Levels were much lower in uncontrolled (p<0.001) and partly-controlled patients (p<0.01) compared to well-controlled subjects. EBC and serum ezrin levels correlated with lung function in asthma patients and serum ezrin levels were negatively correlated with serum IL-13 and periostin. IL-13-induced down-regulation of ezrin expression in PBECs was significantly attenuated by the JAK2 (Janus tyrosine kinase 2) inhibitor TG101348. Ezrin knockdown changed 16HBE cell morphology, enlarged intercellular spaces and increased their permeability. Ezrin expression was decreased in the lung tissue and BALF of 'asthmatic' mice and negatively correlated with BALF IL-13 level. CONCLUSIONS: Ezrin down-regulation is associated with IL-13-induced epithelial damage and might be a potential biomarker of asthma control.
  • Journal article
    Chapman KR, Hurst JR, Fogel RB, Pfister P, Kostikas K, Wedzicha JA, SUNSET investigatorset al., 2019,

    Reply to: Different background, short duration, inappropriate participants may harm your conclusion

    , American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 390-392, ISSN: 1073-449X
  • Journal article
    Schleich F, Bikov A, Mathioudakis AG, McDonnell M, Andersson C, Bonini M, Uller L, Idzko M, Singh D, Lopez-Campos JL, Bossios A, Adcock IM, Usmani O, Spanevello A, Bonvini SJet al., 2019,

    Research highlights from the 2018 European Respiratory Society International Congress: airway disease.

    , ERJ Open Research, Vol: 5, ISSN: 2312-0541

    The annual European Respiratory Society (ERS) International Congress (held in Paris in 2018) was once again a platform for discussion of the highest-quality scientific research, cutting-edge techniques and innovative new therapies within the respiratory field. This article discusses only some of the high-quality research studies presented at this year's Congress, with a particular focus on airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiectasis and cough, as presented through Assembly 5 of the ERS (Airway Diseases: Asthma and COPD). The authors establish the key take-home messages of these studies, compare their findings and place them in the context of current understanding.
  • Journal article
    Tregoning JS, Mallia P, 2019,

    Modulating airway glucose to reduce respiratory infections

    , Expert Review of Respiratory Medicine, Vol: 13, Pages: 121-124, ISSN: 1747-6348
  • Journal article
    Erriah M, Pabreja K, Fricker M, Baines KJ, Donnelly LE, Bylund J, Karlsson A, Simpson JLet al., 2019,

    Galectin-3 enhances monocyte-derived macrophage efferocytosis of apoptotic granulocytes in asthma

    , Respiratory Research, Vol: 20, ISSN: 1465-9921

    BackgroundGalectin-3 is a 32 kDa protein secreted by macrophages involved in processes such as cell activation, chemotaxis and phagocytosis. Galectin-3 has previously been shown to improve the ability of airway macrophages to ingest apoptotic cells (efferocytosis) in chronic obstructive pulmonary disease (COPD) and may be of interest in non-eosinophilic asthma (NEA) which is also characterised by impaired efferocytosis. It was hypothesised that the addition of exogenous galectin-3 to monocyte-derived macrophages (MDMs) derived from donors with NEA would enhance their ability to engulf apoptotic granulocytes.MethodsEligible non-smoking adults with asthma (n = 19), including 7 with NEA and healthy controls (n = 10) underwent a clinical assessment, venepuncture and sputum induction. MDMs were co-cultured with apoptotic granulocytes isolated from healthy donors with or without exogenous recombinant galectin-3 (50 μg/mL) and efferocytosis was assessed by flow cytometry. Galectin-3 expression and localisation in MDMs was visualised by immunofluorescence staining and fluorescence microscopy. Galectin-3, interleukin (IL)-6 and CXCL8 secretion were measured in cell culture supernatants by ELISA and cytometric bead array.ResultsBaseline efferocytosis (mean (±standard deviation)) was lower in participants with asthma (33.2 (±17.7)%) compared with healthy controls (45.3 (±15.9)%; p = 0.081). Efferocytosis did not differ between the participants with eosinophilic asthma (EA) (31.4 (±19.2)%) and NEA (28.7 (±21.5)%; p = 0.748). Addition of galectin-3 significantly improved efferocytosis in asthma, particularly in NEA (37.8 (±18.1)%) compared with baseline (30.4 (±19.7)%; p = 0.012). Efferocytosis was not associated with any of the clinical outcomes but was negatively correlated with sputum macrophage numbers (Spearman r = −&thi
  • Journal article
    Hersh CP, Adcock IM, Celedon JC, Cho MH, Christiani DC, Himes BE, Kaminski N, Mathias RA, Meyers DA, Quackenbush J, Redline S, Steiling KA, Tabor HK, Tobin MD, Wurfel MM, Yang IV, Koppelman GHet al., 2019,

    High-throughput sequencing in respiratory, critical care, and sleep medicine research. An Official American Thoracic Society Workshop Report

    , Annals of the American Thoracic Society, Vol: 16, Pages: 1-16, ISSN: 2329-6933

    High-throughput, “next-generation” sequencing methods are now being broadly applied across all fields of biomedical research, including respiratory disease, critical care, and sleep medicine. Although there are numerous review articles and best practice guidelines related to sequencing methods and data analysis, there are fewer resources summarizing issues related to study design and interpretation, especially as applied to common, complex, nonmalignant diseases. To address these gaps, a single-day workshop was held at the American Thoracic Society meeting in May 2017, led by the American Thoracic Society Section on Genetics and Genomics. The aim of this workshop was to review the design, analysis, interpretation, and functional follow-up of high-throughput sequencing studies in respiratory, critical care, and sleep medicine research. This workshop brought together experts in multiple fields, including genetic epidemiology, biobanking, bioinformatics, and research ethics, along with physician-scientists with expertise in a range of relevant diseases. The workshop focused on application of DNA and RNA sequencing research in common chronic diseases and did not cover sequencing studies in lung cancer, monogenic diseases (e.g., cystic fibrosis), or microbiome sequencing. Participants reviewed and discussed study design, data analysis and presentation, interpretation, functional follow-up, and reporting of results. This report summarizes the main conclusions of the workshop, specifically addressing the application of these methods in respiratory, critical care, and sleep medicine research. This workshop report may serve as a resource for our research community as well as for journal editors and reviewers of sequencing-based manuscript submissions in our research field.
  • Journal article
    Pavlidis S, Takahashi K, Kwong FNK, Xie J, Hoda U, Sun K, Elyasigomari V, Agapow P, Loza M, Baribaud F, Chanez P, Fowler SJ, Shaw DE, Fleming LJ, Howarth PH, Sousa AR, Corfield J, Auffray C, De Meulder B, Knowles R, Sterk PJ, Guo Y, Adcock IM, Djukanovic R, Chung KF, U-BIOPRED study groupet al., 2019,

    "T2-high" in severe asthma related to blood eosinophil, exhaled nitric oxide and serum periostin

    , European Respiratory Journal, Vol: 53, ISSN: 0903-1936

    BACKGROUND: Type-2 (T2) immune responses in airway epithelial cells (AECs) classifies mild-moderate asthma into a T2-high phenotype. We examined whether currently-available clinical biomarkers can predict AEC-defined T2-high phenotype within U-BIOPRED cohort. METHODS: The transcriptomic profile of AECs obtained from brushings of 103 patients with asthma and 44 healthy controls was obtained and gene set variation analysis used to determine the relative expression score of T2 asthma using a signature from IL-13-exposed AECs. RESULTS: 37% of asthmatics (45% non-smoking severe asthma, n=49, 33% of smoking or ex-smoking severe asthma, n=18 and 28% mild-moderate asthma, n=36) were T2-high using AEC gene expression. They were more symptomatic with higher levels of nitric oxide in exhaled breath (FeNO) and of blood and sputum eosinophils but not of serum IgE or periostin. Sputum eosinophilia correlated best with the T2-high signature. FeNO (≥30 ppb) and blood eosinophils (≥300/µL) gave a moderate prediction of T2-high asthma. Sputum IL-4, IL-5 and IL-13 protein levels did not correlate with gene expression. CONCLUSION: T2-high severe asthma can be predicted to some extent from raised levels of FeNO, blood and sputum eosinophil counts, but serum IgE or serum periostin were poor predictors. Better bedside biomarkers are needed to detect T2-high.
  • Journal article
    Shrine N, Portelli MA, John C, Soler Artigas M, Bennett N, Hall R, Lewis J, Henry AP, Billington CK, Ahmad A, Packer RJ, Shaw D, Pogson ZEK, Fogarty A, McKeever TM, Singapuri A, Heaney LG, Mansur AH, Chaudhuri R, Thomson NC, Holloway JW, Lockett GA, Howarth PH, Djukanovic R, Hankinson J, Niven R, Simpson A, Chung KF, Sterk PJ, Blakey JD, Adcock IM, Hu S, Guo Y, Obeidat M, Sin DD, van den Berge M, Nickle DC, Bossé Y, Tobin MD, Hall IP, Brightling CE, Wain LV, Sayers Iet al., 2019,

    Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

    , Lancet Respiratory Medicine, Vol: 7, Pages: 20-34, ISSN: 2213-2600

    BACKGROUND: Few genetic studies that focus on moderate-to-severe asthma exist. We aimed to identity novel genetic variants associated with moderate-to-severe asthma, see whether previously identified genetic variants for all types of asthma contribute to moderate-to-severe asthma, and provide novel mechanistic insights using expression analyses in patients with asthma. METHODS: In this genome-wide association study, we used a two-stage case-control design. In stage 1, we genotyped patient-level data from two UK cohorts (the Genetics of Asthma Severity and Phenotypes [GASP] initiative and the Unbiased BIOmarkers in PREDiction of respiratory disease outcomes [U-BIOPRED] project) and used data from the UK Biobank to collect patient-level genomic data for cases and controls of European ancestry in a 1:5 ratio. Cases were defined as having moderate-to-severe asthma if they were taking appropriate medication or had been diagnosed by a doctor. Controls were defined as not having asthma, rhinitis, eczema, allergy, emphysema, or chronic bronchitis as diagnosed by a doctor. For stage 2, an independent cohort of cases and controls (1:5) was selected from the UK Biobank only, with no overlap with stage 1 samples. In stage 1 we undertook a genome-wide association study of moderate-to-severe asthma, and in stage 2 we followed up independent variants that reached the significance threshold of p less than 1 × 10-6 in stage 1. We set genome-wide significance at p less than 5 × 10-8. For novel signals, we investigated their effect on all types of asthma (mild, moderate, and severe). For all signals meeting genome-wide significance, we investigated their effect on gene expression in patients with asthma and controls. FINDINGS: We included 5135 cases and 25 675 controls for stage 1, and 5414 cases and 21 471 controls for stage 2. We identified 24 genome-wide significant signals of association with moderate-to-severe asthma, including several signals in innate or adaptive im

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://www.imperial.ac.uk:80/respub/WEB-INF/jsp/search-t4-html.jsp Request URI: /respub/WEB-INF/jsp/search-t4-html.jsp Query String: id=854&limit=20&page=4&respub-action=search.html Current Millis: 1714052100523 Current Time: Thu Apr 25 14:35:00 BST 2024