| Objective:To analyze the clinical characteristics of children with bronchial asthma(hereinafter referred to as asthma)with different levels of exhaled nitric oxide(FeNO),and to provide help for the classification of asthma in children;to dynamically observe the changes of peripheral blood cytokines(IL-4,IL-5,IL-9,IL-17 and IL-21)in children with asthma,and to analyze their possible pathological mechanisms,so as to provide new basis for the diagnosis and treatment of asthma.Methods:We selected 5-12 year-old asthma patients who first visited respiratory clinic of Children's Hospital Affiliated to Suzhou University from December 2017 to September 2018.According to the guideline for prevention and treatment of bronchial asthma(2016 edition),the patients were divided into two groups according to the level of FeNO:normal group(FeNO<25ppb)and elevated group(FeNO?25ppb).The clinical manifestations,pulmonary function of children in different groups were observed dynamically in 1 month,3 months and 6 months,and the levels of IL-4,IL-5,IL-9,IL-17 and IL-21 in peripheral blood of the two groups were detected and compared.To analyze its clinical significance.Results:A total of 41 children with bronchial asthma,27 males and 14 females,were included in this study.The ratio of males to females was 1.92:1.Age ranged from 5 to 12 years with a median age of 7 years.The patients were followed up for 6 months.Healthy children aged 5-12 years were randomly selected as control group,with no gender limitation.According to the level of FeNO,the patients were divided into two groups.The clinical characteristics and cytokines of the two groups were compared and analyzed.In the elevated FeNO group,the clinical manifestations were cough in 18 cases(18/22),wheezing in 13 cases(13/22),and chest tightness in 2 cases(2/22).20 cases(20/22)were accompanied by rhinitis and/or atopic dermatitis.There were 14 cases(14/22)with asthma/rhinitis/atopic dermatitis in first-degree relatives.There were 11 patients with intermittent state(11/22),9 patients with mild persistence(9/22)and 2 patients with moderate persistence(2/22).In the normal group of FeNO,15 cases(15/19)had cough,15 cases(15/19)had wheeze and 6 cases(6/19)had chest tightness.Ten cases(10/19)were accompanied by rhinitis and/or atopic dermatitis.Eight of the first-degree relatives had asthma/rhinitis/atopic dermatitis(8/19).There were 8 patients in intermittent state(8/19),10 patients in mild state(10/19)and 1 patient in moderate state(1/19).Compared with the normal FeNO group,the patients with rhinitis and/or atopic dermatitis in the elevated FeNO group were more than those in the normal FeNO group(P<0.05).The median of FeNO abnormal group before treatment and 1 month,3 months and 6 months after treatment were 42 ppb,33 ppb,23 ppb and 15 ppb,respectively.The median of FeNO normal group before treatment and 1 month,3 months and 6 months after treatment were 13 ppb,15 ppb,13 ppb and 10 ppb,respectively.There were significant differences between the two groups before treatment and 1 and 3 months after treatment(P<0.05).At 6 months of treatment,there was no significant difference between the two groups(P>0.05).Compared with the control group,FEV1/FVC and MMEF in the high FeNO group and the normal FeNO group before treatment were lower than those in the control group(P<0.05).There was no significant difference in FEV1/FVC between the elevated group and the normal group at 1,3 and 6 months after treatment(P>0.05),but the values of FEV1/FVC between the two groups were lower than those of the control group(P<0.05).The MMEF of the elevated FeNO group was lower than that of the normal FeNO group at 1 month of treatment(Z=-2.078,P=0.038);there was no significant difference between the elevated FeNO group and the normal FeNO group at 3 and 6 months of treatment(P>0.05).Compared with the control group,the MMEF of the FeNO elevated group was lower than that of the control group at 1 month of treatment(Z=-3.653,P<0.001),and there was no significant difference between the two groups at 3 and 6 months of treatment(P>0.05).At 3 months,MMEF in the normal group was lower than that in the control group(Z=-2.797,P=0.005);at 1 month and 6 months,there was no significant difference in MMEF between the normal group and the control group(P>0.05).The difference of pulmonary function indexes between the two groups before and after treatment was compared.It was found that the improvement of FEV1/FVC and MMEF in the elevated FeNO group was more obvious than that in the normal FeNO group.Nineteen of the 22 patients in the elevated FeNO group achieved stable clinical symptoms at 3-month follow-up,and nine of the 11 patients who completed 6-month follow-up achieved stable clinical symptoms.The bronchial provocation test changed from positive to negative,9 cases turned negative in 3 months and 7 cases turned negative in 6 months.Fourteen of the 19 patients in the FeNO normal group achieved stable clinical symptoms at 3-month follow-up,and nine of the 11 patients who completed 6-month follow-up achieved stable clinical symptoms.The bronchial provocation test changed from positive to negative,7 cases turned negative in 3 months and 5 cases turned negative in 6 months.In the FeNO abnormal group,17 cases(17/22)had elevated eosinophils in peripheral blood.Allergens were negative in 2 cases(2/22),dust mite allergy in 20 cases(20/22)and above grade 4,fungal allergy in 5 cases(5/22),cat hair and dog hair allergy in 2 cases(2/22),animal dandruff allergy in 1 case(1/22),pollen allergy in 3 cases(3/22)and food allergy in 4 cases(4/22).Eosinophils in peripheral blood increased in 10 cases(10/19)of normal FeNO group.There were 5 cases(5/19)with negative allergen,16 cases(16/19)with dust mite allergy,all of which were above grade 4,7 cases(7/19)with mould allergy and 5 cases(5/19)with food allergy.There was no difference in allergen expression between the elevated FeNO group and the normal FeNO group(P>0.05).The levels of IL-4,IL-5,IL-9,IL-17 and IL-21 in peripheral blood of 41 patients with asthma were higher than those of the control group before treatment and 1 month after treatment(P<0.05).After 3 months of treatment,there was no significant difference in the levels of IL-9 between the elevated FeNO group and the normal FeNO group(P>0.05);the levels of IL-4,IL-5,IL-17 and IL-21 in the elevated FeNO group and the normal FeNO group were higher than those in the control group(P<0.05).At 6 months after treatment,the levels of IL-5 and IL-21 in the elevated FeNO group were higher than those in the control group(P<0.05);the levels of IL-4,IL-9 and IL-17 in the elevated FeNO group were not significantly different from those in the control group(P>0.05).There was no significant difference in the level of IL-4 between the normal group and the control group(P>0.05);the levels of IL-5,IL-17 and IL-21 in the normal group were higher than those in the control group(P<0.05),and the levels of IL-9 were lower than those in the control group(P<0.05).Before treatment,the levels of IL-4 and IL-5 in the elevated FeNO group were higher than those in the normal FeNO group(P<0.05);the levels of IL-9 in the elevated FeNO group were not significantly different from those in the normal FeNO group(P>0.05);the levels of IL-17 and IL-21 in the elevated FeNO group were lower than those in the normal FeNO group(P<0.05).One month after treatment,the levels of IL-4 and IL-5 in the elevated FeNO group were higher than those in the normal FeNO group(P<0.05);the levels of IL-9 in the elevated FeNO group were not significantly different from those in the normal FeNO group(P>0.05);the levels of IL-17 and IL-21 in the elevated FeNO group were lower than those in the normal FeNO group(P<0.05).At 3 months after treatment,there was no significant difference in IL-4 and IL-5 levels between the two groups(P>0.05);there was no significant difference in IL-9 level between the elevated FeNO group and the normal FeNO group(P>0.05);the levels of IL-17 and IL-21 in the elevated FeNO group were lower than those in the normal FeNO group(P<0.05).At 6 months after treatment,there was no significant difference in IL-4 and IL-5 levels between the two groups(P>0.05),but the levels of IL-4 and IL-5 in the elevated FeNO group were significantly improved compared with those in the normal FeNO group;the levels of IL-9 in the elevated FeNO group were higher than those in the normal FeNO group(P<0.05);the levels of IL-17 and IL-21 in the elevated FeNO group were lower than those in the normal FeNO group(P<0.05).There was no correlation between IL-5,IL-17 and FeNO(both P>0.05);there was a positive correlation between the level of IL-4,IL-9,IL-21 and FeNO in the high FeNO group(P<0.05);there was no correlation between the level of IL-4,IL-5,IL-9,IL-17,IL-21 and FeNO in the normal FeNO group(P>0.05).Conclusion:1.The clinical characteristics of asthma patients with different levels of exhaled nitric oxide are different.Patients with high levels of exhaled nitric oxide are more likely to have rhinitis,eczema and atopic dermatitis.2.Significant cytokines such as Th2/Th9/Th17 secreted from peripheral blood of asthmatic patients are involved in the immunopathology of asthma;IL-4,IL-9 and IL-21 are positively correlated with the level of FeNO.3.The clinical symptoms and signs of asthma patients can not accurately reflect the phenotype of asthma.FeNO is more helpful to the classification of asthma and reflect the improvement before and after treatment. |
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