The Study Of The Relationship Between Biomass Smoke And Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease with some significant extrapulmonary effects that may contribute to the severity in individual patients. Its pulmonary component is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases. COPD is a global disease with a high and increasing prevalence. Evidence showed that some kind of intervention can reduce the prevalence of COPD. It has been estimated that indoor air pollution resulting from the combustion of solid fuels may be one of the leading contributors to the global burden of disease.Exposure to indoor air pollution may be responsible for nearly 2 million excess deaths in developing countries and for some 4% of the global burden of disease. There is increasing evidence for a possible association between COPD and the use of biomass fuels for cooking and heating in developing countries.However,the extent of the association between biomass smoke and COPD among different Population, the duration of biomass smoke on COPD and the relation between biomass smoke and cigarette smoke is not fully known.Indoor air pollution is a major global public health threat requiring greatly increased efforts in the areas of research and policy-making.COPD is a system disease.However,the clinical research of COPD were restricted,because it is very differcult to obtain the sample of each system.We only can get the sample of blood.However,the vary of the biomarker in blood is not parallelled with lung and the other organs. So, several kinds of COPD animal model developed.However,there is no COPD animal model caused by biomass smoke.Exposure to biomass smoke is a risk factor for COPD.And COPD is a system disease with system oxidative stress, however there is no information about system oxidative stress caused by biomass smoke and about the difference of oxidative stress between biomass smoke and cigarette smoke.Objective: To get the information about the extent of the association between biomass smoke and COPD among different Population, the duration of biomass smoke on COPD and the relationship between biomass smoke and cigarette smoke. To compare the pathological morphology caused by biomass smoke and cigarette smoke.To compare the system oxidative stress caused by exposure to biomass smoke and cigarette smoke.Part I Risk of chronic obstructive pulmonary disease from exposure to biomass smoke: Result from meta-analysisMethods:We searched the Medline, Embase, LILACS and reviewed citations in relevant articles to identify 15 epidemiologic (11 cross-sectional and 4 case-control) studies that met inclusion criteria. Data were extracted and analyzed independently by two investigators using a standardized protocol.Results: Overall, people exposed to biomass smoke have odds ratio (OR) of 2.44 (95 percent confidence interval (95% CI) 1.9-3.33) for developing COPD, compared with those not exposed to biomass smoke. Biomass smoke exposure was consistently a risk factor for developing COPD in women (OR: 2.73, 95% CI: 2.28-3.28),in men (OR: 4.30, 95% CI: 1.85-10.01), in Asian population (OR: 2.31, 95% CI: 1.41-3.78) ,in Non-Asian population (OR: 2.56, 95% CI: 1.71-3.83),in the phenotype of chronic bronchitis (OR: 2.56, 95% CI: 1.77-3.70),in the phenotype of COPD (OR: 2.65, 95% CI: 1.75-4.03),and in cigarettes smoker (OR=4.39, 95%CI:1.40-4.66) and in cigarettes nonsmoker (OR=2.55, 95%CI: 2.06-3.15). Conclusions: Exposure to biomass smoke is a risk factor for COPD. There is interaction between cigarette and biomass smoke.Part II The influence of biomass smoke on rat lung pathological morphologyMethods: Sprague Dawley Rat were divided into three groups: control group(C group) rats were exposed to fresh air; biomass smoke group(BS group) were exposed to biomass smoke; cigarette smoke(CS) group were exposed to cigarette smoke. All rats were exposed to the smoke/fresh air 45 minutes a time and twice a day for 100 days. During the exposure time, the concentration of O2,SO2,CO and NO were detected. On the end of day 100, animals were sacrificed. Lung tissues were obtained for histological detections using H&E staining. Sera were detected for il-8. BALF were obtained for cell analysis.Result: During the exposure time, the concentration of O2,SO2,CO and NO in the biomass smoke group were (20.31±0.21)%,(981.72±429.59) mg/m3,(3.44±3.36) mg/m3 and (2.59±1.71) mg/m3 respectively and the concentration of O2,SO2,CO and NO in the cigarette group were (20.28±0.15)%,(745.56±683.24) mg/m3,(12.64±11.44) mg/m3 and (3.37±0.52) mg/m3 respectively. The pathological morphology showed that airway epithelia were intact, ciliary arrangements were regular and the structures of alveoli were normal in C group; Characteristic pathological changes of bronchitis and emphysema were observed in BS group and CS group.The pathological score of airway abnormities was higher in CS group(32.66±13.84) and BS group(32.25±12.51) than that in C group (11.11±9.84). The MLI in BS group (130.62±33.64μm) and CS (119.03±26.20μm) were longer than that in C group( 89.84±17.34um ). The MAN in BS group(169.21±76.33/mm2) and CS group (173.86±68.33/mm2 )were smaller than that in C group (280.26±103.95/mm2 ).The serum concentration of IL-8 was higher in CS group(188.14±20.85 pg/ ml) and BS group (240.79±161.28 pg/ml) than that in C group(107.91±35.84 pg/ml).The total inflammatory cells count and the proportion of neutrophils of BALF in BS group and CS group was higher than in C group. The total white blood cell,red blood cell and Hemoglobin in BS group were higher than that in CS group and c group.Conclusion: Exposure to biomass smoke and cigarette smoke will lead to emphysema. The pathological morphology induced by biomass smoke and cigarette smoke were similar.PART III The study of system oxidative stress in the rat exposure to biomass smoke and cigarette smokeMethod: The activities of superoxide dismutase (SOD) in sera, the total ability of antioxidant in lung tissue homogenate and in heart tissue homogenate,the levels of glutathione (GSH), malondialdehyde (MDA)in sera,lung tissue homogenate,heart tissue homogenate and liver homogenate, the activities of iNOS in in sera,lung tissue homogenate,heart tissue homogenate and the activities of GST in lung tissue homogenate and heart tissue homogenate were measured .The expressions of GCLC-mRNA,GSTM1-mRNA,GSTP-mRNA and SLPI-mRNA in the lung tissue and the GCLC-mRNA,GSTM1-mRNA and GSTP-mRNA in heart tissue were respectively measured with real-time-PCR methods. The expressions ofγ-GCSc(GCLC)protein were measured with immunohistochemisty and Western-blot. Result: The activities of serum superoxide dismutase (SOD) in BS group(223.91±56.86 u/ml) and CS group (218.65±65.60u/ml) were lower than that in C group(283.11±41.71 u/ml). The total ability of antioxidant in lung tissue homogenate and heart homogenate in CS group were lower than that in BS group and C group. The levels of MDA in heart tissue homogenate in BS and CS group were lower than that in C group. The levels of MDA in lung tissue homogenate in BS group were higher than that in C group and CS group. The levels of MDA in liver tissue homogenate and sera were similar in the three groups. The activities of iNOS in lung tissue homogenate in BS group were lower than that in CS group and C group. The activities of iNOS in heart tissue homogenate in BS group and CS group were lower than that in C group. There is no difference of activities of iNOS in sera in the three group. There is no difference of the levels of glutathione (GSH) in sera,lung tissue homogenate,heart tissue homogenate and liver homogenate between the three group. The activities of GST in lung tissue homogenate in CS group (28.43±8.80 RFU/min/ mgpro) were higher than that in BS group(15.44±11.34 RFU/min/ mgpro) and C group(20.54±10.12)RFU/min/ mgpro). The activities of GST in heart tissue homogenate in CS group (4.35±1.94) RFU/min/ mgpro were lower than that in BS group(6.27±1.31 RFU/min/mgpro) and C group(6.76±1.26RFU/min/mgpro).For lung,the expressions of GCLC-mRNA in CS group were stronger than that in BS group and C group. The expressions of GSTP1-mRNA in BS group were weaker than that in CS group and C group.For heart, The expressions of GSTM1-mRNA in BS group and CS group were stronger than that in C group;There is no difference of the expressions of GSTP-mRNA and GCLC-mRNA in BS,CS group and C group.The immunohistochemisty showed that a few GCLC were expressed in endochylema of alveolar and airway epithelial cells in control group.The GCLC were expressed in BS group and CS group were stronger than that in C group. The more the pulmonary fibrosis is, the stronger of the GCLC expressed. Western-blot analysis also showed that the GCLC were expressed stronger in CS group and BS group than in C group. Conclusion: Exposure to biomass smoke and cigarette smoke will lead to system oxidative stress.There is some difference of system oxidative stress between the two kind of exposure.