The Role Of Neutrophil Elastase,Alpha 1 Antitrypsin,Human Neutrophil Peptides In The Acute Exacerbation Of Chronic Obstructive Pulmonary Disease

Background An exacerbation of COPD is an acute worsening of respiratory symptoms beyond the range of daily variation that results in additional therapy.Exacerbations negatively impact health status,rates of hospitalisation and mortality.The prognosis of AECOPD patients who need to be admitted to ICU because of respiratory failure or combined with other serious diseases is also the worst.The imbalance of the protease-antiprotease system is an important pathogenesis mechanism of COPD.Neutrophil elastase(NE)is released by activated neutrophils and macrophages which can stimulates mucus secretion and induces apoptosis of small airways and alveolar epithelial cells.Furthermore,it can also have the role of decompose collagen and fibronectin,which result the destruction of alveolar.Human neutrophil Peptides(HNPs)which released by primary particles of neutrophils and are the most abundant protein stored in neutrophil azure granules,it can clear pathogenic and regulate immunity.?1-antitrypsin(A1AT)is mainly synthesized and released by hepatocytes which has a broad inhibitory effect on proteases.A1 AT also has the effects of anti-inflammatory,inhibiting alveolar cell apoptosis and reducing the oxidative stress in the lung.A1 AT can also bind to HNPs and inhibit HNPs activity.The most important triggered factor of AECOPD are upper respiratory tract virus infection and tracheal-bronchial bacterial infection.When the body becomes infected,the released ofNE,HNPs and A1 AT will be increased.However,it is also unclear about the dynamic change of NE,HNPs and A1 AT levels in the blood of AECOPD patients.whether monitoring the dynamic levels of NE,HNPs and A1 AT in the blood of AECOPD patients can help to understand the progression of infections diseases and patients response to treatment.Whether NE-A1 AT balance / imbalance is related to different outcome of AECOPD patients.This study intends to dynamically monitor the levels of plasma NE,HNPs and A1 AT in AECOPD patients,to explore the relationship between its dynamic change and the prognosis of AECOPD patients,and to provide new direction for future clinical treatment.Objective To investigate the correlation between the dynamic changes of NE,HNPs and A1 AT and the outcome of AECOPD and its value in evaluating the prognosis of AECOPD patients.Methods This study is a retrospective case control study,We recruited 73 AECOPD pati ents from the Department of Intensive Care Medicine of the First Affiliated Hospit al of Guangzhou Medical University from January 1,2014 to December 1,2018.20 COPD stable patients were enrolled who had been diagnosed with COPD in ou r hospital and were currently in stable phase.50 healthy volunteers from physical examination center in the same hospital were enrolled as normal control group.AE COPD patients were divided into survival group and non-survival group based on t heir ICU outcome.Peripheral blood were collected with 48 h,3rd day,5th day after AECOPD patients staying in ICU,Collect peripheral blood from stable COPD pat ients and healthy volunteers,recorded they clinical data.The plasma levels of NE,HNPs and A1 AT were measured by ELISA.Compare the concentrations of NE,HNPs and A1 AT in the plasma of healthy volunteers,COPD stable patients and A ECOPD patients;Analyze the dynamic changes of NE,HNPs and A1 AT expressio n of 48 h,day3,day5 in AECOPD patients.Results 1.In AECOPD non-survival group,the proportion of blood neutrophils,t he level of lactate?procalcitonin?troponin I and the APACHE II score were higher than the proportion of blood neutrophils,lactate,procalcitonin,troponin I,APACHE II score of AECOPD survival group.The serum total protein lev el,the serum albumin level of the AECOPD non-survival were lower than ser um total protein level,serum albumin level of AECOPD survival group.In A ECOPD non-survival group,Combined with more septic shock.All of P <0.05.2.The NE,HNPs and A1 AT concentration of AECOPD patients in ICU was significantly higher than that in COPD stable patients and healthy volunte ers.All of P <0.05.3.In AECOPD survival group,the NE concentration on day5 lower than on 48 h,P=0.045.The concentration of NE in AECOPD non-survival group on day5 h as higher trand than that of the survival group on day5,P=0.072.the concentration of HNPs in AECOPD non-survival group on day5 had a higher trend than that of AECOPD survival group on day5,P=0.075.In AECOPD survival group,the A1 A T concentration on day5 lower than on day3,P=0.013.There is a good positive c orrelation between the level of NE and HNPs.Conclusion The levels of plasma NE,HNPs and A1 AT of AECOPD patients were signifi cantly higher than those of stable COPD and healthy volunteers.The levels of plas ma NE and A1 AT of the AECOPD survival group showed a decline trend over th e disease progresses;The NE level of the AECOPD non-survival group on day5 te nded to be higher than those of the survival group.There is a positive correlation between the level of NE and HNPs.NE-A1 AT imbalance may be part of the cau se of adverse outcomes in AECOPD patients.