The Value Of Alveolar Nitric Oxide Concentration In The Treatment Of Initial Low FeNO Asthma Patients

Objective:The essential characteristic of bronchial asthma is chronic airway inflammation.The lesion site of inflammation of the airway varies from person to person,and both large and small airways can be involved.Thus,identifying the location and assessing the degree of airway inflammation is of utter importance in asthma management.It has been found that the fraction of exhaled nitric oxide（FeNO）is correlated with the number of eosinophils in sputum,which can be used as a new indicator to evaluate the degree of eosinophilic airway inflammation,and can also be used as a reference to predict the therapeutic effect of asthma.According to the Global Initiative for Asthma（GINA）,FeNO>50ppb indicates that ICS treatment can achieve satisfying effect.But the guideline fails to give definite reference standards for patients with 25ppb≤FeNO≤50ppb,in which case,whether ICS treatment can benefit or not still needs to be carefully selected based on the clinical characteristics of the patient.Extended analysis of FeNO shows that detectingNO levels in exhaled air at different flow rates can distinguish the sources ofNO in the central large airway(FeNO₅₀)and the peripheral airways/alveolar nitric oxide-concentration（CaNO）.Though the role of FeNO in the diagnosis and treatment of asthma has been recognized by the guideline,whether CaNO can be used to guide the treatment of asthma has no agreement in both domestic and abroad.In order to addressing the above questions,this paper adopts a prospective research method to collect outpatient asthma patients,use CaNO as predictor,coupling by using budesonide formoterol inhalation powder to treat selected patients and keeping follow-up,so as to explore the role of CaNO in predicting the curative effect of ICS+LABA for patients that have initially low FeNO asthma and to guide the use of outpatient drugs and provide evidence for clinical medication.Methods:We collected patients who were treated in the outpatient department of the Department of Respiratory and Critical Care Medicine of our hospital from November2018 to June 2020 and had recurrent respiratory symptoms such as chest tightness,wheezing,shortness of breath,or chronic cough,or accompanied by airway hypersensitivity（fume,cold air and other stimuli can easily cause coughing）.After chest X-ray or chest CT,FeNO,CaNO and pulmonary function examinations,patients with positive bronchodilation test and FeNO≤50 ppb were chosen in this research.They were divided into CaNO elevated group and CaNO normal group according to the level of CaNO.We recorded the gender,age,height,weight,body surface area,asthma symptom control test（ACT）score,main symptoms,accompanying symptoms and positive physical examination results of the enrolled patients in detail.Then we gave them ICS+LABA（budesonide formoterol inhalation powder 160μg:4.5μg/inhalation,twice a day）treatment for at least 4 weeks.During the treatment,the patient’s condition changes were recorded by telephone or outpatient follow-up.After 4 weeks,the ACT score was evaluated again and FeNO,CaNO and lung function were reexamined.Results:60 patients met the enrollment criteria in this research,including 26 in the normal CaNO group and 34 in the CaNO elevated group.The pulmonary function and ACT score of the two groups of patients improved to varying degrees after treatment.The ACT score,peak expiratory flow（PEF）,and maximal expiratory flow after 25%of the FVC has not been exhaled(MEF₂₅)and Maximal mid-expiratory flow(MEF_75-25)in the CaNO elevated group were improved more significantly than the normal CaNO group,and the difference was statistically significant（P<0.05）.Correlation analysis showed that CaNO level was not correlated with MEF₂₅ and MEF_75-25（r=-0.10,r=-0.04,P>0.05）,but was positively correlated with the changes of MEF₂₅ and MEF_75-25 before and after treatment（r=0.29,r=0.38,P<0.05）.Conclusions:Distal airway/alveolar inflammation can help explain the reversible airflow obstruction originating from the peripheral airway.The increase in CaNO level suggests that patients can benefit from ICS+LABA treatment as CaNO an indicator of distal airway inflammation.Monitoring peripheral airway/alveolar inflammation can provide higher-quality medical evidence for asthma management.