Paediatric acute wheeze: aberrant epithelial responses to rhinovirus A and C

<bold>Introduction:</bold> Acute wheeze and asthma (AWA) in children can result in hospital presentation and are associated with rhinovirus C (RV-C) or RV-A infection. Children with RV-C have shorter times to recurrence and increased severity. We hypothesised that nasal epithelial cells (NECs) collected from children during AWA respond aberrantly to infection, with RV species-specific responses. <bold>Methods:</bold> AWA (n=14; 12 males; mean age 7.7±2.8 (SD) years) and non-wheezing control (NWC; n=13; 8 males; 7.7±1.12 years) NECs were cultured at air-liquid interface and infected with clinical isolates of RV-C15 or RV-A16 at a clinically relevant titre (1×105 copies/ml). Over 72hr, viral load was measured via qPCR, and IL6, IL8, CXCL10, and CCL5 via ELISA. Data was presented as fold-change to non-infected unless stated. <bold>Results:</bold> Non-infected AWA NECs had higher levels of IL6 (AWA 12.22±35.48 vs NWC 0.12±0.12 pg/µg protein; p<0.05); IL8 (AWA 16.22±14.50 vs NWC 4.09±2.66 pg/µg protein; p<0.05), and CXCL10 (AWA 1.09±0.69 vs NWC 0.22±0.12 pg/µg protein; p<0.05). Viral load peaked at 24hr and was similar in AWA and NWC. CCL5 release was dampened post RV-C infection in AWA (24hr AWA -1.20±2.11 vs NWC 0.70±2.31 p>0.05; 48hr AWA 0.83±2.28 vs NWC 3.85±2.31 p<0.01; 72hr AWA 1.15±1.70 vs NWC 2.83±2.28 p<0.05), yet heightened post RV-A (24hr AWA 2.63±2.35 vs NWC 1.13±0.76 p<0.01; 48hr AWA 4.39±2.51 vs NWC 2.91±1.21 p<0.05; 72hr AWA 4.65±2.90 vs NWC 2.71±1.37 p<0.01). In AWA, CCL5 release was delayed with RV-C compared to RV-A (24hr RV-C -1.19±1.04 vs RV-A 2.63±2.35 p<0.001), and similar by 48hr. <bold>Conclusion:</bold> AWA NECs were pro-inflammatory, and had an impaired CCL5 response particularly to RV-C, which may be key to developing new therapeutics.