Comprehensive Evaluation Of Asthma,Asthma-COPD Overlap And COPD Using Multiple Inflammatory Indexes: A Clinical Study

BackgroundChronic respiratory diseases(CRD)are a group of heterogeneous disorders characterized by chronic airway and/or lung diseases,and are the third leading cause of death in the world.In 2017,nearly 545 million people worldwide suffered from CRD,resulting in 3.91 million deaths.The most common cause of death in CRD is chronic obstructive pulmonary disease(COPD),followed by asthma.Therefore,definite diagnosis and timely treatment are particularly important to reduce the disease burden of CRD.Despite the fact that asthma and COPD are two well-defined diseases,some patients have the clinical characteristics of both asthma and COPD,which is known as asthma-COPD overlap(ACO).ACO is an understudied group.At present,there is no consensus on the definition of ACO,and the clinical guidelines for the identification and management of ACO remain controversial.A large number of studies have indicated that patients with ACO have worse prognosis and more frequent exacerbations than those with asthma or COPD alone.Therefore,there is an urgent need for some biomarkers to assist distinguish asthma,ACO and COPD,and to explore the treatable characteristics of the diseases,thus carry out precise treatment.The pathogenesis of CRD is complex and not completely clear.At present,it is generally believed that the pathological basis of CRD is chronic nonspecific inflammation.It is well known that asthma is mainly mediated by CD4~+T lymphocytes,eosinophils(EOS)and mast cells,while COPD is mainly mediated by CD8~+T lymphocytes,neutrophils and macrophages.The inflammatory mechanism of patients with ACO is a mixed inflammatory pattern caused by the overlap of inflammatory pathways in asthma and COPD.Therefore,the analysis of inflammatory indexes in hemogram to establish biomarkers to distinguish and evaluate asthma,ACO and COPD has important clinical significance.ObjectiveIn order to find inflammatory biomarkers that can assist clinicians distinguish and evaluate asthma,ACO and COPD,the purposes of this study include:1)to observe the expression of inflammatory indexes in patients with asthma,ACO and COPD to identify the endotype of the disease(the pathophysiological mechanisms);2)to find the objective markers that can distinguish the three diseases and reflect GOLD category of COPD,so as to guide clinical treatment according to objective indexes to achieve the goal of precision medicine;3)to explore the relationship between inflammatory biomarkers and patients’symptoms,symptom control and lung function to evaluate the prognosis of the diseases.MethodsThe study enrolled 259 eligible patients,including 79 with asthma,63 with ACO,and117 with COPD.The baseline data,blood routine test and cytokines were collected.Multinomial logistic regression was used to establish inflammatory biomarkers to distinguish asthma,ACO and COPD;Spearman correlation test was performed to analyze the relationship between inflammatory indexes and GOLD category of COPD patients;Linear correlation analysis was adopted to determine the relationship between inflammatory indexes and the symptoms,symptom control and lung function of patients.Results1.The difference of inflammatory indexes among three groups of diseases.Through statistical analysis,it was found that there were significant differences in blood routine indexes among the three groups of diseases.The EOS in patients with asthma/ACO was higher than in patients with COPD,and the neutrophil-lymphocyte ratio(NLR)and systemic inflammation response index(SIRI)was lower than in patients with COPD;the lymphocyte-monocyte ratio(LMR)in asthma patients was higher than in ACO/COPD,and the eosinophil-basophil ratio(EBR)in ACO patients was higher than in COPD.Secondly,the results of cytokine detection among three groups showed that the level of interleukin-10(IL-10)in patients with asthma/ACO was higher than in COPD,while IL-17 was lower than in patients with COPD.2.The ability of inflammatory indexes to distinguish three groups of diseases.The results showed that with ACO as the reference group,the indexes of platelet and NLR were higher,while the level of platelet/lymphocyte ratio(PLR)was lower in asthma/COPD patients;compared with ACO patients,the level of EOS in COPD patients was lower,and EBR was higher.At the same time,it was found that cytokines have little effect on disease differentiation.3.The relationship between inflammatory indexes and comprehensive assessment ofCOPD severity.The patients with ACO and COPD were divided into four groups according to GOLD category to compare the differences of inflammatory indexes among subgroups.It was found that the PLR,SIRI and IL-6 in group D were higher,while the LMR were lower compared with other subgroups.At the same time,Spearman correlation test showed that EOS,PLR,EBR,systemic immune-inflammatory index(SII),SIRI and IL-6 were positively correlated with the severity of the disease,while LMR was negatively correlated with the severity of the disease.4.The relationship between inflammatory indexes and symptom control of patients.Because the symptoms of asthma and ACO are intermittent and episodic,theasthma control test(ACT)was used to evaluate the symptom control of asthma andACO.The correlation analysis of inflammatory indexes and ACT score found thatEOS,IL-1β,IL-2,IL-6,IL-8 and interferon-γ(IFN-γ)were negatively correlated withsymptom control of patients.5.The relationship between inflammatory indexes and the symptom severity and lungfunction of patients.Since patients with non-acute asthma have mild symptoms,we focused on the evaluation of symptoms in patients with ACO and COPD according to the COPD assessment test(CAT)score.Linear correlation analysis was used to assess the relationship between inflammatory indexes and the severity of symptoms.The results showed that hemoglobin and LMR were negatively correlated with symptom severity,while EOS,EBR,SIRI and IL-6 were positively correlated with symptom severity.It was also found that LMR was positively correlated with lung function.ConclusionsThe results of this study indicated that inflammatory indexes can be used as an auxiliary tool to distinguish asthma,ACO and COPD,and to estimate the prognosis of the disease.The clinical application value of different inflammatory indexes was different.Platelet,NLR,PLR and EOS-related indexes were helpful to distinguish asthma,ACO and COPD;inflammatory indexes such as EOS,EBR and IL-6 can be used to comprehensively evaluate the severity of COPD;EOS,IL-1β,IL-2,IL-6,IL-8 and IFN-γcan be used to evaluate symptom control of patients;and hemoglobin,LMR,IL-6 and EOS-related indexes can assess the severity of symptoms,and LMR was also related to lung function of patients.In addition to predicting the symptom control of asthma and ACO patients,cytokine as a clinical evaluation tool has relatively limited application value in CRD patients.