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 infectio ns, 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 exce ssive airway narrowing in asthma. We tested the hypothesis that experi mental infection with inhaled wild-type rhinovirus 16 (RV16) increases the maximal degree of airway narrowing in response to bronchoconstric tor stimuli in patients with mild to moderate asthma. Fourteen nonsmok ing 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 o r a placebo was administered by pipette, atomizer, and nebulizer in eq ual doses into both nostrils on two consecutive days. Dose-response cu rves for inhaled methacholine were recorded 1 d before and 2, 7, and 1 5 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 gr oup. There was no significant change in baseline FEV(1) during the stu dy in either group (p = 0.06). However, there was a significant increa se 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%, res pectively) (p = 0.009). The increase in maximal response was significa ntly 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 rhino virus causes a prolonged increase in the maximal degree of airway narr owing in response to methacholine in asthmatic subjects in vivo. This suggests that virus-induced excessive airway narrowing can contribute to exacerbations of asthma.