Clinical Study On The Response Of Asthmatic Patients To Leukotriene Receptor Antagonist Therapy

Objective To measure concentrations of cysteiny1-leukotrienes(CysLTs) in body fluid and respiratory samples,ie,induced sputum and expired breath consendate(EBC) , observe the circadian variations of leukotriene level in asthmatic patients.To monitor the changes of clinical symptom score(Asthma control questionnaire, ACQ), pulmonary function(FEV₁) and CysLTs level before and after therapy with leukotriene receptor antagonist Montelukast to evaluate therapeutic response to Montelukast in different asthma type and explore the predictive indices of therapeutic reponse in order to provide evidence for individualized treatment.Methods Mild to moderate asthmatic patients who were newly diagnosed or withdraw of regular therapy for more than one year or inhale corticosteroids less than 10 days in recent one month were enrolled and treated with 10mg Montelukast sodium for 1 month.ACQ scores and FEV₁% were measured before and after treament.Full day urine samples were collected from 9:00AM to 3:00PM,3:00PM to 12:00PM,and 12:00PM to 9:00AM.The concentrations of cysteinyl-leukotriene E4(LTE4) were measured by ELISA before and after therapy while the LTD4 in induced sputum and EBC were detected in 3:00PM in order to compare correlation with urine LTE4.Results A total of 49 subjects were enrolled and 40 subjects accomplished the study. Accoding to therapeutic efficacy standard, 10 subjects(25%) was defined as responders 11 subjects(27.5%) as non-responders and 19 subjects (47.5%) as median-responders. Urine LTE4 of responders was significantly higher than those of median-responders and non-responders(P<0.05).ACQ scores,FEV₁% and Urine LTE4 of responders improved after therapy significantly(P<0.05). Otherwise symptoms and lung function were not improved obviously in median-responders and non-responders. Different asthmatic type had different therapeutic response to Montelukast.Better therapeutic response was observed in nocturnal asthmatic, exercise-induced asthma and asthma with rhinitis.Nocturnal asthma urine LTE4 at night was significantly higher than that at day, however, this circadian rhythm was not revealed in other asthma patients. LTD4 in induced sputum and EBC revealed positive correlation with urine LTE4.Conclusions (1).Urinary LTE4 level is an optimal biomarker for making a pharmacologic choice and predicting therapy response. (2) Different asthmatic type had varied therapeutic response to leukotriene receptor antagonist while patients with nocturnal asthmatic behaved most siginifficantly.(3) Patients with nocturnal asthma not other asthma manifest obvious circadian rhythm of urine LTE4 level.(4)Concentrations of LTD4 in induced sputum ,EBC and urine revealed consistency,suggesting uLTE4 is a simple and accurate methed for detecting CysLTs.