The Effect And Mechanism Of Leukotriene Receptor Antagonist For The Treatment Of Asthma In Cigarette Smokers

Bronchial asthma(asthma) is a chronic inflammatory disorder of airway, characterized by airway hyper-responsiveness(AHR), reversible airflow obstruction, mucus hypersecretion and elevated serum Ig E levels. Eosinophils, mast cells, T lymphocytes, neutrophils, airway smooth muscle cells(ASMCs), airway epithelial cells and other inflammatory cells, as well as various cytokines, chemokines and other mediators including histamine, tryptase, and leukotriene, are implicated in the pathophysiology of asthma. It has been demonstrated that smoking is closly related to the onset of asthma. It reported that compared with asthmatics who don't smoke cigarettes, asthmatics who smoke cigarettes for a long time manifest more serious symptoms such as breathing, chest tightness and cough, faster decline of lung function and rapider disease progression, which results in increasing incidence of asthma, hospitalization rate and mortality. And it suggests that smoking is an important reason for inducing or aggravating asthma.At present, anti-asthma drugs mainly include corticosteroid, beta-2 receptor agonist, leukotriene regulator, theophylline, cholinergic blocker and Ig E monoclonal antibody. It has been demonstrated that glucocorticoid is the most effective anti-inflammatory drug to treat asthma. And leukotriene receptor antagonists, such as montelukast and zafirlukast, also play an important role in the treatment of asthma, which are helpful to relieve clinical symptoms, improve lung function and reduce airway hyper-responsiveness.The epidemiological data showed that the prevalence of smoking among asthma patients was approximately the same as in the population at large. There were a lot of clinical studies about medication treatment of asthma. However, these studies were based on evidence from clinical trials that exclude patients who smoke cigarettes, and those exclusive patients account for a considerable proportion, about one third, of the asthmatic population. Until recently, there has been a little information regarding the effect of cigarette smoking on the response to asthma therapy. The best strategy for treating these patients is still unknown. In this study, we focus on the effect and potential mechanism of leukotriene receptor antagonist, montelukast, for the treatment of asthma in cigarette smokers. And previous researches provide the rationale for this study. Purpose:To investigate the effect and potential mechanism of leukotriene receptor antagonist, montelukast, for the treatment of asthma in cigarette smokers Methods:Data of 46 cases of asthmatics who smoke cigarettes were reviewed from department of respiratory medicine in first affiliated hospital of Zhengzhou University during January 2014 to January 2015, and were divided into 2 groups randomly, treatment group and control group, 23 cases in each group. All asthma patients received budesonide and formoterol fumarate powder for inhalation(Symbicort Turbuhaler, 160?g/4.5?g/inhale) 1 inhale/time, two times per day as basic therapy. And the asthma patients in treatment group were additionally given montelukast 10 mg once per night for 3 months. The score of asthma control test(ACT), pulmonary function, fractional exhaled nitric oxide(Fe NO), serum Ig E level, the eosinophil ratio(Eos%) in peripheral blood and in induced sputum, and urine leukotrience E4(LTE4) were measured and compared between two groups before and after 3 months of treatment. Meanwhile, the number and proportion of acute attack of asthma, the usage of glucocorticoid and salbutamol under emergency treatment, and all adverse reactions in both groups were recorded during 3 months of treatment. Results:The score of ACT, the percentage of forced expiratory volume in 1 second(FEVl) in expected value(FEVl%), the peak expiratory flow(PEF), Fe NO, serum Ig E level, the eosinophil ratio(Eos%) in peripheral blood and in induced sputum, and urine LTE4 were measured before treatment. And no significant differences were observed between two groups(P>0.05). After 3 months of treatment, the score of ACT, FEVl%, PEF were improved(P<0.05) in control group, but there were no significant differences in serum Ig E level, Fe NO, the eosinophil ratio in peripheral blood and in induced sputum, and urine LTE4(P>0.05). In treatment group, the score of ACT, FEVl% and PEF were increased, while urine LTE4 were declined, and the differences were statistically significant compared with control group(P<0.05). However, no obvious improvements were observed in serum Ig E level, Fe NO, the eosinophil ratio in peripheral blood and in induced sputum after 3 months of treatment(P>0.05). Within 3 months of treatment, the number of people with acute attack of asthma in control group and treatment group was 8 and 5, respectively(P<0.05). And the ratio of patients who use glucocorticoid in treatment group was lower than that of control group(P<0.05), as well as salbutamol. The occurrence rates of adverse reactions during treatment in both groups were very low, and the symptoms were mild. Conclusion:Leukotriene receptor antagonist, montelukast, is beneficial to improving the score of ACT and lung function, decreasing the level of urine LTE4, reducing the frequency of acute attack of asthma and the usage of glucocorticoid and salbutamol under emergency treatment in asthmatics who smoke cigarettes. Therefore, montelukast has an inhibitory effect on the airway inflammation caused by massive release of leukotriene.