Experimental rhinovirus infection induces symptomatic and immunological exacerbation in bronchiectasis

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Background: Viruses are commonly detected during bronchiectasis exacerbations, but their causal role in driving exacerbation pathogenesis remains unproven. We sought to establish a first-in-man model of rhinovirus (RV) challenge in bronchiectasis to confirm causation and study the immunopathogenesis of exacerbations. Methods: Adults with bronchiectasis (aged 18–65) underwent baseline assessment before supervised RV-A16 inoculation and sequential follow-up with daily symptom scores and lung function monitoring. Flow cytometry analysed granulocyte populations in peripheral blood, sputum and BAL at baseline and post-infection. Results: Two participants have been inoculated with RV-A16 to date; infection was well tolerated with no adverse events. Both subjects developed increases in upper and lower respiratory tract symptoms commencing at day 3 post-infection, peaking between days 5-14 and returning to baseline by day 25. Both subjects experienced declines in FEV1, with reductions of 880ml (24% drop from baseline) and 690ml (18% drop from baseline) observed between days 10-14, and recovering to baseline by day 21. Divergent granulocyte responses were observed. One subject demonstrated elevations in blood and sputum eosinophil counts with associated increases in fractional exhaled nitric oxide (FeNO). The second subject showed a predominantly neutrophilic granulocyte response without any increase in FeNO. Conclusion: Early results indicate that experimental RV infection in bronchiectasis is safe, well tolerated and induces clinical features of exacerbation with diverse granulocytic responses. Further validation and detailed results from the model will be presented at the Congress.