The Correlation Between Peripheral Blood Cell Parameters And Airway Inflammatory Phenotype In Asthma Exacerbations

Background and ObjectionBronchial asthma(asthma)is a kind of common chronic airway inflammation diseases,it is mainly characterized by the reversible airflow limitation,airway hyper-responsiveness and airway inflammation with the clinically feature of breathing,cough,sputum and there is about 300 million of the world's population who is suffering from asthma.The pathogenesis and mechanism of asthma is very complicated without consensus up to now.Asthma exacerbation is the most common cause of asthma condition aggravation,which is an important factor of disability and death of asthma patients.To date,asthma exacerbation in clinically is usually defined by the symptoms of cough,wheezing,shortness of breath which are aggravated than before.In addition,asthma exacerbation is often accompanied by reduced expiratory flow with the inducing factors of respiratory infections,exposure to allergens and so on according to the Chinese experts consensus on the evaluation and management of asthma exacerbation in 2008.Asthma exacerbation is placing great burden to the social economy and medical system.Prof Lin has conducted a study on asthma patients who received medical treatment in Grade ?A hospitals with the cause of asthma exacerbation in 29 provinces all over China from 2013 to 2014 and he found that median hospitalization cost was 9045 yuan per capita which was significantly higher than the cost for maintenance treatment all over the year in patients with asthma.There is a close relationship between asthma exacerbation and airway inflammation and the phenotype of airway inflammation influences clinical characteristics and treatment response.While the airway inflammatory phenotype is not immutable,plenty of previous researches have been focusing on asthma patients in a stable phase,however most patients are hospitalized because of asthma exacerbation when the patient's airway inflammatory phenotype may have been changed,the corresponding response to treatment may be also different.It is of great significance to distinguish the airway inflammatory phenotypes for asthma treatment and prognosis.Although induced sputum is the gold standard test for phenotyping asthma airway inflammation,there are some shortcomings of the test,such as the course of induced sputum examination and the processing of sputum specimens are relatively complicated and time-consuming,with the requirement of professional laboratory technical personnel operation,so a more accessible method is needed for clinical practice.Peripheral blood cell counts are one of the most common and widely used test items in clinical practice and it may be a useful,non-invasive procedure to quantify inflammatory cells to detect the subtypes of inflammation in asthma exacerbation.Most patients are admitted to hospital because of acute asthma exacerbation when the airway inflammatory phenotypes may have been changed,so it is needed to re-evaluate the airway inflammation phenotype to guide the treatment and prognosis of further judgment.In addition,novel blood cell parameters derived from a full blood count have been associated with the development inflammation and tumor in recent years.Asthma is one of the most common chronic airway inflammatory diseases in the respiratory system and the changes and significance of these blood cell ratio parameters in the acute asthma exacerbation are not very clear.Therefore,this study is mainly focusing on the correlation between peripheral blood cells and their derived ratio parameters and airway inflammatory phenotypes in asthma exacerbation.Methods and materialsThis study was carried out in Respiratory and critical medical department in Nanfang Hospital of Southern Medical University,Guangzhou,Guangdong,China from September 1,2012 to September 30,2017.All patients admitted to the hospital because of asthma exacerbation were included in the study.The inclusion criteria were:1.Minimal age of 18 and consistent with the asthma diagnosis by the American Thoracic Society(ATS);2.All patients needed to meet the condition of asthma exacerbation which was defined by the Chinese experts consensus on the evaluation and management of asthma exacerbation in 2008 with the symptoms of wheezing,cough and chest tightness which were new or increasing original symptoms with the characteristics of dyspnea and reduced expiratory flow.The exclusion criteria were:1.With heart,brain,liver,kidney and other serious organ diseases;2.With various malignant tumors;3.With fever,lung infection,etc.;4.Pregnant women;5.Unwilling to cooperate or have mental illness;6.Other reasons not suitable for inclusion in the experiment.Statistical analysisAll statistical analyses were performed using SPSS software,Version 20.0 of the SPSS System for Macintosh.Results were reported as significant when P<0.05.The results were expressed as mean ± SD for continuous variables and median with interquartile range when data were not normally distributed.Categorical data were reported using frequencies and percentages.A Kruskal-Wallis test was performed in the different subgroups of subjects with asthma.Variance analysis was used for the Multiple means.Spearman's rank correlation coefficient was used to assess the association between blood cell count and sputum cell count.The performance characteristics of the blood count variables were examined by receiver-operating characteristic(ROC)curves to determine the concentrations of eosinophils,neutrophils or monocytes which best defined eosinophilic asthma,neutrophilic asthma or non-eosinophilic asthma based on the sputum cell count.ResultsThis retrospective study recruited 215 eligible patients who were made up of 75 males(34.9%)and 140 females(65.1%)with a ratio of 1:1.87.All patients were 18 to 81 years old with an average age of(52.31 + 13.33)years.None of the patients had an acute asthma exacerbation before and after the examination of induced sputum.Subjects were classified as having neutrophilic asthma(n = 89,41.4%),eosinophilic asthma(n = 56,26.05%),mixed granulocytic asthma(n = 36,16.74%)and paucigranulocytic asthma(n= 34,15.81%).Immunoglobulin E(IgE)in eosinophilic asthma group was higher than the other 3 groups(P<0.05).However other clinical information,including the sex ratio,age,history of childhood wheezing,family history,history of allergies,Body Mass Index(BMI),years of course of disease,different admission season,length of stay,severity of disease,FEV1/predicted value,FEV1/FVC,total number of white blood cells,CRP,PCT and FeNO in four asthma groups was no significant statistical difference(P>0.05).For the whole group,there was a significant positive relationship between blood eosinophil parameters and the percentage of sputum eosinophils when asthma exacerbation.These blood eosinophil parameters included not only the absolute blood eosinophil count and eosinophil percentage(r=0.566,P=0.000;r=0.626,P=0.000;respectively),but also ratios like ENR,EMR and ELR(r=0.617,P=0.000;r=0.555,P=0.000;r=0.562,P=0.000;respectively).However there was a weaker but significant correlations between sputum neutrophil percentage and absolute blood neutrophil count(r=0.158,P=0.021),blood neutrophil percentage(r=0.256,P=0.000),blood NLR(r=0.15,P=0.028),blood NMR(r=0.135,P=0.048),blood ENR(r=-0.378,P=0.000)when asthma exacerbation.There was no significant relationship between sputum neutrophil percentage and absolute white blood cells,absolute blood lymphocytes,blood lymphocytes percentage,absolute blood mononuclear cells,blood mononuclear cell percentage,blood PLR(r = 0.07,0.44,0.085,0.039,0.036,0.012;respectively;P>0.05).In the patients with asthma exacerbation the ROC curve analysis identified blood eosinophil percentage as the best predictor for eosinophilic phenotypes,with an area under the curve(AUC)of 0.908(P = 0.000),the best threshold of 5.8%,the sensitivity of 85.7%,the specificity of 86.8%,the positive predictive value of 86.7%,the negative predictive value of 85.9%.Peripheral blood ENR was also a good indicator,with the AUC of 0.904(P =0.000),the optimal threshold of 0.095,the sensitivity of 85.7%,and the specificity of 84.3%.In addition,absolute blood eosinophil is also highly predictive with an area under the curve of 0.872(P =0.000)at a blood eosinophil cut-off of 0.335 x 109/L,and this yielded a sensitivity of 85.7%,a specificity of 78%.Blood ELR and blood EMR were also good indicators for the determination of eosinophilic airway inflammation when asthma exacerbation with an area under the curve of 0.885,0.879 respectively.Neutrophilic asthma could also be detected by blood parameters,but with less accuracy.Blood neutrophil percentage was best predictor for neutrophilic asthma with an area under the curve of 0.683(P =0.000)at a blood neutrophil percentage cut-off of 64.45%,and this yielded a sensitivity of 49.4%,a specificity of 79.4%,70.6%positive predictive value and 61.1%negative predictive value.The absolute blood neutrophil,blood NLR and blood NMR could also detect the neutrophilic asthma,but with less accuracy and the areas under the curve were 0.613,0.628,0.620 respectively at the optimal threshold of 3.24 × 109/L,2.32,10.56 respectively.Blood ENR was negatively correlated with sputum neutrophil percentage(r=-0.378),and the ROC curve also confirmed that there was no meaning for estimating neutrophilic asthma with the area under the curve of 0.241..Conclusion1.When asthma exacerbation,peripheral blood eosinophil percentage,the absolute blood eosinophil count,blood ELR,blood ENR,blood EMR can accurately predict the sputum eosinophilic inflammation.It was feasible to use peripheral blood for the estimate and monitoring of eosinophilic inflammation in patients with asthma exacerbation.2.However,peripheral blood neutrophils and their derived ratio parameters had a weaker capacity to predict the neutrophilic asthma when asthma exacerbation.It was not accurate to use peripheral blood test to assess neutrophilic inflammation in asthmatic patients.