RHINOVIRUS INHALATION CAUSES LONG-LASTING EXCESSIVE AIRWAY NARROWING IN RESPONSE TO METHACHOLINE IN ASTHMATIC SUBJECTS IN-VIVO

Exacerbations of asthma are often associated with respiratory infections, and particularly those caused by rhinovirus. The causative role of rhinovirus in these acute episodes is still unclear, since it has not been determined whether or not infection with the virus promotes excessive airway narrowing in asthma. We tested the hypothesis that experimental infection with inhaled wild-type rhinovirus 16 (RV16) increases the maximal degree of airway narrowing in response to bronchoconstrictor stimuli in patients with mild to moderate asthma. Fourteen nonsmoking subjects with atopic asthma and normal FEV(1) values participated in a double-blind, placebo-controlled, parallel study. A total dose of 3 x 10(4) Of the 50% tissue-culture-infective dose (TCID50) of RV16 or a placebo was administered by pipette, atomizer, and nebulizer in equal doses into both nostrils on two consecutive days. Dose-response curves for inhaled methacholine were recorded 1 d before and 2, 7, and 15 d after RV16 infection or placebo. The response to methacholine was measured by the percent decrease in FEV(1), and the maximal degree of airway narrowing was expressed by the average response on the plateau of the dose-response curve. In the seven subjects receiving the virus, RV16 infection was confirmed in nasal washings and/or by an increase in antibody titer, whereas these tests were negative in the placebo group. There was no significant change in baseline FEV(1) during the study in either group (p = 0.06). However, there was a significant increase in the maximal response to methacholine on Days 2, 7, and 15 in the RV16-treated group as measured by the decline in FEV(1) over baseline (mean difference+/-SEM of 4.8+/-1.4%, 7.8+/-2.8%, and 8.7+/-1.8%, respectively) (p = 0.009). The increase in maximal response was significantly correlated with worsening of the asthma symptom score (r = 0.68) (p = 0.007), and with a decrease in peripheral blood lymphocyte counts (r = 0.86) (p = 0.01). We conclude that inhalation of wild-type rhinovirus causes a prolonged increase in the maximal degree of airway narrowing in response to methacholine in asthmatic subjects in vivo. This suggests that virus-induced excessive airway narrowing can contribute to exacerbations of asthma.