Rhinovirus 39 infection in allergic and nonallergic subjects

Abstract

To determine if individuals with allergic rhinitis are hyperresponsive to upper respiratory tract viral infections, 20 allergic and 18 nonallergic, susceptible, adult volunteers were challenged and infected with rhinovirus type 39 before the pollen seasons. Before challenge and on each of 6 days of cloister, all volunteers were interviewed for symptoms and completed a test battery consisting of evaluations of secretion production by weighed tissues, nasal patency by active posterior rhinomanometry, nasal clearance by the dyed saccharin technique, pulmonary function by spirometry, eustachian tube function by sonotubometry, and middle ear status by tympanometry. The symptomatology and pathophysiology resulting from the rhinovirus infection were consistent with those reported in previous studies with this challenge system. Between-group comparisons revealed no differences in symptom presentation, nasal secretion production, or overall pathophysiologic response. However, for decreased mucociliary clearance rate, increased nasal congestion, eustachian tube dysfunction, and symptoms of sneezing, the allergic group demonstrated an earlier onset compared with that of the nonallergic group. The biologic significance of the differences in onset of dysfunction is tempered by the observation that the temporal pattern of responses in the allergic group was similar with that of nonallergic subjects in previous studies. The results of the present study do not support the hypothesis of a physiologic hyperresponsiveness to rhinovirus type 39 infection in allergic subjects during nonallergy seasons.

Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells

“…Intranasal challenge in human volunteers with rhinovirus has been shown to attenuate mucociliary clearance (41). Thus, it is conceivable that, in addition to increasing paracellular permeability, RV facilitates secondary bacterial infection of the airway epithelium by attenuating mucociliary clearance.…”

Mechanism of rhinovirus-induced changes in airway smooth muscle responsiveness.

“…This association has been inferred from a host of clinical studies, as well as investigations incorporating various experimental animal models that express the proasthmatic phenotype. Accordingly, altered airway responsiveness has been reported after the administration of different proinflammatory agents into the lung including sensitizing antigens, ozone inhalation, activated leukocyte products, and chemotactic factors (17,18), in addition to the instillation of various viral respiratory pathogens (19,20). Collectively, these studies suggest a complex interrelationship between specific viral respiratory pathogens, activated inflammatory cells, airway epithelial cells, and altered ASM function.…”

Rhinovirus infection induces mucus hypersecretion

“…Subjects scored eight symptoms (5)(6)(7)27). The sum of sneezing, congestion, and rhinorrhea replies was termed the nasal score.…”

“…Twenty-four hours after admission to cloister (end of study day 0), all subjects were intranasally inoculated with ϳ300 units of a 50% tissue culture infection dose of a safety-tested clinical isolate of RV-h (supplied by Dr. Jack Gwaltney, Charlottesville, VA) delivered as coarse drops in two doses within a 15-min period (5,12). At the end of study day 5, the subjects were dismissed from the cloister, but they returned to the laboratory on days 19-21 for phlebotomy to assess convalescent antibody titers and for the evaluation of allergy status.…”

“…Subjects were recruited by newspaper advertisement from the population and surrounding community of the University of Pittsburgh (PA). Potential subjects were screened by history for previous nasal or otologic disease, were given a general physical examination, had a urinalysis, and had phlebotomy for assays of markers of hepatic and renal function and for measurement of serum antibodies to human immunodeficiency virus (HIV) and RV-h with standard methods (5,27). Subjects were excluded if they presented with findings of, or a history suggestive of, systemic illness or recent upper respiratory tract infection, if they had marked elevations in the assayed parameters indicative of hepatic or renal impairment, if they required prescription medication for any condition other than birth control, or if they had antibodies to HIV.…”