Asthma diagnosis and treatment
The role of rhinovirus in asthma exacerbations

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Rhinoviruses are a major cause of asthma exacerbations in children and adults. With the use of sensitive RT-PCR methods, respiratory viruses are found in approximately 80% of wheezing episodes in children and in approximately one half of such episodes in adults. Rhinovirus is a member of the family Picornaviridae, and acute rhinovirus infections occur predominantly in the upper airway. This virus has also been identified in the lower airway, and it might cause acute wheezing through the production of proinflammatory mediators with a resulting neutrophilic inflammatory response. Precisely how this process leads to increases in airway hyperresponsiveness and airway obstruction is not fully established. However, risk factors for wheezing with colds include asthma and atopy, extremes in age, and perhaps having a deficient TH1 response to rhinovirus. With the use of in vitro models and experimental inoculation studies, significant advances have led to a better understanding of the mechanisms by which rhinovirus infections cause asthma exacerbations. Advances in our understanding of this interaction might provide knowledge that could ultimately lead to specific treatment modalities to prevent and/or treat this significant burden of asthma exacerbations.

Section snippets

What role does RV play in asthma exacerbations?

Asthma exacerbations are most commonly precipitated by viral URIs, particularly with RV,2 and often occur despite concurrent use of appropriate controller medications. Detecting respiratory viruses—in particular, RV—by culture methodology alone has been insensitive and has previously underestimated the role of respiratory viruses in asthma exacerbations, especially in adults. Viral detection rates in asthma exacerbations have significantly increased with the use of sensitive methods and have

What are the virologic features of RVs?

The genera RV and Enterovirus are classified within the family Picornaviridae. There are more than 100 serotypes of RV; this explains, in part, the lack of an effective vaccine against the major etiologic agent causing the common cold. RV is a small, single-stranded RNA virus whose capsid contains 4 proteins (Fig 1). Three of these proteins, VP1, VP2, and VP3, are located on the surface of the capsid and are responsible for its antigenic diversity; the fourth, VP4, is located inside the virus

Are RV infections limited to the upper airway?

An infection with RV leads to symptoms of the common cold, which is primarily an upper airway illness. Because RV is primarily an infection of the upper airway, early research efforts were directed toward determining whether (a) RV infections could infect the lower airways directly and provoke asthma, (b) their actions on asthma occurred via indirect mechanisms due to the upper airway infection only, or (c) a combination of the 2 methods is responsible. Insight into these questions could

What are the effects of RV infection on the mechanisms of airway physiology in asthma?

Multiple studies demonstrate the adverse effects of RV on airway physiology in asthma. In school-age children, symptoms of either upper or lower respiratory tract infection were shown to last a week, and during these infectious episodes, the peak flow rates fell for a median duration of 2 weeks.2 In another study, asthmatic subjects were experimentally inoculated with RV-16 and found to demonstrate modest changes in increased airway hyperresponsiveness, airway obstruction, and inflammation.15

How does RV modulate inflammatory mediators of epithelial cells contributing to asthma exacerbations?

Epithelial cells are the principal targets of RV infections, allow viral replication, and likely initiate immune responses (Fig 3).20, 21 Papadopoulos et al10 found local induction of proinflammatory mediators that could provide a mechanism to explain how lower airway infection can lead to inflammation and asthma. RV infection resulted in an increase in mRNA expression and subsequent translation of IL-6, IL-8, and IL-16. This also occurred with RANTES, a C-C chemokine with chemoattractant

What are the risk factors for wheezing with a cold?

Various risk factors increase the susceptibility of subjects for more severe lower respiratory complications from an RV infection, such as wheezing, bronchitis, and pneumonia (Table I). These include having low neutralizing antibody titers to RV, being an infant, being elderly, having chronic lung disease, being a smoker, and being an individual with existing asthma.22

In addition, subjects who are low producers of IFN-γ in response to RV and are atopic appear to be more at risk for wheezing or

Summary

The importance of RV in asthma exacerbations is established in both adults and children. The complex mechanisms by which their interaction provokes asthma are becoming better understood. RV appears to have a direct and negative impact on the lower airways and causes an increase in obstructive airway symptoms and physiology. This effect on airway function is felt to occur as the virus upregulates proinflammatory cytokines and predisposes the asthmatic patient to more severe respiratory

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