Can Inhaled Corticosteroids Prevent Asthma Exacerbations?

Dhananjay Desai; Salman Siddiqui; Christopher Brightling


Curr Opin Pulm Med. 2011;17(1):16-22. 

In This Article

Asthma Exacerbations: Aetiology and Pathogenesis

Asthma exacerbations are typically a consequence of a 'trigger' in particular viruses as well as other pathogens, allergens and additional environmental factors such as pollutants.[12] Viral infections are the cause of an exacerbation in about 65% of adults[13] and 80% of children.[14,15] Of these, human rhinovirus is the dominant virus in about two-thirds of cases. Atypical bacterial infections (Mycoplasma and Chlamydophilia pneumoniae) are associated with chronic asthma and exacerbations,[16] but their importance is questioned. Importantly, synergism between triggers in particular allergens and virus is likely to be important.[17] Asthmatics do not have more colds than nonasthmatics,[18] but do develop lower respiratory tract infections and exacerbate in response to colds. This suggests that in addition to the multiple triggers there is a 'permissive environment' in asthma increasing the risk of exacerbations in response to triggers. Indeed, there is emerging evidence that the innate immune response in asthma is impaired, that airway inflammation may modulate the response to triggers and genetic polymorphisms may confer an increased risk of exacerbations.[19]

In support of the view of altered innate immunity in-vitro bronchial epithelial cells derived from asthmatics have deficient production of interferon (IFN)-β in response to the rhinovirus, which results in a reduction of viral apoptosis.[20] Exogenous replacement of IFN-β conferred protective effects by reducing viral replication. In addition, type III interferons (IFN-λ) are also deficient in asthmatic airways in response to experimental colds.[21] This generalized impairment of host type I and type III interferon responses in asthma is likely to mediate enhanced rhinovirus replication. Lung clearance is also reduced in asthma, with cilial motility and orientation markedly abnormal particularly in severe disease.[22]

Airway inflammation is a cardinal feature of asthma and its pattern is heterogeneous.[23] At exacerbation events there is a further influx of neutrophils, eosinophils, activated lymphocytes and increased secretion of pro-inflammatory cytokines,.[24,25] Monoclonal antibody therapy directed towards interleukin (IL)-5, a critical cytokine involved in eosinophil maturation and survival,[26] leads to a substantial reduction in peripheral blood and sputum eosinophilia.[27,28] This reduction in eosinophilic inflammation by anti-IL-5 does not translate into altered symptoms or lung function,[29•] but in a 1-year study of severe refractory asthmatics there was a 40% reduction in the frequency of severe exacerbations. It is unlikely that this therapy would have modulated the exposure or frequency of colds. Therefore, the most plausible explanation for the reduction in exacerbations is that the presence of eosinophilic inflammation promotes the development of an exacerbation in combination with a viral infection. The mechanism of the synergistic effect is unclear, but may be mediated by increased mucus production or altered mucus composition leading to mucus plugging.

These data support the view that therapies directed towards airway inflammation will reduce the frequency of asthma exacerbations, but suggest that other approaches to upregulate the innate immune response or reduce the impact of triggers may all have therapeutic benefit.


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