A Systematic Review Of The Risk Factors Of COPD Frequent Acute Exacerbation Phenotype And A Study On The Distribution Of TCM Syndrome Element

Purpose:To explore the risk factors related to the frequent exacerbation phenotype of chronic obstructive pulmonary disease（COPD）by systematically evaluating the published literature.Moreover,explore the distribution law of TCM syndrome elements in patients with frequent exacerbation phenotype of COPD in the stable period and clarify the TCM pathogenesis characteristics.And thus further analyze the internal correlation between them,which could guide clinical accurate syndrome differentiation,realize personalized diagnosis and treatment,and provide a basis for early intervention and prevent disease progression.Material and method:The first part was based on electronic retrieval and manual retrieval,and 8 Chinese and English databases were comprehensively searched,including Sino Med,CKNI,VIP,Wang Fang Data,the Cochrane Library,Pub Med,Web of Science and Embase.The two researchers read the literature independently and conducted literature screening according to the criteria of inclusion.Newcastle Ottawa scale was used to evaluate the literature quality of the case-control studies,cohort studies,and the evaluation scale recommended by Agency for Healthcare Research and Quality was used to evaluate the literature quality of the cross-sectional studies.The final included clinical data were extracted and cross-checked.Stata 12.0 software was used to classify the included risk factors with merged statistics in the form of odds ratio and mean difference.The second part was a retrospective study conducted in patients with frequent exacerbation of COPD were selected from the electronic medical record system in the Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,all of whom has hospitalized in the outpatient department or inpatient department of the respiratory department from January2021 to December 2021.Their clinical data were respectively collected by the two researchers,including gender,age,course of COPD,number of acute exacerbations in the past year,clinical symptoms,signs,tongue,and pulse information in the stable period.Syndrome Differentiation factor Scale and Syndrome Element Diagnostic Criteria in Syndrome Differentiation written by Professor Zhu Wenfeng was referred to judge whether the element is tenable.SPSS statistics 26.0 software was used to cluster the syndrome element results,and summarize the distribution law of TCM syndrome elements in patients with frequent exacerbation phenotype of COPD.Results:1.A total of 39 studies were included,with 5506 participants involved,2431 in the experimental group and 3075 in the control group.A total of 48 factors were extracted,including general information,medical history,symptoms and signs,lung function,hematological indicators,sputum culture,prevention and treatment,etc.28 factors were associated with frequent exacerbations of COPD.Of these,10 were risk factors for frequent acute exacerbations,including age[WMD=0.99,95%CI=（0.37,1.62）,P=0.002],smoking index（pack-years）[WMD=5.04,95%CI=（1.49,8.59）,P=0.005],duration of disease[WMD=1.52,95%CI=（0.55,2.5）,P=0.002],combinedasthma[OR=1.87,95%CI=（1.43,2.45）,P<0.001],Modified British Medical Research Council scores（m MRC）[WMD=0.64,95%CI=（0.52,0.76）,P<0.001],arterial partial pressure of carbon dioxide（Pa CO₂）[WMD=5.43,95%CI=（3.51,7.34）,P<0.001],white blood cell（WBC）[WMD=0.59,95%CI=（0.2,0.97）,P=0.003],neutrophil%（NEUT%）[WMD=5.59,95%CI=（1,10.18）,P=0.017],C-reactive protein（CRP）[SMD=0.99,95%CI=（0.31,1.67）,P=0.004],positive sputum culture[OR=6.5,95%CI=（3.84,11.02）,P<0.001].3protective factors include forced expiratory volume in the first second（FEV1）[WMD=-0.15,95%CI=（-0.2,-0.11）,P<0.001],forced expiratory volume in the first second in percent predicted values（FEV1%）[WMD=-7.32,95%CI=（-9.63,-5.01）,P<0.001],FEV1%≥50%[OR=0.42,95%CI=（0.25,0.68）,P=0.001].The protective factors include FEV1,FEV1%,and FEV1%≥50%.15 uncertain risk factors include body mass index（BMI）,length of stay,m MRC score≥2,COPD assessment test（CAT）score,St George’s respiratory questionnaire（SGRQ）score,wheezing,forced vital capacity（FVC）,FEV1/FVC,inspiratory capacity%（IC%）,forced expiratory flow 25-75%（FEF25-75%）,hydrogen ion concentration（p H）,procalcitonin（PCT）,fibrinogen（FIB）,LY（lymphocyte）),use inhaled corticosteroids（ICS）,and vaccination.2.A total of 82 related cases were included,and the syndrome database and syndrome element database of patients with frequent acute exacerbation of COPD were established.A total of 10 disease location elements（lung,kidney,heart,spleen,liver,chest,stomach,surface,large intestine,mind）and 21 disease syndrome elements（deficiency syndrome elements include qi deficiency,yin deficiency,yang deficiency,blood deficiency,qi deficiency,fluid deficiency,qi escape.Solid syndrome elements include phlegm,fire[heat],blood stasis,fluid retention,dampness,qi stagnation,water retention,cold,stirring blood,blood-heat,（external）wind,dryness,stirring wind,blood-cold）were extracted.The main disease location elements were lung,kidney,heart,and spleen,while the main disease syndrome elements were qi deficiency,yin deficiency,phlegm,yang deficiency,fire[heat],and blood stasis.The clustering results indicated that the core syndrome elements were qi and yin deficiency of lung and kidney,interior obstruction of turbid phlegm,deficiency and debilitation of heart yang,the combination of phlegm and stagnant heat,fluid retention in the chest and hypochondrium,deficiency of defense qi that fails to protect the body,blood deficiency of liver and spleen,and the combination of qi stagnation,dampness encumbrance,and water retention.Conclusion:1.The risk factors of frequent exacerbation in COPD include age,smoking index（pack-years）,duration of disease,asthma,m MRC score,Pa CO₂,WBC,NEUT%,CRP,and positive sputum culture.The protective factors include FEV1,FEV1%,and FEV1%≥50%.2.Disease location in patients with frequent exacerbation phenotype of COPD mainly include lung,kidney,heart,spleen,liver,and chest cavity.Disease nature mainly includes qi deficiency,yin deficiency,phlegm,yang deficiency,blood stasis,fire and heat,and fluid retention.Pathogenesis is summarized as the location of the disease is in the lung and closely related to the kidney,spleen,heart,and liver.The disease is complex in deficiency and excess,based on the root of qi and yin deficiency and the five internal organs deficiency,and the branch of phlegm and fluid retention,phlegm and heat combination,and the obstruction of collaterals by blood stasis.There was internal correlation between risk factors and TCM syndrome elements,and their organic combination could provide an objective basis for syndrome differentiation.