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Am. J. Respir. Crit. Care Med., Volume 160, Number 4, October 1999, 1375-1380

Experimental Rhinovirus 16 Infection Causes Variable Airway Obstruction in Subjects with Atopic Asthma

KATRIEN GRÜNBERG, MIEKE C. TIMMERS, ERIC P. A. de KLERK, ELLIOT C. DICK, and PETER J. STERK

Department of Pulmonology and Department of Virology, Leiden University Medical Center (LUMC), Leiden, The Netherlands; and Respiratory Virus Research Laboratory, University of Wisconsin, Madison, Wisconsin

Exacerbations of asthma are often associated with rhinovirus infections. However, it has not been investigated whether rhinovirus infection can induce variable airway obstruction in asthma. We examined the effect of experimental rhinovirus 16 (RV16) infection on daily home recordings of FEV1 in 27 subjects (nonsmoking, atopic, mildly asthmatic) who participated in a parallel placebo-controlled study. The subjects used a microspirometer to record FEV1 three times daily from 4 d before until 10 d after RV16 (n = 19) or placebo (n = 8) inoculation. In addition, symptoms of asthma and symptoms of common cold were scored. Airway hyperresponsiveness to histamine was measured 3 d before and on Days 4 and 11 after RV16/placebo administration. Home recordings of FEV1 decreased significantly after RV16 infection, reaching a minimum 2 d after inoculation (ANOVA, p =< 0.005), which was significantly different from placebo (p =< 0.004). In the RV16 group the lowest FEV1 (expressed as a percentage of personal best) during Days 0-3 after infection (mean ± SEM: 78.7 ± 2.6% versus baseline: 85.6 ± 1.2%, p = 0.008) correlated significantly with the cold score (r = -0.47, p = 0.04), asthma score (r = -0.47, p = 0.04), and with the decrease in airway hyperresponsiveness on Day 4 as compared with baseline (r = 0.50, p = 0.03). We conclude that experimental RV16 infection augments variable airway obstruction in subjects with asthma. This favors a causative role for rhinovirus colds in asthma exacerbations, and is in keeping with rhinovirus-induced worsening of airway inflammation.




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