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Abstract
Viral respiratory tract infections are important triggers for exacerbations of asthma and have been found in the majority of wheezing episodes in both children and adults. Of the respiratory tract viruses identified in these circumstances, rhinoviruses are most commonly found. Experimental human models of rhinovirus infection offer great potential for improving our understanding of virus-induced airway inflammation and offer significant opportunity for improved disease management in asthma. Thus far, human experimental infection studies in asthma have used high doses of virus inoculums (10 000 TCID50). Using a low dose would better mimic the natural course of infection and in allow a more representative inflammatory response to be studied.
In this pilot study, five mild–moderate atopic asthmatic subjects and five non-asthmatic healthy controls all with negative RV-16 serology were infected with 10 TCID50 RV16. The aim was to establish whether this low dose was suitable for future experimental infection studies. Daily morning peak flow, FEV1 and symptom scores were recorded until day 10 following inoculation. Nasal lavage for viral load was obtained on day 0, 3, 4, 5, 6, 7 and 10 and measured using Taqman.
Results 3/5 atopic asthmatic and 3/5 healthy volunteers developed the subjective feeling of a common cold associated with objective evidence of RV16 in their nasal lavage. The three asthmatic subjects also developed lower respiratory symptoms along with an average fall in their peak flow of 86.7 l/min (15.1%) in keeping with an exacerbation. None of the healthy volunteers developed lower respiratory symptoms or had any change in their lung function measurements.
Conclusion Low-dose RV16 challenge is sufficient to induce clinical signs of an asthma exacerbation in a majority (60%) of asthmatic subjects. A higher dose of virus such as 100 TCID50 will more likely result in a larger proportion of subjects clinically infected whilst still allowing a more natural course of infection to develop. It is possible that factors other than negative RV16 serology at screening are important determinants of who becomes infected with rhinovirus. Further research is needed to identify what these factors may be.