Changes And Clinical Application Of Small Airway Parameters In Patients With Cough Variant Asthma

Background:Cough variant asthma(CVA)is easily confused with other etiologies of chronic cough and is easily overlooked and misdiagnosed clinically,since it presents with only cough but no wheezing as in classic asthma.Because CVA can develop into classic asthma after several years,the study of pathophysiology and clinical characteristics of CVA is essential to prevent or delay the transition from CVA to classic asthma.At present,most research on asthma are focused on classic asthma,and the pathophysiological and clinical characteristics of CVA have not been clarified.Some studies have shown that maximum mid-expiratory flow(MMEF),as a small airway function parameter,can identify asthmatic patients early,and the diagnostic value of MMEF combined with fractional exhaled nitric oxide(FeNO)for CVA is higher.Impulse Oscillometry(IOS),as a method to measure small airway function,requires minimal patient cooperation and is suitable for use in both children and adults.At present,there are few studies on the small airway in CVA patients,especially the prospective study of the diagnostic value of IOS for CVA.Therefore,it is of great practical significance to explore the changes of small airway function in patients with CVA and its diagnostic value in the diagnosis and treatment of CVA.Objective:To explore the characteristics of small airway function and the diagnostic value of small airway parameters in CVA,so as to provide evidence for the pathological characteristics and early diagnosis of CVA.Methods:To review the information of patients with chronic cough who visited the respiratory clinic of Zhujiang Hospital of Southern Medical University from August 2017 to July 2018 and completed the pulmonary function test and FeNO at the same time.According to national and international guidelines,the patients were divided into CVA group and NCVA group.The characteristics of small airway function were compared between the two groups.CVA-predictive values were analyzed via the area under receiver operating characteristic curves(AUC).Optimal cutoff values were determined by maximizing the sum of sensitivity and specificity.In order to verify the the conclusions of the retrospective study,all suspected CVA patients from August 2018 to December 2018 were included continually.Healthy subjects without respiratory symptoms were also included.IOS,lung function test and FeNO test were performed on suspected CVA patients by the same researcher.IOS and lung function test were performed on healthy subjects.According to the diagnostic criteria,patients suspected of CVA were divided into CVA group and Non cough variant asthma(NCVA)group.The characteristics of small airway function in CVA group,NCVA group and healthy group were compared.For suspected CVA subjects,ROC curves were used to analyze and compare the diagnostic value of each measurement parameter for CVA.Results:1.The proportion of subjects with allergic rhinitis in CVA group was significantly higher than that in NCVA group(P<0.05).2.The small airway parameters(MEF50,MEF25,MMEF)and X5 in CVA group were significantly lower than those in NCVA group and healthy control group(P<0.05),and AX was significantly higher than those in NCVA group and healthy control group(P<0.05).3.The small airway parameters(MEF50,MEF25 and MMEF)of lung function test were moderately correlated with Zrs,R5-R20,X5 and AX(P<0.05),while r were<0.5,there was no strong correlation parameters.4.The areas under ROC curves of MMEF,X5 and FeNO in diagnosing CVA were 0.712,0.734 and 0.822,respectively.There was no difference in diagnostic value of the three AUCs(P>0.05).The optimum cutoff value of MMEF was 77.50%(sensitivity:82.05%,specificity:57.58%,PPV:43.24%,NPV:89.06%).The optimum cutoff value of X5 was-0.10 kpa.L-1.s-1(sensitivity:79.49%,specificity:57.58%,PPV:33.70%,NPV:82.61%).The optimum cutoff value of FeNO was 31.5 ppb(sensitivity:56.41%,specificity:94.95%,PPV:55.00%,NPV:82.65%).5.The area under ROC curve of CVA diagnosed by MMEF or X5 combined with FeNO was significantly higher than that of single measurement parameter(P<0.05).MMEF<57.4%predicted value and FeNO>25ppb strongly predicted CVA(sensitivity:74.36%,specificity:88.89%,PPV:77.78%,NPV:75.19%).X5<-0.12 kpa.L-1.s-1 and FeNO>29ppb also strongly predicted CVA(sensitivity:79.49%,specificity:94.95%,PPV:100%,NPV:76.72%)Conclusion:1.Patients with CVA often have allergic rhinitis.2.Small airway dysfunction is present in patients with CVA,which is reflected by decreased MEF50,MEF25,MMEF and X5,and increased AX.There is no strong correlation between the small airway parameter of the lung function test and the IOS measurement,and the two tests can not replace each other.3.MMEF,X5 and FeNO have moderate diagnostic value for CVA,and negative predictive value is higher.The combined use of MMEF or X5 and FENO increased the AUC,significantly higher than either parameter alone.MMEF<57.4%and FeNO>25ppb predicted value or X5<-0.12 kpa.L-1.s-1 and FeNO>29ppb strongly predicted CVA.