| BackgroundAllergic rhinitis (AR) has become a global chronic disease, and is on the rise year by year. Epidemiological survey showed that 10% to 25% of population in the world had suffered from it[1]. The average prevalence was 25% in European [2]. In China the average prevalence was 11.4% for adults [3]. Currently, the main recognized allergic rhinitis mechanism is the nasal mucosa of chronic inflammation which is led by IgE mediated Th2 immune response after allergen in external environment acted on atopy individuals. The main clinical symptoms are sneezing, watery stuff, itchy nose, nasal congestion and so on[4]. At the same time, it can also seriously affect the patient’s life and work, and merger or aggravate the whole body other diseases such as bronchial asthma, nasal polyps.Main process involved in the pathogenesis of allergic rhinitis is Th2 cells hyperfunction[5], and then the cells release a series of inflammatory mediators to cause nasal mucosa of chronic inflammation. The main of mediators are histamine and leukotriene[6]. At present, the greatest progress is that both in allergic reaction speed phase and late phase has the release of leukotriene. This discovery has changed treatment concept of allergic rhinitis and makes anti leukotriene treatment an equal status with antihistamine treatment and nasal hormone therapy. Principle of the allergic rhinitis treatment includes avoiding allergens contacted, publicity and education, drug control and allergen specific immunotherapy. Drug treatment is currently the main measures of treatment of allergic rhinitis, and also the principal mean in our country. The classical drugs include nasal corticosteroids, oral antihistamines, leukotriene drug resistance and so on. Now clinical basic control drugs include the second generation of antihistamine drugs, anti leukotriene drugs and nasal hormonal. Most of the reports have appeared on the treatment of nasal symptoms to take control measures. What’s more, there is a large number of literature or meta-analysis reported that combination is superior to the single drug treatment after using the above three kinds of different combination drug for the treatment of allergic rhinitis.But the establishment and evaluation of treatment is still based on nasal symptom or the patient quality of life which are subjective expressions. And then for patients with allergic rhinitis nasal symptoms in allergic medium, the research of correlation about nasal symptoms is not much, and still less joint adopts objective strong laboratory as a research project. In addition to the earlier known histamine playing an important role in allergic rhinitis, it found leukotriene plays a main role on nasal symptoms and pathogenesis of allergic rhinitis. But the types of symptoms caused by both of them may be different or focused.To more objectively reflect each of the actual situation in vivo and in vitro when the patient is sick, this study is according to the patients’ nasal symptoms, combining with the main medium, histamine and leukotriene D4 (LTD4) in peripheral blood and nasal secretions, to group the allergic rhinitis patients. And it also designed a variety of combination treatment mode, observe the improvement of nasal symptoms before and after treatment, the content changes of histamine and leukotriene D4, the changes of histamine HI receptor and leukotriene receptor gene expression, and then observe which kind of combination is the optimal treatment combination mode, to lay a new foundation for exploring the new areas to individualized treatment of allergic rhinitis.ObjectiveExplore the histamine and leukotriene (Cys-LT) major clinical manifestations and laboratory tests in allergic rhinitis the clinical classification and the role of personalized treatment of mode selection and significance. According to patients with allergic rhinitis nasal symptoms, combined with peripheral blood and allergic reaction to the main medium of histamine in nasal secretions and leukotriene D4 content detection to clinical grouping of AR, design a variety of combination treatment mode, improve observation before and after treatment of nasal symptoms, change the content of histamine and leukotriene D4, histamine H1 receptor and leukotriene D4 CysLTl receptor gene expression changes, and to explore the optimal treatment combination mode, explore the new areas to lay a foundation for individualized treatment of allergic rhinitis.MethodBetween January 2014 and June 2015 in the zhujiang hospital, Southern Medical University clinic patients with allergic rhinitis (AR), combined with the clinical main symptoms and comprehensive evaluation about determination of histamine and leukotriene D4 content in peripheral blood and nasal secretions, are divided into sneezing group, nasal congestion group and mixed group.Three groups above were divided into the following four sub-groups including as Loratadine, Loratadine+mometasone furoate(MF), Montelukast+MF, Loratadine+ Montelukast+MF for sneezing group; Montelukast, Montelukast+MF, Loratadine+MF, Montelukast+Loratadine+MF for nasal congestion group and Loratadine+ MF, Montelukast+ MF, Loratadine+ Montelukast, Loratadine+Montelukast+ MF for mixed group during the administration periods of 2 week,4week and 8 week. And then the validity of pre-and post-medication was evaluated by total nasal symptom or single nasal symptom VAS scores (TNSS), the reducing index (RI) and the levels of histamine and leukotriene D4. Meanwhile, the expression of mRNA and protein of histamine HI and CysLTl receptors was detected with real time fluorescent quantitation PCR and western blot respectively for pre-and post-treatment.Experimental data is shown with x+S, with SPSS 19.0 statistical analysis, and data conforms to normal distribution. Two independent samples t test is used in contrast between histamine and leukotriene D4 in peripheral blood and nasal secretions with healthy controls. Pearson correlation test is used in correlation analysis between single symptoms score (sneezing, nasal congestion) and histamine and leukotriene D4 in peripheral blood and nasal secretions. Significant level is 0.05, double side inspection. P< 0.05 is considered the difference is statistically significant.Result1. Correlation analysis between single symptoms score (sneezing, nasal congestion) and histamine and leukotriene D4 in peripheral blood and nasal secretionsSneezing score of AR patients was 5.58±2.59, has a highly positive correlation (r= 0.79,0.78, P< 0.05) with histamine in peripheral blood nasal secretion, and no correlation with LTD4 (r= 0.22,0.18, P< 0.05); Nasal congestion score is 5.34±2.36, has a highly positive correlation (r= 0.74,0.72, P< 0.05) with LTD4 in peripheral blood nasal secretion, and no correlation with histamine (r= 0.01, 0.01, P<0.05).2. Correlation analysis between histamine and leukotriene D4 in peripheral blood and nasal secretionsHistamine content is 8.39±4.07ng/ml in peripheral blood,5.06±2.47 ng/ml in nasal secretions, and both are highly correlated (r= 0.99, P< 0.001); LTD4 content is 0.356±0.155 ng/ml, LTD4 content in nasal secretions of 0.215±0.092 ng/ml, and both are highly correlated (r= 0.98, P< 0.001).3. Histamine H1 and CysLT1 receptor mRNA expression changes (real-time fluorescent quantitative PCR) before and after 4 weeks treatment.Histamine HI receptor mRNA levels before treatment was statistically different from after treatment and control group (P all< 0.05), but there was no statistically significant difference between after treatment and control group (P> 0.05); CysLTl receptor mRNA levels before treatment was statistically different from after treatment and control group (P all< 0.05), but there was no statistically significant difference between after treatment and control group (P> 0.05).4. Histamine H1 and CysLT1 receptor protein expression changes (real-time fluorescent quantitative PCR) before and after 4 weeks treatmentHistamine H1 receptor protein levels before treatment was statistically different from after treatment and control group (P all< 0.05), but there was no statistically significant difference between after ireatment and control group (P> 0.05); CysLTl receptor protein levels before treatment was statistically different from after treatment and control group (P all< 0.05), but there was no statistically significant difference between after treatment and control group (P> 0.05)5. Changes of total nasal symptom integral index in each group after treatment for 2 weeks,4 weeks and 8 weeksIn sneezing group, after treatment for 2 weeks, total symptom score reducing index (TSSRI) of L+J group was obviously higher than that of L group (P< 0.05), and had no statistical difference with M+J group and L+M+J group (P> 0.05); TSSRI of L+M+J group was obviously higher than that of L and M+J group (P< 0.05); After treatment for 4 weeks, TSSRI of L+J group was obviously higher than that of L and M+J group (P all< 0.05), and had no statistical difference with L+M +J group (P> 0.05); TSSRI of L+M+J group was obviously higher than that of L and M+J group (P all< 0.05); After treatment for 8 weeks, TSSRI of L+J group was obviously higher than that of L and M+J group (P all< 0.05), and had no statistical difference with L+M+J group (P> 0.05); TSSRI of L+M+J group was obviously higher than that of L and M+J group (P all< 0.05).In nasal congestion group, after treatment for 2 weeks, TSSRI of M+J group was obviously higher than that of M group and L+J group (P all< 0.05), and had no statistical difference with L + M + J group (P> 0.05); TSSRI of L + M + J group was obviously higher than that of L and M + J group (P< 0.05); TSSRI of M group had no statistical difference with L + J group (P> 0.05); After treatment for 4 weeks, TSSRI of M + J group was obviously higher than that of M and L+J group (P< 0.05), and had no statistical difference with L+M+J group (P> 0.05); TSSRI of L +M+J group was obviously higher than that of M and L+J group (P< 0.05); TSSRI of M group had no statistical difference with L+J group (P> 0.05); After treatment for 8 weeks, TSSRI of M+J group was obviously higher than that of M and L+J group (P all< 0.05), and had no statistical difference with L+M+J group (P> 0.05); TSSRI of L+M+J group was obviously higher than that of M and L+J group (P all< 0.05). TSSRI of M group was obviously higher than that of L+J group (P<0.05).In mixed group, after treatment 2 weeks, TSSRI of L+M+J group was obviously higher than that of the others (P all< 0.05); L+J group had no statistical difference with M+J group (P> 0.05), TSSRI of both were obviously higher than that of L+M group (P all< 0.05); After treatment for 4 weeks, TSSRI of L+M+J group was obviously higher than that of the others (P all< 0.05); L+J group had no statistical difference with M+J group (P> 0.05), TSSRI of both were obviously higher than that of L+M group(P all< 0.05); After treatment for 8 weeks, TSSRI of L+M+J group was obviously higher than that of the others (P all< 0.05); L+M group had no statistical difference with L+J group and M+J group (P all> 0.05).6. Reducing index (RI) of single nasal symptoms (sneezing, nasal congestion), histamine and LTD4 in peripheral blood and nasal secretions, after treatment for 4 weeks.In sneezing group, sneezing RI and histamine RI in peripheral blood and nasal secretion of L+J and L+M+J group had no statistical difference significance (P all> 0.05), significantly higher than the other two groups (P all< 0.001); Nasal congestion RI and LTD4 RI in peripheral blood and nasal secretion of M+J and L+ M + J group had no statistical difference significance (P all> 0.05), significantly higher than the other two groups (P all< 0.001).In nasal congestion group, sneezing RI and histamine RI in peripheral blood and nasal secretion of L + J and L + M + J group had no statistical difference significance (P all> 0.05). significantly higher than the other two groups (P all< 0.001); Nasal congestion RI and LTD4 RI in peripheral blood and nasal secretion of M + J and L + M + J group had no statistical difference significance (P all> 0.05), significantly higher than the other two groups (P all< 0.001).In mixed group, sneezing RI and histamine RI in peripheral blood and nasal secretion of L + J and L + M + J group had no statistical difference significance (P all> 0.05), significantly higher than the other two groups (P all< 0.001); Nasal congestion RI and LTD4 RI in peripheral blood and nasal secretion of M + J and L + M + J group had no statistical difference significance (P all> 0.05), significantly higher than the other two groups (P all< 0.001).Conclusion1. Sneezing score was positively correlated to histamine content in peripheral blood and nasal secretions in the three groups; Nasal congestion score was positively correlated to LTD4 content in peripheral blood and nasal secretions in the three groups.2. For the allergic rhinitis patients sneezing predominantly, the effect of loratadine jointed mometasone furoate (MF) and three drug combinations is all of the best, quite; For the allergic rhinitis patients nasal congestion predominantly, the effect of montelukast jointed mometasone furoate (MF) and three drug combinations is all of the best, quite. For the allergic rhinitis patients mixed, the effect of three drug combinations is all of the best. Histamine H1 and CysLT1 receptor mRNA and protein expression in each group after treatment were reduced.The adoption of histamine and leukotriene main clinical symptom scores in combination with its laboratory tests can be more objective and accurate clinical classification of allergic rhinitis. This personalized treatment according to classification of allergic rhinitis not only has good effect, but also meets the requirement of medical and health economics. |
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