Clinical And Experimental Study Of Acupuncture Treatment With The “treating Liver” Method On Allergic Rhinitis

The global incidence of allergic rhinitis(AR)has shown a sharp upward trend,in the last 20 years,with a conservative estimation of over 500 million patients,with 40 million in china.The most common symptoms of AR are sneezing,followed by rhinorrhea,nasal itching,nasal congestion,ocular and throat symptoms.AR main associated diseases are asthma and allergic skin diseases,the latter including urticaria,eczema,contact dermatitis and angioedema.WHO has brought forward the“One airway,one disease”concept in ARIA(Allergic Rhinitis and its Impact on Asthma Initiative),pointing out that AR was a high-risk factor in bronchial asthma.AR is also known to generate anxiety,depression and other psychological disorders.According to Chinese Traditional Medicine(TCM),rhinitis is caused by an attack of the nasal passages by exogenous pathogenic factors in patients that have a specific constitution.There are two causing factors responsible for AR,one being the patient's constitution,with mainly lung,spleen and kidney's deficiency and the other is based on constitutional weakness associated to excess factors as in the invasion of exogenous pathogens,obstruction of the nasal passage due to accumulated fluids.Moreover the function of liver also plays an important role in the pathogenesis of AR.Liver's control over the regulation of Qi is important when regulating ascension and descent of the Qi in the whole body in order to maintain the normal organ function.Emotions are under heart control and rely on Qi and blood for proper functioning.According to the five elements theory,liver represents the mother of heart,it can store the blood and control the circulation of Qi in the whole body.Liver can also control emotions and regulate the function of lung,spleen and kidneys.According to western medicine,Ig E mediated non-infectious inflammation of the nasal mucosa is the root of AR pathogenesis.Th1/Th2 plays an important role in the regulation of the Ig E synthesis.IFN-?,which is secreted by Th1 cells,inhibits Ig E synthesis,when IL-4 secreted by Th2 cells plays a major role in the induction of Ig E synthesis.In atopic individuals,Th2 cells are dominant thereof regulating Ig E synthesis and cell recruitment in the inflammation site.In the allergen sensitization stage,the precursors of CD4⁺change to Th2.Following the Th2 response,the effect of IFN-?will be inhibited by the IL-4.The imbalance of Th1/Th2 is a major factor in AR.Thus,monitoring the dynamic changes of IFN-?and IL-4 will reveal the balance of Th1 and Th2.The principles of AR acupuncture treatment are based on its pathogenesis,which includes reinforcing the qi of lung,reinforcing the qi of spleen,reinforcing the qi of kidney,and eliminating the pathogen factor.The main points selected are the local acupoints and there are associated points corresponding to the TCM patterns.Various acupuncture methods can be used,such as moxibustion,acupoint injection,cupping,bloodletting and electro-acupuncture.There are no large-scale randomized controlled trials reported for Acupuncture for AR treatment.Treatment in western medicine includes avoiding contact with allergens,oral antihistamines,nasal glucocorticoids and anticholinergics,oral leukotriene receptor antagonist,color TZDs,decongestants,immune therapy and surgical treatment.Adverse reactions from drug cannot be totally avoided,especially the anaphylactic shock caused by immunotherapy.Recurrent AR also leads to gradual loss of efficacy with drugs being reused on a long time course.Acupuncture is easy to apply,with high efficacy and less adverse reactions.Based on these considerations and following the medical knowledge base,we designed a randomized controlled clinical trial and model guinea pigs to investigate the efficacy and mechanism of action of acupuncture.1.Randomized controlled clinical trialObjective:To evaluate the clinical effects and the impact on the immune mechanisms of acupuncture AR treatment when applying the“treating liver”method.Methods:A total of 40 cases of patients with moderate to severe persistent AR were included,central randomization was applied to allocate them in the treatment group(20 cases)and in the control group(20 cases).In the treatment group acupuncture was applied with the needling of the following points:Yingxiang(LI20),Dazhui(GV14),Taichong(LR3),Hegu(LI4),Ganshu(BL18),Baihui(GV20),Yintang(GV29),Feishu(BL13),Pishu(BL20),and Shenshu(BL23).Electro-acupuncture was applied on Baihui(GV20),Yintang(GV29)and Yingxiang(LI20)bilaterally with continuous wave and 2Hz frequency.Mild reinforcing and reducing methods were applied on the remaining acupoints.Acupuncture sessions were applied every other day,3times a week during 4 weeks and needles were retained for 20 minutes in every session.In the control group,oral administration of hydrochloric acid cetirizine was applied with 10mg once daily for 4 weeks.Evaluation:Nasal symptom score(TNSS)and serum total Ig E were evaluated before and after treatment in both groups.At the same time,patients were required to record their TNSS daily.TNSS and total Ig E values were analyzed before and after treatment,including every week average TNSS(patient diary recording during 7 days)during treatment.WBC,ALT,AST and SCr were evaluated to monitor the safety of acupuncture and drug therapy.Results:(1)When comparing the treatment group with the control group before and after treatment,there was no significant TNSS difference(P>0.05).There was a significant TNSS difference before and after treatment in the treatment group(P=0.001)as well as in the control group(P=0.046).There was no statistically significant changes in TNSS in both groups at the first week(P=0.054),second week(P=0.719),third week(P=0.762)and fourth week(P=0.142).Compared to the screening period average TNSS showed statistically significant changes(P=0.003)in the treatment group,starting from the third week up to the end of the treatment period.Average TNSS showed statistical differences(P<0.05)in the control group,from the first week to the fourth week.(2)When comparing the treatment group with the control group before and after treatment,there was no significant difference in total Ig E levels(P=0.129).There was no significant difference in total Ig E levels before and after the treatment both in the treatment group and in the control group(P>0.05).Conclusion:Similar nasal symptoms improvement were seen in patients suffering from AR,whether using the acupuncture treatment with the“treating liver”method or with the use of hydrochloric acid cetirizine.Acupuncture which becomes effective after the sixth session does not show the fast acting efficacy that can be evident when using pharmacological treatment.This trial failed to show any evident effect of acupuncture treatment or hydrochloric acid cetirizine on total Ig E values.2 Guinea pig models experimentMaterial:40 healthy England Hartley guinea pigs,20 males and 20 females,SPF level.Method:40 guinea pigs were randomly divided into 5 groups according to their sex as follows:group 1(blank control group),group 2(model control group),groups 3(drug group),group 4(standard acupuncture group)and group5(“treating liver”acupuncture group).Every group included 8 guinea pigs,with4 males and 4 females.Group 2-5 reproduced the AR model.Basic sensitization was used in the first period with intraperitoneal injection of normal saline 1ml+OVA 0.45 mg+Al(OH)₃ 30mg,with 1ml each time,every other day,with a total of 7 injections.Local allergens were used 3 days after the end of the intraperitoneal injection with saline 4ml+OVA 120mg(concentration 3%),each instillation of 50ul into the guinea pigs'two nostrils,once daily for 10consecutive days.Saline as a control was used in Group 1,with the same steps as in group 2-5.Immediately after the local sensitization and within 30 minutes in the 5^th to 10^th times,the behavior score of guinea pigs was recorded,including scratching nose,sneezing and running nose.A total score?5 point was considered as a successful model.Intervention was carried out after the 10^th local sensitization:there was no intervention on group 1 and groups 2.In group 3 budesonide was sprayed into both nostrils,1 spray(64ug)in each nostril.Group 4 was given acupuncture with the following acupoints:Yingxiang(LI20)and Feishu(BL13).Group 5was given acupuncture with the following acupoints:Yingxiang(LI20),Feishu(BL13),Ganshu(BL18)and Taichong(LR3).Needles on Feishu(BL13)and Ganshu(BL18)were not retained.Needling was applied bilaterally on every acupoints.Needles on other acupoints were retained for 20 minutes.Group 3-5were treated with daily sessions for a total of 15 sessions.On the day following the 5^th,10^thand 15^th intervention,local allergens were used thrice with the guinea pigs.In group 2-5 saline 4ml+OVA 120mg(concentration 3%)was used,while in group 1 saline was used as a control,50ul in each nostril instillation.Immediately after the local sensitization,the behavior scores during a 30 minutes period were recorded.Three days from the last intervention,narcosis was used on the guinea pigs using 10%chloral hydrate.Then blood from abdominal aorta was taken for the test of serum IFN-?,IL-4,and total Ig E(ELISA).Results:(1)28(male 15/female 13)guinea pigs were successful models,before the intervention,the body weight did not differ in the five groups.The average behavior scores were different between group 1 and each of the remaining groups(group 2-5).The behavior scores within the blank control group and model control group was significantly different during the intervention period(P=0.033),gender did not affect the score.(2)Behavior scores did not change(P=0.588)after intervention in the blank control group.The behavior scores decreased(P=0.002)after the intervention in the model control group.There was no statistical difference of IFN-?,IL-4 and total Ig E values between group 1 and group 2(P>0.05).(3)There were no difference on behavior scores,IFN-?,IL-4 and total Ig E values,during the intervention period,in the model control group,drug group and the standard acupuncture group(P>0.05),gender had no effect on the above indicators(P>0.05).(4)There were no difference on behavior scores,IFN-?,IL-4 and total Ig E values,during the intervention period,in the model control group,drug group and the“treating liver”acupuncture group(P>0.05),gender did not affect these indicators(P>0.05).(5)There were no difference on behavior score,IFN-?,IL-4 and total Ig E,in the intervention period,in the model control group,standard acupuncture group and the“treating liver”acupuncture group(P>0.05),gender did not affect these indicators(P>0.05).Conclusion:This experiment failed to show any evidence of budesonide nasal spray,standard acupuncture treatment or the“treating liver”acupuncture method on immunological parameters.The reason could be linked to the specific acupuncture mechanism,the quality of AR model reproduction in guinea pigs,observation time in the evaluation and most probably the serum collection points.This indicates the necessity for further studies to be carried out.The results of the clinical trial and experiment of AR model in guinea pigs showed that nasal symptoms in allergic rhinitis patients can improve with the“treating liver”acupuncture method,but its efficacy is slower compared to medication with hydrochloric acid cetirizine.The lack of evidence of an acupuncture effect on the immunological mechanism in this study,indicate that a different approach is necessary in order to study the acupuncture mechanism,therefore the necessity for further studies.