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)

Rhinovirus-induced lower respiratory illness is increased in asthma and related to virus load and Th1/2 cytokine and IL-10 production

“…2b; r ϭ 0.79, P ϭ 0.01), but none in normal subjects. There was also a strong significant inverse correlation between the change in PC 20 and virus load in the asthmatic group ( Fig. 2d; r ϭ Ϫ0.77, P ϭ 0.016).…”

“…Human experimental RV infection in mild asthmatic volunteers report RV infection is associated with augmented physiological and inflammatory responses to allergen challenge (16, 17) and reductions in PEF (18), forced expiratory volume in 1 s (FEV 1 ) (19), and increases in bronchial hyperreactivity (20). However, studies that have investigated both asthmatic and normal subjects have not demonstrated differences between subject groups in reductions in lung function or lower airway inflammatory responses (21,22).…”

Sinus computed tomography scan and markers of inflammation in vocal cord dysfunction and asthma

“…It is tempting to propose that acute viral infection among patient would precipitate increased sinus changes and an exacerbation of asthma. [23][24][25] Further understanding of the relationship between sinus disease and exacerbations of asthma will need prospective studies in which the change in sinus CT at the time of an attack can be related to evidence of viral infection, allergen exposure, and inflammation. However, the problem will remain difficult to resolve without better understanding of the immunologic mechanisms that lead to persistent eosinophil-rich inflammation in the sinuses.…”

Rhinovirus Infection Induces Expression of Its Own Receptor Intercellular Adhesion Molecule 1 (ICAM-1) via Increased NF-κB-mediated Transcription

“…The increased airway reactivity demonstrated in experimental rhinovirus infections in asthmatic subjects (9,10) and atopic subjects (11) and the induction by rhinovirus of late asthmatic responses to inhaled allergen (8,11) also provide indirect evidence of a link between lower respiratory inflammation during rhinovirus experimental infections and the mechanisms of virus-induced asthma exacerbations. Finally, evidence that the lymphocytic and eosinophilic inflammation observed during rhinovirus experimental infections (7)(8)(9) is probably also an important mechanism involved in virus-induced asthma exacerbations comes from the fact that asthma exacerbations have been induced by experimental rhinovirus infections (9,12).…”