To the Editor:
The majority of asthma exacerbations are associated with respiratory virus infections, mostly rhinoviruses (RVs) [1], due to enhanced inflammation in the airways [2]. These occur despite symptom control with inhaled corticosteroids (ICS) [3]. Experimental RV infection is a valuable tool for studying virus-induced exacerbations [2, 4], but has, to date, involved only corticosteroid-naïve asthmatics. We have, therefore, modified a validated infection protocol [4] to inoculate 11 subjects whose asthma was well controlled with ICS. As this was the first experimental infection in patients at risk of severe exacerbations, a cautious study design was implemented. All subjects were followed-up twice daily by SMS text messages during the study. We used RV16, a strain used safely in previous studies, which replicates in vitro to a similar extent but induces less inflammation and cell death than other strains [5]. We also chose a 10-fold lower inoculation dose of the same stock used in previous studies [6]. The design allowed for dose escalation if necessary (this proved to be unnecessary as all subjects developed cold symptoms at this dose). As a final precaution, the delivery device generated particles of 30–100 μm, restricting delivery to the nose (aerosols ≥16 μm are deposited in the upper respiratory tract (URT) [7]), thus closely mimicking natural infection, i.e. limiting direct lung exposure during inoculation.
Symptoms of URT infection, asthma, and measurements of lower respiratory tract (LRT) function were recorded post-inoculation. Infection was confirmed by quantitative (q)PCR for RV16 in nasal lavage and sputum and by determining serum anti-RV16 titres. At least a ≥four-fold increase in titres in convalescent serum or shedding of RV16 in the airways was evidence of successful infection. We also studied innate immune responses …