Study On The Sequential Changes Of Symptoms, Small Airway Function And Airway Inflammation In Chronic Cough With Brongchial Hyperresponsiveness

BackgroundChronic cough is a common medical problem,and it is also one of the most common reasons for patients who visit respiratory out-patient hospitals at all levels.Unexplained chronic cough,also referred to chronic cough,which regarded cough as the only symptom or the main symptom in clinical,usually longer than 8 weeks and X-ray or even CT showed without obvious abnormality.There are many classification method of chronic cough.Much clinical limitations according to the etiological classification.According to the clinical phenotype can be divided into two types with and without brongchial hyperresponsiveness?BHR?.In this study,chronic cough patients with BHR were selected,who responded well to inhaled corticosteroids combined with bronchodilators?ICS/LABA?.The 2015 guideline of diagnosis and management of chronic cough identified that these patients should be treated for at least 8 weeks,and some need long-term treatment.According to GRADE?grading of recommendations assessment,development and evaluation?,these suggestion comply with‘2D'.Grade 2D is a lower level and the treatment course is too general.On the one hand,too long course of treatment can lead to high medical costs and increasing economic burden.On the other hand,too short course of treatment can lead to poor efficacy and easy to relapse.Thus,it is of great significance to establish a definite treatment course for chronic cough with BHR.Objective1.To investigate the specific treatment course of chronic cough with BHR through the study on the sequential changes of symptoms,small airway function and airway inflammation.2.To explore the value of pulmonary function test index in the follow-up of chronic cough with BHR.MethodNewly diagnosed chronic cough patients who visited respiratory clinics of the 940Hospital of Joint Logistic Support force of Chinese People's Liberation Army in Lanzhou?the original Lanzhou General Hospital of Lanzhou Military Command?,a total of 303 patients were enrolled from May 2018 to December 2018 with positive bronchial provocation test?BPT?is required.All patients were classified into two groups based on the BPT,the mild BHR and the severe BHR.Standard treatment with budesonide/formoterol 160?g/4.5?g twice daily was given for about 3⁴ months?depending on the patient's state?,and during which montelukast?10mg/table,once daily?was added in the initial first month.Telephone,WeChat or outpatient follow-up at different time points was performed at the end of 2-week,4-week,8-week,12-week after the enrollment.At each visit,subjects underwent clinical symptom and completed cough symptom scores and sputum scores.Subjects with outpatient follow-up underwent pulmonary function test,collected the exhaled breath condensate?EBC?and detected its nitrite?NO₂^-?,hydrogen?H₂O₂?and pH.In addition,10 healthy employees in our hospital were taken as the control group,collected the EBC and NO₂^-,H₂O₂ and pH were detected in EBC.Result1.A total of 105 patients were followed up for 12 weeks finally,including 43 patients in group A?mild BHR group?and 62 patients in group B?severe BHR group?.A total of 38patients which completed lung function test and EBC were enrolled,including 17 in group C?mild BHR group?and 21 in group D?mild BHR group?.2.During 12 weeks follow-up,the sputum scores,daily cough symptom scores,nightly cough symptom scores and totally cough symptom scores of two groups were gradually lower,there were statistically significant?P<0.05?.All scores of two groups in 4-week and follow-up treatment were significantly lower than baseline?P<0.05?,in addition,all scores of group A were already decreased in 2-week?P<0.05?,while nightly cough symptom scores and totally cough symptom scores in 2-week of group B were significantly lower than in 2-week?P<0.05?.Nightly cough symptom scores and totally cough symptom scores in 4-week was significantly lower than in 2-week of two groups?P<0.05?.All scores of two groups in 8-week were significantly lower than in 4-week except for sputum scores?P<0.05?.All scores of two groups in 12-week was lower than in 8-week,but there was no significant difference?P>0.05?.3.All index of lung function test were gradually increased in group C during the whole treatment process,with statistically significant differences in peak expiratory flow?PEF?,FEV1/FVC%,maximal mid expiratory flow?MMF?and forced expiratory flow in 75%vital capacity?FEF75%??P<0.05?.Only MMF increased between 4-week and baseline,8-week and4-week,differences were statistically significant?P<0.05?.All index of two groups in 12-week was higher than in 8-week,but there was no significant difference?P>0.05?.4.All index of lung function test were gradually increased in group D during the whole treatment process,with statistically significant differences in forced vital capacity?FVC?,PEF,MMF,FEF75%,forced expiratory flow in 50%vital capacity?FEF50%?and forced expiratory flow in 25%vital capacity?FEF25%??P<0.05?.PEF,MMF,FEF75%in 4-week were significantly higher than baseline?P<0.05?.There was no significant difference between4-week and 8-week?P>0.05?.MMF and FEF25%in 12-week were significantly higher than in8-week of group D?P<0.05?.5.There were statistically significant differences in two groups during the whole treatment process that the reduction of NO₂^-concentration and the increase of pH?P<0.05?.The reduction of NO₂^-and the increase of pH were statistically significant between 8-week,12-week and baseline?P<0.05?,and the pH in 4-week was significantly higher than baseline in group C?P<0.05?.The concentration of NO₂^-of group C in 8-week was significantly lower than in 4-week?P<0.05?.The concentration of NO₂^-of group D in 12-week was significantly lower than in 8-week?P<0.05?,but there was no significant difference in group C?P>0.05?.There was no significant difference in H₂O₂ concentration of two groups during the whole treatment?P>0.05?.Conclusion1.For patients of chronic cough with BHR,the treatment course varies according to the degree of BHR:1.1 For patients with mild BHR,the recovery of clinical symptoms,lung function test and inflammatory indicators are consistent,so we can develop a treatment course of 8 weeks or longer according to the symptoms.1.2 For patients with severe BHR,the recovery of clinical symptoms is earlier than lung function test and inflammatory indicators,so we can develop a treatment course of 12 weeks or longer according to combination with these three aspects.2.Pulmonary function index MMF is more sensitive in patients of chronic cough with BHR,which can be used as an indicator to evaluate the treatment effect during follow-up.