Viral and Allergen-Induced Asthma Exacerbations: Population Based and Mechanistic Studies | Peter W. Heymann, MD

January 27, 2016 by School of Medicine Webmaster   |   Leave a Comment

Date: Friday February 5, 2016
Time: 12:00 PM until 1:00 PM
Location: Battle Building, Quayle Learning Center

Objectives:

Understand the relationship between viral respiratory tract infections and allergic inflammation in provoking asthma exacerbations in children and young adults.

Consider the treatment implications derived from the research results.

Research Description

The relationship between viral infections and allergic inflammation in the pathogenesis of asthma exacerbations in children and young adults has been the focus of our research. To examine this relationship, several cross-sectional studies of children treated for acute wheezing in the hospital and emergency room (ER) have been completed, initially in Virginia and more recently in Costa Rica.  These studies have shown that virus-induced wheezing is most common in the pediatric population and is strongly associated with infections caused by rhinovirus (RV) after 3 years of age (1,2). Additionally, these investigations have shown that over 80% of children treated for RV-induced wheezing in the hospital or ER were atopic. Taken together, these studies indicate that the combination of an RV infection and allergen-induced airway inflammation act synergistically to provoke an attack of asthma. Moreover, the risk for wheezing triggered by RV is significantly associated with high titers of IgE ab in serum, predominantly to dust mite allergen in our studies (3).

In order to study the pathogenic events provoked by RV in greater detail, we have been using the experimental RV challenge model which is the only study design available for evaluating mechanisms before the onset of infection, and during the early phase of viral replication before cold symptoms develop to examine innate events. Our initial studies have shown that the response to an experimental inoculation with RV is significantly increased in asthmatics who, like those in our cross-sectional studies, have high levels of total serum IgE, whereas viral loads (assessed by qPCR for RV) were similar among the asthmatic and non-asthmatic subjects who have participated in these investigations (4,5). The asthmatic individuals with high levels of IgE also had evidence of inflammation in their airways prior to the infection when their asthma was clinically well controlled, as judged by eosinophil cationic protein in their nasal washes and FeNO, a biomarker of inflammation in the lower airway. Through collaboration, our current studies are employing the RV infection model and a system’s biology approach to provide a more comprehensive, mechanistic understanding of how allergic inflammation influences the immune response to RV in the asthmatic host, including an on-going investigation involving the administration of omalizumab (a humanized monoclonal anti-IgE antibody) to establish an IgE blockade prior to and during the infection in a randomized, double blind placebo controlled trial.

References:

  1. Heymann PW, Carper HT, Murphy DD, Platts-Mills TAE, Patrie J, McLaughlin AP, Erwin EA, Shaker MS, Hellems M, Peerzada J, Hayden FG, Hatley TK, Chamberlain R.   Viral infections in relation to age, atopy, and the season of admission among children hospitalized for wheezing. J Allergy Clin Immunol 2004; 114:239-247.

 

  1. Heymann PW, Platts-Mills TAE, Johnston SL. The role of viral infections, atopy, and anti-viral immunity in the etiology of wheezing exacerbations among children and young adults. Pediatr Infect Dis J. 2005; 24(11 Suppl): S217-222.

 

  1. Soto-Quiros M, Avila L, Platts-Mills TA, Hunt JF, Erdman DD, Carper H, Murphy DD, Odio S, James HR, Patrie JT, Hunt W, O’Rourke, Davis MD, Steinke, JW, Lu X, Kennedy, J, Heymann PW. High titers of IgE antibody to dust mite allergen and risk for wheezing among asthmatic children infected with rhinovirus. J Allergy Clin Immunol June, 2012; 129: 1499-1505.

 

  1. Zambrano JC, Carper HT, Rakes GP, Patrie J, Murphy DD, Platts-Mills TAE, Hayden FG, Gwaltney Jr JM, Hatley TK, Owens AM, Heymann PW. Experimental rhinovirus challenges in adults with mild asthma: The response to infection in relation to IgE. J Allergy Clin Immunol. 2003;111:1008-1016.

 

  1. Kennedy JL, Shaker M, McMeen V, Gern J, Carper H, Murphy D, Lee WM, Bochkov YA, Vrtis RF, Platts-Mills T, Patrie J, Borish L, Steinke JW, Woods WA, Heymann PW. Comparison of viral load in individuals with and without asthma during infections with rhinovirus. Am J Crit Care Med 2014; 189: 532-9.

 

**Lunch will be served at 11:45**


Contact cline@virginia.edu for more information

 

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