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Nitrative stress in refractory asthmaHisatoshi Sugiura, MD, PhD,a Yuichi Komaki, MD, PhD,b Akira Koarai, MD, PhD,a and Masakazu Ichinose, MD,PhDa Wakayama and Miyagi, Japan Asthma affects 5-7% of the population of North America and Europe. Most asthma is mild to moderate and controllable with -agonists, with or without inhaled steroids. Then there are 5% of asthmatics with have refractory asthma, stubbornly resistant to ordinary methods, who need a lot of medication to control their asthma and still have persistent symptoms, asthma exacerbations, or airflow obstruction despite their high medication use. These patients have a low quality of life and a high demand on healthcare resources. This study, published in the February 2008 issue of The Journal of Allergy and Clinical Immunology, takes a close look at this group to see whether patients with refractory asthma have more nitrative stress in their airways. Nitrative stress may not be as familiar a concept as oxidative stress which also affects the asthmatic airways, but it is coming under increasing scrutiny. Respiratory inflammation and hyperresponsiveness are associated with too much nitric oxide (NO) in the airways. For example, in viral pneumonia caused by the flu, NO plays a role in inflaming the lungs and making things much worse. Likewise, patients with severe asthma have too much NO which rapidly reacts with superoxide anions to produce highly reactive nitrogen species (RNSs). RNSs damage the lining of the airways and can be a cause of inflammation in asthma. To make things worse, they have been reported to cause airway remodeling which may be associated with permanent airflow obstruction in patients with refractory asthma. There is little information on nitrative stress in the airways of refractory asthmaics. The aim of this study, therefore, was to evaluate the degree of nitrative stress in refractory asthma. Ichinose and colleagues evaluated levels of nitrative stress markers, including exhaled nitric oxide (eNO), in 10 healthy controls, 10 patients with well-controlled asthma, and eight patients with refractory asthma. They found that nitrative stress markers were significantly increased in refractory asthma compared with well controlled asthma. Because RNSs have inflammatory and remodeling actions in tissues, these mediators may be related to the refractory nature and extent of asthma. If that is the case, specific inhibitors or scavengers of reactive nitrogen species (RNS) may become a therapeutic target for refractory asthma. |
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