Rhinovirus infections: induction and modulation of airways inflammation in asthma

There is renewed interest in the role of respiratory virus infections in the pathogenesis of asthma and in the development of exacerbations in pre-existing disease. This is due to the availability of new molecular and experimental tools. Circumstantial evidence points towards a potentially causative role as well as to possibly protective effects of certain respiratory viruses in the cause of allergic asthma during early childhood. In addition, it now has become clear that exacerbations of asthma, in children as well as adults, are mostly associated with respiratory virus infections, with a predominant role of the common cold virus: rhinovirus. Careful human in vitro and in vivo experiments have shown that rhinovirus can potentially stimulate bronchial epithelial cells to produce pro-inflammatory chemokines and cytokines, may activate cholinergic- or noncholinergic nerves, increase epithelial-derived nitric oxide synthesis, upregulate local ICAM-1 expression, and can lead to nonspecific T-cell responses and/or virus-specific T-cell proliferation. Experimental rhinovirus infections in patients with asthma demonstrate features of exacerbation, such as lower airway symptoms, variable airways obstruction, and bronchial hyperresponsiveness, the latter being associated with eosinophil counts and eosinophilic cationic protein levels in induced sputum. This suggests that multiple cellular pathways can be involved in rhinovirus-induced asthma exacerbations. It is still unknown whether these mechanisms are a distinguishing characteristic of asthma. Because of the limited effects of inhaled steroids during asthma exacerbations, new therapeutic interventions need to be developed based on the increasing pathophysiological knowledge about the role of viruses in asthma