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Niespodziana K, Borochova K, Pazderova P, et al., 2020, Toward personalization of asthma treatment according to trigger factors, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 145, Pages: 1529-1534, ISSN: 0091-6749
Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.
Farne H, Glanville N, Johnson N, et al., 2020, The CRTH2 Antagonist Timapiprant Does Not Alter the Response Rhinovirus Infection in Asthma: A Randomized, Placebo-Controlled Trial, International Conference of the American-Thoracic-Society, Publisher: AMER THORACIC SOC, ISSN: 1073-449X
Sever P, Johnston SL, 2020, The Renin-Angiotensin system and SARS-CoV-2 infection: A role for the ACE2 receptor?, Journal of the Renin-Angiotensin-Aldosterone System, Vol: 21, Pages: 1-2, ISSN: 1470-3203
Johnston JS, Johnston ES, Johnston SL, 2020, The importance of timing of a population level intervention on COVID-19 mortality
<jats:title>Abstract</jats:title><jats:p>COVID-19 poses an immense and immediate threat to global public health. Population level interventions (PLIs) impact this threat, with estimable large effects on reducing mortality. Many countries worldwide have currently zero/low mortality and many have yet to implement such PLIs. The importance of timing of PLI implementation on mortality outcomes is poorly understood. We extracted cumulative daily country-specific COVID-19 mortality for France, Germany, Italy, Spain and the UK to examine country-specific mortality trends and found that all five countries experienced COVID-19 mortality epidemics initially of exponential nature. We estimated the magnitude of effect on mortality of the nationwide PLI implemented on day 18 of Italy’s mortality epidemic and assessed the importance of timing of PLI implementation by computing the effect of implementation of a PLI of this magnitude at various times on subsequent mortality. The nationwide PLI in Italy saved an estimated 6,170 lives by day 30 of the Italian epidemic. Implementing a PLI with this effect magnitude in a country of 60 million people on the day of the first death, and on days 7, 10, 14 and 17 thereafter, compared to implementation on day 18, resulted in substantially greater numbers of lives saved. Implementation on day 1 resulted in an additional 3,477 lives saved, 6,955 intensive care unit admissions and 52,162 hospital admissions prevented, beyond that achieved by implementation on day 18. PLI implementation earlier than day 18 substantially enhances benefit. Intervention on the day of the first mortality event in a country achieves the greatest benefit.</jats:p>
Nikonova A, Khaitov M, Jackson DJ, et al., 2020, M1-like macrophages are potent producers of anti-viral interferons and M1-associated marker-positive lung macrophages are decreased during rhinovirus-induced asthma exacerbations, EBioMedicine, Vol: 54, Pages: 1-14, ISSN: 2352-3964
BackgroundMacrophages (Mф) can be M1/M2 polarized by Th1/2 signals, respectively. M2-like Mф are thought to be important in asthma pathogenesis, and M1-like in anti-infective immunity, however their roles in virus-induced asthma exacerbations are unknown. Our objectives were (i) to assess polarised Mф phenotype responses to rhinovirus (RV) infection in vitro and (ii) to assess Mф phenotypes in healthy subjects and people with asthma before and during experimental RV infection in vivo.MethodsWe investigated characteristics of polarized/unpolarized human monocyte-derived Mф (MDM, from 3–6 independent donors) in vitro and evaluated frequencies of M1/M2-like bronchoalveolar lavage (BAL) Mф in experimental RV-induced asthma exacerbation in 7 healthy controls and 17 (at baseline) and 18 (at day 4 post infection) people with asthma.FindingsWe observed in vitro: M1-like but not M2-like or unpolarized MDM are potent producers of type I and III interferons in response to RV infection (P<0.0001), and M1-like are more resistant to RV infection (P<0.05); compared to M1-like, M2-like MDM constitutively produced higher levels of CCL22/MDC (P = 0.007) and CCL17/TARC (P<0.0001); RV-infected M1-like MDM were characterized as CD14+CD80+CD197+ (P = 0.002 vs M2-like, P<0.0001 vs unpolarized MDM). In vivo we found reduced percentages of M1-like CD14+CD80+CD197+ BAL Mф in asthma during experimental RV16 infection compared to baseline (P = 0.024).InterpretationHuman M1-like BAL Mф are likely important contributors to anti-viral immunity and their numbers are reduced in patients with allergic asthma during RV-induced asthma exacerbations. This mechanism may be one explanation why RV-triggered clinical and pathologic outcomes are more severe in allergic patients than in healthy subjects.FundingERC FP7 Advanced grant 233015, MRC Centre Grant G1000758, Asthma UK grant 08–048, NIHR Biomedical Research Centre funding scheme, NIHR BRC Centre grant P26095, the Predicta FP7
Guvenel A, Jozwik A, Ascough S, et al., 2020, Epitope-specific airway-resident CD4+ T-cell dynamics during experimental human RSV infection, Journal of Clinical Investigation, Vol: 130, Pages: 523-538, ISSN: 0021-9738
Background: Respiratory syncytial virus (RSV) is an important cause of acute pulmonary disease and one of the last remaining major infections of childhood for which there is no vaccine. CD4+ T-cells play a key role in antiviral immunity, but they have been little studied in the human lung. Methods: Healthy adult volunteers were inoculated intranasally with RSV A Memphis 37. CD4+ T-cells in blood and lower airway were analysed by flow cytometry and immunohistochemistry. Bronchial soluble mediators were measured using quantitative PCR and MesoScale Discovery. Epitope mapping was performed by IFN-γ ELISpot screening, confirmed by in vitro MHC binding. Results: Activated CD4+ T-cell frequencies in bronchoalveolar lavage correlated strongly with local CXCL10 levels. Thirty-nine epitopes were identified, predominantly towards the 3’ end of the viral genome. Five novel MHC-II tetramers were made using an immunodominant F-EFY epitope restricted to HLA-DR4, -DR9 and -DR11 (combined allelic frequency: 15% in Europeans) and G- DDF restricted to HLA-DPA1*01:03/DPB1*02:01 and -DPA1*01:03/DPB1*04:01 (allelic frequency: 55%). Tetramer labelling revealed enrichment of resident memory CD4+ T-cells (TRM) cells in the lower airway; these TRM displayed progressive differentiation, down-regulation of co- stimulatory molecules and elevated CXCR3 expression as infection evolved. Conclusion: Human infection challenge provides a unique opportunity to study the breadth of specificity and dynamics of RSV-specific T-cell responses in the target organ, allowing the precise investigation of TRM recognising novel viral antigens over time. The new tools that we describe enable precise tracking of RSV-specific CD4+ cells, potentially accelerating the development of effective vaccines.
Johnston SL, 2020, IFN Therapy in Airway Disease: Is Prophylaxis a New Approach in Exacerbation Prevention?, American Journal of Respiratory and Critical Care Medicine, Vol: 201, Pages: 9-11, ISSN: 1073-449X
Kumar K, Kebadze T, Losa F, et al., 2020, Clinically relevant beta 2-agonists Induce and augment rhinovirus-induction of asthma-relevant pro-inflammatory mediators in human bronchial epithelial cells, International Conference of the American-Thoracic-Society, Publisher: American Thoracic Society, ISSN: 1073-449X
Singanayagam A, Johnston SL, 2019, Not just the common cold: Rhinovirus infection in lung allograft recipients, RESPIROLOGY, Vol: 24, Pages: 1134-1135, ISSN: 1323-7799
Kumar K, Losa F, Kebadze T, et al., 2019, SHORT-ACTING AND LONG-ACTING β2-AGONISTS UPREGULATE ASTHMA-RELEVANT PRO-INFLAMMATORY MEDIATORS IN HUMAN AIRWAY EPITHELIAL CELLS WHILE SHORT-ACTING MUSCARINIC ANTAGONISTS DO NOT, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A88-A88, ISSN: 0040-6376
Singanayagam A, Loo S-L, Calderazzo MA, et al., 2019, Antiviral immunity is impaired in COPD patients with frequent exacerbations, American Journal of Physiology: Lung Cellular and Molecular Physiology, Vol: 317, Pages: L893-L903, ISSN: 1040-0605
Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (>2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the anti-viral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cell-intrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro RV-infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 weeks following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate anti-microbial immunity in the lung could be a viable strategy for prevention/treatment of frequent exacerbations.
Radermecker C, Sabatel C, Vanwinge C, et al., 2019, Locally instructed CXCR4(hi) neutrophils trigger environment-driven allergic asthma through the release of neutrophil extracellular traps, Nature Immunology, Vol: 20, Pages: 1444-1455, ISSN: 1529-2908
Low exposure to microbial products, respiratory viral infections and air pollution are major risk factors for allergic asthma, yet the mechanistic links between such conditions and host susceptibility to type 2 allergic disorders remain unclear. Through the use of single-cell RNA sequencing, we characterized lung neutrophils in mice exposed to a pro-allergic low dose of lipopolysaccharide (LPS) or a protective high dose of LPS before exposure to house dust mites. Unlike exposure to a high dose of LPS, exposure to a low dose of LPS instructed recruited neutrophils to upregulate their expression of the chemokine receptor CXCR4 and to release neutrophil extracellular traps. Low-dose LPS–induced neutrophils and neutrophil extracellular traps potentiated the uptake of house dust mites by CD11b+Ly-6C+ dendritic cells and type 2 allergic airway inflammation in response to house dust mites. Neutrophil extracellular traps derived from CXCR4hi neutrophils were also needed to mediate allergic asthma triggered by infection with influenza virus or exposure to ozone. Our study indicates that apparently unrelated environmental risk factors can shape recruited lung neutrophils to promote the initiation of allergic asthma.
Marcellini A, Contoli M, Casolari P, et al., 2019, ICS/LABA effects on antiviral innate immune response. An in vitro analysis, European-Respiratory-Society (ERS) International Congress, Publisher: EUROPEAN RESPIRATORY SOC JOURNALS LTD, ISSN: 0903-1936
Bourdin A, Bjermer L, Brightling C, et al., 2019, ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions, European Respiratory Journal, Vol: 54, Pages: 1-25, ISSN: 0903-1936
Despite the use of effective medications to control asthma, severe exacerbations in asthma are still a major health risk and require urgent action on the part of the patient and physician to prevent serious outcomes such as hospitalisation or death. Moreover, severe exacerbations are associated with substantial healthcare costs and psychological burden, including anxiety and fear for patients and their families. The European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS) set up a task force to search for a clear definition of severe exacerbations, and to also define research questions and priorities. The statement includes comments from patients who were members of the task force.
Singanayagam A, Glanville N, Cuthbertson L, et al., 2019, Inhaled corticosteroid suppression of cathelicidin drives dysbiosis and bacterial infection in chronic obstructive pulmonary disease, Science Translational Medicine, Vol: 11, Pages: 1-13, ISSN: 1946-6234
Bacterial infection commonly complicates inflammatory airway diseases such as chronic obstructive pulmonary disease (COPD). The mechanisms of increased infection susceptibility and how use of the commonly prescribed therapy inhaled corticosteroids (ICS) accentuates pneumonia risk in COPD are poorly understood. Here, using analysis of samples from patients with COPD, we show that ICS use is associated with lung microbiota disruption leading to proliferation of streptococcal genera, an effect that could be recapitulated in ICS-treated mice. To study mechanisms underlying this effect, we used cellular and mouse models of streptococcal expansion with Streptococcus pneumoniae, an important pathogen in COPD, to demonstrate that ICS impairs pulmonary clearance of bacteria through suppression of the antimicrobial peptide cathelicidin. ICS impairment of pulmonary immunity was dependent on suppression of cathelicidin because ICS had no effect on bacterial loads in mice lacking cathelicidin (Camp-/-) and exogenous cathelicidin prevented ICS-mediated expansion of streptococci within the microbiota and improved bacterial clearance. Suppression of pulmonary immunity by ICS was mediated by augmentation of the protease cathepsin D. Collectively, these data suggest a central role for cathepsin D/cathelicidin in the suppression of antibacterial host defense by ICS in COPD. Therapeutic restoration of cathelicidin to boost antibacterial immunity and beneficially modulate the lung microbiota might be an effective strategy in COPD.
Johnston S, St Hill M, 2019, Ivor Norman Lennox Johnston OBITUARY, BMJ-BRITISH MEDICAL JOURNAL, Vol: 366, ISSN: 1756-1833
Finney LJ, Belchamber KBR, Fenwick PS, et al., 2019, Human rhinovirus impairs the innate immune response to bacteria in alveolar macrophages in chronic obstructive pulmonary disease, American Journal of Respiratory and Critical Care Medicine, Vol: 199, Pages: 1496-1507, ISSN: 1073-449X
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.
Benedikz EK, Bailey D, Cook CNL, et al., 2019, Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway, SCIENTIFIC REPORTS, Vol: 9, ISSN: 2045-2322
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Narean JS, Glanville N, Nunn CM, et al., 2019, Epitope mapping of antibodies induced with a conserved rhinovirus protein generating protective anti-rhinovirus immunity, Vaccine, Vol: 37, Pages: 2805-2813, ISSN: 0264-410X
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.
Calderazzo MA, Trujillo-Torralbo M-B, Finney LJ, et al., 2019, Inflammation and infections in unreported chronic obstructive pulmonary disease exacerbations, International Journal of Chronic Obstructive Pulmonary Disease, Vol: 2019, Pages: 823-832, ISSN: 1176-9106
Purpose: COPD patients often do not report acute exacerbations to healthcare providers – unreported exacerbations. It is not known whether variances in symptoms, airway obstruction, aetiology and inflammatory responses account for differences in reporting of COPD exacerbations. The aims of the study were to compare symptoms, lung function changes, aetiology and inflammatory markers between exacerbations that were reported to healthcare providers or treated, with those that were unreported and untreated.Patients and methods: We recruited a cohort of COPD patients and collected clinical data and blood and airway samples when stable and during acute exacerbations. Virological and bacterial analyses were carried out and inflammatory markers measured.Results: We found no differences in symptoms, lung function, incidence of infection and inflammatory markers between reported and unreported exacerbations. Subjects who reported all exacerbations had higher BODE scores, lower FEV1 and more exacerbations compared with those who did not.Conclusion: The failure to report exacerbations is not related to the severity, aetiology or inflammatory profile of the exacerbation. Patients with less severe COPD and less frequent exacerbations are less likely to report exacerbations. The decision to report an exacerbation is not an objective marker of exacerbation severity and therefore studies that do not count unreported exacerbations will underestimate the frequency of clinically significant exacerbations. A better understanding of the factors that determine non-reporting of exacerbations is required to improve exacerbation reporting.
Menditto E, Costa E, Midão L, et al., 2019, Adherence to treatment in allergic rhinitis using mobile technology. the mask study, Clinical and Experimental Allergy, Vol: 49, Pages: 442-460, 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.
Petrova NV, Emelyanova AG, Gorbunov EA, et al., 2019, Retraction notice to "Efficacy of novel antibody-based drugs against rhinovirus infection: In vitro and in vivo results" [Antiviral Research 142 (2017) 185-192]., Antiviral Res, Vol: 164, Pages: 176-176
Lan F, Zhong H, Zhang N, et al., 2019, IFN-λ1 enhances <i>Staphylococcus aureus</i> clearance in healthy nasal mucosa but not in nasal polyps, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 143, Pages: 1416-+, ISSN: 0091-6749
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Potaczek DP, Unger SD, Zhang N, et 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
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Bousquet J, Bedbrook A, Czarlewski W, et 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.
Dunning J, Blankley S, Hoang LT, et 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.
Greiller CL, Suri R, Jolliffe DA, et 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
Human rhinoviruses commonly cause upper respiratory infections, which may be complicated by secondary bacterial infection. Vitamin D replacement reduces risk of acute respiratory infections in vitamin D-deficient individuals, but the mechanisms by which such protection is mediated are incompletely understood. We therefore conducted experiments to characterise the influence of the major circulating metabolite 25-hydroxyvitamin D (25[OH]D) and the active metabolite 1,25-dihydroxyvitamin D (1,25[OH]2D) on responses of a respiratory epithelial cell line (A549 cells) to infection with a major group human rhinovirus (RV-16). Pre-treatment of A549 respiratory epithelial cells with a physiological concentration (10-7M) of 25(OH)D induced transient resistance to infection with RV-16 and attenuated RV-16-induced expression of the genes encoding intercellular adhesion molecule 1 (ICAM-1, a cell surface glycoprotein that acts as the cellular receptor for major group rhinoviruses) and platelet-activating factor receptor (PAFR, a G-protein coupled receptor implicated in adhesion of Streptococcus pneumoniae to respiratory epithelial cells). These effects were associated with enhanced expression of the genes encoding the NF-κB inhibitor IκBα and the antimicrobial peptide cathelicidin LL-37. Our findings suggest possible mechanisms by which vitamin D may enhance resistance to rhinovirus infection and reduce risk of secondary bacterial infection in vitamin D-deficient individuals.
Bousquet J, Hellings PW, Agache I, et 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.
Zhu J, Message SD, Mallia P, et al., 2019, Bronchial mucosal Interferon-α/β and pattern recognition receptor expression in experimental rhinovirus-induced asthma exacerbations, Journal of Allergy and Clinical Immunology, Vol: 143, Pages: 114-125.e4, 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.
Edwards MR, Ritchie AI, Johnston SL, 2019, Exacerbations of chronic respiratory diseases, RHINOVIRUS INFECTIONS: RETHINKING THE IMPACT ON HUMAN HEALTH AND DISEASE, Editors: Bartlett, Wark, Knight, Publisher: ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD, Pages: 137-168, ISBN: 978-0-12-816417-4
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