Analysis Of Clinical Features Of Mixed Granulocytic Asthma In Non-acute Episode Phase

Background and objectiveBronchial asthma, shorted for asthma, is a heterogeneous disease, which usually characterized by chronic airway inflammation. Asthma causes symptoms such as wheezing, shortness of breath, chest tightness and cough that vary over time in their occurrence, frequency and intensity. These symptoms are associated with variable expiratory airflow. Usually, airway hyperresponsiveness and chronic inflammation are homochronous presence of asthma. Asthma is one of the most common chronic lung diseases clinically, which has higher morbidity and high mortality.Asthma is a heterogeneous disease, with complicated pathogenesis, diverse clinical manifestation and various pathophysiologic changes. In 2009, Global Initiative for asthma (GINA) first proposed the concept of phenotype, and propounded that the classification of the phenotype of asthma might help to know the clinical treatment and prognostic judgement. The asthma inflammatory phenotype mainly has the following kinds:eosinophilic asthma (EA), neutrophilic asthma (NA)、paucigranulocytic asthma (PA), and mixed granulocytic asthma(MA). The classification of these four inflammatory phenotype is based on the percentage of granulocyte in induced sputum:eosinophilic asthma:eosinophil ratio in sputum>1.01%; neutrophilic asthma:neutrophil ratio in sputum>61%; paucigranulocytic asthma:eosinophil ratio in sputum<1.01%, and neutrophil ratio <61%; mixed granulocytic asthma:eosinophil ratio in sputum>1.01%, and neutrophil ratio in sputum>61%. However, classification of inflammatory phenotype was redivided by Gibson in 2009. He put forward that the classification of eosinophil in induced sputum should not use 1.01% as critical value, but 3%. Similarly, the differential blood count may also divided asthma into four different phenotypes, and the percentage was also similar to that divided by induced sputum.The four asthma inflammatory phenotype’s clinical features are as follows:(1) eosinophilic asthma:typical asthma, and frequently associated with atopic disease. Have higher proportion of family history; younger onset age; glucocorticoid treatment has a better effect relatively. And meanwhile, may indicate inadequate corticosteroid therapy; (2) neutrophilic asthma:always associated with several risk factors:acute infection such as viral or bacterial; chronic infection such as chlamydia or adenovirus; smoking; environmental pollutants, like ozone, NO2; occupational antigens; endotoxin exposure; obesity. (3) mixed granulocytic asthma: often see in severe asthma exacerbations or refractory asthma; (4) paucigranulocytic asthma:mean well controlled or intermittent asthma; or may consider alternative diagnosis.Asthma Control Questionnaire-5(ACQ-5) is a rating scale for evaluation of asthma control level, which involves symptoms in the day and night, activity limitation degree, and airway diameter. The gold standard to assess the severity of asthma is lung function test. However, whether there is a relationship between lung function test and ACQ-5? Whether ACQ-5 may use to assess the severity of asthma? The answer of these two questions may find in our research. Besides, because asthma inflammatory phenotype has complicated pathogenesis and diverse clinical manifestation, whether ACQ-5 could use to assess the severity of different inflammatory phenotype is still unknown.Previous research mainly focused on eosinophilic asthma and neutrophilic asthma, especially the eosinophilic asthma. However, the clinical features of mixed granulocytic asthma are rarely reported. The clinical characteristics of mixed granulocytic asthma were discussed in this study, and may help to improve the recognition of this type of asthma for clinical doctors.MethodWe retrospectively reviewed 134 cases of asthma outpatients in non-acute episode phase seen in the NanFang hospital from March 2012 to February 2014, to the exclusion of other lung diseases including airway infections. The clinical data of these patients’ cases were collected using our hospital computerized medical records database, which included the demographic data, Asthma Control Questionnaire (ACQ-5) and pulmonary function tests (PFT). Sputum and venous blood of these patients were also collected and analyzed for cell differential. We divided the 134 cases into the Mix granulocytic asthma group and the non-Mix granulocytic asthma group depending on their sputum eosinophils≥ 3% and the neutrophils≥ 64%. We compared the clinical characteristics and survey the difference between the two groups.Result1.1 General characteristics of asthma patientsThere is 134 patients with asthma comply with the inclusion criteria and exclusion criteria, with average age 41.11± 12.18, among which, there is 69 male patients (51.59%) and 65 female patients (48.51%). The average body mass index (BMI) is 22.36±3.33 kg/m2.43 patients (32.09%) combined with allergic rhinitis,56 patients (41.79%) have allergy history,40 patients (29.85%) are smoker, and 11 patients (8.21%) have been treated by inhaled corticosteroids (ICS).1.2 The inflammatory phenotype of asthma patients Based on the percentage of granulocyte in induced sputum, all asthma patients were divided into two different inflammatory phenotypes:22 patients (16.42%) were mixed granulocytic asthma, and 112 patients (83.58) were non-mixed granulocytic asthma.1.3 The distribution of severity of asthma in two different inflammatory phenotypes In Mix granulocytic asthma and non-Mix granulocytic asthma, the distribution of different severity degree of asthma was similar. The constituent ratio of two inflammatory phenotypes in the three severity degree of asthma (mile asthma, moderate asthma, and severe asthma) had no significant difference (P>0.05).1.4 The clinical characteristics of Mix granulocytic asthma Age, smoking history, BMI, allergies history, ICS treatment, white blood cell count(WBC), lymphocytic count(LYM), eosinophil count(EOS) and neutrophil count(NEU) had no statistically significant difference in the Mix granulocytic asthma group compared with the non-Mix granulocytic asthma group (P>0.05). Compared to the non-Mix granulocytic asthma group, a significant decrease in the first second forced vital capacity (FEV1), FEV1 as a percentage of predicted value(FEV1%), the rate of peak expiratory flow(PEF), the number of sputum macrophage and the scores of ACQ-5 was noticeably higher in the Mix granulocytic asthma group. All the results were statistically significant difference (P<0.05).1.5 The difference of ACQ-5 in different severity degree of asthma The ACQ-5 score in the mile asthma group was 1.65±1.17(n=60), in the moderate asthma group was 2.05±1.14(n=39), and in the severe asthma group was 2.39±1.19(n=35). The ACQ-5 score had no significant difference between the mile asthma group and the moderate asthma group (P>0.05), and also had no significant difference between the moderate asthma group and the severe asthma group (P> 0.05). However, the ACQ-5 score in the mile asthma group was significantly lower than the severe asthma group (P= 0.03).1.6 The correlation between inflammatory markers and ACQ-5 score, FEV 1% in all asthma patients In all asthma patients, both WBC and neutrophil (NEU) had significant positive correlation with ACQ-5 score(rWBC=0.229, rNEU=0.270, P< 0.05, respectively); FEV 1% had significant negative correlation with ACQ-5 score(P <0.05, r=-0.257). However, WBC, NEU, eosinophil (EOS) and FEV 1% had no correlation with ACQ-5 score (P>0.05).1.7 The correlation between inflammatory markers and ACQ-5 score, FEV 1% in non-Mix granulocytic asthma group In non-Mix granulocytic asthma group, both WBC and NEU had significant positive correlation with ACQ-5 score(rWBC= 0.258, rNEU=0.249, P<0.05, respectively); FEV 1% had significant negative correlation with ACQ-5 score(P <0.05, r=-0.256), WBC had significant negative correlation with FEV 1%(P< 0.05, r=-0.197). However, WBC and EOS had no correlation with FEV 1% (P>0.05), EOS had no correlation with ACQ-5 score (P>0.05).1.8 The correlation between inflammatory markers and ACQ-5 score, FEV 1% in Mix granulocytic asthma group In Mix granulocytic asthma group, EOS had significant negative correlation with ACQ-5 score(P< 0.05, r=-0.502). However, both WBC and NEU had no correlation with ACQ-5 score (P>0.05). WBC, NEU and EOS had no correlation with FEV 1% score (P>0.05). FEV 1% had no correlation with ACQ-5 score (P>0.05).1.9 The correlation between NEU%, EOS% and sputum NEU%, sputum EOS% in asthma patients Respectively make correlation analysis for all asthma patients, non-Mix granulocytic asthma group and Mix granulocytic asthma group, we found that EOS% had significant positive correlation with sputum EOS%(P<0.05), had significant negative correlation with sputum NEU%(P< 0.05). However, NEU% had no correlation with sputum NEU%, sputum EOS%(P>0.05).Conclusion:1. Mixed granulocytic asthma was more severe among the asthma outpatients with lower FEV 1%.2. the number of sputum macrophage was noticeably higher in the Mix granulocytic asthma group.3. ACQ-5 scores was highly consistent with the severity of asthma patients.4. WBC, NEU in peripheral blood may be more suitable for evaluating asthma control level than the severity of asthma.5. EOS in peripheral blood may be related to the asthma control level in mixed granulocytic asthma.6. WBC, NEU in peripheral blood may be related to the asthma control level in non-mixed granulocytic asthma, and WBC was also correlation with the severity of asthma patients.7. EOS% was consistent with sputum EOS%.