Airway Inflammation And Prognosis In Subjects With Allergic Rhinitis

Allergic rhinitis (AR) is a symptomatic disorder of the nose induced afterallergen exposure by an immunoglobulin E(IgE)-mediated inflammation of themembranes lining the nose Different kinds of immunocells and cytokines involves inits pathophysiology. So far, the prevalence of AR in adults and children isapproximately9~42%and is increasing year by year.1.4~39.7%.children between13and14years old children are reporting symptoms of AR.Therefore, allergic rhinitis asa global health problem has attracted worldwide attention and been taken seriously.AR and asthma always coexist in the same patient,and the relationship between themhas been demonstrated in numerous studies.About10~40%asthmatics also suffersAR,Treatment for nasal symptoms can effectively improve the symptoms of asthmaand decrease the use of rescue medications.Airway inflammation and bronchialhyperreactivity could be detected in some patients with isolated AR,even though noneof those patients shows any symptoms related to lower airway,such ascough,wheeze,dyspnea etc.Several studies had demomstrated that AR might graduallydevelop into asthma,however,most of those abservation studies were done byquestionnaires and did not describe the gradual inflammatory change in airway.Ourstudy aims to abserve the inflammatory change in upper and lower airway of patientswith isolated AR and investigate the interrelationship between AR and asthma. Part Ⅰ Airway inflammatory charactors of isolatedallergic rhinitisObjectivesTo determine the airway inflammatory charactors of isolated allergic rhinitisMethodsPatients who visited ENT outpatient clinic only for nasal symptoms and collegestudents who volunteer themselves with or without nasal symptoms form Guangzhoumedical college between1stJan,2011and12ndDec,2011were recruited.All eligiblesubjects were divided into three groups: allergic rhinitis group, non-allergic rhinitisgroup and healthy control.According to ARIA-2008,subjects who had typical nasalsymptoms,physical signs,positive skin prick test and/or airborne allergen specific IgEwould fall into allergic rhinitis group,subjects who had typical nasal symptoms andphysical signs,but with negtive skin prick test and airborne allergen specific IgEwould fall into non-allergic rhinitis group. Healthy subjects were defined as studentswho did not have anaphylasis history, nasal symptoms and physical signs and hadnegtive skin prick test and airborne allergen specific IgE. All subjects included in ourresearch had normal chest X-ray,no history of chronic systematic diseases,includingchronic cough,asthma etc,no respiratory infection8weeks prior to our research, nonasal or facial injury,no deviated septum.None of them was smoker or ex-smoker andall female subjects were neighter pregnant nor in laction period. Oral/nasalcorticosteroids,anti-histamin and leukotriene receptor antagonist were suspended4weeks ahead of the recruitment.The protocol was approved by the Ethics Committeeof The First Affiliated Hospital of Guangzhou Medical College.Informed writtenconsents were given to all subjects.Peripheral five-classify blood examinations (eosinophil count＞0.30×109/L aspositive criterion), measurements of exhaled nitric oxide concentration (FENO>25ppb as postive criterion), nasal lavage fluid differentiation cytology tests (eosinophil count＞3.47/×200as positive criterion), spirometry tests, methacholinebronchial provocation tests (a≥15%and≥20%fall in FEV1as susceptive positiveand positive criterion, respectively) and induced sputum differential cytology tests(eosinophil percentage＞2.5%as positive criterion) were performed. The characterand difference in peripheral blood cells, systemic, upper and lower airwayinflammation as well as airway hyperresponsiveness among three groups werecompared. T-test, one-way analysis of variance (ANOVA) and chi-square continuouscorrection test was adopted for comparison between two groups, among multiplegroups, and comparison on rates, respectively.Correlation was employed to determinethe relationship between airway inflammation,duration, severity andairwayhyperresponsiveness.Results1. A total of190subjects with allergic rhinitis,79with non-allergic rhinitis, and54healthy controls were enrolled.All subjects were not reporting lower airwayassociated symptoms,such as cough, wheezing, and dyspnea. Subjects in allergicrhinitis group aged19.45±0.76years old,19.49±0.83years old in non-allergic rhinitisgroup and19.66±0.75years old in healthy controls.The proportion(male/female) inallergic rhinitis group was98/94, in non-allergic rhinitis group is35/45,in healthy was23/31.No significance difference in age,gender propotion,body mass index amongthree groups.2. The median duration in allergic rhinitis was4(5~20)years, in non-allergicrhinitis group is3(0.5~17)years. The severity of rhinitis in15(7.8%)subjects inallergic rhinitis group and20（25%）subjects in non-allergic rhinitis group weremild,in177(92.2%)subjects in allergic rhinitis group and59（75%）subjects in non-allergic rhinitis group were moderate to severe.Rhinitis in in134(69.8%)subjects inallergic rhinitis group and58（73.42%）subjects in non-allergic rhinitis group wereintermittent,in58(30.2%)subjects in allergic rhinitis group and21（26.58%）subjects innon-allergic rhinitis group were perennial.3. Peripheral blood eosinophil count was0.15（0.02~1.24）×109/L in allergic rhinitis group,0.10（0.02~1.62）×109/L in non allergic rhinitis group and0.08（0.01~0.34）×109/L in healthy control group.There was significant statistic differencebetween groups (P<0.05). The positive rate of peripheral blood eosinophil count was13.16%in allergic rhinitis group,10.26%in non allergic rhinitis group and1.85%inhealthy control group (P<0.01), respectively. The positive rate of peripheral bloodeosinophil count in both of allergic rhinitis and non-allergic rhinitis groups werehigher than healthy group (P<0.05). There was no significant statistic differencebetween allergic rhinitis and non-allergic rhinitis groups (P>0.05).4. Eosinophil count in nasal lavage fluid in allergic rhinitis group was3.65(0.00~427.00)×200/HE, which had statistical difference (P<0.05) with that ofnon-allergic rhinitis group0.05(0~106.75)×200/HE and healthy control group0.00(0.00~25.8)×200/HE. Both of allergic rhinitis group and non-allergic group werehigher than healthy group (P<0.05).The positive rate of eosinophil count in nasallavage fluid was59.89%,28.35%and5.00%(P<0.01), respectively,which was higherin allergic rhinitis group than the other two groups.5. The percentage of eosinophil in induced sputum in allergic rhinitis group was1.00(0.00~65.5)%, which was higher than that in non-allergic rhinitis group0.00(0.00~21.67)%and normal control group0.00(0.00~11.00)%(all P<0.01). Thepositive rate of eosinophil percentage in induced sputum was30.81%,8.97%and2.83%in AR, NAR and normal control group. There were significant differencesbetween groups(All P<0.001).6. Fractional exhaled nitric oxide of AR group was20.00(5.00~78.00)ppb, whichwhich was higher than that in non-allergic rhinitis group NAR group16.00(8.00~71.00)ppb and normal control group12.00(6.00~30.00)ppb(All P<0.05).There was statistic difference between non-allergic rhinitis and healthy controls(P<0.05).The positive rate in allergic rhinitis group was35.82%, which was higherthan that in NAR group and normal control group (13.21%and5.13%, respectively)(P<0.05).7. No stastistical difference was shown in major spirometry parameters among three groups (all P＜0.05). The total number of susceptive positive and positive rateof bronchial provocation test in AR group was8.9%, which was higher than that innormal control group (0%)(P＜0.05).There were no stastistical difference betweenallergic rhinitis and non-allergic rhinitis,non-allergic rhinitis and healthy control(AllP>0.05).The percentage of eosinophil in induced sputum,eosinophil count in nasallavage and FeNO were simultaneously higher in AR subjects with bronchialhyperresponsiveness than AR subjects with normal bronchial reactivity(P<0.05).8. There are linear correlation between FeNO and percentage of eosinophil ininduced sputum in subjects with allergic rhinitis (rs=0.498,P<0.01). Subjects withallergic rhinitis with increased percentage of eosinophil in induced sputum tended tohave abnormal FeNO at the same time(rs=0.434,P<0.01).Both of the percentage ofeosinophil in induced sputum and level of FeNO value were risk factor of BHR.9. In allergic rhinitis group, FeNO, percentage of eosinophil in inducedsputum,eosinophil count in nasal lavage being abnormal at same time had linearcorrelation with bronchial hyperreactivity(rs=0.434,P<0.01).Isolated increase in FeNO,percentage of eosinophil in induced sputum,eosinophil count in nasal lavagerespectively did not associate with bronchial hyperreactivity((All P>0.05).10. No linear correlation between percentage of eosinophil in induced sputum orFeNO and duration of the disease in allergic rhinitis subjects(rs=0.0.112,P>0.05;rs=0.191,P<0.05).Duration in subjects with increased percentage of eosinophil ininduced sputum was comparable to that in subjects with normal percentage ofeosinophil in induced sputum(P>0.05); Duration in subjects with increased FeNO wascomparable to that in subjects with normal FeNO(P>0.05); Subjects with allergicrhinitis with different sverity of the disease were comparable in number of subjectswith increase percentage of eosinophil in induced sputum or FeNO(All P>0.05);Percentage of eosinophil in induced sputum and FeNO were comparable in subjectswith allergic rhinitis with different sverity of the disease(P>0.05).Conclusions1. Lower airway eosinophilic inflammation,airway hyperresponsiveness and increased FeNO value could exist in AR patients without lower airway symptoms,andthe severity of inflammation was not in line with the duration or severity of thedisease;2. Airway hyperresponsiveness tends to appear in AR patients with airwayeosinophilic inflammation accompanied with increased FeNO.Part Ⅱ Prognosis of allergic rhinitisObjectiveTo determine the change of airway inflammation and brochial responsiveness inpatients with allergic rhinitis.MethodsPatients with allergic rhinitis and healthy adults who participated our studybetween1stJan,2011and12ndDec,2011were recruited between July,2012andMay,2013.. All subjects included in our research had normal chest X-ray,no history ofchronic systematic diseases,including chronic cough,asthma etc,no respiratoryinfection8weeks prior to our research, no nasal or facial injury,no deviatedseptum.None of them was smoker or ex-smoker and all female subjects were neighterpregnant nor in laction period. Oral/nasal corticosteroids,anti-histamin andleukotriene receptor antagonist were suspended4weeks ahead of the recruitment.Theprotocol was approved by the Ethics Committee of The First Affiliated Hospital ofGuangzhou Medical College.Informed written consents were given to all subjectsPeripheral blood routine test (eosinophil count＞0.30×109/L as positive criterion),measurements of exhaled nitric oxide concentration (FENO>25ppb as postivecriterion), nasal lavage fluid differentiation cytology tests (eosinophil count＞3.47/×200as positive criterion), spirometry tests, methacholine bronchial provocationtests (a≥15%and≥20%fall in FEV1as susceptive positive and positive criterion,respectively) and induced sputum differential cytology tests (eosinophil percentage ＞2.5%as positive criterion) were performed again. The character and difference insystemic, upper and lower airway inflammation as well as airwayhyperresponsiveness between two different groups or parameters between two visitsin same group were compared. T-test or paired T-test, one-way analysis of variance(ANOVA) and chi-square continuous correction test was adopted for comparisonbetween two groups.Results1.In a total of190interviewees who were interviewed on telephone,30of themlost contact,160of them successfully filled the brief questionnares;twenty-three of160interviewees were symptom-free for at least one year,122of who still had nasalsymptoms;two interviewees reported a improvement in nasal symptoms,while nasalsymptoms worsened in47interviewees,and remained level in73interviewees.oneinterviewee once felt chestightness when nasal symptoms appeared,non of the rest ofinterviewees reported asthmatic symptoms or been diagnosed asthma;the duration ofcough in130interviewees was no more than1week,which was induced by commoncold,12interviewees once had subacute cough(3~8weeks),which induced by coldstimulation or common cold;only one patient once suffered chronic cough which wastriggered by cold stimulation.2.A total of60subjects with allergic rhinitis(30females and30males,aged19.83±2.36years old),20healthy controls(11females and9males,aged19.6±2.54years old) were enrolled.All subjects were not reporting lower airway associatedsymptoms,such as cough, wheezing, and dyspnea..No significance difference inage,gender propotion,body mass index among three groups.3. In allergic rhinitis group, the severity of rhinitis in5(12%)subjects were midand in55(88%)subjects were moderate to severe;Rhinitis in45(75%)subjects in wereintermittent,in15(25%)subjects were perennial;51subjects were symptom-free at leastone week prior to the study;14subjects were reporting improvement in nasalsymptoms;VAS score decreased at the second visit(V2) compared with the first visit（V1）(P<0.05); 4. Significant difference in percentage of eosinophil in induced sputum betweentwo visits (V1vs V2:4（0.00~65.5）%vs1.00（0.00~27.25）%)was observed insubjects with allergic rhinitis（P=0.018）.At both of the first(V1) and the second visit(V2), percentage of eosinophil in induced sputum in allergic rhinitis group was higherthan that in healthy control group(P<0.01).The fluctuation of percentage of eosinophilin induced sputum between two visits was higher than that in healthy group(P<0.05);5. FEF75%/pred（%）decreased at the second,compared with the first visit inallergic rhinitis group(P<0.05).At second visit, FEF75%/pred（%）was higher in allergicrhinitis than that in healthy group;there were no difference in other spirometryparameters;The fluctuation of spirometry parameters in allergic rhinitis group betweentwo visits was comparable to healthy group（P>0.05）;new AR with BHR at V2had alower FEF25-75/pred%than that at V1(P<0.05).6. Significant difference in eosinophil count in nasal lavage between two visits(V1:10.55（0.00~131.8）个/×200（HE）vs V2:0.05（0.00~69.6）个/×200（HE）)wasobserved in subjects with allergic rhinitis（P<0.01）; The fluctuation of eosinophilcount in nasal lavage between two visits was higher than that in healthygroup(P<0.05);7. FeNO in allergic rhinitis group was higher than healthy group at both visits（All P<0.05）.There were no statistic difference within allergic rhinitis group andhealthy group between two visits (All P>0.05).8. AR patients with recent increased Eos%in induced sputum at V2visit hadlower FEF25-75/pred（%）and higher FeNO than AR patients with normal Eos%ininduced sputum at both visits.（P<0.05）.Conclusions1. AR patient with absence of lower airway related symptoms would not developinto asthma in a short-term.2. Bronchial hyperresponsiveness,impaired small airway function(FEF75%/pred)and lower airway eosinophilic inflammation gradually appears in patients withisolated allergic rhinitis;.