Rhinovirus Inhalation Causes Long-Lasting Excessive Airway Narrowing in Response to Methacholine in Asthmatic Subjects In Vivo

Abstract

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 FEV1 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 FEV1, 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 FEV1 during the study in either group (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)