P2‐13: Cold‐shock proteins are upregulated in asthma patients with cold airway hyperresponsiveness and provoke increase in MUC5AC expression under cooling

Background and Aims: Cold season is usually accompanied by deterioration in lung function and increased exacerbation rate in asthma and COPD patients. CIRBP, RBM3 and SRSF5 are RNA-binding cold-shock proteins (CSP) inducible by several stress factors. In spite of involvement in cellular response to cooling, these CSP are poorly characterized in terms of their role in temperature-induced respiratory reactions. The aim of the study was to investigate the association between cold airway hyperresponsiveness (CAH), CSP and MUC5AC expression in asthma patients. Methods: Fifty-two patients with mild-to-moderate asthma underwent 3-min isocapnic cold air ( 20 C) hyperventilation test via nasal mask or mouthpiece on separate days. Change in lung function parameters was measured by spirometry. CIRBP, RBM3, SRSF5 and MUC5AC expression was assessed in brush-biopsies of nasal epithelium by RT-qPCR. Results: Basal expression of CSP was tended to be increased in asthma patients with CAH. In particular, CIRBP was upregulated 5.2-fold (p=0.13), RBM3 4.8-fold (p=0.09), SRSF5 4.5-fold (p=0.11). In the enrolled patients nasal cooling further increased CSP expression. CIRBP increased 3.6-fold (p=0.03), RBM3 3.5-fold (p=0.01), SRSF5 3.4-fold (p=0.02). MUC5AC expression initially was 1.9-fold higher (p n.s.) in patients with CAH but after the cold air hyperventilation the difference became more significant (3.6-fold, p=0.03). We observed a correlation between basal expression of CSP and cold-induced expression of MUC5AC (CIRBP R=0.39 (p=0.03), RBM3 R=0.42 (p=0.02), SRSF3=0.47 (p=0.009)). Conclusions: Increased CSP expression in the airways of asthma patients may contribute to MUC5AC hypersecretion under cold exposition. The study was supported by RFBR (20-515-53004).