Role Of Ambient Fine Particulate Matter Exposure In The Development And Progression Of Chronic Obstructive Pulmonary Disease And Its Potential Mechanisms

Background: A multitude of epidemiological evidence from studies have shown that airborne particulate matter pollution is associated with increased morbidity and mortality of chronic obstructive pulmonary disease.However,the underlying mechanism has not yet been elucidated.The aim of this study was to investigate the role of airborne fine particulate pollution in the development of chronic obstructive pulmonary disease and its mechanism.Methods: We first conducted a cross-sectional study of the population between the urban(high PM2.5)and the rural(low PM2.5)to observe the effects of different levels of PM2.5 on the morbidity of COPD in the population and the impacts on smoking subjects with COPD.Then,we incubated human bronchial epithelial cells with different concentrations of PM2.5 for 24 h.The expression levels of IL-6 and IL-8 were detected by ELISA.Immunoblotting was used to determine the levels of MMPs,TGF-?1 and fibronectin.At the same time,twenty four C57 BL / 6 mice(male,6-8 weeks,18-20g)were randomly divided into four groups:(1)control group : mice were exposed to filtered air;(2)cigarette smoke-exposed group: mice were exposed to cigarette smoke passively in PAB-S200 Animal Passive Smoking Exposure System for 2h/d for 5d/wk.(3)PM2.5-exposed group: mice were exposed to PM2.5 for 6h/d for 5d/wk.(4)PM2.5 + cigarette smoke exposure group: mice were exposed to passive cigarette smoke for 2h/d and PM2.5 for 6h/d for 5d/wk.To better simulate the development of COPD over a substantial duration of individual life,we have conducted a 10-month modeling cycle.The lung function was measured by Ani Res2005 animal lung function analysis system.The morphological changes of lung tissue and infiltration of inflammatory cells in lung tissue were observed by HE staining.ELISA,immunohistochemistry and Sirius red staining were used to detect the expression levels of proteins.Results: In the cross study of population,we found that the effect of PM2.5 on the morbidity of COPD in the population varies with the levels of PM2.5 and PM2.5,together with cigarette smoke,has an synergistical impacts on the development and progression of COPD in the population.In normal human bronchial epithelial cells,PM2.5 exposure could not only up-regulate secretion of proinflammatory cytokines(IL-6 and IL-8)and MMPs,TGF-?1 and fibronectin involving in lung airway remodeling,but also enhance the role of cigarette smoke extract on the productions of these proteins.Moreover,long-term PM2.5 exposure can induce decreased lung function,emphysematous changes and pulmonary inflammation in mouse models.Furthermore,PM2.5 can markedly enhance cigarette smoke-induced pulmonary inflammation,airway remodeling and lung function decrease.Conclusion: In short,long-term exposure to PM2.5 can induce decreased lung function,emphysematous lesions and airway inflammation.Most importantly,long-term PM2.5 exposure can also obviously strengthen cigarette smoke-induced the changes of chronic obstructive pulmonary disease.Background: We conducted this study to identify the influences and synergistic effects of smoking status and polymorphisms in HHIP on COPD and lung function decline.Methods: A cohort containing 306 patients and 743 healthy subjects were recruited from 25,000 subjects.All selected subjects had chronic cough for over 2 years or a smoking history above 20 pack-years.After 8 years,all subjects were divided into two cohorts according to whether they had quit smoking or not.A follow-up of all patients was completed after another period of 10 years.Three variants in HHIP were genotyped to investigate the impacts of gene susceptibility on the development of COPD and lung function decline.Results: During the follow-up tests,FEV1 ratios decreased more significantly in COPD patients than in healthy subjects.For variant rs7654947,FEV1 decreased more significantly in CC and CT subjects than in TT subjects.FEV1 in COPD patients with a CC genotype from smoking cohorts reduced markedly when compared to ex-smoking cohorts.Conclusions: Our results showed that smoking and HHIP variant rs7654947 were associated with COPD development and lung function decline.Moreover,we found that cigarette smoking and gene susceptibility have cooperative effects on COPD risk and lung function decline.