The Values Of Fractional Exhaled Nitric Oxide In The Diagnosis And Treatment Of Chronic Cough

Background Chronic cough,defined as a cough lasting for 8 weeks or longer with normal chest radiographs, is one of the most frequent complaints in clinics. The main causes of chronic cough include:cough variant asthma (CVA), eosino-philic bronchitis (EB), upper airway cough syndmme, and gastroesphageal refux,et al. Distinguished from other causes, CVA and EB are characterized by eosinophilic airway inflammation. Therefore eosinophilic airway inflammation markers are important for the differential diagnosis and management of chronic cough. Fractional exhaled nitric oxide (FENO) has been suggested as a useful way of monitoring airway inflammation with the advantages of non-invasiveness, simple and reproducibility. There is a good correlation between FENO values and sputum eosinophils in asthma patients. FENO has been recommended as a airway inflammation marker for asthma by GINA and Chinese asthma guidline. However, the values of FENO in the diagnosis and treatment of chronic cough is uncertain.The objective of the study is to evaluates the value of FENO in the diagnosis and treatment of chronic cough prospectively.The methods and results are as follow.1. The FENO levels of healthy non-smokers were tested by the NIOXMINO analyzer. Thirty subjects,15 males and 15 females, were were recruited according to the inclusion criteria and exclusion criteria after lung function test and allergen skin prick test. FENO tests are finished according to the standard precedures of ATS/ERS recommandation. The results showed that the FENO level of healthy non-smokers is (18±5)ppb, in Gaussian distribution, with the 95% normal range of (8-27) ppb.There is no significant difference of FENO level between male and female ((18±4)ppb vs (17±6)ppb, P=0.29). The FENO level of the subjects older than 40 yr is (20±5)ppb, higher than the youngers (16±5ppb, P=0.04)2. The diagnostic value of FENO in the diagnosis of chronic cough was evaluated.106 Subjects with chronic cough were recruited from the outpatient clinic of the respiratory department in China-Japan Friendship Hospital. All the patients accepted FENO tests, sputum cell counts, pulmonary function tests, airway hyperresponsiveness (AHR), serum IgE, cough symptom scores and Licester cough Questionnaire (LCQ) before and after treatment of 4 weeks. The results showed final diagnosis was 39 with CVA,30 EB and 37 with other causes. FENO levels in CVA (54±21 ppb) were significantly higher than those in EB (34±17 ppb, P<0.01) and other causes (21±10 ppb, P<0.01), FENO levels in EB were higher than other causes (P<0.01). To diagnose CVA from chronic cough, the optimal FENO cutoff value was 40 ppb, with sensitivity of 75%, specificity of 86%, positive predictive value of 77%, negative predictive value of 86%, accuracy of 81%. To diagnose EB from non-asthma chronic cough, the optimal FENO cutoff value was 31 ppb, with sensitivity of 63%, specificity of 92%, positive predictive value of 88%, negative predictive value of 92%, accuracy of 72%. FENO levels had significant correlations with sputum eosinophils, AHR or cough symptom scores (P<0.01), and had correlations with non-specific IgE, and LCQ scores.3. The value of FENO to predict the response to inhaled corticosteroid of CVA or EB patients was evaluated. The results showed the baseline FENO level of the subjects whose coughs were relieved after inhaled corticosteroids therapy was (63±42) ppb, higher than bad-responders'levle (28±13ppb, P <0.01). There are significant correlations between the percentage of FENO decrease and the percentage of sputum eosinophils decrease or the cough symptom scores decrease. To distinguish the good resonders from bad responders, the optimal baseline FENO cutoff value was 36 ppb, with sensitivity of 82%, specificity of 93%, positive predictive value of 94%, negative predictive value of 83%, accuracy of 87%.Conclusion The FENO level of healthy non-smokers is in Gaussian distribution, the elderly higher than the youngers. Significant increase of FENO level helps to make the diagnosis of CVA or EB, with a good specificity. Chronic cough patients with FENO value more than 36 ppb are indicated to response to inhaled corticosteroids therapy.