Editors' ChoiceAsthma

If I Had a Nickel for Every Wheeze

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Science Translational Medicine  21 Mar 2012:
Vol. 4, Issue 126, pp. 126ec51
DOI: 10.1126/scitranslmed.3004014

Human rhinoviruses (HRVs) are normally quite innocuous: They cause the common cold and the sniffles. Although most of us suffer through our winter colds with warm soup and rest, people with asthma may not fare as well. An upper respiratory infection (URI) with HRV can precipitate an acute asthma crisis, leading to increased wheezing and respiratory symptoms. Epidemiologic studies show that up to 80% of childhood asthma exacerbations are associated with viral URI. Of these respiratory viruses, infection with HRVs is the leading cause of URI and precedes at least half of pediatric asthma exacerbations. However, it remains a mystery as to whether HRV infection specifically elicits acute asthma exacerbations.

To answer this question, Miller et al. prospectively studied 409 asthmatic children presenting with URI with or without wheezing. They wanted to determine the role of HRV in pediatric asthma exacerbations and the mechanism (or mechanisms) mediating their wheezing. The authors found that URI with HRV specifically associated with asthma exacerbations, despite no differences in viral titers, HRV species, Th1/Th2 cytokine levels, or allergic molecules (immunoglobulin E) in subjects’ respiratory tracts.

Type III interferons (IFNs), such as type III IFNλ, can be induced by viral infections. Because acute asthma exacerbations have also been attributed to altered modulation of type III IFNλ after HRV infection, the authors investigated this cytokine in their study population. They found that type III IFNλ1 levels were higher in wheezing children infected with HRV as compared with non-wheezing children, and type III IFNλ1 levels were higher as the wheezing severity increased. After adjusting for levels of this cytokine, the authors found that HRV-positive subjects were no longer more likely to wheeze than were those who were HRV-negative, and IFNλ1 remained a strong predictor of wheezing independent of HRV infection status. They conclude that type III IFNλ1 mediates acute exacerbations in the context of HRV URI, and that modulation of this cytokine may be a novel therapeutic target for HRV-induced exacerbations.

The relevance to pediatric asthma is that this study evaluated several leading hypotheses on the immunological mechanisms of viral-induced asthma exacerbations. Although it does not definitively prove causation, this research suggests a causative or mechanistic role for type III IFNλ1 during asthma attacks and presents an opportunity to confirm causation in animal models and for the development of a novel therapy for children with asthma.

E. Miller et al., A mechanistic role for type III IFNλ1 in asthma exacerbations mediated by human rhinoviruses. Am. J. Resp. Crit. Care. Med. 185, 508–516 (2012). [PubMed]

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