ASTHMA AND ALLERGIC DISEASE CENTER

Summary

Principal Investigator: Thomas A Platts Mills
Abstract: DESCRIPTION (provided by applicant): The research program of the University of Virginia has focused on investigating the etiology of asthma, looking both at risk factors for the disease and the complex events surrounding an acute episode. These studies have provided extensive evidence about effects of chronic exposure to indoor allergens, as well as the relevance of viruses to acute episodes in the hospital;the role of chronic sinus disease;and most recently the effects of pH changes in the lung lining fluid. In addition, the studies have addressed the mechanisms by which T cells contribute as effector cells and regulatory cells in allergic disease. The four projects of the current proposal are presented as separate and distinct research plans, but they have developed from, and will continue to involve, strong interactions at multiple levels. Project 1: Allergen exposure, IgE responses, and total IgE in relation to asthma in at risk populations: The studies will investigate: a) the interaction between home exposure, sensitization, and inflammatory responses among adult patients presenting with acute asthma;b) lung symptoms and asthma among teenage children in rural and city schools, focusing on the interaction between physical fitness, obesity, and metabolic syndrome on the one hand, and allergic responses and inflammation on the other. Project 2: CD25+CD4+ T cells and IgE-mediated disease in humans: The phenotype and function of a novel CD25+CD4+ subset associated with IgE responses will be analyzed. Studies will include investigation of the link between these cells and IgE by monitoring circulating T cells in children with atopic dermatitis during the first years of life, and examining the effects of anti-lgE therapy on discrete T cell subsets in asthmatic subjects. Project 3: Impact of chronic hyperplastic eosinophilic sinusitis on asthma: Studies will investigate the hypothesis that the sinus tissue contributes to the systemic inflammatory response through the production of, and recirculation of, TH2-like lymphocytes, eosinophils, basophils, and fibrocytes;and that those cells in turn influence sinus associated lymphatic tissue, bone marrow, and the lungs. Project 4: Mechanisms of pH deviation in asthma and chronic cough: Using new methods of measuring exhaled breath pH, the studies will focus on distinguishing between patients with primary airway acidification and gastric acid aspiration. The studies will address cellular and biochemical pathology related to airway acidification in the setting of chronic cough or acute asthma exacerbations. PROJECT 1: Allergen Exposure, IgE Responses, and Total IgE in Relation to Asthma in at Risk Populations (PI Platts-Mills, T.) PROJECT 1 DESCRIPTION (provided by applicant): Over the last 40 years of the 20th century asthma has become epidemic in most of the Western World. In particular asthma has become an important cause of school absenteeism, hospitalization and mortality among populations living in poverty in the cities of the United States. Although many changes are thought to have contributed to the increase the real reasons for the time course (i.e. 1960-2000) are not clear. However it is clear that the majority of African American children and adults admitted to hospital with asthma are allergic to one or more indoor allergens, particularly those from dust mite or cockroach. Over this same time period there have been major changes in lifestyle leading to decreased time outdoors, more time sedentary and a rise in obesity. To further understand the interaction between different factors contributing to asthma, several different approaches will be employed. The first will use new techniques to measure allergen and endotoxin exposure in homes, and a novel approach to measuring IgE antibodies specific for airborne particles. The objective is to investigate the dose response relationship between exposure and immune responses to allergens for patients living in poverty. The second aim is to assess the relationships between IgE ab response and inflammation among the patients presenting to an emergency department with asthma. These patients are consistently -70% uninsured and 50% from a minority group. In this study the inflammation associated with asthma will be studied using both "traditional" markers such as eosinophilia, exhaled NO (eNO) and sinus CT score;as well as measurements of cytokines in serum and leukotrienes in urine. Finally teenagers aged 14-16 years will be studied to determine the independent effects of physical activity, obesity and allergic sensitization on asthmatic symptoms and airway inflammation. The participants will complete an exercise protocol with lung function and will be assessed for evidence of inflammation and allergic sensitization. The objective is to answer whether obesity, decreased fitness, or the metabolic syndrome influence the symptoms or the physiological effects of asthma. As in specific aim 2, inflammation will be assessed both by traditional markers and by assay of cytokines and leukotrienes. These studies will be applied to both rural and city school age children. The overall objective is to understand the effects of obesity, physical activity and allergic sensitization in relation to symptoms of breathlessness and airway obstruction.
Funding Period: ----------------2006 - ---------------2011-
more information: NIH RePORT

Top Publications

  1. ncbi T-cell responses to allergens
    Judith A Woodfolk
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908 1355, USA
    J Allergy Clin Immunol 119:280-94; quiz 295-6. 2007
  2. pmc High titers of IgE antibody to dust mite allergen and risk for wheezing among asthmatic children infected with rhinovirus
    Manuel Soto-Quirós
    Hospital Nacional de Ninos, San Jose, Costa Rica
    J Allergy Clin Immunol 129:1499-1505.e5. 2012
  3. pmc Delayed anaphylaxis to red meat in patients with IgE specific for galactose alpha-1,3-galactose (alpha-gal)
    Scott P Commins
    Department of Internal Medicine and Pediatrics, Division of Allergy and Immunology, University of Virginia Health System, Charlottesville, VA 22908, USA
    Curr Allergy Asthma Rep 13:72-7. 2013
  4. pmc Galactose-α-1,3-galactose and delayed anaphylaxis, angioedema, and urticaria in children
    Joshua L Kennedy
    Division of Allergy and Immunology, Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA
    Pediatrics 131:e1545-52. 2013
  5. pmc Physical deconditioning as a cause of breathlessness among obese adolescents with a diagnosis of asthma
    Yun M Shim
    Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America
    PLoS ONE 8:e61022. 2013
  6. pmc Tick bites and red meat allergy
    Scott P Commins
    Department of Internal Medicine, Division of Allergy and Immunology, University of Virginia Health System, Charlottesville, Virginia 22908, USA
    Curr Opin Allergy Clin Immunol 13:354-9. 2013
  7. pmc Sensitization to food and inhalant allergens in relation to age and wheeze among children with atopic dermatitis
    J A Wisniewski
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA, USA
    Clin Exp Allergy 43:1160-70. 2013
  8. pmc Exhaled breath condensate: an overview
    John Hunt
    Department of Pediatrics Pulmonology, Allergy and Immunology, Box 800386, University of Virginia, Charlottesville, VA 22908, USA
    Immunol Allergy Clin North Am 27:587-96; v. 2007
  9. pmc Exhaled breath condensate pH assays
    John Hunt
    Department of Pediatrics Pulmonology, Allergy, and Immunology, Box 800386, University of Virginia, Charlottesville, VA 22908, USA
    Immunol Allergy Clin North Am 27:597-606; vi. 2007
  10. ncbi Targeting Fel d 1 to FcgammaRI induces a novel variation of the T(H)2 response in subjects with cat allergy
    Kathryn E Hulse
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908 1355, USA
    J Allergy Clin Immunol 121:756-762.e4. 2008

Scientific Experts

  • John W Steinke
  • Elizabeth A Erwin
  • Scott P Commins
  • Spencer C Payne
  • Kathryn E Hulse
  • Judith A Woodfolk
  • James T Patrie
  • Amanda J Reefer
  • John Hunt
  • Thomas A E Platts-Mills
  • Libby A Kelly
  • Martin D Chapman
  • J A Wisniewski
  • Joshua L Kennedy
  • Yun M Shim
  • Peter W Heymann
  • Manuel Soto-Quirós
  • Rachana Agrawal
  • S B Early
  • Victor H Engelhard
  • M Moloney
  • Walter M Oliveira
  • W Xin
  • J A Woodfolk
  • Luis Matos
  • Sean Lucas
  • J Patrie
  • R Agrawal
  • Richard C Herring
  • T A Platts-Mills
  • Arthur L Weltman
  • Thomas A Platts-Mills
  • Amy P Stallings
  • Haley R James
  • L Workman
  • S Minnicozzi
  • T W Song
  • Charles J Lane
  • Lisa Workman
  • Anubha Tripathi
  • Autumn Burnette
  • P W Heymann
  • Judith Weltman
  • Deborah D Murphy
  • Michael D Davis
  • William Hunt
  • Xiaoyan Lu
  • Dean D Erdman
  • Joshua Kennedy
  • Hayley R James
  • Holliday Carper
  • Lydiana Avila
  • John F Hunt
  • Ashli K O'Rourke
  • Silvia Odio
  • Julia A Wisniewski
  • Josephine A Lannigan
  • Steven F Ziegler
  • James Patrie
  • Michael D Solga
  • Paul W Wright
  • K Brown-Steinke
  • L Borish
  • P Huyett
  • Shama M Satinover

Detail Information

Publications26

  1. ncbi T-cell responses to allergens
    Judith A Woodfolk
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908 1355, USA
    J Allergy Clin Immunol 119:280-94; quiz 295-6. 2007
    ..Experimental techniques and approaches for analyzing allergen-specific T cells and identifying novel T-cell epitopes are described that may lead to new T-cell-based therapies...
  2. pmc High titers of IgE antibody to dust mite allergen and risk for wheezing among asthmatic children infected with rhinovirus
    Manuel Soto-Quirós
    Hospital Nacional de Ninos, San Jose, Costa Rica
    J Allergy Clin Immunol 129:1499-1505.e5. 2012
    ..The relevance of allergic sensitization, as judged by titers of serum IgE antibodies, to the risk of an asthma exacerbation caused by rhinovirus is unclear...
  3. pmc Delayed anaphylaxis to red meat in patients with IgE specific for galactose alpha-1,3-galactose (alpha-gal)
    Scott P Commins
    Department of Internal Medicine and Pediatrics, Division of Allergy and Immunology, University of Virginia Health System, Charlottesville, VA 22908, USA
    Curr Allergy Asthma Rep 13:72-7. 2013
    ..This IgE Ab response cross-reacts with cat and dog but does not appear to pose a risk for asthma; however, it may impair diagnostic testing in some situations...
  4. pmc Galactose-α-1,3-galactose and delayed anaphylaxis, angioedema, and urticaria in children
    Joshua L Kennedy
    Division of Allergy and Immunology, Department of Internal Medicine, University of Virginia Health System, Charlottesville, VA 22908, USA
    Pediatrics 131:e1545-52. 2013
    ..We sought to determine whether IgE antibody to α-Gal was present in sera of pediatric patients who reported idiopathic anaphylaxis or urticaria...
  5. pmc Physical deconditioning as a cause of breathlessness among obese adolescents with a diagnosis of asthma
    Yun M Shim
    Department of Medicine, University of Virginia, Charlottesville, Virginia, United States of America
    PLoS ONE 8:e61022. 2013
    ..Despite the high prevalence of obesity few studies have investigated the cardiopulmonary physiology of breathlessness in obese children with a diagnosis of asthma...
  6. pmc Tick bites and red meat allergy
    Scott P Commins
    Department of Internal Medicine, Division of Allergy and Immunology, University of Virginia Health System, Charlottesville, Virginia 22908, USA
    Curr Opin Allergy Clin Immunol 13:354-9. 2013
    ..Ongoing work regarding the cause and distribution of this IgE response is reviewed...
  7. pmc Sensitization to food and inhalant allergens in relation to age and wheeze among children with atopic dermatitis
    J A Wisniewski
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA, USA
    Clin Exp Allergy 43:1160-70. 2013
    ..Longitudinal studies remain limited in their ability to characterize how IgE antibody responses evolve in AD, and their relationship with asthma...
  8. pmc Exhaled breath condensate: an overview
    John Hunt
    Department of Pediatrics Pulmonology, Allergy and Immunology, Box 800386, University of Virginia, Charlottesville, VA 22908, USA
    Immunol Allergy Clin North Am 27:587-96; v. 2007
    ..Conscientious assay technique will likely find in EBC any substance of substantially high enough concentration in the airway lining fluid...
  9. pmc Exhaled breath condensate pH assays
    John Hunt
    Department of Pediatrics Pulmonology, Allergy, and Immunology, Box 800386, University of Virginia, Charlottesville, VA 22908, USA
    Immunol Allergy Clin North Am 27:597-606; vi. 2007
    ..EBC pH measures remain the most successful manner to date to evaluate the role of airway acidification in respiratory disease...
  10. ncbi Targeting Fel d 1 to FcgammaRI induces a novel variation of the T(H)2 response in subjects with cat allergy
    Kathryn E Hulse
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908 1355, USA
    J Allergy Clin Immunol 121:756-762.e4. 2008
    ..Induction of CD4+ T cells that produce IL-10 or IFN-gamma is central to the protective effects of conventional allergen immunotherapy...
  11. pmc Targeting allergen to Fc gammaRI: a strategy to treat allergic disease?
    Kathryn E Hulse
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, Virginia 22908, USA
    Curr Opin Allergy Clin Immunol 8:547-52. 2008
    ..This article discusses the immunomodulatory capacity of a molecule (H22-Fel d 1), which targets the major cat allergen, Fel d 1, to the high affinity IgG receptor, Fc gammaRI, on human dendritic cells...
  12. pmc Microarray analysis of distinct gene transcription profiles in non-eosinophilic chronic sinusitis with nasal polyps
    Spencer C Payne
    Department of Otolaryngology Head and Neck Surgery, University of Virginia School of Medicine, Charlottesville, Virginia, USA
    Am J Rhinol 22:568-81. 2008
    ....
  13. pmc Functional analysis of -351 interleukin-9 promoter polymorphism reveals an activator controlled by NF-kappaB
    S B Early
    Asthma and Allergic Diseases Center, Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908 1355, USA
    Genes Immun 10:341-9. 2009
    ..Individuals carrying the A allele of the IL-9 promoter display increased synthesis of IL-9, which may result in strong Th2 immune responses and a modulation of their susceptibility to infectious, neoplastic, parasitic or atopic disease...
  14. pmc Anaphylaxis syndromes related to a new mammalian cross-reactive carbohydrate determinant
    Scott P Commins
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, USA
    J Allergy Clin Immunol 124:652-7. 2009
    ..Here we review the evidence relating to carbohydrates in food allergy and anaphylaxis and discuss the implications of a new mammalian cross-reactive carbohydrate determinant...
  15. pmc Targeting allergen to FcgammaRI reveals a novel T(H)2 regulatory pathway linked to thymic stromal lymphopoietin receptor
    Kathryn E Hulse
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908 1355, USA
    J Allergy Clin Immunol 125:247-56.e1-8. 2010
    ..The molecule H22-Fel d 1, which targets cat allergen to FcgammaRI on dendritic cells (DCs), has the potential to treat cat allergy because of its T-cell modulatory properties...
  16. pmc Galactose-α-1,3-galactose-specific IgE is associated with anaphylaxis but not asthma
    Scott P Commins
    Division of Allergy and Immunology, University of Virginia, Charlottesville, Virginia, USA
    Am J Respir Crit Care Med 185:723-30. 2012
    ..These antibodies, which are induced by ectoparasitic ticks, can give rise to positive skin tests or serum assays with cat extract...
  17. pmc Epidemiological analysis of chronic rhinitis in pediatric patients
    Elizabeth A Erwin
    Center for Innovation in Pediatric Practice, Nationwide Children s Hospital, Columbus, Ohio 43205, USA
    Am J Rhinol Allergy 25:327-32. 2011
    ..Nonallergic rhinitis is a poorly understood entity, especially among pediatric patients...
  18. pmc The indoor air and asthma: the role of cat allergens
    Libby A Kelly
    University of Virginia Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908, USA
    Curr Opin Pulm Med 18:29-34. 2012
    ..The objective is to discuss recent progress in our understanding of the role of the indoor environment in asthma, focusing on the special role of cat allergens...
  19. pmc Flow cytometry imaging identifies rare T(H)2 cells expressing thymic stromal lymphopoietin receptor in a "proallergic" milieu
    Amanda J Reefer
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908 1355, USA
    J Allergy Clin Immunol 126:1049-58, 1058.e1-10. 2010
    ..Expression of TSLP receptor on the surface of activated T(H)2 cells could amplify T(H)2 responses at inflamed sites through the direct actions of TSLP...
  20. pmc The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-α-1,3-galactose
    Scott P Commins
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA, USA
    J Allergy Clin Immunol 127:1286-93.e6. 2011
    ..Most of these patients had tolerated meat for many years previously. The implication is that some exposure in adult life had stimulated the production of these IgE antibodies...
  21. ncbi Local class switching in nonallergic rhinitis
    Spencer C Payne
    Department of Otolaryngology Head and Neck Surgery, University of Virginia Health System, Charlottesville, Virginia 22908 0713, USA
    Curr Opin Otolaryngol Head Neck Surg 19:193-8. 2011
    ..This review analyzes the available data to describe the current understanding of this process as it relates to nonallergic rhinitis...
  22. ncbi The role of regulatory T cells in atopic dermatitis
    Rachana Agrawal
    Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908 1355, USA
    Curr Probl Dermatol 41:112-24. 2011
    ....