Asthma exacerbations: a molecular dichotomy between antiviral and pro‐inflammatory responses revealed

Acute exacerbations are the major cause of morbidity, mortality and healthcare costs for individuals with asthma. They are the main cause of hospitalizations and are poorly controlled by current medication. It is therefore disappointing that we still know so little about the mechanistic details of asthma exacerbations. In this issue of EMBO Molecular Medicine , Bartlett et al. suggest that the transcription factor NF‐κB, and specifically its subunit p65, is a key determinant of acute exacerbations of asthma, and propose a molecular dichotomy in the regulation of pro‐inflammatory versus antiviral responses in asthmatic individuals that is mediated by p65 NF‐κB and the type I interferon (IFN) system (Bartlett et al, 2012).Asthma exacerbations are mostly triggered by respiratory infections of which rhinoviruses (RV), ssRNA viruses of the Picornaviridae family that cause common cold, are the most frequent (Busse et al, 2010). Other respiratory tract infections that can also trigger exacerbations include influenza, parainfluenza and respiratory syncytial virus in children. Asthmatic patients have increased susceptibility to respiratory infections, especially of the lower respiratory tract, and respiratory infections cause in turn more severe episodes of dyspnoea and wheezing in these patients. Presence of allergic sensitization further increases the risk for infections, the severity of exacerbations and the chances for hospital admission compared to non‐sensitized asthmatic individuals. It is therefore essential to understand the complex interplay between sensitivity to infections, viral clearance and exacerbation of asthmatic inflammation in order to pave the way for the development of novel therapeutics.. . .it is possible to dissociate antiviral from pro‐inflammatory responses simply by inhibiting the p65 subunit of NF‐κB. . . To explain virus‐induced exacerbations, several hypotheses have been advanced that attribute asthma attacks to immune‐mediated exacerbations, direct viral injury, or both (Jackson et al, 2011). Virus infections can fuel innate and adaptive …