Experimental rhinovirus challenges in adults with mild asthma: response to infection in relation to IgE.
BACKGROUND
Although most children and young adults with asthma are atopic, exacerbations of asthma are frequently associated with viral respiratory tract infections, especially those caused by rhinovirus (HRV).


OBJECTIVE
Young atopic adults with mild asthma were evaluated before and during an experimental HRV infection to test the hypothesis that airway inflammation before virus inoculation may be a risk factor for an adverse response to HRV.


METHODS
Experimental HRV infections were evaluated in 16 allergic volunteers with mild asthma and 9 nonatopic control patients (age, 18 to 30 years). Before virus inoculation, each participant was screened with tests for lung function, prick skin tests for sensitization to common aeroallergens, measurements of total serum IgE, and serum neutralizing antibody to rhinovirus-16 (the serotype used for inoculation). The response to infection was monitored for 21 days by using symptom diary cards, tests for lung function, and markers of airway inflammation in nasal washes, blood, and expired air.


RESULTS
During the infection, asthmatic patients had cumulative upper and lower respiratory tract symptom scores that were significantly greater over the course of 21 days than scores from the control patients. At baseline, the asthmatic patients also had increased sensitivity to methacholine and significantly lower values for FEV(1) (percent predicted) than the control patients (geometric mean and intraquartile values: 87% [79% to 91%] for the asthmatic patients and 101% [90% to 104%] for the control patients, P <.03). Among the patients with mild asthma, 6 had levels of total serum IgE that were substantially elevated (range, 371 to 820 IU/mL) compared with 10 who had lower levels (range, 29 to 124 IU/mL). Those with high levels of IgE had significantly greater lower respiratory tract symptom scores during the initial 4 days of the infection than the low IgE group. They also had higher total blood eosinophil counts at baseline, increased eosinophil cationic protein in their nasal washes (>200 ng/mL), and augmented levels of expired nitric oxide at baseline and during peak cold symptoms. In contrast, levels of soluble intracellular adhesion molecule-1 in nasal wash supernatants from the asthmatic patients with high IgE were diminished, both at baseline and during the infection.


CONCLUSIONS
The reduced lung function and increased markers of inflammation observed before virus inoculation in the asthmatic patients who had high levels of total serum IgE may be risk factors for an adverse response to infections with HRV.
Department of Pediatrics, University of Virginia Health System, Charlottesville, VA 22908-0386, USA.
Juan C
JC
Zambrano
Holliday T
HT
Carper
Gary P
GP
Rakes
James
J
Patrie
Deborah D
DD
Murphy
Thomas A E
TA
Platts-Mills
Frederick G
FG
Hayden
Jack M
JM
Gwaltney
Tina K
TK
Hatley
Angela M
AM
Owens
Peter W
PW
Heymann
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000276:immunology*; D001798:Blood Proteins / Q000032:analysis; D003139:Common Cold; D047091:Eosinophil Granule Proteins; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008168:Lung / Q000503:physiopathology; D008297:Male; D009297:Nasal Mucosa / Q000737:chemistry; D009569:Nitric Oxide / Q000096:biosynthesis; D010850:Picornaviridae Infections / Q000209:etiology* / Q000276:immunology; D012229:Rhinovirus; D012260:Ribonucleases
D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D007073:Immunoglobulin E; D012260:Ribonucleases