Influence of Montelukast on the State of Eosinophil Activation in Asthmatic Children

Background:  Eosinophils play an important role in inflammation asthma. In asthma, the leukotrienes are implicated in pathophysiological mechanisms. The antileukotriene montelukast inhibits proinflammatory cytokines and decreases half-life of eosinophils. However, the influence of montelukast on the activation of eosinophils is not clear yet. Therefore, the objective of this work was to evaluate the effect of montelukast on the state of activation of eosinophils in children with persistent asthma. Methods:  It was selected 83 asthmatic children, from 2 to 18 years old, that were randomly assigned to treatment with montelukast or placebo for 12 weeks and 10 healthy control children. Asthma severity was assessed by the criteria of Global Initiative for Asthma (GINA, 2010). Peripheral blood was taken from children after parents informed consent. The activation of eosinophils was assessed by morphological parameters after adherence to slide, before and after 12 weeks of treatment with montelukast or placebo. The following morphological parameters were evaluated: normal eosinophils, spreading, rounding, presence of localized and generalized pseudopods, release of small, moderate and large quantity of granules, cytoplasmatic vacuoles, cluster of free eosinophils granules, cell degeneration and cell communication. Results:  The number of eosinophils with normal feature in peripheral blood showed an inverse correlation with the severity of asthma, while the emission of widespread pseudopods and isolated granules showed positive correlation with the severity of  asthma (p<0,0001; Spearman correlation test). Montelukast was able to reduce the number of eosinophils in peripheral blood from 513 cells/mm³ to 485 cells/mm³ (p=0.017, paired t test) after treatment, and to increase the proportion of eosinophils with normal feature from 45% to 51% (p=0.03; Wilcoxon test). The drug was also able to decrease the median of eosinophils with rounded feature (1.5 versus 0) and that releasing free eosinophil granules (2.25 versus 0.5) after 12 weeks of treatment compared to placebo, respectively (p= 0.005; Mann Whitney test). Conclusions:   Our data showed, for the first time, that montelukast is able to modify the activation of eosinophils correlated with clinical severity.  Parameters of eosinophil activation could be used to the follow up of response to montelukast treatment of asthma individuals.