A Comparative Study Of Devices For Measuring Exhaled Nitric Oxide And A Study Of Asthma Phenotype Based On Exhaled Nitric Oxide And Pulmonary Function Classification

Section Ⅰ A comparative study of devices for measuring exhaled nitric oxide in patients with asthma[Background]Exhaled nitric oxide is one of the indicators reflecting airway inflammation in patients with asthma and the importance of the results is self-evident.In recent years,many types of devices that measure exhaled nitric oxide have applied in clinical practices,which can not only detect fractional exhaled nitric oxide(FeNO)level,but also can measure concentration of alveolar nitric oxide(CaNO).Previous studies only compared the consistency between different exhaled nitric oxide instrument on the FeNO level,however,comparisons at the CaNO level are unknown.Therefore,it is necessary to further analyze the differences between different exhaled nitric oxide instruments on the CaNO level.[Objective]Different exhaled nitric oxide instruments were compared on difference,consistency,clinical relevance and repeatability from FeNO and CaNO levels.[Method]In this study,four commercialized instruments were adopted,among which UBBA200,Sunvou-CA2122 and RuiBreath N1 instruments could be used to measure both FeNO and CaNO.However,NIOX VERO is the most widely used instrument for FeNO measurement in China mainland and aboard,which is deemed to the control in this study.Friedman test was used for comparison between groups to evaluate the difference of each instruments.MedCalc software was devoted to analyzing the consistency between different instruments.Standard deviation and coefficient of variation were appropriate for evaluating the repeatability of each instrument.ROC curve was suitable for evaluating the ability of CaNO value measured by each instrument to predict small airway dysfunction,and Pearson correlation coefficient was used to evaluate the correlation between CaNO and FeNO value measured by each instrument and the percentage of eosinophil in sputum.[Result]A total of 73 patients with asthma were included in the current study.63 asthmatic patients were used to compared the difference,consistency and clinical relevance.Another 10 asthmatic patients were used to compare repeatability between different instruments.In terms of difference,as to FeNO detection,there is no significant difference between the results measured by NIOX VERO,UB-BA200 and Sunvou-CA2122 instruments,however,they were significantly different from those measured by RuiBreath N1(P<0.001)and the results of RuiBreath N1 were generally higher.For CaNO detection,the results measured by UB-BA200 and Sunvou-CA2122 had no statistical significance(P=1.000),but they were significantly different from those measured by RuiBreath N1(P<0.001)and the RuiBreath N1 instrument yielded generally higher results.In terms of consistency,FeNO detection showed that NIOX VERO had the best consistency with UB-BA200.As to CaNO detection,UB-BA200 displayed better consistency with Sunvou-CA2122 than RuiBreath N1.In terms of clinical relevance,the CaNO value measured by UB-BA200 was positively correlated with percentage of eosinophils in sputum and FeNO value(r=0.301,P=0.027;r=0.697,P<0.001).Furthermore,the CaNO value measured by UBBA200 exhibited a better ability to predict small airway dysfunction compared to SunvouCA2122(AUC=0.69,P=0.030).In terms of repeatability,the reproducibility of UBBA200 was better than that of Sunvou-CA2122 with lower standard deviation and coefficient of variation in the repeated measurements.[Conclusion]By analyzing the difference,consistency,clinical relevance and repeatabiliay of the instruments,we conclude that UB-BA200 is more suitable for further studies of the clinical significance of CaNO.Section Ⅱ A study of asthma phenotype based on exhaled nitric oxide and pulmonary function classification[Background]Exhaled nitric oxide is an indicator of airway inflammation in asthma,which includes FeNO reflected inflammation of the atmospheric tract,and CaNO reflected inflammation of the small airway.Exhaled nitric oxide can be applied to monitor airway inflammation,risk of acute asthma attacks,and responsiveness to inhaled corticosteroid therapy.Forced expiratory volume in 1 second(FEV1)and Forced expiratory flow between 25%and 75%(FEF25-75%)are indicators of pulmonary function that reflect obstruction of large and small airways respectively.They are closely related to airflow limitation,severity of asthma and symptom control level.Through the combined detection of exhaled nitric oxide and lung function,the severity of asthma patients can be evaluated comprehensively and systematically,and it will be beneficial to the disease management and precise treatment.[Objective]By combining exhaled nitric oxide and pulmonary function indexes,the clinical characteristics of different types of asthma patients were analyzed to provide scientific basis for future treatment and management of asthma patients.[Method]A retrospective study with 369 patients with asthma were collected.Finally,290 patients were included in the asthma phenotype study based on FeNO and FEV1 classification,while 238 patients were included in the asthma phenotype study based on CaNO and FEF25-75 classification.60 patients were consistent with prognostic analysis.Single-factor ANOVA test was used for inter-group comparisons of quantitative data.Ztest was suitable for comparison between groups of qualitative data.Wilcoxon test was applied to intra-group comparisons of quantitative data.Multivariate regression was utilized to analyze the effects of the change in exhaled nitric oxide and lung function on prognostic factors in patients with asthma.[Result]1.In asthma phenotype studies based on FeNO and FEV1 classifications,the patients with asthma are divided into four phenotypes,such as Type Ⅰ(NOnormal EVnormal),Type Ⅱ(NOhighEVnormal),Type Ⅲ(NOhighEVlow)and Type Ⅳ(NOnormalEVlow).The total IgE of Type Ⅱ and Type Ⅲ was significantly higher than that of Type Ⅰ(P<0.001).The daily requirement of inhaled corticosteroids(ICS)was significantly increased in patients with Type Ⅲ asthma compared with Type Ⅰ,Type Ⅱ and Type Ⅳ(P<0.001).Patients with Type Ⅲ had lower symptom control level than those with Type Ⅰ and Type Ⅱ(P<0.05).Lung function indicators(such as FVC%,PEF%,FEF25-75%,FEF50%and FEF75%)in patients with Type Ⅲ and Type Ⅳ asthma were all worse than those corresponding to Type Ⅰ and Type Ⅱ(P<0.001).Patients with Type Ⅱ and Type Ⅲ asthma had significantly higher levels of airway inflammation(such as CaNO,percentage of eosinophils in sputum,and number of eosinophils in blood)than those with Type Ⅰ and Type Ⅳ(P<0.001).However,after 3 months of standardized treatment,patients with Type Ⅲ had significantly higher rates of improvement in lung function indicators(such as FVC%,PEF%,FEF25-75%,FEF50%and FEF75%)and airway inflammation(such as number of eosinophils in blood)than patients with other types of asthma(P<0.05).Compared with the change rate of FeNO,the change rate of FEV1 had a greater effect on symptom control score,airflow obstruction,and peripheral blood eosinophils.2.In asthma phenotype studies based on CaNO and FEF25-75 classifications,the patients with asthma are divided into four phenotypes,such as Type Ⅰ(NOnormalEFnormal),Type Ⅱ(NOhighEFnormal),Type Ⅲ(NOhighEFlow)and Type Ⅳ(NOnormalEFlow).The age of onset,total IgE(Immunoglobulin E,IgE)and the daily requirement of ICS for Type Ⅲwere significantly higher than those of Type Ⅰ(P<0.001).Patients with Type Ⅲ had poorer lung function indicators(such as FVC%,FEV1%,PEF%and FEF50%)and higher levels of airway inflammation(such as percentage of eosinophils in sputum)than other types(P<0.001).However,after 3 months of standardized treatment,patients with TypeⅢ showed greater improvement from baseline in symptom control(such as ACT score and AQLQ score),lung function(such as FEV1%,FVC%,PEF%,FEF50%and FEF75%),and airway inflammation(such as FeNO and percentage of eosinophils in sputum)(P<0.05).The change rate of FEF25-75%conferred a stronger impact on both symptom control score(ACT score)and airflow obstruction(such as FEV1%,FVC%,FEF50%and FEF75%),however,the change rate of CaNO had a greater effect on the prognosis of neutrophils and esoinophils in sputum.[Conclusion]Patients with asthma with high exhaled nitric oxide and airflow obstruction have worse symptom control,poorer lung function,higher levels of inflammation and need higher daily ICS requirement.However,their prognosis improves significantly from baseline after treatment.The change rate of FEV1%and FEF25-75%have a greater effect on the prognosis of ACT score and airflow obstruction,while the change rate of CaNO have greater influence on the prognosis of eosinophils and neutrophils in sputum.