Susceptibility to rhinovirus-induced early wheezing as a risk factor for subsequent asthma development

2022 ◽  
Vol 18 ◽  
Author(s):  
Hannele Mikkola ◽  
Minna Honkila ◽  
Terhi Tapiainen ◽  
Tuomas Jartti
Keyword(s):  
Risk Factor ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Airway Remodeling ◽  
Early Years ◽  
Virus Infections ◽  
Prevention Strategies ◽  
Syncytial Virus ◽  
Interferon Responses

Abstract: Rhinovirus is one of the two most common viral agents that cause bronchiolitis in young children. During the first 12 months, it is second to the respiratory syncytial virus, but after 12 months, it begins dominating the statistics. Wheezing and dry cough are typical clinical symptoms indicative of rhinovirus-induced bronchiolitis, although overlap of symptoms with other virus infections is common. Several studies have shown that atopic predisposition and reduced interferon responses increase susceptibility to rhinovirus-induced wheezing. More recent studies have found that certain genetic variations at strong asthma loci also increase susceptibility. Rhinovirus-induced wheezing in the early years of life is known to increase the risk of subsequent asthma development and may be associated with airway remodeling. This risk is increased by aeroallergen sensitization. Currently, there are no clinically approved preventive treatments for asthma. However, studies show promising results indicating that children with rhinovirus-affected first-time wheezing respond to bronchodilators in terms of less short-term symptoms and that controlling airway inflammatory responses with anti-inflammatory medication may markedly decrease asthma development. Also, enhancing resistance to respiratory viruses has been a topic of discussion. Primary and secondary prevention strategies are being developed with the aim of decreasing the incidence of asthma. Here, we review the current knowledge on rhinovirus-induced early wheezing as a risk factor for subsequent asthma development and related asthma-prevention strategies.

Lung epithelial NOX/DUOX and respiratory virus infections

2014 ◽  
Vol 128 (6) ◽  
pp. 337-347 ◽  
Author(s):  
Nathalie Grandvaux ◽  
Mélissa Mariani ◽  
Karin Fink
Keyword(s):  
Respiratory Virus ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Conditional Knockout ◽  
In Vivo Studies ◽  
Virus Infections ◽  
Lung Epithelial ◽  
Respiratory Virus Infections

Determining the role of NADPH oxidases in the context of virus infection is an emerging area of research and our knowledge is still sparse. The expression of various isoforms of NOX/DUOX (NADPH oxidase/dual oxidase) in the epithelial cells (ECs) lining the respiratory tract renders them primary sites from which to orchestrate the host defence against respiratory viruses. Accumulating evidence reveals distinct facets of the involvement of NOX/DUOX in host antiviral and pro-inflammatory responses and in the control of the epithelial barrier integrity, with individual isoforms mediating co-operative, but surprisingly also opposing, functions. Although in vivo studies in mice are in line with some of these observations, a complete understanding of the specific functions of epithelial NOX/DUOX awaits lung epithelial-specific conditional knockout mice. The goal of the present review is to summarize our current knowledge of the role of individual NOX/DUOX isoforms expressed in the lung epithelium in the context of respiratory virus infections so as to highlight potential opportunities for therapeutic intervention.

Preventive Interventions for Youth Suicide: A Risk Factor-Based Approach

2000 ◽  
Vol 34 (3) ◽  
pp. 388-407 ◽  
Author(s):  
Jane M. Burns ◽  
George C. Patton
Keyword(s):  
Risk Factor ◽  
Suicide Prevention ◽  
Suicidal Behaviour ◽  
Research Evaluation ◽  
Current Knowledge ◽  
Preventive Interventions ◽  
Youth Suicide ◽  
Prevention Strategies ◽  
Clinical Interventions ◽  
Traditional Approaches

Objective: This review draws on current knowledge of risk for youth suicide to categorise strategies for intervention. Its goal is to identify areas of ‘research need’ and to provide an evidence base to identify ‘best buy’ preventive interventions for youth suicide. Method: The design, development, implementation and evaluation of prevention strategies ranging from clinical interventions to population-based universal approaches are considered within five risk factor domains: individual, family, community, school and peer. Results: There is a paucity of evidence on the effects of interventions targeting depression and suicidal behaviour. Nevertheless, there are effective indicated, selective and universal interventions for important risk factors for depression and suicidal behaviour. Little evidence has emerged to support the efficacy of some traditional approaches to suicide prevention, such as school based suicide education programs and telephone hotlines. Conclusions: Youth suicide prevention strategies in Australia have generally employed traditional approaches that focus on clinical interventions for self-harmers, restricting access to lethal means, providing services to high risk groups and enhancing general practitioner responses. Both program development and research evaluation of interventions for many important risk and protective factors for suicide have been neglected.

scholarly journals Siglec-H-Deficient Mice Show Enhanced Type I IFN Responses, but Do Not Develop Autoimmunity After Influenza or LCMV Infections

2021 ◽  
Vol 12 ◽  
Author(s):  
Nadine Szumilas ◽  
Odilia B. J. Corneth ◽  
Christian H. K. Lehmann ◽  
Heike Schmitt ◽  
Svenia Cunz ◽  
...  
Keyword(s):  
Autoimmune Disease ◽  
Inflammatory Responses ◽  
Type I Interferon ◽  
Acute Infection ◽  
Murine Cytomegalovirus ◽  
Type I ◽  
Virus Infections ◽  
Mcmv Infection ◽  
Interferon Responses ◽  
Deficient Mice

Siglec-H is a DAP12-associated receptor on plasmacytoid dendritic cells (pDCs) and microglia. Siglec-H inhibits TLR9-induced IFN-α production by pDCs. Previously, it was found that Siglec-H-deficient mice develop a lupus-like severe autoimmune disease after persistent murine cytomegalovirus (mCMV) infection. This was due to enhanced type I interferon responses, including IFN-α. Here we examined, whether other virus infections can also induce autoimmunity in Siglec-H-deficient mice. To this end we infected Siglec-H-deficient mice with influenza virus or with Lymphocytic Choriomeningitis virus (LCMV) clone 13. With both types of viruses we did not observe induction of autoimmune disease in Siglec-H-deficient mice. This can be explained by the fact that both types of viruses are ssRNA viruses that engage TLR7, rather than TLR9. Also, Influenza causes an acute infection that is rapidly cleared and the chronicity of LCMV clone 13 may not be sufficient and may rather suppress pDC functions. Siglec-H inhibited exclusively TLR-9 driven type I interferon responses, but did not affect type II or type III interferon production by pDCs. Siglec-H-deficient pDCs showed impaired Hck expression, which is a Src-family kinase expressed in myeloid cells, and downmodulation of the chemokine receptor CCR9, that has important functions for pDCs. Accordingly, Siglec-H-deficient pDCs showed impaired migration towards the CCR9 ligand CCL25. Furthermore, autoimmune-related genes such as Klk1 and DNase1l3 are downregulated in Siglec-H-deficient pDCs as well. From these findings we conclude that Siglec-H controls TLR-9-dependent, but not TLR-7 dependent inflammatory responses after virus infections and regulates chemokine responsiveness of pDCs.

Vascular pathophysiology of hypertension

2017 ◽  
Author(s):  
Tomasz J. Guzik ◽  
Rhian M. Touyz
Keyword(s):  
Cardiovascular Disease ◽  
Smooth Muscle ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Smooth Muscle ◽  
Inflammatory Responses ◽  
Clinical Symptoms ◽  
Peripheral Resistance ◽  
Vascular Stiffness ◽  
Vascular Pathology

Hypertension is a multifactorial disease, in which vascular dysfunction plays a prominent role. It occurs in over 30% of adults worldwide and an additional 30% are at high risk of developing the disease. Vascular pathology is both a cause of the disease and a key manifestation of hypertension-associated target-organ damage. It leads to clinical symptoms and is a key risk factor for cardiovascular disease. All layers of the vascular wall and the endothelium are involved in the pathogenesis of hypertension. Pathogenetic mechanisms, whereby vascular damage contributes to hypertension, are linked to increased peripheral vascular resistance. At the vascular level, processes leading to change sin peripheral resistance include hyper-contractility of vascular smooth muscle cells, endothelial dysfunction, and structural remodelling, due to aberrant vascular signalling, oxidative and inflammatory responses. Increased vascular stiffness due to vascular remodelling, adventitial fibrosis, and inflammation are key processes involved in sustained and established hypertension. These mechanisms are linked to vascular smooth muscle and fibroblast proliferation, migration, extracellular matrix remodelling, calcification, and inflammation. Apart from the key role in the pathogenesis of hypertension, hypertensive vasculopathy also predisposes to atherosclerosis, another risk factor for cardiovascular disease. This is linked to increased transmural pressure, blood flow, and shear stress alterations in hypertension, as well as endothelial dysfunction and vascular stiffness. Therefore, understanding the mechanisms and identifying potential novel treatments targeting hypertensive vasculopathy are of primary importance in vascular medicine.

scholarly journals Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and Summer Seasonality of HCoV-HKU1

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 515 ◽  
Author(s):  
Nehemya Friedman ◽  
Hadar Alter ◽  
Musa Hindiyeh ◽  
Ella Mendelson ◽  
Yonat Shemer Avni ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Medical Center ◽  
Hospitalized Patients ◽  
Pcr Analysis ◽  
Virus Infections ◽  
Summer Period ◽  
The Public ◽  
Syncytial Virus ◽  
Human Coronaviruses ◽  
One Year

Human coronaviruses (HCoVs) cause mild to severe respiratory diseases. Six types of HCoVs have been discovered, the most recent one termed the Middle East respiratory syndrome coronavirus (MERS-CoV). The aim of this study is to monitor the circulation of HCoV types in the population during 2015–2016 in Israel. HCoVs were detected by real-time PCR analysis in 1910 respiratory samples, collected from influenza-like illness (ILI) patients during the winter sentinel influenza survey across Israel. Moreover, 195 HCoV-positive samples from hospitalized patients were detected during one year at Soroka University Medical Center. While no MERS-CoV infections were detected, 10.36% of patients in the survey were infected with HCoV-OC43 (43.43%), HCoV-NL63 (44.95%), and HCoV-229E (11.62%) viruses. The HCoVs were shown to co-circulate with respiratory syncytial virus (RSV) and to appear prior to influenza virus infections. HCoV clinical symptoms were more severe than those of RSV infections but milder than influenza symptoms. Hospitalized patients had similar HCoV types percentages. However, while it was absent from the public winter survey, 22.6% of the patients were HCoV-HKU1 positives, mainly during the spring-summer period.

scholarly journals The Met1-linked ubiquitin machinery in inflammation and infection

2021 ◽  
Vol 28 (2) ◽  
pp. 557-569
Author(s):  
Berthe Katrine Fiil ◽  
Mads Gyrd-Hansen
Keyword(s):  
Cell Death ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Post Translational Modification ◽  
Ubiquitin Chain ◽  
Cellular Processes ◽  
Polymeric Chains ◽  
Cellular Machinery ◽  
Pleiotropic Functions ◽  
Interferon Responses

AbstractUbiquitination is an essential post-translational modification that regulates most cellular processes. The assembly of ubiquitin into polymeric chains by E3 ubiquitin ligases underlies the pleiotropic functions ubiquitin chains regulate. Ubiquitin chains assembled via the N-terminal methionine, termed Met1-linked ubiquitin chains or linear ubiquitin chains, have emerged as essential signalling scaffolds that regulate pro-inflammatory responses, anti-viral interferon responses, cell death and xenophagy of bacterial pathogens downstream of innate immune receptors. Met1-linked ubiquitin chains are exclusively assembled by the linear ubiquitin chain assembly complex, LUBAC, and are disassembled by the deubiquitinases OTULIN and CYLD. Genetic defects that perturb the regulation of Met1-linked ubiquitin chains causes severe immune-related disorders, illustrating their potent signalling capacity. Here, we review the current knowledge about the cellular machinery that conjugates, recognises, and disassembles Met1-linked ubiquitin chains, and discuss the function of this unique posttranslational modification in regulating inflammation, cell death and immunity to pathogens.

scholarly journals Chronic Wasting Due to Liver and Rumen Flukes in Sheep

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 549
Author(s):  
Alexandra Kahl ◽  
Georg von Samson-Himmelstjerna ◽  
Jürgen Krücken ◽  
Martin Ganter
Keyword(s):  
Fasciola Hepatica ◽  
Clinical Symptoms ◽  
Current Knowledge ◽  
Infection Intensity ◽  
Liver Parenchyma ◽  
Trematode Species ◽  
Helminth Infections ◽  
Juvenile Worm ◽  
Juvenile Stages ◽  
Common Liver Fluke

Grazing sheep and goats are constantly exposed to helminth infections in many parts of the world, including several trematode species that causes a range of clinical diseases. The clinical picture of flukes is dependent upon the organs in which they develop and the tissues they damage within the respective organs. Accordingly, infections with the common liver fluke Fasciola hepatica, which, as juvenile worm migrates through the liver parenchyma for several weeks, may be associated with hepatic disorders such as impairment of carbohydrate, protein and fat metabolism, followed by chronic wasting. In contrast, the lancet fluke Dicrocoelium dendriticum, which does not exhibit tissue migration and thus does not lead to major tissue damage and bleeding, also does not lead to significant clinical symptoms. Rumen flukes such as Cotylophoron daubneyi cause catarrhal inflammation during their migration through the intestinal and abomasal epithelium during its juvenile stages. Depending on the infection intensity this may result in a range of clinical symptoms including diarrhoea, inappetence or emaciation. In this review, we aim to provide an update on the current knowledge on flukes particularly concerning the clinical relevance of the most important fluke species in sheep.

scholarly journals Understanding Chronic Venous Disease: A Critical Overview of Its Pathophysiology and Medical Management

2021 ◽  
Vol 10 (15) ◽  
pp. 3239
Author(s):  
Miguel A. Ortega ◽  
Oscar Fraile-Martínez ◽  
Cielo García-Montero ◽  
Miguel A. Álvarez-Mon ◽  
Chen Chaowen ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Current Knowledge ◽  
Varicose Veins ◽  
Clinical Signs ◽  
Clinical Manifestations ◽  
Significant Loss ◽  
Venous Hypertension ◽  
Chronic Venous Disease ◽  
Venous Disease ◽  
Environmental Agents

Chronic venous disease (CVD) is a multifactorial condition affecting an important percentage of the global population. It ranges from mild clinical signs, such as telangiectasias or reticular veins, to severe manifestations, such as venous ulcerations. However, varicose veins (VVs) are the most common manifestation of CVD. The explicit mechanisms of the disease are not well-understood. It seems that genetics and a plethora of environmental agents play an important role in the development and progression of CVD. The exposure to these factors leads to altered hemodynamics of the venous system, described as ambulatory venous hypertension, therefore promoting microcirculatory changes, inflammatory responses, hypoxia, venous wall remodeling, and epigenetic variations, even with important systemic implications. Thus, a proper clinical management of patients with CVD is essential to prevent potential harms of the disease, which also entails a significant loss of the quality of life in these individuals. Hence, the aim of the present review is to collect the current knowledge of CVD, including its epidemiology, etiology, and risk factors, but emphasizing the pathophysiology and medical care of these patients, including clinical manifestations, diagnosis, and treatments. Furthermore, future directions will also be covered in this work in order to provide potential fields to explore in the context of CVD.

scholarly journals 1719. Respiratory Syncytial Virus-Associated Hospitalization Rates among US Infants: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S843-S843
Author(s):  
John M McLaughlin ◽  
Farid L Khan ◽  
Heinz-Josef Schmitt ◽  
Yasmeen Agosti ◽  
Luis Jodar ◽  
...  
Keyword(s):  
Public Health ◽  
Respiratory Syncytial Virus ◽  
Active Surveillance ◽  
Meta Analysis ◽  
The United States ◽  
Administrative Claims ◽  
Prevention Strategies ◽  
Hospitalization Rates ◽  
Syncytial Virus ◽  
The Impact

Abstract Background Understanding the true magnitude of infant respiratory syncytial virus (RSV) burden is critical for determining the potential public-health benefit of RSV prevention strategies. Although global reviews of infant RSV burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design. Methods We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants. We also examined the impact of key study characteristics on these estimates. Results After review of 3058 articles through January 2020, we identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants < 1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate= 19.4 (95%CI= 17.9–20.9). Study type was associated with RSV hospitalization rates (P =.003), with active surveillance studies having pooled rates per 1000 (11.1; 95%CI: 9.8–12.3) that were half that of studies based on administrative claims (21.4; 95%CI: 19.5–23.3) or modeling approaches (23.2; 95%CI: 20.2–26.2). Conclusion Applying the pooled rates identified in our review to the 2020 US birth cohort suggests that 73,680 to 86,020 RSV-associated infant hospitalizations occur each year. To date, public-health officials have used conservative estimates from active surveillance as the basis for defining US infant RSV burden. The full range of RSV-associated hospitalization rates identified in our review better characterizes the true RSV burden in infants and can better inform future evaluations of RSV prevention strategies. Disclosures John M. McLaughlin, PhD, Pfizer (Employee, Shareholder) Farid L. Khan, MPH, Pfizer (Employee, Shareholder) Heinz-Josef Schmitt, MD, Pfizer (Employee, Shareholder) Yasmeen Agosti, MD, Pfizer (Employee, Shareholder) Luis Jodar, PhD, Pfizer (Employee, Shareholder) Eric Simões, MD, Pfizer (Consultant, Research Grant or Support) David L. Swerdlow, MD, Pfizer (Employee, Shareholder)

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