The Research Of Phenotypes And Individual Treatment Of Bronchial Asthma

Objective:With the concept of precision medicine-a new model for disease management-being proposed, according to biological information and clinical manifestation, the individual precision treatment is likely to be carried out in the future. Bronchial asthma is a heterogeneous disease. Analyse the features of clinical manifestation, lung function and biomarker of different phenotypes of patients with asthma and evaluate the effectiveness of individualized treatment, so as to improve the level of diagnosis, treatment and decrease the morality.Method:1. The phenotypes of patients with asthma:(1)one hundred and seven patients with asthma and thirty normal persons were enrolled. (2) There are two methods of grouping:1) ?The group of allergic asthma(64 patients); ?The group of non-allergic asthma(43 patients); 2) ?The group of eosinophilic asthma;(2)the group of neutrophilic asthma;(3)the group of paucigranulocytic asthma;(Dthe group of mixed granulocytic asthma. (3)We collected the general information, clinical manifestation, ACT, HAD, pulmonary function test, arterial blood gas analysis, Fractional exhaled Nitric(FeNO), eosinophil?neutrophil and the concentration of IL-5?8?13?17 in induced sputum and blood?the concentration of IgE in serum. (4) Compare the difference of the parameters between the groups. (5) Evaluate the diagnostic value of FeNO?peripheral eosinophil?concentration of IgE in eosinophilic asthma.2. The research of individual treatment method and effect.(1) Compare the examination index before and after treatment. (2)Th individual treatment method:? patients with allergic asthma:three month therapy of ICS+LABA and montelukast sodium were given to 20 patients.?atients with neutrophilic asthma:ICS+LABA and clarithromycin were given to 5 patients.?atients with severe asthma who have repeated episodes in spite of regular medicine(ICS+LABA):2 patients received bronchial thermoplasty.Results:1.The feature of phenotype of patients with allergic and non-allergic asthma:(1)Compared with non-allergic asthma, in allergic asthma group, the first onset age is younger, the course of the disease is longer, the score of ACT is lower, the level of FEV1% and MMEF75/25% is lower, the mutation rates of FEV1 and PEF after the inhalation of salbutamol are higher(P<0.05). (2) Compared with non-allergic asthma, in allergic asthma group, the level of FeNO is higher, the concentration of IgE in serum is higher, the percent of eosinophil in in peripheral blood and in induced aputum are both higher, the porption of eosinophilic asthma is higher and the proption of neutrophilic asthma is lower (P<0.05). (3) Compared with non-allergic asthma, in allergic asthma group, the concentration of IL-5 and IL-13 in serum and sputum are higher, the concentration of IL-8 and IL-17 in serum and sputum are lower (P<0.05).2.The feature of phenotypes of different airway inflammation:(1)Compared with paucigranulocytic asthma, FEV1%?FEV1/FVC%?FEF50%?FEF75%? MMEF75/25% are lower and the first onset age is younger in group of eosinophilic asthma, PEF% is lower in group of neutrophilic asthma, the score of ACT and PaO2 are lower in group of eosinophilic asthma and group of neutrophilic asthma(P<0.05). (2)In eosinophilic asthma group, the level of FeNO, the concentration of IgE and the percent of eosinophil in peripheral blood are higher than that in group of neutrophilic asthma and group of paucigranulocytic asthma(P<0.05). The level of FeNO is higher in group of paucigranulocytic asthma than group of neutrophilic asthma(P<0.05).(3) In eosinophilic asthma group, the concentration of IL-5 and IL-13 in serum and sputum are higher than that in group of neutrophilic asthma and group of paucigranulocytic asthma(P< 0.05). In group of neutrophilic asthma, the concentration of IL-8in serum and sputum is higher than that in group of neutrophilic asthma and group of paucigranulocytic asthma(P<0.05). (4) In the external validation cohort, ROC AUC for FeNO level is 73.3%(P=0.002,95%CI 0.607?0.860) and for eosinophil in peripheral blood 78.4%(P=0.000,95%CI 0.667?0.901) to detect eosinophilic asthma.3. Individual treatment methods and effect:(1)In allergic asthma group, after treatment given to 20 patients, the percent of eosinophil in induced sputum, the percent of eosinophil in peripheral blood, the concentration of IgE, IL-15 and IL-13 in serum and sputum, the level of FeNO and positive rate of HAD decreased significantly (P<0.05), ACT?FEV,%pred?FEV1/FVC and PEF increased (P<0.05). (2)In neutrophilic asthma group, after treatment, the percent of neutrophilic in induced aputum, the concentration of IL-18 in serum and sputum decreased significantly (P<0.05) and FEV1%pred?PEF and ACT increased (P<0.05). (3)After bronchial thermoplasty, FEV1%?FEV1/FVC?PEF%? MMEF75/25%?postFEV1/FVC and ACT all improved in this two patients, and more significantly in first patient. In addition, the percent of eosinophil in peripheral blood both decreased obviously. Before treatment, two patients both have hypoxemia but the oxygenaration show normal after treatment.Conclusions:1. For patients with allergic asthma, the first onset age is younger, the pulmonary function injury is more obvious, the control level is lower, the level of FeNO and the percent of eosinophil in sputum and peripheral blood are higher. Eosinophilic asthma is the main part of allergic asthma; neutrophilic asthma and paucigranulocytic are the main part of non-allergic asthma.2. Pulmonary ventilation function, PaO2 and the control level are lower in patients with eosinophilic asthma and neutrophilic asthma than that in patients with paucigranulocytic asthma. The level of FeNO, the concentration of IgE and the percent of eosinophil in peripheral blood are higher in patients with eosinophilic asthma than that in patients of neutrophilic asthma and paucigranulocytic asthma.3. Eosinophilic asthma is closely related to Th2 immune pathway and neutrophilic asthma is closely related to Th17 immune pathway. The interleukin in serum and sputum, FeNO and eosinophil in peripheral blood had a great value to identify the airway inflammation type of asthma patients.4. Bronchial asthma is a heterogeneous disease. Individual treatment based on different phenotype can improve the therapy effect. ICS+LABA proves obvious effect in the therapy of allergic asthma; Clarithromycin can increase the therapentic effect for the patients with neutrophilic asthma; Bronchial thermoplasty can improve the syndrome and pulmonary function for the patients with severe asthma who have repeated episodes in spite of regular medicine, but more clinical research is needed to understand the long-term outcomes of the new therapeutic method.