Imperial College London

ProfessorSebastianJohnston

Faculty of MedicineNational Heart & Lung Institute

Asthma UK Clinical Chair
 
 
 
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Contact

 

+44 (0)20 7594 3764s.johnston

 
 
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Assistant

 

Mr Christophe Tytgat +44 (0)20 7594 3849

 
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Location

 

343Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Publication Type
Year
to

539 results found

Sam Narean J, Glanville N, Nunn CM, Niespodziana K, Valenta R, Johnston SL, McLean GRet al., 2019, Epitope mapping of antibodies induced with a conserved rhinovirus protein generating protective anti-rhinovirus immunity., Vaccine, Vol: 37, Pages: 2805-2813

Human rhinovirus (RV) infections are the principle cause of common colds and precipitate asthma and chronic obstructive pulmonary disease (COPD) exacerbations. Currently there is no vaccine for RV which is largely due to the existence of ∼160 serotypes/strains. We demonstrated previously that immunising mice with highly conserved VP4 and VP2 regions of the RV polyprotein (RV-A16 VP0) generated cross-reactive immunity to RV in vivo. The current study investigated and mapped the epitopes of RV-A16 VP0 that are targets for antibodies in serum samples from VP0 immunisation and RV challenge studies in mice. Recombinant capsid proteins, peptide pools and individual peptides spanning the immunogen sequence (RV-A16 VP0) were assessed for IgG binding sites to identify epitopes. We found that peptide pools covering the C-terminus of VP4, the N-terminus of VP2 and the neutralising NIm-II site within VP2 were bound by serum IgG from immunised mice. The NIm-II site peptide pool blocked IgG binding to the immunogen RV-A16 VP0 and individual peptides within the pool binding IgG were further mapped. Thus, we have identified immunodominant epitopes of RV vaccine candidate RV-A16 VP0, noting that strong IgG binding antibodies were observed that target a key neutralising epitope that is highly variable amongst RV serotypes.

JOURNAL ARTICLE

Singanayagam A, Johnston SL, 2019, Not just the common cold: Rhinovirus infection in lung allograft recipients., Respirology

JOURNAL ARTICLE

Petrova NV, Emelyanova AG, Gorbunov EA, Edwards MR, Walton RP, Bartlett NW, Aniscenko J, Gogsadze L, Bakhsoliani E, Khaitov MR, Johnston SL, Tarasov SA, Epstein OIet al., 2019, Efficacy of novel antibody-based drugs against rhinovirus infection: In vitro and in vivo results (Retraction of Vol 142, Pg 185, 2017), ANTIVIRAL RESEARCH, Vol: 164, Pages: 176-176, ISSN: 0166-3542

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

Lan F, Zhong H, Zhang N, Johnston SL, Wen W, Papadopoulos N, Zhang L, Bachert Cet al., 2019, IFN-lambda 1 enhances Staphylococcus aureus clearance in healthy nasal mucosa but not in nasal polyps, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 143, Pages: 1416-+, ISSN: 0091-6749

JOURNAL ARTICLE

Greiller CL, Suri R, Jolliffe DA, Kebadze T, Hirsman AG, Griffiths CJ, Johnston SL, Martineau ARet al., 2019, Vitamin D attenuates rhinovirus-induced expression of intercellular adhesion molecule-1 (ICAM-1) and platelet-activating factor receptor (PAFR) in respiratory epithelial cells, JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, Vol: 187, Pages: 152-159, ISSN: 0960-0760

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

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

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 M, Johnston SL, Akdis CA, Becker S, Bachert C, Papadopoulos NG, Garn H, Renz HEet al., 2019, Development of antirhinoviral DNAzymes for effective prevention of asthma exacerbations, Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology (AAAAI), Publisher: MOSBY-ELSEVIER, Pages: AB99-AB99, ISSN: 0091-6749

CONFERENCE PAPER

Calderazzo MA, Trujillo-Torralbo M-B, Finney LJ, Singanayagam A, Bakhsoliani E, Padmanaban V, Kebadze T, Aniscenko J, Elkin SL, Johnston SL, Mallia Pet al., 2019, Inflammation and infections in unreported chronic obstructive pulmonary disease exacerbations, INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Vol: 14, Pages: 823-832, ISSN: 1178-2005

JOURNAL ARTICLE

Menditto E, Costa E, Midão L, Bosnic-Anticevich S, Novellino E, Bialek S, Briedis V, Mair A, Rajabian-Soderlund R, Arnavielhe S, Bedbrook A, Czarlewski W, Annesi-Maesano I, Anto JM, Devillier P, De Vries G, Keil T, Sheikh A, Orlando V, Larenas-Linnemann D, Cecchi L, De Feo G, Illario M, Stellato C, Fonseca J, Malva J, Morais-Almeida M, Pereira AM, Todo-Bom A, Kvedariene V, Valiulis A, Bergmann KC, Klimek L, Mösges R, Pfaar O, Zuberbier T, Cardona V, Mullol J, Papadopoulos NG, Prokopakis EP, Bewick M, Ryan D, Roller-Wirnsberger RE, Tomazic PV, Cruz AA, Kuna P, Samolinski B, Fokkens WJ, Reitsma S, Bosse I, Fontaine JF, Laune D, Haahtela T, Toppila-Salmi S, Bachert C, Hellings PW, Melén E, Wickman M, Bindslev-Jensen C, Eller E, O'Hehir RE, Cingi C, Gemicioğlu B, Kalayci O, Ivancevich JC, Bousquet J, MASK groupet al., 2018, Adherence to treatment in allergic rhinitis using mobile technology. the mask study, Clinical and Experimental Allergy, ISSN: 0954-7894

BACKGROUND: Mobile technology may help to better understand the adherence to treatment MASK-rhinitis (Mobile Airways Sentinel NetworK for allergic rhinitis) is a patient-centered ICT system. A mobile phone app (the Allergy Diary) central to MASK is available in 22 countries. OBJECTIVES: To assess the adherence to treatment in allergic rhinitis patients using the Allergy Diary App. METHODS: An observational cross-sectional study was carried out on all users who filled in the Allergy Diary from January 1, 2016 to August 1, 2017. Secondary adherence was assessed by using the modified Medication Possession Ratio (MPR) and the Proportion of days covered (PDC) approach. RESULTS: 12,143 users were registered. 6,949 users reported at least one VAS data recording. Among them, 1,887 users reported ≥ 7 VAS data. 1,195 subjects were included in the analysis of adherence. 136 (11.28%) users were adherent (MPR ≥70% and PDC ≤ 1.25), 51 (4.23%) were partly adherent (MPR ≥70% and PDC =1.50) and 176 (14.60%) were switchers. On the other hand, 832 (69.05%) users were non-adherent to medications (MPR<70%). Of those, the largest group was non-adherent to medications and the time interval was increased in 442 (36.68%) users. CONCLUSION AND CLINICAL RELEVANCE: Adherence to treatment is low. The relative efficacy of continuous versus on-demand treatment for AR symptoms is still a matter of debate.This study shows an approach for measuring retrospective adherence based on a mobile app. This represent a novel approach also for analyzing medication taking behavior in a real-world setting. This article is protected by copyright. All rights reserved.

JOURNAL ARTICLE

Farne H, Groves HT, Gill SK, Stokes I, McCulloch S, Karoly E, Trujillo-Torralbo M-B, Johnston SL, Mallia P, Tregoning JSet al., 2018, Comparative Metabolomic Sampling of Upper and Lower Airways by Four Different Methods to Identify Biochemicals That May Support Bacterial Growth, FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, Vol: 8, ISSN: 2235-2988

JOURNAL ARTICLE

Finney LJ, Belchamber KBR, Fenwick PS, Kemp SV, Edwards MR, Mallia P, Donaldson G, Johnston SL, Donnelly LE, Wedzicha JAet al., 2018, Human Rhinovirus Impairs the Innate Immune Response to Bacteria in Alveolar Macrophages in COPD., Am J Respir Crit Care Med

Rationale Human rhinovirus (HRV) is a common cause of COPD exacerbations. Secondary bacterial infection is associated with more severe symptoms and delayed recovery. Alveolar macrophages clear bacteria from the lung and maintain lung homeostasis through cytokine secretion. These processes are defective in COPD. The effect of HRV on macrophage function is unknown. Objectives To investigate the effect of HRV on phagocytosis and cytokine response to bacteria by alveolar macrophages and monocyte derived macrophages (MDM) in COPD and healthy controls. Methods Alveolar macrophages were obtained by bronchoscopy and MDM by adherence. Macrophages were exposed to HRV 16 (multiplicity of infection 5), polyI:C 30μg/ml, interferon (IFN)-β 10μg/ml, IFN-γ 10μg/ml or medium control for 24 hours. Phagocytosis of fluorescently-labelled Haemophilus influenzae or Streptococcus pneumoniae was assessed by fluorimetry. CXCL8, TNF and IL-10 release was measured by ELISA. Main Results HRV significantly impaired phagocytosis of H. influenzae by 23% in MDM (n=37) and 18% in alveolar macrophages (n=20) in COPD. HRV also significantly reduced phagocytosis of S. pneumoniae by 33% in COPD MDM. There was no effect in healthy controls. Phagocytosis of H. influenzae was impaired by polyI:C but not IFN-β or IFN-γ. HRV significantly reduced cytokine responses to H. influenzae. The IL-10 response to H. influenzae was significantly impaired by polyI:C, IFN-β and IFN-γ. Conclusions HRV impairs phagocytosis of bacteria in COPD which may lead to an outgrowth of bacteria. HRV also impairs cytokine responses to bacteria via the TLR3/IFN pathway which may prevent resolution of inflammation leading to prolonged exacerbations in COPD.

JOURNAL ARTICLE

Jolliffe DA, Greiller CL, Mein CA, Hoti M, Bakhsoliani E, Telcian AG, Simpson A, Barnes NC, Curtin JA, Custovic A, Johnston SL, Griffiths CJ, Walton RT, Martineau ARet al., 2018, Vitamin D receptor genotype influences risk of upper respiratory infection, BRITISH JOURNAL OF NUTRITION, Vol: 120, Pages: 891-900, ISSN: 0007-1145

JOURNAL ARTICLE

Bousquet J, Arnavielhe S, Bedbrook A, Bewick M, Laune D, Mathieu-Dupas E, Murray R, Onorato GL, Pepin JL, Picard R, Portejoie F, Costa E, Fonseca J, Lourenco O, Morais-Almeida M, Todo-Bom A, Cruz AA, da Silva J, Serpa FS, Illario M, Menditto E, Cecchi L, Monti R, Napoli L, Ventura MT, De Feo G, Larenas-Linnemann D, Fuentes Perez M, Huerta Villabolos YR, Rivero-Yeverino D, Rodriguez-Zagal E, Amat F, Annesi-Maesano I, Bosse I, Demoly P, Devillier P, Fontaine JF, Just J, Kuna TP, Samolinski B, Valiulis A, Emuzyte R, Kvedariene V, Ryan D, Sheikh A, Schmidt-Grendelmeier P, Klimek L, Pfaar O, Bergmann KC, Mosges R, Zuberbier T, Roller-Wirnsberger RE, Tomazic P, Fokkens WJ, Chavannes NH, Reitsma S, Anto JM, Cardona V, Dedeu T, Mullol J, Haahtela T, Salimaki J, Toppila-Salmi S, Valovirta E, Gemicioglu B, Yorgancioglu A, Papadopoulos N, Prokopakis EP, Bosnic-Anticevich S, O'Hehir R, Ivancevich JC, Neffen H, Zernotti E, Kull I, Melen E, Wickman M, Bachert C, Hellings P, Palkonen S, Bindslev-Jensen C, Eller E, Waserman S, Sova M, De Vries G, van Eerd M, Agache I, Casale T, Dykewickz M, Naclerio RN, Okamoto Y, Wallace DVet al., 2018, MASK 2017: ARIA digitally-enabled, integrated, person-centred care for rhinitis and asthma multimorbidity using real-world-evidence, CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 8, ISSN: 2045-7022

JOURNAL ARTICLE

Tang HHF, Teo SM, Belgrave DCM, Evans MD, Jackson DJ, Brozynska M, Kusel MMH, Johnston SL, Gern JE, Lemanske RF, Simpson A, Custovic A, Sly PD, Holt PG, Holt KE, Inouye Met al., 2018, Trajectories of childhood immune development and respiratory health relevant to asthma and allergy, ELIFE, Vol: 7, ISSN: 2050-084X

JOURNAL ARTICLE

Makris S, Johnston S, 2018, Recent advances in understanding rhinovirus immunity, F1000Research, Vol: 7, ISSN: 2046-1402

Rhinoviruses are the most common cause of upper respiratory tract infections. However, they can induce exacerbations of chronic obstructive pulmonary disease and asthma, bronchiolitis in infants, and significant lower respiratory tract infections in children, the immunosuppressed, and the elderly. The large number of rhinovirus strains (currently about 160) and their antigenic diversity are significant obstacles in vaccine development. The phenotype of immune responses induced during rhinovirus infection can affect disease severity. Recognition of rhinovirus and a balance of innate responses are important factors in rhinovirus-induced morbidity. Immune responses to rhinovirus infections in healthy individuals are typically of the T helper type 1 (Th1) phenotype. However, rhinovirus-driven asthma exacerbations are additionally characterised by an amplified Th2 immune response and airway neutrophilia. This commentary focuses on recent advances in understanding immunity toward rhinovirus infection and how innate and adaptive immune responses drive rhinovirus-induced asthma exacerbations.

JOURNAL ARTICLE

Teo SM, Tang HHF, Mok D, Judd LM, Watts SC, Pham K, Holt BJ, Kusel M, Serralha M, Troy N, Bochkov YA, Grindle K, Lemanske RF, Johnston SL, Gern JE, Sly PD, Holt PG, Holt KE, Inouye Met al., 2018, Airway Microbiota Dynamics Uncover a Critical Window for Interplay of Pathogenic Bacteria and Allergy in Childhood Respiratory Disease, CELL HOST & MICROBE, Vol: 24, Pages: 341-+, ISSN: 1931-3128

JOURNAL ARTICLE

Mallia P, Webber J, Gill SK, Trujillo-Torralbo M-B, Calderazzo MA, Finney L, Bakhsoliani E, Fame H, Singanayagam A, Footitt J, Hewitt R, Kebadze T, Aniscenko J, Padmanaban V, Molyneaux PL, Adcock IM, Barnes PJ, Ito K, Elkin SL, Kon OM, Cookson WO, Moffat MF, Johnston SL, Tregoning JSet al., 2018, Role of airway glucose in bacterial infections in patients with chronic obstructive pulmonary disease, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 142, Pages: 815-+, ISSN: 0091-6749

JOURNAL ARTICLE

Lan F, Zhang N, Holtappels G, De Ruyck N, Krysko O, Van Crombruggen K, Braun H, Johnston SL, Papadopoulos NG, Zhang L, Bachert Cet al., 2018, Staphylococcus aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell-derived Cytokines, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 198, Pages: 452-463, ISSN: 1073-449X

JOURNAL ARTICLE

Chairakaki A-D, Saridaki M-I, Pyrillou K, Mouratis M-A, Koltsida O, Walton RP, Bartlett NW, Stavropoulos A, Boon L, Rovina N, Papadopoulos NG, Johnston SL, Andreakos Eet al., 2018, Plasmacytoid dendritic cells drive acute asthma exacerbations, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 142, Pages: 542-+, ISSN: 0091-6749

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 AB, Alhamdan F, Akdis M, Edwards MR, Johnston SL, Akdis CA, Becker S, Bachert C, Papadopoulos NG, Garn H, Renz Het al., 2018, Development and characterization of effective DNAzymes against human rhinoviruses, Congress of the European-Academy-of-Allergy-and-Clinical-Immunology (EAACI), Publisher: WILEY, Pages: 370-370, ISSN: 0105-4538

CONFERENCE PAPER

, 2018, Incorrect Numbers of Adverse Events Reported., JAMA Intern Med, Vol: 178

JOURNAL ARTICLE

Singanayagam A, Glanville N, Girkin JL, Ching YM, Marcellini A, Porter JD, Toussaint M, Walton RP, Finney LJ, Aniscenko J, Zhu J, Trujillo-Torralbo M-B, Calderazzo MA, Grainge C, Loo S-L, Veerati PC, Pathinayake PS, Nichol KS, Reid AT, James PL, Solari R, Wark PAB, Knight DA, Moffatt MF, Cookson WO, Edwards MR, Mallia P, Bartlett NW, Johnston SLet al., 2018, Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723

JOURNAL ARTICLE

Mousnier A, Bell AS, Swieboda DP, Morales-Sanfrutos J, Perez-Dorado I, Brannigan JA, Newman J, Ritzefeld M, Hutton JA, Guedan A, Asfor AS, Robinson SW, Hopkins-Navratilova I, Wilkinson AJ, Johnston SL, Leatherbarrow RJ, Tuthill TJ, Solari R, Tate EWet al., 2018, Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus, NATURE CHEMISTRY, Vol: 10, Pages: 599-606, ISSN: 1755-4330

JOURNAL ARTICLE

Dunning J, Blankley S, Hoang LT, Cox M, Graham CM, James PL, Bloom CI, Chaussabel D, Banchereau J, Brett SJ, Moffatt MF, O'Garra A, Openshaw PJMet al., 2018, Progression of whole-blood transcriptional signatures from interferon-induced to neutrophil-associated patterns in severe influenza, NATURE IMMUNOLOGY, Vol: 19, Pages: 625-+, ISSN: 1529-2908

JOURNAL ARTICLE

Custovic A, Belgrave D, Lin L, Bakhsoliani E, Telcian AG, Solari R, Murray CS, Walton RP, Curtin J, Edwards MR, Simpson A, Rattray M, Johnston SLet al., 2018, Cytokine Responses to Rhinovirus and Development of Asthma, Allergic Sensitization, and Respiratory Infections during Childhood, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 197, Pages: 1265-1274, ISSN: 1073-449X

JOURNAL ARTICLE

Ghebre MA, Pang PH, Diver S, Desai D, Bafadhel M, Haldar K, Kebadze T, Cohen S, Newbold P, Rapley L, Woods J, Rugman P, Pavord ID, Johnston SL, Barer M, May RD, Brightling CEet al., 2018, Biological exacerbation clusters demonstrate asthma and COPD overlap with distinct mediator and microbiome profiles., Journal of Allergy and Clinical Immunology, ISSN: 0091-6749

BACKGROUND: Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous. OBJECTIVE: We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations. METHODS: Patients with severe asthma or moderate-to-severe COPD were prospectively recruited to a single centre. Sputum mediators were available in 32 asthma and 73 COPD patients assessed at exacerbation. Biologic clusters were determined using factor and cluster analyses on a panel of sputum mediators. Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters. RESULTS: The asthma and COPD patients had different clinical characteristics and inflammatory profiles, but similar microbial ecology. Three exacerbation biologic clusters were identified. Cluster 1 was COPD predominant, with 27 COPD and 7 asthma patients exhibiting elevated blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6R, TNFα, TNF-R1, TNF-R2, and VEGF), and proportion of the bacterial phylum Proteobacteria. Cluster 2 had 10 asthma and 17 COPD patients with elevated blood and sputum eosinophil counts, Type 2 (T2) mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportion of the bacterial phylum Bacteroidetes. Cluster 3 had 15 asthma and 29 COPD subjects with elevated Type 1 (T1) mediators (CXCL10, CXCL11, and IFN-ϒ) and proportions of phyla Actinobacteria and Firmicutes. CONCLUSIONS: A biologic clustering approach revealed three subgroups of asthma and COPD exacerbations each with different percentages of overlapping asthma and COPD patients. The sputum mediator and microbiome profiles were distinct between clusters. CLINICAL IMPLICATIONS: Sputum mediator and microbiome profiling can determine the distinct and overlapping asthma and COPD biologic exacerbation clusters, highlighting the heterogeneity of these exacerbations.

JOURNAL ARTICLE

Zhu J, Message SD, Mallia P, Kebadze T, Contoli M, Ward CK, Barnathan ES, Mascelli MA, Kon OM, Papi A, Stanciu LA, Edwards MR, Jeffery PK, Johnston SLet al., Bronchial mucosal Interferon-α/β and pattern recognition receptor expression in experimental rhinovirus-induced asthma exacerbations, Journal of Allergy and Clinical Immunology, ISSN: 0091-6749

BACKGROUND: The innate immune system senses viral infection via pattern recognition receptors (PRRs) leading to type I interferon (IFN) production: their roles in rhinovirus (RV)-induced asthma exacerbations in vivo are uncertain. OBJECTIVES: To compare bronchial mucosal type I IFN and PRR expression at baseline and following RV infection in atopic asthmatic and control subjects. METHODS: Immunohistochemistry was used to detect expression of IFN-α, IFN-β and the PRRs, toll-like receptor (TLR)-3, melanoma-differentiation-associated gene-5 (MDA-5) and retinoic-acid-inducible protein-I (RIG-I) in bronchial biopsies from 10 atopic asthmatics and 15 non-asthmatic non-atopic controls at baseline and on day four and six weeks following RV infection. RESULTS: We observed IFN-α/β deficiency in bronchial epithelium at three time points in asthma in vivo. Lower epithelial IFN-α/β expression was related to greater virus load, worse airway symptoms, airway hyperresponsiveness (AHR) and reductions in lung function during RV infection. We found lower frequencies of bronchial subepithelial monocytes/macrophages expressing IFN-α/β in asthma during infection. IFN deficiency at baseline was not accompanied by deficient PRR expression in asthma. Both epithelial and subepithelial PRR expression was induced during RV infection. RV infection increased numbers of subepithelial IFN/PRRs-expressing inflammatory cells were related to greater virus load, AHR and reductions in lung function. CONCLUSIONS: Bronchial epithelial IFN-α/β expression and numbers of subepithelial IFN-α/β-expressing monocytes/macrophages during infection were both deficient in asthma. Lower epithelial IFN-α/β expression was associated with adverse clinical outcomes following RV infection in vivo. Increases in subepithelial cells expressing IFN/PRRs during infection were also related to greater virus load/illness severity.

JOURNAL ARTICLE

Silkoff PE, Flavin S, Gordon R, Loza MJ, Sterk PJ, Lutter R, Diamant Z, Turner RB, Lipworth BJ, Proud D, Singh D, Eich A, Backer V, Gern JE, Herzmann C, Halperin SA, Mensinga TT, Del Vecchio AM, Branigan P, San Mateo L, Baribaud F, Barnathan ES, Johnston SLet al., 2018, Toll-like receptor 3 blockade in rhinovirus-induced experimental asthma exacerbations: A randomized controlled study, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 141, Pages: 1220-1230, ISSN: 0091-6749

JOURNAL ARTICLE

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