Response to infections in patients with asthma and atopic disease: An epiphenomenon or reflection of host susceptibility?
Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-8300, USA.The Journal of allergy and clinical immunology (Impact Factor: 11.48). 08/2012; 130(2):343-51. DOI: 10.1016/j.jaci.2012.05.056
Associations between respiratory tract infections and asthma inception and exacerbations are well established. Infant respiratory syncytial virus and rhinovirus infections are known to be associated with an increased risk of asthma development, and among children with prevalent asthma, 85% of asthma exacerbations are associated with viral infections. However, the exact nature of this relationship remains unclear. Is the increase in severity of infections an epiphenomenon, meaning respiratory tract infections just appear to be more severe in patients with underlying respiratory disease, or instead a reflection of altered host susceptibility among persons with asthma and atopic disease? The main focus of this review is to summarize the available levels of evidence supporting or refuting the notion that patients with asthma or atopic disease have an altered susceptibility to selected pathogens, as well as discussing the biological mechanism or mechanisms that might explain such associations. Finally, we will outline areas in need of further research because understanding the relationships between infections and asthma has important implications for asthma prevention and treatment, including potential new pathways that might target the host immune response to select pathogens.
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- "Thus, the association between severe RSVinfection and asthma is reciprocal  . Despite extensive research efforts, safe and effective vaccines against RSV are currently unavailable. "
ABSTRACT: Subunit vaccines comprised of glycoprotein D (gD-2) failed to prevent HSV-2 highlighting need for novel strategies. To test the hypothesis that deletion of gD-2 unmasks protective antigens, we evaluated the efficacy and safety of an HSV-2 virus deleted in gD-2 and complemented allowing a single round of replication on cells expressing HSV-1 gD (Delta gD(-/+gD-1)). Subcutaneous immunization of C57BL/6 or BALB/c mice with Delta gD(-/+gD1) provided 100% protection against lethal intravaginal or skin challenges and prevented latency. Delta gD(-/+gD1) elicited no disease in SCID mice, whereas 1000-fold lower doses of wild-type virus were lethal. HSV-specific antibodies were detected in serum (titer 1:800,000) following immunization and in vaginal washes after intravaginal challenge. The antibodies elicited cell-mediated cytotoxicity, but little neutralizing activity. Passive transfer of immune serum completely protected wild-type, but not Fc gamma-receptor or neonatal Fc-receptor knock-out mice. These studies demonstrate that non-neutralizing Fc-mediated humoral responses confer protection and support advancement of this attenuated vaccine.
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ABSTRACT: Last year's "Advances in pediatric asthma: moving forward" concluded the following: "Now is also the time to utilize information recorded in electronic medical records to develop innovative disease management plans that will track asthma over time and enable timely decisions on interventions in order to maintain control that can lead to disease remission and prevention." This year's summary will focus on recent advances in pediatric asthma on modifying disease activity, preventing asthma exacerbations, managing severe asthma, and risk factors for predicting and managing early asthma, as indicated in Journal of Allergy and Clinical Immunology publications in 2012. Recent reports continue to shed light on methods to improve asthma management through steps to assess disease activity, tools to standardize outcome measures in asthma, genetic markers that predict risk for asthma and appropriate treatment, and interventions that alter the early presentation of asthma to prevent progression. We are well on our way to creating a pathway around wellness in asthma care and also to use new tools to predict the risk for asthma and take steps to not only prevent asthma exacerbations but also to prevent the early manifestations of the disease and thus prevent its evolution to severe asthma.
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