Airway remodeling in asthma: tumor of the airway?

properties and the therapy has been shown to have an acute and sustained beneficial effect on lung function (changes in FEV 1 ) in chronic persistent asthma [6] . Antileukotrienes do not have major side effects and appear to be well tolerated by most patients [7] , but a limitation of their widespread use may be due to the large percentage of nonresponders [8] . However, for those intolerant or resistant to corticosteroids but responsive to antileukotrienes, treatment with leukotriene inhibitors has become an invaluable therapeutic option. There are two types of leukotriene inhibitors: the leukotriene receptor antagonists such as montelukast and those that inhibit leukotriene formation such as zileuton. Zileuton is an inhibitor of the enzyme 5-lipoxygenase, which forms leukotrienes from arachidonic acid. The network of signaling pathways associated with leukotrienes is complex and is not completely understood [6] . The findings by Chen et al. [2] have shed light on this subject, specifically with regard to perturbations in the signaling pathways seen in allergen-sensitized animals. They have identified some potentially important downstream molecular players in leukotriene signaling in ovalbumin-sensitized rats with chronic inflammation, thickened airway walls and reduced lung function. They also showed that zileuton significantly reduced the expression of biomarkers of chronic inflammation, significantly reversed the airway remodeling and improved lung function in these sensitized, bronchohyperresponsive rats. A thickened airway wall with increased airway smooth muscle mass and extracellular matrix deposition as a result of airway remodeling is a hallmark of persistent asthma. The mechanism underlying the remodeling process is not entirely clear. It is thought that the chronic airway inflammation seen in asthma is a major contributor, but anti-inflammatory strategies often do not bring resolution to airway remodeling [1] . Findings reported by Chen et al. [2] in this issue of Respiration explore the effects of the leukotriene inhibitor (zileuton) on airway remodeling in an ovalbumin-sensitized rat model and revealed that downstream pathways of leukotriene stimulation contribute to airway remodeling. Furthermore, the leukotriene signaling appears to follow the same pathways as those considered to be linked to tumorigenesis [3, 4] . These findings suggest a common mechanism underlying the increase in airway tissue mass seen in chronic asthma and the tumor growth seen in malignancy. The primary components of asthma treatment separately target acute airway obstruction and chronic airway inflammation. Bronchodilators (predominately β 2 agonists) are used to treat the acute symptoms and corticosteroids are used to control inflammation. Increasingly, antileukotriene agents are being added to inhaled corticosteroids in combination therapy, especially for severe asthma. Antileukotrienes are also used on their own as a frontline therapy, mostly for mild asthma [5] . Antileukotrienes have both anti-inflammatory and bronchodilatory Published online: August 29, 2013