The Diagnosis Of Asthma By Fractional Exhaled Nitric Oxide And The Analysis Of The Relationship Between Fractional Exhaled Nitric Oxide And Allergen Specific IgE

Part one: Fractional exhaled nitric oxide in the diagnosis of bronchial asthma.Bronchial asthma is a chronic inflammatory airway disease which is caused byvariety of inflammatory cells. Airway inflammation leads to symptoms (cough, wheezing,shortness of breath, chest tightness, etc.), reversible airflow limitation, airwayhyperresponsiveness and remodeling of the airway.At present, the diagnosis andmonitoring of bronchial asthma is based on symptoms, physical examination,measurements of airway obstruction by means of forced exriratory volume in one second,assessment of bronchodilator response, and bronchial challenge tests to assess bronchialhyperresponsiveness, etc. However, symptoms and the positive results of lung functioncan not directly reflects the degree of airway inflammation of bronchial asthma.Therefore,directly measuring airway inflammation may be more appropriate for the diagnosis andmonitoring of bronchial asthma.Currently, the measurement methods of airway inflammation in bronchial asthma patients include bronchoscopy mucosal biopsy, bronchoscopy lavage fluid, cytologicalanalysis of induced sputum and detection of exhaled breath condensate, ect.The formertwo methods are invasive techniques.These methods are therefore not applicable in routineclinical practice. Cytological analysis of induced sputum is a relatively noninvasive test,but it may produce temporary decrements in lung function, and the processing of thesample is time-consuming, expensive, and requires skilled technicians. Currently,examination of exhaled breath condensate is lack of uniform methods and standards.Fractional exhaled nitric oxide has been proposed as a safe, non-invasive, simple,repeatable test to assess airway inflammatory. So far, the results of fractional exhalednitric oxide are not consistent on the accuracy of the diagnosis of bronchial asthmabecause of different race, living environment and other factors.Objective: The aim of this study was to assess the validity and accuracy of fractionalexhaled nitric oxide in the diagnosis of bronchial asthma, and to determine a cutoff valuefor the diagnosis of asthma. Our results may provide a new method for the diagnosis ofbronchial asthma.Method: Total109patients with asthma-like symptoms (cough, wheezing, shortness ofbreath, chest tightness, etc.) were recruited consecutively from respiratory medicineoutpatient clinic of xijing hospital. Firstly, the fractional exhaled nitric oxideconcentrations were measured using fractional exhaled nitric oxide analyzer (NIOXMINO Aerocrine AB, Sweden). Then pulmonary function were tested. Bronchial asthmawas diagnosed on the basis of the presence of symptoms, positive bronchodilator test and(or) airways hyperresponsiveness. The validity was assessed and the optimal cutoff valueof fractional exhaled nitric oxide was determined by the means of the receiver operatingcharacteristic (ROC) curves.Results: Total109patients were enrolled，47patients were diagnosed with asthma and62were not. The median fractional exhaled nitric oxide level in asthma patients was70partsper billion compared with16parts per billion in non-asthmas,P <0.001. The area underreceiver operating characteristic curve gave values of0.808(95%confidence interval：0.719to0.896) for fractional exhaled nitric oxide. From0.70to0.90is moderate of diagnostic accuracy. Optimal cut off value for the diagnosis of bronchial asthma byfractional exhaled nitric oxide level is41parts per billion. A cut off valuel of fractionalexhaled nitric oxide>41parts per billion gave a sensitivity of68.1%, a specificity of83.9%, a positive predictive value of76.2%，a negative predictive value of77.6%for thediagnosis of bronchial asthma. The fractional exhaled nitric oxide value is≤41parts perbillion in15(31.9%) bronchial asthma patients. Meanwhile, the fractional exhaled nitricoxide value is>41ppb in10(16.1%) non-asthmatics.Conclusion: The accuracy of fractional exhaled nitric oxide for the diagnosis of bronchialasthma is higher. It can be used as the auxiliary tool to support the diagnosis of bronchialasthma.Part two: The analysis of the relationship between fractional exhaled nitric oxide andallergen specific IgE in bronchial asthma patients.Bronchial asthma is characterized as allergic airway inflammation and airwayhyperresponsiveness which is mainly mediated through eosinophils and mast cells. Inaddition to the inherent genetic factors, environmental factors also play an very importantrole in the pathogenesis of asthma, which include allergens, infections, exercise, climatechange, smoking, etc. Allergen is one of the most important environmental factors. Mostcommon allergens include inhaled allergens (mmites, house dust, fungi, plants, animaldander, etc.), ingestion of allergens (egg white, milk, seafood, fruits, peanuts/soybeans,etc.)，and contact allergens (dyes, cosmetics, etc.), and so on. On the other hand, fractionalexhaled nitric oxide is a marker of asthmatic airway inflammation, which can be used aasa index of supporting the disgnosis of asthma, monitoring the airway inflammation,evaluating the efficacy of inhaled steroid, adjusting the dose of steroid and evaluating thetreatment compliance. Moreover, many studies described the correlation of fractionalexhaled nitric oxide and eosinophilic airway inflammation, which is measured througheosinophil counting in sputum, bronchoscopy lavage fluid, bronchoscopy mucosal biopsyand peripheral blood. However, very few data can be obtained about the correlation ofFENO and allergen specific IgE.Objective: The aim of this study was to examine whether the level of fractional exhaled nitric oxide is correlated with the level of serum allergen spcific IgE, total IgE in patientswith asthma.Methods: Total of125asthma patients were recruited consecutively from respiratorymedicine outpatient clinic of xijing hospital. Fractional exhaled nitric oxide was measuredby fractional exhaled nitric oxide tester (NIOX MINO Aerocrine AB, Sweden). sIgE andtotal IgE were measured by AllergyScreen (sensitive screening) system the (Germanymoers City Mediwiss produced). Data were analyzed using Pearson correlation method.Results: In125asthma patients,73cases is allergen specific IgE positive,52cases isallergen specific IgE negative. Geometric mean of fractional exhaled nitric oxide inpositive Allergen specific IgE (55ppb) patients is significantly higher than that in negativeallergen specific IgE (31ppb) patients (P<0.001). Two-variable correlation analysisindicated that there are a significant positive association between HDM-specific IgE levels(ln) and fractional exhaled nitric oxide levels (ln), r=0.7417, P<0.001. Two-variablecorrelation analysis indicated that there are a weak positive association betweenfungi-specific IgE levels (ln) and fractional exhaled nitric oxide levels (ln), r=0.488,P>0.05. Fractional exhaled nitric oxide levels increased with number of allergens and totalIgE levels.Conclusion: Allergen is one of the factors in determining the level of fractional exhalednitric oxide. Fractional exhaled nitric oxide leves is closely related to the degree ofallergen sensitization.