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Do early-life viral infections cause asthma?

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Epidemiologic associations between viral lower respiratory infections (LRIs) and asthma in later childhood are well known. However, the question of whether such infections cause asthma or unmask asthma in a susceptible host has still not been settled. Most early evidence centered on the role of the respiratory syncytial virus; however, recent studies highlight a potential role for human rhinovirus as a risk factor for asthma. The links between early-life viral LRI and subsequent asthma are generally via wheeze; however, the presence of wheeze does not give any information about why the child is wheezing. Wheeze in early life is, at best, a fuzzy phenotype and not specific for subsequent asthma. The risk of asthma after viral LRI is increased in the presence of allergic sensitization in early life and if the infection is more severe. Atopy-associated mechanisms also appear to be involved in viral-induced acute exacerbations of asthma, especially in prolonging symptomatology after the virus has been cleared from the lungs. Breaking the nexus between viral respiratory infections and asthma may be possible with interventions designed to inhibit atopy-related effectors mechanisms from participating in the host response to respiratory viral infections.

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What have we learned from the epidemiologists?

The link between viral respiratory infections in early life and subsequent childhood asthma has been the subject of much study and debate for decades. Although much of the earlier literature centered on the link between hospitalization for acute viral bronchiolitis, most commonly because of infection with the respiratory syncytial virus (RSV), recent investigations into wheezing in childhood have included more comprehensive viral assessments using modern molecular techniques in community-based

Susceptible host, virus-induced damage, or both?

Cogent arguments can, and have been, mounted for the association between early-life viral respiratory infections and childhood asthma being caused by the virus unmasking a susceptible host, or the virus causing damage to the airways that induces remodeling and results in asthma (see review5). In physiological terms, the presence of wheeze simply implies the presence of flow limitation during expiration. Wheeze can result from small airways (eg, resulting from adverse in utero exposures that

Does the response to a respiratory viral infection differ in those with asthma?

When respiratory viruses enter the lower airway, they infect bronchial epithelial cells (BECs) triggering an antiviral response aimed at containing and eliminating the infection. Infected BECs secrete a variety of products, including IFNs and proinflammatory cytokines such as IL-8. Recent reports demonstrated that the type III IFN, IFN-λ, is the major interferon secreted by infected BECs, followed by the type I IFN, IFN-β.16 These IFNs induce the BEC to undergo apoptosis, thus limiting viral

Can the nexus among viral respiratory infections, atopy, and asthma be broken?

A key component in developing therapeutic options to prevent the development of asthma is to be able to identify those children who are truly at high risk.4 Clearly every child who develops a wLRI in early life is not at risk of childhood asthma. As is clear from the majority of the epidemiologic literature, wheeze is used both as an indication of LRI and as an indication of developing asthma. However, as outlined, wheeze is a physiological phenomenon and gives no clue to the cause of the

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Supported by grants from the National Health and Medical Research Council, Australia.

Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest.

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