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Abstract: Recurrent severe asthma exacerbations are associated with decreased lung growth or accelerated loss of lung function and add substantially to both the cost and morbidity associated with asthma. Risk factors for acute exacerbations include previous acute exacerbation, young age, poorly controlled asthma, and, in particular, viral respiratory tract infections. Exacerbations in school-aged children have been associated with sensitization to aeroallergens, particularly severe exacerbations requiring hospitalization, in which up to 90% of the affected group is atopic and has a viral infection. This apparent comorbidity is the subject of ongoing controversy, but recent studies have provided a plausible and testable hypothesis that might explain how atopy contributes to the exacerbation process. Notably, cross-linking of high-affinity IgE receptors (FcεRI) on plasmacytoid dendritic cells2 and myeloid dendritic cells3 of atopic subjects at airway mucosal infection sites, leading to attenuation of type 1 interferon production and enhancement of proinflammatory TH2 cytokine production, respectively, markedly amplifies local inflammation.1-3 This amplification process is IgE dependent, and hence blocking of available IgE during winter periods, which are at high risk for viral infection, might protect against these events.
Several recent studies support this general concept. First, the addition of omalizumab, a humanized IgG1 anti-IgE mAb, to regular inhaled steroids given to children with inadequately controlled atopic asthma reduced their exacerbations by 43% compared with placebo. Second, in the Inner-City Asthma Study the addition of omalizumab to guidelines-based therapy reduced the number of days with asthma symptoms and reduced the proportion of study participants having 1 or more exacerbations from 48.8% to 30.3% across the 1-year treatment period. The strongest effect was on exacerbations occurring during the fall virus season. Third, short-term preseasonal treatment with omalizumab blunted the ensuing fall asthma “epidemic” in atopic schoolchildren.
An important question arising from these observations is whether reducing virus-associated exacerbations in a single season is a sufficient “circuit breaker” to decelerate progression of asthma toward chronicity