460 results found
Chairakaki A-D, Saridaki M-I, Pyrillou K, et al., 2018, Plasmacytoid dendritic cells drive acute asthma exacerbations, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 142, Pages: 542-+, ISSN: 0091-6749
Custovic A, Belgrave D, Lin L, et 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
Dhariwal J, Cameron A, Wong E, et al., 2018, Pulmonary Innate Lymphoid Cell Responses During Rhinovirus-Induced Asthma Exacerbations, American-Academy-of-Allergy-Asthma-and-Immunology / World-Allergy-Organization Joint Congress, Publisher: MOSBY-ELSEVIER, Pages: AB195-AB195, ISSN: 0091-6749
Dunning J, Blankley S, Hoang LT, et 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
Edwards MR, Walton RP, Jackson DJ, et al., 2018, The potential of anti-infectives and immunomodulators as therapies for asthma and asthma exacerbations, ALLERGY, Vol: 73, Pages: 50-63, ISSN: 0105-4538
Ghebre MA, Pang PH, Diver S, et 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.
Jolliffe DA, Greiller CL, Mein CA, et al., 2018, Vitamin D receptor genotype influences risk of upper respiratory infection., Br J Nutr, Vol: 120, Pages: 891-900
SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, P for trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (P for trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.
Lan F, Zhang N, Holtappels G, et 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
Mallia P, Webber J, Gill SK, et 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
Moskwa S, Piotrowski W, Marczak J, et al., 2018, Innate Immune Response to Viral Infections in Primary Bronchial Epithelial Cells is Modified by the Atopic Status of Asthmatic Patients, ALLERGY ASTHMA & IMMUNOLOGY RESEARCH, Vol: 10, Pages: 144-154, ISSN: 2092-7355
Mousnier A, Bell AS, Swieboda DP, et 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
Potaczek DP, Unger SD, Zhang N, et 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
Potaczek DP, Unger SD, Zhang N, et al., 2018, Development and characterization of DNAzyme candidates demonstrating significant efficiency against human rhinoviruses., J Allergy Clin Immunol
BACKGROUND: Infections with human rhinoviruses (RVs) are responsible for millions of common cold episodes and the majority of asthma exacerbations, especially in childhood. No drugs specifically targeting RVs are available. OBJECTIVE: We sought to identify specific anti-RV molecules based on DNAzyme technology as candidates to a clinical study. METHODS: A total of 226 candidate DNAzymes were designed against 2 regions of RV RNA genome identified to be sufficiently highly conserved between virus strains (ie, the 5'-untranslated region and cis-acting replication element) by using 3 test strains: RVA1, RVA16, and RVA29. All DNAzymes were screened for their cleavage efficiency against in vitro-expressed viral RNA. Those showing any catalytic activity were subjected to bioinformatic analysis of their reverse complementarity to 322 published RV genomic sequences. Further molecular optimization was conducted for the most promising candidates. Cytotoxic and off-target effects were excluded in HEK293 cell-based systems. Antiviral efficiency was analyzed in infected human bronchial BEAS-2B cells and ex vivo-cultured human sinonasal tissue. RESULTS: Screening phase-generated DNAzymes characterized by either good catalytic activity or by high RV strain coverage but no single molecule represented a satisfactory combination of those 2 features. Modifications in length of the binding domains of 2 lead candidates, Dua-01(-L12R9) and Dua-02(-L10R11), improved their cleavage efficiency to an excellent level, with no loss in eminent strain coverage (about 98%). Both DNAzymes showed highly favorable cytotoxic/off-target profiles. Subsequent testing of Dua-01-L12R9 in BEAS-2B cells and sinonasal tissue demonstrated its significant antiviral efficiency. CONCLUSIONS: Effective and specific management of RV infections with Dua-01-L12R9 might be useful in preventing asthma exacerbations, which should be verified by clinical trials.
Ritchie AI, Singanayagam A, Wiater E, et al., 2018, beta(2)-agonists enhance asthma-relevant inflammatory mediators in human airway epithelial cells, American Journal of Respiratory Cell and Molecular Biology, Vol: 58, Pages: 128-132, ISSN: 1044-1549
Silkoff PE, Flavin S, Gordon R, et 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
Singanayagam A, Glanville N, Girkin JL, et al., 2018, Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations, NATURE COMMUNICATIONS, Vol: 9, ISSN: 2041-1723
Teo SM, Tang HHF, Mok D, et 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: 341-352.e5
Repeated cycles of infection-associated lower airway inflammation drive the pathogenesis of persistent wheezing disease in children. In this study, the occurrence of acute respiratory tract illnesses (ARIs) and the nasopharyngeal microbiome (NPM) were characterized in 244 infants through their first five years of life. Through this analysis, we demonstrate that >80% of infectious events involve viral pathogens, but are accompanied by a shift in the NPM toward dominance by a small range of pathogenic bacterial genera. Unexpectedly, this change frequently precedes the detection of viral pathogens and acute symptoms. Colonization of illness-associated bacteria coupled with early allergic sensitization is associated with persistent wheeze in school-aged children, which is the hallmark of the asthma phenotype. In contrast, these bacterial genera are associated with "transient wheeze" that resolves after age 3 years in non-sensitized children. Thus, to complement early allergic sensitization, monitoring NPM composition may enable early detection and intervention in high-risk children.
Aab A, Wirz O, van de Veen W, et al., 2017, Human rhinoviruses enter and induce proliferation of B lymphocytes, ALLERGY, Vol: 72, Pages: 232-243, ISSN: 0105-4538
Bousquet J, Bewick M, Cano A, et al., 2017, BUILDING BRIDGES FOR INNOVATION IN AGEING: SYNERGIES BETWEEN ACTION GROUPS OF THE EIP ON AHA, JOURNAL OF NUTRITION HEALTH & AGING, Vol: 21, Pages: 92-104, ISSN: 1279-7707
Bousquet J, Farrell J, Crooks G, et al., 2017, Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5) (vol 6, 29, 2016), CLINICAL AND TRANSLATIONAL ALLERGY, Vol: 7, ISSN: 2045-7022
Dhariwal J, Cameron A, Trujillo-Torralbo M-B, et al., 2017, Mucosal Type 2 Innate Lymphoid Cells Are a Key Component of the Allergic Response to Aeroallergens, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 195, Pages: 1586-1596, ISSN: 1073-449X
Edwards MR, Saglani S, Schwarze J, et al., 2017, Addressing unmet needs in understanding asthma mechanisms, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936
Edwards MR, Strong K, Cameron A, et al., 2017, Viral infections in allergy and immunology: How allergic inflammation influences viral infections and illness, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, Vol: 140, Pages: 909-920, ISSN: 0091-6749
Farne HA, Johnston SL, 2017, Immune mechanisms of respiratory viral infections in asthma, CURRENT OPINION IN IMMUNOLOGY, Vol: 48, Pages: 31-37, ISSN: 0952-7915
Finney LJ, Belchamber K, Kemp S, et al., 2017, HUMAN RHINOVIRUS IMPAIRS PHAGOCYTOSIS OF HAEMOPHILUS INFLUENZAE IN ALVEOLAR MACROPHAGES IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE, Winter Meeting of the British-Thoracic-Society, Publisher: BMJ PUBLISHING GROUP, Pages: A112-A112, ISSN: 0040-6376
Guedan A, Swieboda D, Charles M, et al., 2017, Investigation of the Role of Protein Kinase D in Human Rhinovirus Replication, JOURNAL OF VIROLOGY, Vol: 91, ISSN: 0022-538X
Hansel TT, Tunstall T, Trujillo-Torralbo M-B, et al., 2017, A Comprehensive Evaluation of Nasal and Bronchial Cytokines and Chemokines Following Experimental Rhinovirus Infection in Allergic Asthma: Increased Interferons (IFN-gamma and IFN-lambda) and Type 2 Inflammation (IL-5 and IL-13), EBIOMEDICINE, Vol: 19, Pages: 128-138, ISSN: 2352-3964
Johnston SL, Mansur A, Chauhan A, 2017, Incorrect Conclusions Concerning Antibiotics and Asthma Exacerbation, JAMA INTERNAL MEDICINE, Vol: 177, Pages: 598-598, ISSN: 2168-6106
Naveed S-U-N, Clements D, Jackson DJ, et al., 2017, Matrix Metalloproteinase-1 Activation Contributes to Airway Smooth Muscle Growth and Asthma Severity, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 195, Pages: 1000-1009, ISSN: 1073-449X
Papadopoulos NG, Androutsopoulou A, Akdis C, et al., 2017, Asthma research in Europe: a transformative agenda for innovation and competitiveness, EUROPEAN RESPIRATORY JOURNAL, Vol: 49, ISSN: 0903-1936
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