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Rhinovirus human asthma study

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https://www.readbyqxmd.com/read/28861088/the-unresolved-role-of-interferon-%C3%AE-in-asthma-bronchiale
#1
REVIEW
Nina Sopel, Andreas Pflaum, Julia Kölle, Susetta Finotto
Asthma bronchiale is a disease of the airways with increasing incidence, that often begins during infancy. So far, therapeutic options are mainly symptomatic and thus there is an increasing need for better treatment and/or prevention strategies. Human rhinoviruses (HRVs) are a major cause of asthma exacerbations and might cause acute wheezing associated with local production of pro-inflammatory mediators resulting in neutrophilic inflammatory response. Viral infections induce a characteristic activation of immune response, e...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28827284/rhinovirus-infection-of-ormdl3-transgenic-mice-is-associated-with-reduced-rhinovirus-viral-load-and-airway-inflammation
#2
Dae Jin Song, Marina Miller, Andrew Beppu, Peter Rosenthal, Sudipta Das, Maya Karta, Christine Vuong, Amit Kumar Mehta, Michael Croft, David H Broide
Orosomucoid like 3 (ORMDL3), a gene localized to chromosome 17q21, has been linked in epidemiologic studies to childhood asthma and rhinovirus (RV) infections. As the single nucleotide polymorphisms linking ORMDL3 to asthma are associated with increased expression of ORMDL3, we have used hORMDL3(zp3-Cre) mice (which have universal increased expression of human ORMDL3) to determine whether infection of these transgenic mice with RV influences levels of airway inflammation or RV viral load. RV infection of hORMDL3(zp3-Cre) mice resulted in reduced RV viral load assessed by quantitative real-time PCR (lung and airway epithelium), as well as reduced airway inflammation (total bronchoalveolar lavage cells, neutrophils, macrophages, and lymphocytes) compared with RV-infected wild-type mice...
October 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28763071/prevalence-of-respiratory-viruses-in-wheezing-children-not-older-than-24-months-of-age
#3
Martín Bedolla-Barajas, Hilda Montero, Jaime Morales-Romero, Adriana Landa-Cardeña, Jahaziel Díaz, Netzahualpilli Delgado-Figueroa, Luis Gustavo Orozco-Alatorre
INTRODUCTION: Wheezing in children not older than 24 months of age is a frequent event, and viruses are usually the causative agents. The aim of the study was to estimate the prevalence of respiratory viruses in wheezing children who were not older than 24 months of age and who had no history of asthma. METHODS: Fifty-five Mexican children were included in an analytical cross-sectional study. Nasal secretions were obtained by using sterile rayon-tipped applicators to identify the virus by polymerase chain reaction or reverse transcription-polymerase chain reaction: adenovirus, bocavirus, human rhinovirus, influenza virus type A, human metapneumovirus, parainfluenza, rhinovirus, and respiratory syncytial virus...
May 2017: Gaceta Médica de México
https://www.readbyqxmd.com/read/28734844/toll-like-receptor-3-blockade-in-rhinovirus-induced-experimental-asthma-exacerbations-a%C3%A2-randomized-controlled-study
#4
Philip E Silkoff, Susan Flavin, Robert Gordon, Mathew J Loza, Peter J Sterk, Rene Lutter, Zuzana Diamant, Ronald B Turner, Brian J Lipworth, David Proud, Dave Singh, Andreas Eich, Vibeke Backer, James E Gern, Christian Herzmann, Scott A Halperin, Tjeert T Mensinga, Alfred M Del Vecchio, Patrick Branigan, Lani San Mateo, Frédéric Baribaud, Elliot S Barnathan, Sebastian L Johnston
BACKGROUND: Human rhinoviruses (HRVs) commonly precipitate asthma exacerbations. Toll-like receptor 3, an innate pattern recognition receptor, is triggered by HRV, driving inflammation that can worsen asthma. OBJECTIVE: We sought to evaluate an inhibitory mAb to Toll-like receptor 3, CNTO3157, on experimental HRV-16 inoculation in healthy subjects and asthmatic patients. METHODS: In this double-blind, multicenter, randomized, parallel-group study in North America and Europe, healthy subjects and patients with mild-to-moderate stable asthma received single or multiple doses of CNTO3157 or placebo, respectively, and were then inoculated with HRV-16 within 72 hours...
July 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28705625/antiviral-activity-of-gemcitabine-against-human-rhinovirus-in%C3%A2-vitro-and-in%C3%A2-vivo
#5
Jae-Hyoung Song, Seong-Ryeol Kim, Eun-Young Heo, Jae-Young Lee, Dong-Eun Kim, Sungchan Cho, Sun-Young Chang, Byung-Il Yoon, Jeongmin Seong, Hyun-Jeong Ko
Rhinovirus, a major causative agent of the common cold, is associated with exacerbation of asthma and chronic obstructive pulmonary disease. Currently, there is no antiviral treatment or vaccine for human rhinovirus (HRV). Gemcitabine (2',2'-difluorodeoxycytidine, dFdC) is a deoxycytidine analog with antiviral activity against rhinovirus, as well as enterovirus 71, in vitro. However, the antiviral effects of gemcitabine in vivo have not been investigated. In the current study, we assessed whether gemcitabine mediated antiviral effects in the murine HRV infection model...
July 11, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28634031/does-atopy-affect-the-course-of-viral-pneumonia
#6
S B Erdem, D Can, S Girit, F Çatal, V Şen, S Pekcan, H Yüksel, A Bingöl, I Bostancı, D Erge, R Ersu
BACKGROUND: The presence of atopy is considered as a risk factor for severe respiratory symptoms in children. The objective of this study was to examine the effect of atopy on the course of disease in children hospitalised with viral pneumonia. METHODS: Children between the ages of 1 and 6 years hospitalised due to viral pneumonia between the years of 2013 and 2016 were included to this multicentre study. Patients were classified into two groups as mild-moderate and severe according to the course of pneumonia...
June 17, 2017: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/28581749/a-novel-series-of-highly-potent-small-molecule-inhibitors-of-rhinovirus-replication
#7
Jinwoo Kim, Yu Kyoung Jung, Chonsaeng Kim, Jin Soo Shin, Els Scheers, Joo-Youn Lee, Soo Bong Han, Chong-Kyo Lee, Johan Neyts, Jae-Du Ha, Young-Sik Jung
Human rhinoviruses (hRVs) are the main causative pathogen for common colds and are associated with the exacerbation of asthma. The wide variety in hRV serotypes has complicated the development of rhinovirus replication inhibitors. In the current investigation, we developed a novel series of benzothiophene derivatives and their analogues (6-8) that potently inhibit the replication of both hRV-A and hRV-B strains. Compound 6g inhibited the replication of hRV-B14, A21, and A71, with respective EC50 values of 0...
July 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28576493/the-suppression-of-innate-immune-response-by-human-rhinovirus-c
#8
Li-Li Pang, Xin-Hui Yuan, Chang-Sheng Shao, Mao-Zhong Li, Ying Wang, Hui-Min Wang, Guang-Cheng Xie, Zhi-Ping Xie, Yue Yuan, Dong-Mei Zhou, Xiao-Man Sun, Qing Zhang, Yan Xin, Dan-di Li, Zhao-Jun Duan
Rhinovirus C (RV-C), a newly identified group of human rhinoviruses (RVs), is associated with exacerbation of severe asthma. The type I interferon (IFN) response induced by this virus and the mechanisms of evasion of IFN-mediated innate immunity for RV-C remain unclear. In this study, we constructed a full-length cDNA clone of RV-C (LZ651) from a clinical sample. IFN-β mRNA and protein levels were not elevated in differentiated Human bronchial epithelial (HBE) cells at the air-liquid interface infected with RV-C, except in the early stage of infection...
May 31, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28558698/role-of-human-rhinovirus-in-triggering-human-airway-epithelial-mesenchymal-transition
#9
Danielle M Minor, David Proud
BACKGROUND: Structural changes in the airways, collectively referred to as airway remodeling, are a characteristic feature of asthma, and are now known to begin in early life. Human rhinovirus (HRV)-induced wheezing illnesses during early life are a potential inciting stimulus for remodeling. Increased deposition of matrix proteins causes thickening of the lamina reticularis, which is a well-recognized component of airway remodeling. Increased matrix protein deposition is believed to be due to the presence of increased numbers of activated mesenchymal cells (fibroblasts/myofibroblasts) in the subepithelial region of asthmatic airways...
May 30, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28545810/thymic-stromal-lymphopoietin-and-apocynin-alter-the-expression-of-airway-remodeling-factors-in-human-rhinovirus-infected-cells
#10
Joanna Wieczfinska, Rafal Pawliczak
Airway remodeling is a characteristic of bronchial asthma. The process involves the expression of many genes, such as transforming growth factor-beta (TGF-β), tissue inhibitors of metalloproteinases (TIMP-1), MMP and arginase. Human rhinovirus (HRV) is known to cause asthma exacerbations, and viral infections might be involved in the development of airway remodeling. Therefore, the aim of this study was to determine the influence of HRV on the genes involved in airway remodeling and to examine the impact of thymic stromal lymphopoietin (TSLP) and contribution of oxidative stress on airway remodeling in the context of HRV infection...
August 2017: Immunobiology
https://www.readbyqxmd.com/read/28526018/infection-mediated-asthma-etiology-mechanisms-and-treatment-options-with-focus-on-chlamydia-pneumoniae-and-macrolides
#11
REVIEW
Wilmore C Webley, David L Hahn
Asthma is a chronic respiratory disease characterized by reversible airway obstruction and airway hyperresponsiveness to non-specific bronchoconstriction agonists as the primary underlying pathophysiology. The worldwide incidence of asthma has increased dramatically in the last 40 years. According to World Health Organization (WHO) estimates, over 300 million children and adults worldwide currently suffer from this incurable disease and 255,000 die from the disease each year. It is now well accepted that asthma is a heterogeneous syndrome and many clinical subtypes have been described...
May 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28433687/steroid-resistance-of-airway-type-2-innate-lymphoid-cells-from-patients-with-severe-asthma-the-role-of-thymic-stromal-lymphopoietin
#12
Sucai Liu, Mukesh Verma, Lidia Michalec, Weimin Liu, Anand Sripada, Donald Rollins, James Good, Yoko Ito, HongWei Chu, Magdalena M Gorska, Richard J Martin, Rafeul Alam
BACKGROUND: Type 2 innate lymphoid cells (ILC2s) represent an important type 2 immune cell. Glucocorticoid regulation of human ILC2s is largely unknown. OBJECTIVE: We sought to assess steroid resistance of human blood and airway ILC2s from asthmatic patients and to examine its mechanism of induction. METHODS: We studied human blood and lung ILC2s from asthmatic patients and control subjects using flow cytometry and ELISA. RESULTS: Dexamethasone inhibited (P = ...
April 20, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28397284/altered-fatty-acid-metabolism-and-reduced-stearoyl-coenzyme-a-desaturase-activity-in-asthma
#13
N Rodriguez-Perez, E Schiavi, R Frei, R Ferstl, P Wawrzyniak, S Smolinska, M Sokolowska, N A Sievi, M Kohler, P Schmid-Grendelmeier, D Michalovich, K D Simpson, E M Hessel, M Jutel, M Martin-Fontecha, O Palomares, C A Akdis, L O'Mahony
BACKGROUND: Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely under-explored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and non-obese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. METHODS: Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS...
April 11, 2017: Allergy
https://www.readbyqxmd.com/read/28368456/interference-between-respiratory-syncytial-virus-and-human-rhinovirus-infection-in-infancy
#14
Niek B Achten, Pingsheng Wu, Louis Bont, Maarten O Blanken, Tebeb Gebretsadik, James D Chappell, Li Wang, Chang Yu, Emma K Larkin, Kecia N Carroll, Larry J Anderson, Martin L Moore, Chantel D Sloan, Tina V Hartert
Background: Respiratory syncytial virus (RSV) and human rhinovirus (HRV) are the most common viruses associated with acute respiratory tract infections in infancy. Viral interference is important in understanding respiratory viral circulation and the impact of vaccines. Methods: To study viral interference, we evaluated cases of RSV and HRV codetection by polymerase chain reaction in 2 prospective birth cohort studies (the Infant Susceptibility to Pulmonary Infections and Asthma Following RSV Exposure [INSPIRE] study and the Tennessee Children's Respiratory Initiative [TCRI]) and a double-blinded, randomized, controlled trial (MAKI), using adjusted multivariable regression analyses...
April 1, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28328242/human-airway-epithelial-cells-direct-significant-rhinovirus-replication-in-monocytic-cells-by-enhancing-icam1-expression
#15
Xu Zhou, Lingxiang Zhu, Rosa Lizarraga, Yin Chen
Human rhinovirus (RV) is the major cause of common cold, and it also plays a significant role in asthma and asthma exacerbation. The airway epithelium is the primary site of RV infection and production. In contrast, monocytic cells (e.g., monocytes and macrophages) are believed to be nonpermissive for RV replication. Instead, RV has been shown to modulate inflammatory gene expressions in these cells via a replication-independent mechanism. In the study presented here, replication of RV16 (a major-group RV) was found to be significantly enhanced in monocytes when it was cocultivated with airway epithelial cells...
August 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28318885/genetic-association-of-the-functional-cdhr3-genotype-with-early-onset-adult-asthma-in-japanese-populations
#16
Jun Kanazawa, Hironori Masuko, Yohei Yatagai, Tohru Sakamoto, Hideyasu Yamada, Yoshiko Kaneko, Haruna Kitazawa, Hiroaki Iijima, Takashi Naito, Takefumi Saito, Emiko Noguchi, Satoshi Konno, Masaharu Nishimura, Tomomitsu Hirota, Mayumi Tamari, Nobuyuki Hizawa
BACKGROUND: Recent studies have demonstrated that a coding SNP (rs6967330, Cys529→Tyr) in cadherin-related family member 3 (CDHR3), which was previously associated with wheezing illness and hospitalizations in infancy, could support efficient human rhinovirus C (RV-C) entry and replication. Here, we sought to examine the genetic contribution of this variant to the development of adult asthma. METHODS: We performed a candidate gene case-control association study of 2 independent Japanese populations (a total of 3366 adults)...
March 16, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28192616/association-of-ormdl3-with-rhinovirus-induced-endoplasmic-reticulum-stress-and-type-i-interferon-responses-in-human-leucocytes
#17
Y-P Liu, V Rajamanikham, M Baron, S Patel, S K Mathur, E A Schwantes, C Ober, D J Jackson, J E Gern, R F Lemanske, J A Smith
BACKGROUND: Children with risk alleles at the 17q21 genetic locus who wheeze during rhinovirus illnesses have a greatly increased likelihood of developing childhood asthma. In mice, overexpression of the 17q21 gene ORMDL3 leads to airway remodelling and hyperresponsiveness. However, the mechanisms by which ORMDL3 predisposes to asthma are unclear. Previous studies have suggested that ORMDL3 induces endoplasmic reticulum (ER) stress and production of the type I interferon (IFN)-regulated chemokine CXCL10...
March 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28100614/human-rhinovirus-diversity-and-evolution-how-strange-the-change-from-major-to-minor
#18
Nicole Lewis-Rogers, Jon Seger, Frederick R Adler
Rhinoviruses are the most common causes of the common cold. Their many distinct lineages fall into "major" and "minor" groups that use different cell surface receptors to enter host cells. Minor-group rhinoviruses are more immunogenic in laboratory studies, although their patterns of transmission and their cold symptoms are broadly similar to those of the major group. Here we present evolutionary evidence that minor-group viruses are also more immunogenic in humans. A key finding is that rates of amino acid substitutions at exposed sites in the capsid proteins VP2, VP3, and VP1 tend to be elevated in minor-group relative to major-group viruses, while rates at buried sites show no consistent differences...
April 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28046097/glucocorticoid-insensitivity-in-virally-infected-airway-epithelial-cells-is-dependent-on-transforming-growth-factor-%C3%AE-activity
#19
Yuxiu C Xia, Asmaa Radwan, Christine R Keenan, Shenna Y Langenbach, Meina Li, Danica Radojicic, Sarah L Londrigan, Rosa C Gualano, Alastair G Stewart
Asthma and chronic obstructive pulmonary disease (COPD) exacerbations are commonly associated with respiratory syncytial virus (RSV), rhinovirus (RV) and influenza A virus (IAV) infection. The ensuing airway inflammation is resistant to the anti-inflammatory actions of glucocorticoids (GCs). Viral infection elicits transforming growth factor-β (TGF-β) activity, a growth factor we have previously shown to impair GC action in human airway epithelial cells through the activation of activin-like kinase 5 (ALK5), the type 1 receptor of TGF-β...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28024227/the-role-of-outdoor-fungi-on-asthma-hospital-admissions-in-children-and-adolescents-a-5-year-time-stratified-case-crossover-analysis
#20
Rachel Tham, Constance H Katelaris, Don Vicendese, Shyamali C Dharmage, Adrian J Lowe, Gayan Bowatte, Philip Taylor, Pamela Burton, Michael J Abramson, Bircan Erbas
BACKGROUND: Some fungal spores can trigger asthma exacerbation but knowledge of which outdoor fungal spores contribute to asthma hospitalisation is limited. OBJECTIVES: To examine the role of outdoor fungal spores in child and adolescent asthma hospitalisations. METHODS: We conducted a bi-directional time-stratified case-crossover study of child and adolescent asthma hospitalisations over 5 years. Conditional logistic regression assessed the role of 20 fungi taxa (Same day [L0] and lagged [L1-3]) adjusted for maximum temperature, humidity and grass pollen...
April 2017: Environmental Research
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