Reply: the beneficial effect of statins on asthma exacerbations: another point of view.

Abstract

From the Authors: We appreciate the comments by Drs. Chang and Shin regarding our article describing an association between statin exposure and decreased asthma-related emergency department visits and oral corticosteroid use in a population-based cohort of more than 16,000 adults (1). Drs. Chang and Shin proposed another mechanism through which statins may reduce asthma severity, namely that statins have an antioxidative effect on lipid peroxidation in the lungs. Although the pleiotropic effects of statins have been highlighted in several studies, the mechanisms through which statins exert these effects are unclear and likely multiple in nature. One of the mechanisms discussed in our article is the antiinflammatory and immunomodulatory effects of statins. Statins have been shown to inhibit proinflammatory cytokine expression from T cells (2) and reduce proinflammatory cytokine production, such as IFN-γ and IL-5 (3). In murine models of asthma, simvastatin also modulates IL-13 inducible cytokines (4). Taken together, these immunomodulatory effects potentially reduce pulmonary inflammation. We agree with Drs. Chang and Shin that statins may exert their beneficial effects through other mechanisms. Oxidative stress plays an important role in the pathogenesis of asthma, especially in the setting of acute exacerbations. Environmental factors, such as air pollution, have been associated with release of reactive oxygen species by neutrophils in the airways, with some individuals more susceptible than others (5). Interestingly, statins have been shown to up-regulate plasma levels of antioxidant enzymes such as glutathione peroxidase and superoxide dismutase in patients with type II diabetes (6), attesting to the direct scavenging effect of statins on free radicals. To our knowledge, these studies have mostly been performed for cardiovascular diseases and diabetes, but not yet in asthma. Several clinical studies have reported beneficial effects of statins in different lung diseases, including asthma, acute lung injury, and lung cancer, with ongoing clinical trials in these fields. However, we have limited knowledge about the mechanisms behind the pleiotropic effects of statins. Better understanding of these mechanisms will not only shed light on the pathogenesis of asthma but also allow the identification of novel therapeutic targets.