Virus‐provoked rhinitis and asthma in allergic patients

Abstract

SummaryRhinovirus, influenza, parainfluenza or respiratory syncytial virus not only provoke upper respiratory tract infections (URI) but also can precipitate asthma in adults and children, many of whom also manifest allergic respiratory disease. It has been postulated that patients with allergic rhinitis experience more pronounced symptoms and pathophysiology during URI than individuals without allergy. These observations have provided limited insight into the pathogenesis of URI in allergic patients. To better define these relationships several groups of investigators have examined the effect of experimental virus infection on volunteers with and without allergic rhinitis and with and without asthma. Lemanski et al. showed that Rhinovirus 16 (RV16) was able to modify bronchial hyperreactivity and late phase allergic asthmatic reactions. Calhoun et al. demonstrated that RV16 potentiated airway inflammation after segmental allergen bronchoprovocation in allergic subjects. Experimental RV16 infection also provoked a modest increase in histamine responsiveness accompanied by a modest increase in bronchial and intranasal lymphocytes and eosinophils. Yet, experimental RV16 infection did not trigger asthma or changes in spirometry or changes in bronchial reactivity to histamine or bradykinin in normal subjects. Studies in our laboratories using experimental Rhinovirus 39 (RV39) infection did not alter pulmonary measurements or methacholine responses in normal healthy allergic subjects. These results were surprising, as enhanced WBC histamine release was observed in the same RV39‐infected allergic subjects and was similar to that observed in RV16 infection described by others. The RV39‐infected allergic subjects also showed acute increases in serum IgE as well as changes of cellular immune parameters. Bardin et al. described more severe nasal symptoms as well as increased nasal albumin in allergic rhinitis subjects experimentally infected with RV16. However, allergic subjects infected with RV39 did not show a physiologic hyper‐responsiveness during a nonallergy season. Analysis of nasal secretions during RV39 infection did show more vascular permeability in allergic subjects. Experimental infection with RV39 and Influenza A has provoked eustachian tube obstruction, otitis media and rarely acute otitis. These studies of volunteers experimentally infected with virus suggest that atopy alone does not predispose to more severe symptoms but combining URI with allergen exposure enhanced allergen‐induced inflammation. Recent studies implicate cytokines as participants in these virus‐provoked responses. Increases in nasal lavage concentrations of IL‐6 were found during experimental URIs caused by RV39, Influenza A and respiratory syncytial virus and coincide with peaks in symptomatology and pathophysiology. Moreover, IL‐6 applied directly to the nasal mucosa in noninfected allergic subjects reproduced symptoms of rhinitis. Other studies have shown that IL‐10 secretion from peripheral blood white cells was impaired in allergic subjects after experimental infection with Influenza A. It is anticipated that future studies using natural infection as well as experimental virus infection model will further define the mechanisms and relationships of virus infection to allergy and asthma.