Impact Of Allergy Rhinitis On Asthma And Study On Efficacy Of Budesonide/Formoterol In Asthmatics With Different Levels Of Airway Inflammation

Background:Asthma is a common chronic respiratory disease,the incidence of which is increasing in recent years,affecting 1%-18%patients around the world.Airway inflammation,airway hyper-responsiveness and reversible airflow limitation are the main characteristics of asthma.Allergic rhinitis(AR)is a kind of allergic disease of upper respiratory tract.It is found that it is closely related to asthma and has adverse effects on severity and control of asthma.Previous studies on the impacts of AR on asthmatics were assessed by pulmonary functions,symptom scores and small airway function.However,the impact of allergic rhinitis on airway inflammation,airway hyper-responsiveness and allergic conditions in mild and moderate asthmatics has not been reported.The nature of asthma is chronic airway inflammation,and thus it is necessary to receive long-term use of anti-inflammatory drugs.The asthma treatment strategies recommended by guides of Global initiative for asthma(GINA)and other guides are based on clinical symptoms and lung functions,not for the nature of asthma.It is recommended by GINA guides in 2016 that mild to moderate asthmatics use daily low doses of corticosteroids(ICS)and long-acting beta 2-agonists(LABA),plus on-need short-acting beta 2-agonists(SABA).And it is not mentioned that the therapy of asthmatics on basis of their different levels of airway inflammation or FeNO.However,according the American Thoracic Society(ATS)guides on interpretion of FeNO in 2011,different recommendations based on different levels of FeNO were made.It recommended FeNO?50ppb be used to indicate likely responsiveness to corticosteroids while FeNO<25ppb be used to indicate less likely responsiveness to corticosteroids.Budesonide/formoterol can be used not only as maintenance therapy,but also as relief medication,that is SMART treatment protocol(Single inhalant device as both maintenance and reliever therapy).SMART protocol has better safety and effectiveness in the treatment of asthma,and can better improve the clinical symptoms and pulmonary function.But currently different guides on the treatment of asthmatics with different FeNO levels are not reaching a consensus.The guides of GINA suggest that treatment based on FeNO guidance has not yet been recognized and that additional clinical studies are needed.Thus,to explore the impact of allergic rhinitis on asthma and the efficacy of budesonide/formoterol in asthmatics with different levelsof airway inflammation,our study consists of two parts,that is:impact of allergy rhinitis on airway inflammation,airway hyper-responsiveness and allergic condition in mild and moderate asthmatics and the treatment efficacy of budesonide/formoterol in asthmatics with different levels of airway inflammation,which will provide the basis for clinical treatment of asthmatics with AR,as well as with different levels of airway inflammation.Part One:The impact of allergy rhinitis on airway inflammation,airway hyper-responsiveness and allergic condition in mild and moderate asthmaticsObjective:To explore the impact of allergic rhinitis on airway inflammation,airway hyper-responsiveness and allergic conditions of mild and moderate asthmatics.Methods:98 newly diagnosed mild and moderate asthmatics were enrolled from outpaitient department,Zhujiang Hospital of Southern Medical University during December,2015 to December,2016 and they were divided into two subgroups,asthma with allergic rhinitis(AR,n=52)and without AR(n=46).35 healthy persons from medical examination center during the same time were collected as the control group.The subjects were required to complete data acquisition,asthma control test(ACT),asthma control questionnaire-7(ACQ-7),fractional exhaled nitric oxide(FeNO),pulmonary function tests,impulse oscillometry,bronchial provocation test and total immunoglobulin E(IgE)determination and IgE screening specific to common inhalant allergens.Results:1.The FeNO level of overall asthmatics was higher than control group,and the FeNO level of asthma with AR was significantly higher than that of asthma without AR(F=14.132,P=0.000).The rank of total IgE in asthmatics with AR was significantly higher than that in asthmatics without AR and control group(H=18.847,P=0.000).The rank of airway hyper-responsiveness(AHR)in asthmatics with AR were significantly higher than that in asthmatic without AR(Z=-2.014,P= 0.035).2.In asthmatics with AR group,the rank of AHR was moderate positively correlative to FeNO(p=0.316,P=0.022),and was moderate negatively correlative to FEVi/FVC(p=-0.335,P=0.015).Meanwhile,lnFeNO was moderate negatively correlative to FEVi/FVC(r=-0.305,P=0.028).However,these phenomena weren't found in asthmatics without AR group.Conclusions:1.AR,which could aggravate allergic condition,is a common complication of asthma.2.AR might aggravate airway inflammation and increase airway responsiveness,as well as aggravate airway obstruction in mild and moderate asthmatics.Part Two:The treatment efficacy of budesonide/formoterol in asthmatics with different levels of airway inflammationObjective:To explore the efficacy of Budesonide/formoterol in asthmatics with different levelsof airway inflammation and compare the differences between three groups.Methods:A total of 40 asthmatics were recruited from outpaitient department,Zhujiang Hospital of Southern Medical University during May,2015 to September,2016.At entry we collected the baseline and detect the IgE specific to common inhalant allergens.All patients were required to adopt a SMART protocol of budesonide/formoterol,that is,budesonide/formoterol(160?g/4.5?g),1 inhalation,twice daily,plus as needed usage in the following six months.All Patients were followed up for 6 months,with the contents of baseline and follow-up including asthma control test(ACT),asthma control questionnaire-7(ACQ-7),fractional exhaled nitric oxide(FeNO),pulmonary function tests,bronchial provocation test.Results:1.32 subjects with asthma completed the six-month follow-up,with 13 cases in low FeNO group(FeNO<25 ppb),8 cases in intermediate FeNO group(FeNO:25-50 ppb),and 11 cases in high FeNO group(FeNO?50 ppb).2.Receiving SMART protocol of budesonide/formoterol,the scores of ACT could rapidly be improved from uncontrolled level to controlled and tend to be stable in asthmatics with low,intermediate and high FeNO(F=11.644,12.401,13.479,all P<0.05).And so were the ACQ-7 scores(F=8.902,4.411,7.926,all P<0.05).3.FeNO level of overall patients decreased after treatment(F=6.473,P=0.000).The FeNO level of asthmatics in high FeNO group decreased significantly after one-month treatment,declined to intermediate level after two-month treatment and tend to be stable(F=7.851,P=0.000).However,there no significant differences of the FeNO levels before and after treatment in the other two groups(both P>0.05).4.The PEF of overall patients was improved after treatment(F=4.354,P=0.002).PEF was improved in low FeNO group(F=4.054,P=0.007),but not in intermediate and high FeNO groups(both P>0.05).There were no significant differences of other lung functional parameters before and after treatment in three groups(all P>0.05).5.SMART protocol of budesonide/formoterol could reduce the airway hyper-responsiveness(AHR)of overall patients(F=6.005,P=0.000).There no difference in AHR before treatment among three groups(H=4.958,P>0.05).The AHR of low FeNO group was remarkably improved after treatment,even some patients had normal AHR(F=3.236,P=0.007).The AHR of high FeNO group decreased significantly after use of SMART protocol(F=3.478,P=0.021),while that of intermediate FeNO group had no changes after treatment(F==1.013,P=0.407).Conclusions:1.SMART protocol of budesonide/formoterol can be utilized in the treatment of asthmatics with different airway inflammatory levels,whose symptoms could be relieved rapidly in a short time.2.Low FeNO groups had a remarkable efficacy after treatment,and high FeNO group had a better treatment efficacy than moderate FeNO group.Besides,more clinical researches are needed to explore the treatment efficacy of SMART protocol in asthmatics with intermediate FeNO.