| Background and objective:Bronchiectasis is chronic airway inflammatory disease characterized by chronic cough and expectoration.Currently,“vicious circle” theory was recognized as pathogenesis of bronchiectasis,including airway infection,chronic inflammation and airway structural damage.However,the underlying mechanisms are poorly understood.The accelerated aging has been considered as the pathogenesis of chronic airway inflammatory diseases,such as chronic obstructive pulmonary disease(COPD),asthma and idiopathic pulmonary fibrosis(IPF).Bronchiectasis is also a common chronic airway inflammatory disease.Therefore,accelerated aging may also be involved in the occurrence and development of bronchiectasis.Previous studies have shown that lung tissue of bronchiectasis patients aging faster than healthy subjects,that is,the expression of p21 of patients with bronchiectasis was higher than healthy subjects,while sirtuin1 was lower than healthy subjects.However,the relationship between the expression of aging-related biomarkers in the airway epithelium and bronchiectasis severity,acute exacerbation and lung function is unclear.As is known to us,it is difficult to obtain lung tissue in clinical practice and previous studies have shown that peripheral blood can also detect signals of accelerated aging.For example,abnormal expression of aging-related biomarkers can be found in peripheral blood of diseases such as COPD,asthma and IPF.However,the expression of aging-related biomarkers in bronchiectasis peripheral blood remains unknown.Therefore,this study mainly focus on two important scientific issues: 1)To explore the difference expression of aging-related biomarkers between bronchiectasis patients and healthy subjects in peripheral blood mononuclear cells(PBMCs),and to explore their association with the bronchiectasis severity,acute exacerbation and clinical indicators;2)To investigate the expression of some aging-related biomarkers in airway epithelium and their relationship with clinical indicators such as lung function,and to explore the different expression of biomarkers in the airway epithelium of different anatomical sites(large/medium and small airways).Section 1 The association between the expression of aging-related biomarkers in bronchiectasis PBMCs and bronchiectasis severityBackground: Accelerated aging has been found in the PBMCs of patients with COPD,asthma and IPF and bronchiectasis is also a chronic airway inflammatory disease.However,the expression of aging-related biomarkers in bronchiectasis PBMCs and their clinical significance is unknown.Objective: To explore the difference expression of aging-related biomarkers between bronchiectasis patients and healthy subjects in PBMCs,and to explore their association with the bronchiectasis severity,acute exacerbation and clinical indicators Methods: In this prospective cohort study,we enroll 132 bronchiectasis patients and50 healthy subjects and collected their venous blood for detection the expression of aging-related biomarkers.Bronchiectasis patients were followed up every 3-6 months and at exacerbation episodes.Results: During follow-up,a total of 177 peripheral blood samples were collected from 132 patients.The relative telomere length(T/S ratio),the expression of sirtuin1 and Ku80 were significantly decreased in 177 patients with bronchiectasis(P<0.05)compared with healthy subjects [median: 0.88(IQR: 0.73-1.07)vs.0.99(IQR:0.82-1.24),0.89(IQR: 0.77-1.02)vs.0.99(IQR: 0.87-1.09)and 0.87(IQR: 0.78-0.99)vs.0.96(IQR: 0.87-1.11),respectively].The relative telomere length(r=-0.162,P=0.031)and TERT(r=-0.216,P=0.004)were negatively correlated with the bronchiectasis severity.The relative telomere length,the expression of sirtuin1 and Ku80 were positively correlated with FEV1% and FEV1/FVC,but the associations are markedly attenuated after adjustment such as age.The expression of aging-related biomarkers at baseline didn’t predict the risk of acute exacerbation of bronchiectasis during the 1 year follow-up.Conclusions: There were abnormal expression of aging-related biomarkers in bronchiectasis PBMCs,which were associated with the bronchiectasis severity and acute exacerbation,but the expression of all aging-related biomarkers at baseline can’t predict the risk of acute exacerbation of bronchiectasis during the 1-year follow-up.Section 2 The expression of aging-related biomarkers in the epithelium of bronchiectasis airwayBackground: Previous studies have shown that the expression of aging-related biomarker Sirtuin1 in bronchiectasis airway epithelium is decreased,as well as the p21 is highly expressed,but the sample size was small and whether there are differences in the expression of aging-related biomarkers in different anatomical sites of the lung are still unclear.Objective: To investigate the expression of some aging-related biomarkers in airway epithelium and their relationship with clinical indicators such as lung function,and to explore the different expression of biomarkers in the airway epithelium of different anatomical sites(large/medium and small airways).Methods: We collected large/medium airways and small airways from 36 patients with bronchiectasis and 32 control patients,respectively.We assessed the expression levels of aging-related biomarkers sirtuin1,p16 and p21 in airway epithelium by immunohistochemical staining.Results: The aging-related biomarkers were expressed in airway epithelium of both the bronchiectasis group and the control group.Compared with the control group,the proportion of staining positive cells of sirtuin1 was significantly decreased(25.1% vs.57.2%,P=0.001),while there was no significant difference in p16(40.0% vs.44.2%,P=0.113)and p21(30.1% vs.33.7%,P=0.113)between the two groups.The proportion of staining positive cells of sirtuin1 was significantly positively correlated with FEV1%(r=0.294,P=0.014).There was no significant difference in the expression of Sirtuin1,p16 and p21 between the large/medium and small airways of the bronchiectasis group as well as control group.Conclusions: The expression of sirtuin1 was decreased in the epithelium of bronchiectasis,and there was no significant difference between large/medium airways and small airways as well as p16 and p21. |
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