Imperial College London

ProfessorSebastianJohnston

Faculty of MedicineNational Heart & Lung Institute

Asthma UK Clinical Chair
 
 
 
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Contact

 

+44 (0)7931 376 544s.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
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753 results found

Tutino M, Hankinson J, Murray C, Lowe L, Kerry G, Rattray M, Custovic A, Johnston SL, Shi C, Orozco G, Eyre S, Martin P, Simpson A, Curtin JAet al., 2023, Identification of differences in CD4+ T-cell gene expression between people with asthma and healthy controls., Sci Rep, Vol: 13

Functional enrichment analysis of genome-wide association study (GWAS)-summary statistics has suggested that CD4+ T-cells play an important role in asthma pathogenesis. Despite this, CD4+ T-cells are under-represented in asthma transcriptome studies. To fill the gap, 3'-RNA-Seq was used to generate gene expression data on CD4+ T-cells (isolated within 2 h from collection) from peripheral blood from participants with well-controlled asthma (n = 32) and healthy controls (n = 11). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify sets of co-expressed genes (modules) associated with the asthma phenotype. We identified three modules associated with asthma, which are strongly enriched for GWAS-identified asthma genes, antigen processing/presentation and immune response to viral infections. Through integration of publicly available eQTL and GWAS summary statistics (colocalisation), and protein-protein interaction (PPI) data, we identified PTPRC, a potential druggable target, as a putative master regulator of the asthma gene-expression profiles. Using a co-expression network approach, with integration of external genetic and PPI data, we showed that CD4+ T-cells from peripheral blood from asthmatics have different expression profiles, albeit small in magnitude, compared to healthy controls, for sets of genes involved in immune response to viral infections (upregulated) and antigen processing/presentation (downregulated).

Journal article

Pitts OR, Conn DP, Faiez T, Mallia P, Trujillo-Torralbo MB, Footitt J, Johnston SL, Cook PC, Singanayagam Aet al., 2023, T4 THE RESPIRATORY MYCOBIOME IS PERTURBED DURING VIRAL INFECTION IN COPD AND DRIVES TYPE 2 IMMUNOPATHOLOGY AND EXACERBATION SEVERITY, Pages: A3-A4, ISSN: 0040-6376

Introduction The existence of resident fungal communities (‘mycobiome’) within the lungs has only recently been discovered, and their role in health and disease remains unknown. Mycobiota are altered in chronic obstructive pulmonary disease (COPD), but the consequences of these perturbations have not been characterised. Given that fungi can promote type 2 inflammation and mucus hypersecretion, features of COPD that are augmented during exacerbations, we hypothesised that the mycobiome could be a key determinant of exacerbation pathogenesis. Methods We quantified total sputum fungal burden by qPCR at baseline and during infection in separate cohorts of experimentally induced and naturally occurring viral exacerbations of COPD. Fungal burden was correlated with measures of immunopathology and clinical exacerbation severity. Subsequently, we modelled fungal dysbiosis in mice through administration of low dose Aspergillus Fumigatus (a major constituent of the COPD airway mycobiome) prior to infection with rhinovirus A1 to investigate effects upon pulmonary immune responses. Results Individuals with COPD across the two studies (n=52) had increased sputum fungal burden compared to healthy control subjects (n=19) at stable state (figure 1A). Experimental rhinovirus infection led to increased sputum fungal loads from baseline in COPD subjects but not healthy controls with significant differences between these groups at day 9 and 12 post-infection (figure 1B). Similarly, sputum fungal burden increased during virus-associated naturally occurring exacerbations (figure 1C). During experimental challenge, sputum fungal loads positively correlated with viral loads, type 2 inflammatory responses including eotaxin 1/3, IL-4, IL-5 and Muc5ac (figure 1D) and clinical exacerbation severity (lower respiratory tract symptom scores) (figure 1D). In mice, administration of low dose Aspergillus to model airway fungal dysbiosis enhanced rhinovirus replication at 24 hours post-in

Conference paper

Almond M, Jackson M, Jha A, Katosulis O, Pitts O, Tunstall T, Regis E, Dunning J, Byrne A, Mallia P, Kon OM, Saunders K, Karen S, Snelgrove R, Openshaw P, Edwards M, Barclay W, Heaney L, Johnston S, Singanayagam Aet al., 2023, Obesity dysregulates the pulmonary antiviral immune response, Nature Communications, Vol: 14, ISSN: 2041-1723

Obesity is a well-recognized risk factor for severe influenza infections but the mechanisms underlying susceptibility are poorly understood. Here, we identify that obese individuals have deficient pulmonary antiviral immune responses in bronchoalveolar lavage cells but not in bronchial epithelial cells or peripheral blood dendritic cells. We show that the obese human airway metabolome is perturbed with associated increases in the airway concentrations of the adipokine leptin which correlated negatively with the magnitude of ex vivo antiviral responses. Exogenous pulmonary leptin administration in mice directly impaired antiviral type I interferon responses in vivo and ex vivo in cultured airway macrophages. Obese individuals hospitalised with influenza showed dysregulated upper airway immune responses. These studies provide insight into mechanisms driving propensity to severe influenza infections in obesity and raise the potential for development of leptin manipulation or interferon administration as novel strategies for conferring protection from severe infections in obese higher risk individuals.

Journal article

Curren B, Ahmed T, Howard DR, Ashik Ullah M, Sebina I, Rashid RB, Al Amin Sikder M, Namubiru P, Bissell A, Ngo S, Jackson DJ, Toussaint M, Edwards MR, Johnston SL, McSorley HJ, Phipps Set al., 2023, IL-33-induced neutrophilic inflammation and NETosis underlie rhinovirus-triggered exacerbations of asthma., Mucosal Immunol, Vol: 16, Pages: 671-684

Rhinovirus-induced neutrophil extracellular traps (NETs) contribute to acute asthma exacerbations; however, the molecular factors that trigger NETosis in this context remain ill-defined. Here, we sought to implicate a role for IL-33, an epithelial cell-derived alarmin rapidly released in response to infection. In mice with chronic experimental asthma (CEA), but not naïve controls, rhinovirus inoculation induced an early (1 day post infection; dpi) inflammatory response dominated by neutrophils, neutrophil-associated cytokines (IL-1α, IL-1β, CXCL1), and NETosis, followed by a later, type-2 inflammatory phase (3-7 dpi), characterised by eosinophils, elevated IL-4 levels, and goblet cell hyperplasia. Notably, both phases were ablated by HpARI (Heligmosomoides polygyrus Alarmin Release Inhibitor), which blocks IL-33 release and signalling. Instillation of exogenous IL-33 recapitulated the rhinovirus-induced early phase, including the increased presence of NETs in the airway mucosa, in a PAD4-dependent manner. Ex vivo IL-33-stimulated neutrophils from mice with CEA, but not naïve mice, underwent NETosis and produced greater amounts of IL-1α/β, IL-4, and IL-5. In nasal samples from rhinovirus-infected people with asthma, but not healthy controls, IL-33 levels correlated with neutrophil elastase and dsDNA. Our findings suggest that IL-33 blockade ameliorates the severity of an asthma exacerbation by attenuating neutrophil recruitment and the downstream generation of NETs.

Journal article

Radzikowska U, Eljaszewicz A, Tan G, Stocker N, Heider A, Westermann P, Steiner S, Dreher A, Wawrzyniak P, Rückert B, Rodriguez-Coira J, Zhakparov D, Huang M, Jakiela B, Sanak M, Moniuszko M, O'Mahony L, Jutel M, Kebadze T, Jackson DJ, Edwards MR, Thiel V, Johnston SL, Akdis CA, Sokolowska Met al., 2023, Author Correction: Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19., Nat Commun, Vol: 14

Journal article

Johnston SL, Edwards MR, Johnson R, Scott B, Motsi A, Padayachee Y, Cafferkey J, Coultas J, Mallia P, Bolaji J, Kumar K, Park S, Park M, Kim P, Patel N, Cameron A, Schaumberg J, Broom C, Kon OMet al., 2023, Safety and Pharmacodynamics of a Novel Inhaled Tlr Agonist Combination in Gold Stage 0 COPD Subjects During Experimental Rhinovirus Challenge, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Pyle CJ, Patel ND, Wang Z, Tregoning JS, Hamblin P, Butt R, Edwards MR, Shaw S, Johnston SLet al., 2023, A Rhinovirus-A16 VP0 Vaccine Induces Homotypic Humoral and Cellular Immunity, and Following Heterotypic Rhinovirus-A01 Infection, Accelerates Virus Clearance and Induces Cross-strain IFN-γ T Cell and Neutralising Antibody Responses, International Conference of the American-Thoracic-Society (ATS), Publisher: AMER THORACIC SOC, ISSN: 1073-449X

Conference paper

Radzikowska U, Eljaszewicz A, Tan G, Stocker N, Heider A, Westermann P, Steiner S, Dreher A, Wawrzyniak P, Ruckert B, Rodriguez-Coira J, Zhakparov D, Huang M, Jakiela B, Sanak M, Moniuszko M, O'Mahony L, Jutel M, Kebadze T, Jackson JD, Edwards RM, Thiel V, Johnston LS, Akdis AC, Sokolowska Met al., 2023, Rhinovirus-induced epithelial RIG-I inflammasome suppresses antiviral immunity and promotes inflammation in asthma and COVID-19, NATURE COMMUNICATIONS, Vol: 14

Journal article

Antunes KH, Singanayagam A, Williams L, Faiez TS, Farias A, Jackson MM, Faizi FK, Aniscenko J, Kebadze T, Veerati PC, Wood L, Bartlett NW, de Souza APD, Johnston SLet al., 2023, Airway-delivered short-chain fatty acid acetate boosts antiviral immunity during rhinovirus infection, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 151, Pages: 447-+, ISSN: 0091-6749

Journal article

Farne H, Glanville N, Johnson N, Kebadze T, Aniscenko J, Regis E, Zhu J, Trujillo-Torralbo M-B, Kon OM, Mallia P, Prevost A, Edwards M, Johnston S, Singanayagam A, Jackson Det al., 2022, Effect of CRTH2 antagonism on the response to experimental rhinovirus infection in asthma: a pilot randomized controlled trial, Thorax, Vol: 77, Pages: 950-959, ISSN: 0040-6376

Background and aimsThe CRTH2 antagonist timapiprant improved lung function and asthma control in a phase 2 study, with evidence suggesting reduced exacerbations. We aimed to assess whether timapiprant attenuated or prevented asthma exacerbations induced by experimental rhinovirus (RV) infection. We furthermore hypothesized that timapiprant would dampen RV-induced type 2 inflammation and consequently improve antiviral immune responses.MethodsAtopic patients with partially controlled asthma on maintenance inhaled corticosteroids were randomized to timapiprant (n=22) or placebo (n=22) and challenged with RV-A16 three weeks later. The primary endpoint was the cumulative lower respiratory symptom score over the 14 days post-infection. Upper respiratory symptoms, spirometry, airway hyperresponsiveness, exhaled nitric oxide, RV-A16 virus load and soluble mediators in upper and lower airways samples, and CRTH2 staining in bronchial biopsies were additionally assessed before and during RV-A16 infection.ResultsSix subjects discontinued the study and eight were not infected; outcomes were assessed in 16 timapiprant- and 14 placebo-treated, successfully infected subjects. There were no differences between treatment groups in clinical exacerbation severity including cumulative lower respiratory symptom score day 0-14 (difference 3.0 (95% CI -29.0 to 17.0), P=0.78), virus load, antiviral immune responses, or RV-A16-induced airway inflammation other than in the bronchial biopsies, where CRTH2 staining was increased during RV-A16 infection in the placebo- but not the timapiprant-treated group. Timapiprant had a favourable safety profile, with no deaths, serious adverse events, or drug-related withdrawals.ConclusionTimapiprant treatment had little impact on the clinicopathological changes induced by RV-A16 infection in partially controlled asthma.

Journal article

Bruno N, Singanayagam A, Farne HA, Aniscenko J, Glanville N, Pyle CJ, Patel DF, Johnston SL, Snelgrove RJet al., 2022, G-CSF drives pathophysiology of RV-induced allergic asthma exacerbations by potentiating neutrophilic inflammation and ILC2 function, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936

Conference paper

Farne H, Lin L, Jackson D, Rattray M, Simpson A, Custovic A, Joshi S, Wilson P, Williamson R, Edwards M, Singanayagam A, Johnston Set al., 2022, In vivo bronchial epithelial interferon responses are augmented in asthma on day 4 following experimental rhinovirus infection, Thorax, Vol: 77, Pages: 929-932, ISSN: 0040-6376

Despite good evidence of impaired innate antiviral responses in asthma, trials of inhaled interferon-β given during exacerbations showed only modest benefits in moderate/severe asthma. Using human experimental rhinovirus infection, we observe robust in vivo induction of bronchial epithelial interferon response genes four days after virus inoculation in 25 subjects with asthma but not 11 control subjects. This signature correlated with virus loads and lower respiratory symptoms. Our data indicate that the in vivo innate antiviral response is dysregulated in asthma and open up the potential that prophylactic rather than therapeutic interferon therapy may have greater clinical benefit.

Journal article

Lin L, Curtin JA, Regis E, Hirsman A, Howard R, Tutino M, Edwards MR, Prosperi M, Simpson A, Rattray M, Custovic A, Johnston SLet al., 2022, A systems immunology approach to investigate cytokine responses to viruses and bacteria and their association with disease, Scientific Reports, Vol: 12, Pages: 1-14, ISSN: 2045-2322

Patterns of human immune responses to viruses and bacteria and how this impacts risk of infections or onset/exacerbation of chronic respiratory diseases are poorly understood. In a population-based birth cohort, we measured peripheral blood mononuclear cell responses (28 cytokines) to respiratory viruses and bacteria, Toll-like receptor ligands and phytohemagglutinin, in 307 children. Cytokine responses were highly variable with > 1000-fold differences between children. Machine learning revealed clear distinction between virus-associated and bacteria-associated stimuli. Cytokines clustered into three functional groups (anti-viral, pro-inflammatory and T-cell derived). To investigate mechanisms potentially explaining such variable responses, we investigated cytokine Quantitative Trait Loci (cQTLs) of IL-6 responses to bacteria and identified nine (eight novel) loci. Our integrative approach describing stimuli, cytokines and children as variables revealed robust immunologically and microbiologically plausible clustering, providing a framework for a greater understanding of host-responses to infection, including novel genetic associations with respiratory disease.

Journal article

Barbaud A, Garvey LH, Arcolaci A, Brockow K, Mori F, Mayorga C, Bonadonna P, Atanaskovic-Markovic M, Moral L, Zanoni G, Pagani M, Soria A, Jost M, Caubet J-C, Carmo A, Mona A-A, Alvarez-Perea A, Bavbek S, Benedetta B, Bilo MB, Blanca-Lopez N, Bogas HG, Buonomo A, Calogiuri G, Carli G, Cernadas J, Cortellini G, Celik G, Demir S, Dona I, Dursun AB, Eberlein B, Faria E, Fernandes B, Garcez T, Garcia-Nunez I, Gawlik R, Gelincik A, Gomes E, Gooi JHC, Grosber M, Gulen T, Hacard F, Hoarau C, Janson C, Johnston SL, Joerg L, Ozdemir SK, Klimek L, Kosnik M, Kowalski ML, Kuyucu S, Kvedariene V, Laguna JJ, Lombardo C, Marinho S, Merk H, Meucci E, Morisset M, Munoz-Cano R, Murzilli F, Nakonechna A, Popescu F-D, Porebski G, Radice A, Regateiro FS, Rockmann H, Romano A, Sargur R, Sastre J, Hofmeier KS, Sedlackova L, Sobotkova M, Terreehorst I, Treudler R, Walusiak-Skorupa J, Wedi B, Wohrl S, Zidarn M, Zuberbier T, Agache I, Torres MJet al., 2022, Allergies and COVID-19 vaccines: An ENDA/EAACI Position paper, ALLERGY, Vol: 77, Pages: 2292-2312, ISSN: 0105-4538

Journal article

Kolev E, Mircheva L, Edwards MR, Johnston SL, Kalinov K, Stange R, Gancitano G, Vanden Berghe W, Kreft Set al., 2022, <i>Echinacea Purpurea</i> For the Long-Term Prevention of Viral Respiratory Tract Infections During Covid-19 Pandemic: A Randomized, Open, Controlled, Exploratory Clinical Study, FRONTIERS IN PHARMACOLOGY, Vol: 13

Journal article

Jansen K, Satitsuksanoa P, Wirz OF, Schneider SR, van de Veen W, Tan G, Sokolowska M, Message SD, Kebadze T, Glanville N, Mallia P, Akdis CA, Moniuszko M, Johnston SL, Nadeau K, Akdis Met al., 2022, T regulatory cells from atopic asthmatic individuals show a Th2-like phenotype, ALLERGY, Vol: 77, Pages: 1320-1324, ISSN: 0105-4538

Journal article

Cameron A, Dhariwal J, Upton N, Ranz Jimenez I, Paulsen M, Wong E, Trujillo-Torralbo M-B, Del Rosario A, Jackson DJ, Edwards MR, Johnston SL, Walton RP, MRC-GSK Strategic Alliance Consortiumet al., 2022, Type I conventional dendritic cells relate to disease severity in virus-induced asthma exacerbations., Clin Exp Allergy, Vol: 52, Pages: 550-560

RATIONALE: Rhinoviruses are the major precipitant of asthma exacerbations and individuals with asthma experience more severe/prolonged rhinovirus infections. Concurrent viral infection and allergen exposure synergistically increase exacerbation risk. Although dendritic cells orchestrate immune responses to both virus and allergen, little is known about their role in viral asthma exacerbations. OBJECTIVES: To characterize dendritic cell populations present in the lower airways, and to assess whether their numbers are altered in asthma compared to healthy subjects prior to infection and during rhinovirus-16 infection. METHODS: Moderately-severe atopic asthmatic patients and healthy controls were experimentally infected with rhinovirus-16. Bronchoalveolar lavage was collected at baseline, day 3 and day 8 post infection and dendritic cells isolated using fluorescence activated cell sorting. MEASUREMENTS AND MAIN RESULTS: Numbers of type I conventional dendritic cells, which cross prime CD8+ T helper cells and produce innate interferons, were significantly reduced in the lower airways of asthma patients compared to healthy controls at baseline. This reduction was associated serum IgE at baseline and with reduced numbers of CD8+ T helper cells and with increased viral replication, airway eosinophils and reduced lung function during infection. IgE receptor expression on lower airway plasmacytoid dendritic cells was significantly increased in asthma, consistent with a reduced capacity to produce innate interferons. CONCLUSIONS: Reduced numbers of anti-viral type I conventional dendritic cells in asthma are associated with adverse outcomes during rhinovirus infection. This, with increased FcεR1α expression on lower airway plasmacytoid DCs could mediate the more permissive respiratory viral infection observed in asthma patients.

Journal article

Singanayagam A, Footitt J, Marczynski M, Radicioni G, Cross MT, Finney LJ, Trujillo-Torralbo M-B, Calderazzo MA, Zhu J, Aniscenko J, Clarke TB, Molyneaux PL, Bartlett NW, Moffatt MF, Cookson WO, Wedzicha JA, Evans CM, Boucher RC, Kesimer M, Lieleg O, Mallia P, Johnston SLet al., 2022, Airway mucins promote immunopathology in virus-exacerbated chronic obstructive pulmonary disease., Journal of Clinical Investigation, Vol: 132, Pages: 1-16, ISSN: 0021-9738

The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway MUC5AC and MUC5B concentrations during spontaneous and experimentally-induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with virus load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation as Muc5ac-deficient (Muc5ac-/-) mice had attenuated rhinovirus (RV)-induced airway inflammation and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of rhinovirus-induced inflammation in mice. Therapeutic suppression of mucin production using an epidermal growth factor receptor (EGFR) antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identifies a pro-inflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.

Journal article

Makrinioti H, Hasegawa K, Lakoumentas J, Xepapadaki P, Tsolia M, Castro-Rodriguez JA, Feleszko W, Jartti T, Johnston SL, Bush A, Papaevangelou V, Camargo CA, Papadopoulos NGet al., 2022, The role of respiratory syncytial virus- and rhinovirus-induced bronchiolitis in recurrent wheeze and asthma-A systematic review and meta-analysis, PEDIATRIC ALLERGY AND IMMUNOLOGY, Vol: 33, ISSN: 0905-6157

Journal article

Mikus MS, Kolmert J, Andersson L, Ostling J, Knowles RG, Gomez C, Ericsson M, Thorngren J-O, Khoonsari PE, Dahlen B, Kupczyk M, De Meulder B, Auffray C, Bakke PS, Beghe B, Bel EH, Caruso M, Chanez P, Chawes B, Fowler SJ, Gaga M, Geiser T, Gjomarkaj M, Horvath I, Howarth PH, Johnston SL, Joos G, Krug N, Montuschi P, Musial J, Nizankowska-Mogilnicka E, Olsson HK, Papi A, Rabe KF, Sandstrom T, Shaw DE, Siafakas NM, Uhlen M, Riley JH, Bates S, Middelveld RJM, Wheelock CE, Chung KF, Adcock IM, Sterk PJ, Djukanovic R, Nilsson P, Dahlen S-E, James Aet al., 2022, Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation, European Respiratory Journal, Vol: 59, Pages: 1-17, ISSN: 0903-1936

Rationale Asthma phenotyping requires novel biomarker discovery.Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA.

Journal article

Finotto S, Jartti T, Johnston SL, 2022, Editorial: Type I and Type III Interferon Immune Responses in Asthma, FRONTIERS IN IMMUNOLOGY, Vol: 12, ISSN: 1664-3224

Journal article

Philip K, Buttery S, Williams P, Vijayakumar B, Tonkin J, Cumella A, Lottie R, Ogden L, Quint J, Johnston S, Polkey M, Hopkinson Net al., 2022, Impact of COVID-19 on people with asthma: A mixed methods analysis from a UK wide survey, BMJ Open Respiratory Research, Vol: 9, ISSN: 2052-4439

Introduction: The impact of acute COVID-19 on people with asthma appears complex, being moderated by multiple interacting disease-specific, demographic and environmental factors. Research regarding longer-term effects in this group is limited. We aimed to assess impacts of COVID-19 and predictors of persistent symptoms, in people with asthma.Methods: Using data from an online UK-wide survey of 4500 people with asthma (median age 50–59 years, 81% female), conducted in October 2020, we undertook a mixed methods analysis of the characteristics and experience of those reporting having had COVID-19.Results: The COVID-19 group (n=471, 10.5%) reported increased inhaler use and worse asthma management, compared with those not reporting COVID-19, but did not differ by gender, ethnicity or household income. Among the COVID-19 group, 56.1% reported having long COVID, 20.2% were ‘unsure’. Those with long COVID were more likely than those without long COVID to describe: their breathing as worse or much worse after their initial illness (73.7% vs 34.8%, p<0.001), increased inhaler use (67.8% vs 34.8%, p<0.001) and worse or much worse asthma management (59.6% vs 25.6%, p<0.001). Having long COVID was not associated with age, gender, ethnicity, UK nation or household income.Analysis of free text survey responses identified three key themes: (1) variable COVID-19 severity, duration and recovery; (2) symptom overlap and interaction between COVID-19 and asthma; (3) barriers to accessing healthcare.Conclusions: Persisting symptoms are common in people with asthma following COVID-19. Measures are needed to ensure appropriate healthcare access including clinical evaluation and investigation, to distinguish between COVID-19 symptoms and asthma.

Journal article

Dhariwal J, Padayachee Y, Johnston SL, 2022, Respiratory viruses and eosinophilic airway inflammation, ERS Monograph, Vol: 2022, Pages: 204-218, ISSN: 2312-508X

Eosinophils are widely acknowledged as key cells in driving type 2 immune responses against parasitic infection and in mediating allergic disease. Advances in our understanding have suggested that eosinophils may play an important additional role in the host immune response against a range of respiratory virus infections in both health and disease. Eosinophils exert these effects through a diverse range of mechanisms spanning innate and adaptive immunity, including immune sensing via Toll-like receptors, acting as antigen-presenting cells and the secretion of potent antiviral molecules. Recent evidence that anti-IL-5/IL-5 receptor therapies markedly reduce asthma exacerbations in those with activated eosinophilic pathways indicates that eosinophils clearly play an important role in asthma exacerbation pathogenesis. The mechanisms of viral exacerbations in patients treated with biologics are not yet fully understood and further work is needed to assess the impact of eosinophil depletion in this patient cohort.

Journal article

Wirz OF, Jansen K, Satitsuksanoa P, van de Veen W, Tan G, Sokolowska M, Mirer D, Stanic B, Message SD, Kebadze T, Glanville N, Mallia P, Gern JE, Papadopoulos N, Akdis CA, Johnston SL, Nadeau K, Akdis Met al., 2022, Experimental rhinovirus infection induces an antiviral response in circulating B cells which is dysregulated in patients with asthma, ALLERGY, Vol: 77, Pages: 130-142, ISSN: 0105-4538

Journal article

Regis E, Fontanella S, Lin L, Howard R, Haider S, Curtin J, Edwards M, Rattray M, Simpson A, Custovic A, Johnston Set al., 2021, Sex differences in innate anti-viral immune responses to respiratory viruses and in their clinical outcomes in a birth cohort study, Scientific Reports, Vol: 11, Pages: 1-15, ISSN: 2045-2322

The mechanisms explaining excess morbidity and mortality in respiratory infections among males are poorly understood. Innate immune responses are critical in protection against respiratory virus infections. We hypothesised that innate immune responses to respiratory viruses may be deficient in males. We stimulated peripheral blood mononuclear cells from 345 participants at age 16 years in a population-based birth cohort with three live respiratory viruses (rhinoviruses A16 and A1, and respiratory syncytial virus) and two viral mimics (R848 and CpG-A, to mimic responses to SARS-CoV-2) and investigated sex differences in interferon (IFN) responses. IFN-α responses to all viruses and stimuli were 1.34–2.06-fold lower in males than females (P = 0.018 −  < 0.001). IFN-β, IFN-γ and IFN-induced chemokines were also deficient in males across all stimuli/viruses. Healthcare records revealed 12.1% of males and 6.6% of females were hospitalized with respiratory infections in infancy (P = 0.017). In conclusion, impaired innate anti-viral immunity in males likely results in high male morbidity and mortality from respiratory virus infections.

Journal article

Makrinioti H, Bush A, Gern J, Johnston SL, Papadopoulos N, Feleszko W, Camargo CA, Hasegawa K, Jartti Tet al., 2021, The Role of Interferons in Driving Susceptibility to Asthma Following Bronchiolitis: Controversies and Research Gaps, FRONTIERS IN IMMUNOLOGY, Vol: 12, ISSN: 1664-3224

Journal article

Johnston SL, Goldblatt DL, Evans SE, Tuvim MJ, Dickey BFet al., 2021, Airway Epithelial Innate Immunity, FRONTIERS IN PHYSIOLOGY, Vol: 12

Journal article

Makrinioti H, Maggina P, Lakoumentas J, Xepapadaki P, Taka S, Megremis S, Manioudaki M, Johnston SL, Tsolia M, Papaevangelou V, Papadopoulos NGet al., 2021, Recurrent Wheeze Exacerbations Following Acute Bronchiolitis-A Machine Learning Approach, FRONTIERS IN ALLERGY, Vol: 2

Journal article

Bloom CI, Johnston SL, 2021, Decline in respiratory and cardiac admissions during the COVID-19 pandemic: what is the role of common respiratory virus infections?, Respirology, Vol: 26, Pages: 1010-1011, ISSN: 1323-7799

Numerous countries across the globe have introduced a variety of public health measures, non-pharmaceutical interventions (NPIs), to reduce the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and accordingly reduce coronavirus disease 2019 (COVID-19) hospitalizations and mortality. Effective NPIs have at the same time caused considerable changes in healthcare demand for non-COVID-19 conditions. In New Zealand, during the first wave of the pandemic in early 2020, their government instigated a stringent programme of restrictions, with a four-level alert system, including border closure, quarantine for returning travellers, social distancing measures and personal hygiene promotion. High public compliance with NPIs prevented COVID-19 community transmission for 102 consecutive days. In fact, they were so effective that the usual winter influenza surge was also disrupted, with an extraordinary 99.9% reduction in influenza virus detections as compared to previous years and a substantial reduction in all other respiratory viruses, including a 98% reduction in respiratory syncytial virus detections.1 Due to the key role viruses are known to play in many respiratory conditions and are postulated to play in myocardial infarctions and heart failure, it may be hypothesized that the stringent reductions implemented in New Zealand may also have mitigated the incidence of these conditions during that time.

Journal article

Jansen K, Wirz OF, van de Veen W, Tan G, Mirer D, Sokolowska M, Satitsuksanoa P, Message SD, Kebadze T, Glanville N, Mallia P, Skiepko R, Eljaszewicz A, Moniuszko M, Cardoso C, Gern JE, Papadopoulos NG, Akdis CA, Johnston SL, Nadeau KC, Akdis Met al., 2021, Loss of regulatory capacity in Treg cells following rhinovirus infection, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 148, Pages: 1016-+, ISSN: 0091-6749

Journal article

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