京都大学 / 新制・課程博士 / 博士(工学) / 甲第23182号 / 工博第4826号 / 新制||工||1754(附属図書館) / 京都大学大学院工学研究科都市環境工学専攻 / (主査)教授 米田 稔, 教授 高野 裕久, 教授 松井 康人 / 学位規則第4条第1項該当 / Doctor of Philosophy (Engineering) / Kyoto University / DGAM

This work focused on decay and dimensional stability of southern pine lumber and environmental issues associated with emissions released during kiln drying of southern pine. In one study decking boards were treated with a 3% resin acid solution to increase the dimensional stability. The boards were placed on a roof and weathered for two years. The increased water repellency reduced moisture gain following summer rainstorms by one-third compared to untreated matched samples, this significantly reduced splitting by half and cupping by one-third. In one study decking boards from matched samples were weathered for two years in the roof setup described above, and in a fungal ground proximity test. The ground proximity samples had slightly more decay than the roof samples. Correlation between decay ratings for the matched samples was 37%, suggesting above-ground decay susceptibility is dependent on the macro- and micro-environment. Decay in roof exposure was modeled based on moisture content factors, whereas decay in ground proximity was modeled by the resin and fatty acids. One study tested pole sections with varying amounts of sapwood, heartwood, and knots dried in a pilot-scale kiln. A sample of the kiln exhaust was measured for volatile organic compounds. Emissions from poles were similar to clear lumber. Emissions from heartwood poles were less than for heartwood lumber, perhaps due to the poles’ sapwood band. The final study was conducted with clear and knotty lumber kiln dried to below 8% moisture content using three kiln schedules. Wood dried to this lower moisture content is used in interior applications or exported. During drying, a sample of the kiln exhaust was analyzed for total VOCs, and a sample of the kiln exhaust was collected and analyzed for hazardous air pollutants via gas chromatography and spectrophotometry. For all three kiln schedules, mills would reach 10 tons of methanol and thus must comply with maximum achievable control technology standards before reaching 25 tons of methanol, formaldehyde, acetaldehyde, acrolein, and propionaldehyde.

Introdução: Muitos dos efeitos nocivos sobre a saúde humana são provocados por poluentes atmosféricos como as partículas menores que 10 micrômetros de diâmetro (material particulado - PM10). Essas partículas se originam principalmente das emissões de veículos automotores em áreas urbanas. Uma porção significativa do material particulado é constituída por sulfatos, nitratos, metais, hidrocarbonetos e outras substâncias adsorvidas em suas moléculas. A poluição do ar relacionada a emissões de fontes veiculares é um importante problema de saúde pública dos grandes centros urbanos sendo as crianças e adolescentes suscetíveis aos efeitos nocivos dessa poluição. No entanto, existem poucos estudos que avaliaram a associação entre a exposição à poluição do ar e doenças autoimunes nessa população, e para nosso conhecimento, nenhum estudo avaliou a influência dos poluentes atmosféricos sobre a atividade do lúpus eritematoso sistêmico juvenil (LESJ). Objetivos: (1). Avaliar a presença de associação entre variações agudas nas concentrações dos poluentes atmosféricos da Região Metropolitana de São Paulo (RMSP) e o risco de atividade da doença através do Índice de Atividade do Lúpus Eritematoso Sistêmico (SLEDAI-2K) em crianças e adolescentes com LESJ e (2). Avaliar a influência da exposição à poluição atmosférica dos 21 dias anteriores a cada consulta (estrutura de defasagem) sobre risco de atividade da doença através do SLEDAI-2K em crianças e adolescentes com LESJ. Métodos: Estudo longitudinal retrospectivo de painel realizado com base em 409 visitas consecutivas de pacientes com LESJ (critérios do American College of Rheumatology - ACR) que vivem na Região Metropolitana de São Paulo. A atividade da doença foi avaliada de acordo com o Índice de Atividade do Lúpus Eritematoso Sistêmico revisado em 2000 (SLEDAI-2K), e os valores de cada consulta foram divididos em dois grupos: SLEDAI 8. Concentrações diárias de material particulado (PM10), dióxido de enxofre (SO2), dióxido de nitrogênio (NO2), ozônio (O3) e monóxido de carbono (CO) foram avaliados nos 21 dias que antecederam as consultas médicas. Um modelo de equação de estimativa generalizada (EEG) foi utilizado para avaliar o impacto dessas medidas sobre o SLEDAI-2K, considerando os efeitos fixos para medições repetitivas. Os modelos foram ajustados para a velocidade de hemossedimentação (VHS), uso de corticosteróides (prednisona e dose cumulativa de prednisona), anti-maláricos, agentes imunossupressores, presença de infecção nos 20 dias anteriores à consulta médica, temperatura mínima e umidade relativa do ar. Resultados: PM10, NO2 e CO foram fatores de risco para a atividade do LESJ (SLEDAI-2K > 8) aproximadamente duas semanas após a exposição. Um aumento de 13,4 ?g / m3 na média móvel de PM10 (do lag12 ao lag15) foi associado a um aumento de 34% (95% intervalo de confiança - 7,0 - 68,0) no risco de SLEDAI-2K acima de 8. Conclusões: (1). Exposição à poluição atmosférica pode aumentar o risco de atividade da doença nos pacientes com LESJ que residem em grandes cidades e (2). Efeito da exposição à poluição do ar sobre o aumento da atividade do LESJ foi observado 13 dias após a exposição / Introduction: Many of the harmful effects on human health caused by atmospheric pollutants have been linked to particles smaller than 10 micrometers in diameter (PM10). These particles mainly originate from automotive vehicle emissions in urban areas. A significant portion of the particulate matter is composed of sulfates, nitrates, metals, hydrocarbons and other substances adsorbed in these molecules. Air pollution related to vehicular emission sources is an important public health problem in large cities, and children and adolescents are susceptible to the harmful effects of this pollution. However, there are few studies evaluating the association between exposure to air pollutants and autoimmune diseases in this population and to our knowledge, no study has assessed the influence of atmospheric pollutants on disease activity of childhood-onset systemic lupus erythematosus (C-SLE) patients. Objectives: (1). Evaluate the presence of association between acute variations in the concentrations of atmospheric pollutants in the Metropolitan Region of São Paulo (MRSP) and the risk of disease activity through the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) in children and adolescents with C-SLE and (2). Evaluate the influence of exposure to air pollution of 21 days prior to each consultation on risk of disease activity through the SLEDAI-2K in children and adolescents with C-SLE. Methods: A longitudinal panel retrospective study was carried out based on 409 consecutive visits of C-SLE patients (American College of Rheumatology - ACR criteria) living in the Metropolitan Region of São Paulo. Disease activity was evaluated according to Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and the patients were divided in two groups: SLEDAI 8. Daily concentrations of inhaled particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO) were evaluated on the 21 days preceding the medical visits. A generalized estimation equation (GEE) model was used to assess the impact of these measurements on the SLEDAI-2K score, considering the fixed effects for repetitive measurements. The models were adjusted for erythrocyte sedimentation rate (ESR), corticosteroid use (prednisone use and cumulative dose of prednisone), antimalarials, immunosuppressive agents, presence of infection 20 days preceding the medical appointment, minimum temperature and relative humidity. Results: PM10, NO2 and CO were risk factors for C-SLE activity (SLEDAI-2K > 8) approximately two weeks after exposure. A 13,4 ug/m3 increase in PM10 moving average (from lag 12 to lag 15) was associated to a 34 % (95% confidence interval - 7,0 - 68,0) increase in the risk of SLEDAI-2K above 8. Conclusions: (1). Exposure to atmospheric pollution may increase the risk of disease activity in patients with C-SLE residing in large cities and (2). Effect of exposure to air pollution on increasing JSLE activity was observed 13 days after exposure

Made available in DSpace on 2016-08-10T10:53:51Z (GMT). No. of bitstreams: 1 CARLOS JOSE AUGUSTO JUNIOR.pdf: 1975289 bytes, checksum: 6e245efa14283295263d7f411b8c710d (MD5) Previous issue date: 2012-02-17 / During the process of cement manufacture are emissions of various pollutants known to have toxic effects in humans, especially the fractions of smaller particles. The permanent and lasting these pollutants can cause various health problems. One possible way to know the effects of pollution on populations living near cement plants is through the identification of respiratory signs and symptoms among those living. Methods: A crosssectional epidemiological study conducted in Cezarina, Goiás. The sample was randomly selected by cluster sampling. Inclusion criteria were residents who lived for more than 10 years in the city and over the age of 20 years. The instrument used was adapted from the questionnaire British Medical Research Council for research into respiratory signs and symptoms. In addition to the questionnaire data were collected the following variables: sex, age, education, income, time and place of residence in the city, main occupation and workplace. Data were collected by trained staff using household interviews in the period from April 19 to May 31, 2011. Descriptive statistical analysis was performed using SPSS v. 15.0. The Project was submitted to the Ethics Committee from PUC Goiás and approved under opinion number 1674/2011. Results: The mean age was 40.4 years. The average time of residence was 24.1 years. The sample was composed mostly of women (60.9% - p = 0.000). The cement plant was the site of work cited by 11.1%. The prevalence of chronic cough was 23.1%, sputum 22.8%, 29.3% shortness of breath and wheezing 17.9%. Smoking was reported by 16.6% of respondents. Smoking showed a moderate correlation with respiratory signs and symptoms. The place of residence and length of residence were not associated with the frequency of these signs and symptoms. Conclusion: The respiratory signs and symptoms were not associated with the location and length of residence in the city. Smoking showed correlation with all respiratory symptoms studied and it was more prevalent among men. / Durante o processo de manufatura do cimento há emissões de poluentes variados conhecidos por terem efeitos tóxicos em seres humanos, sobretudo as frações de partículas menores. A exposição permanente e duradoura a esses poluentes pode ocasionar diversos agravos à saúde. Uma forma possível de se conhecer os efeitos dessa poluição em populações residentes próximas às fábricas de cimento é utilizando questionários validados para a identificação de sinais e sintomas respiratórios. Métodos: Estudo epidemiológico descritivo transversal de base populacional realizado na zona urbana do município de Cezarina, Goiás, Brasil. A amostragem foi aleatória probabilística por conglomerados. Os critérios de inclusão foram indivíduos residentes há mais de 10 anos na cidade e idade acima de 20 anos. O instrumento utilizado foi adaptado do questionário de British Medical Research Council para a pesquisa de sinais e sintomas respiratórios. Além desse questionário foram colhidos dados referentes às variáveis: sexo, idade, escolaridade, renda, tempo e local de moradia na cidade, ocupação principal e local de trabalho. Os dados foram colhidos através de entrevistas domiciliares realizadas por equipe treinada, no período de 19 de abril a 31 de maio de 2011. Foi realizada análise estatística descritiva utilizando o programa SPSS v.15.0. O projeto foi submetido ao Comitê de Ética da PUC Goiás e aprovado sob o parecer nº 1674/2011. Resultados: A idade média dos entrevistados foi de 40,4 anos (DP ± 11,07). O tempo médio de moradia foi de 24,1 anos (DP ± 10,60). As mulheres representaram 60,9% da amostra (p=0,000). A fábrica de cimento foi citada como o local de trabalho de 11,1% dos entrevistados. A prevalência de tosse foi de 23,1%, expectoração 22,8%, falta de ar 29,3% e chiado no peito 17,9%. Tabagismo foi referido por 16,6% dos entrevistados. O tabagismo apresentou correlação moderada com os sinais e sintomas respiratórios. O local e o tempo de moradia não estiveram associados com a frequência desses sinais e sintomas. Conclusão: Os sinais e sintomas respiratórios não estavam associados com o local e tempo de moradia na cidade. O tabagismo apresentou correlação com os sinais e sintomas respiratórios pesquisados sendo mais prevalentes entre os homens.

Introdução: Em ambientes urbanos, a exaustão dos carros a diesel é uma importante fonte de partículas e gases que afetam diretamente a saúde das pessoas. Como a adição do biodiesel ao diesel é recente, torna-se necessário avaliar o perfil toxicológico dessas emissões e os possíveis efeitos adversos a saúde. Além do mais, a concentração dos poluentes atmosféricos e sua composição físico-química sofrem influências diretas das condições meteorológicas. Esse estudo tem como foco avaliar o perfil toxicológico dos poluentes primários (emitidos diretamente da fonte) e secundários (gerados a partir das condições atmosféricas) por meio de dois estudos. Objetivos: (Estudo I) Avaliar a exposição aguda da exaustão do diesel e biodiesel no perfil inflamatório pulmonar e sistêmico; (Estudo II) Avaliar se a exposição aguda a baixos níveis de partículas ambientais concentradas (PACs) promovem efeitos cardiopulmonares e sistêmicos; e se a magnitude dessas alterações observadas é influenciada pelos períodos (frio/seco e quente/úmido). Métodos: (Estudo I) Camundongos Balb/C foram expostos ao ar filtrado (AF) e a duas concentrações de MP2,5 (600 e 1200 ?g/m3) tanto da exaustão do combustível diesel (D) quanto do biodiesel (BD). As emissões dos poluentes (MP2,5, NO e NO2), temperatura e umidade foram monitorados em tempo real. Os registros da variabilidade da frequência cardíaca (VFC), frequência cardíaca (FC) e da pressão arterial (PA) foram obtidas 30 minutos após a exposição. Após 24 horas os animais foram eutanasiados e foram coletados o lavado broncoalveolar (LBA), o pulmão, o sangue e a medula óssea para avaliar a inflamação pulmonar e sistêmica. A expressão das citocinas (ET-Ar, ET-Br, INOs, ISO, VCAM, IL-8) foram analisadas nos vasos peribronquiolares e no epitélio brônquico. (Estudo II) Camundongos Balb/C foram expostos ao ar filtrado e as PACs na concentração de 200 ?g/m3 geradas no período frio/seco e quente/úmido. A hiperresponsividade pulmonar, VFC, FC, PA foram mensurados 30 minutos após a exposição. Após 24 horas, os animais foram eutanasiados e foram coletados o pulmão e o sangue para avaliar a inflamação pulmonar e sistêmica. Resultados: (Estudo I) As emissões do NO e NO2 foram maiores na exaustão do biodiesel comparado ao diesel. Houve aumento da VFC no BD600, D600 e D1200 comparado ao AF, já a PA reduziu no D1200 comparado ao AF. Houve aumento dos eritrócitos, hematócrito, RDW-SD e reticulócitos no BD1200 e D1200 comparado ao AF; aumento dos eritrócitos, RDW-SD e linfócitos no D600 comparado ao AF; e redução do MCHC no BD1200 e D1200 comparado ao AF. No LBA e na histologia pulmonar foram evidenciados aumento dos neutrófilos no BD600 comparado ao AF. Nos vasos peribronquiolares, houve aumento da expressão da ET-Ar e ET-Br no BD600 comparado ao AF. No epitélio brônquico, houve aumento da expressão da ET-Br no BD600, BD1200, D600 e D1200 comparado ao AF, aumento do VCAM no BD1200 e D600 comparado ao AF. (Estudo II) As PACs geradas nos períodos frio/seco e quente/úmido, induziram alterações nos parâmetros sanguíneos e inflamação pulmonar. PACs geradas no período frio/seco reduziram o volume corpuscular médio (VCM) e elevaram os eritrócitos, hemoglobina, MCHC e o RDW-CV comparado ao AF, no parênquima pulmonar houve um influxo de neutrófilos. Similarmente, as PACs geradas no período quente/úmido reduziram o VCM e elevaram os eritrócitos, hemoglobina, hematócrito e RDW-CV comparado ao AF. Conclusão: A exposição ao biodiesel causou inflamação pulmonar, broncoconstrição dos vasos peribronquiolares e do epitélio brônquico; já a exposição ao diesel desencadeou uma inflamação sistêmica, aumento do estímulo parassimpático e broncoconstrição do epitélio brônquico. Curtas exposições a baixos níveis de PACs induziram modesta, porém, significante inflamação pulmonar e alterações nos parâmetros sanguíneos. Em adição, nossos dados suportam o conceito de que alterações nas condições climáticas modificam levemente a toxicidade das partículas, já que a dose administrada de PACs geradas durante o período frio/seco produziram uma resposta mais exacerbada / Background: In urban environments, the exhaust of diesel cars is an important source of particles and gases that directly affect people\'s health. As the addition of biodiesel to diesel is recent, it is necessary to evaluate the toxicological profile of these emissions and the possible adverse health effects. Moreover, the concentration of air pollutants and their physico-chemical composition suffer direct influences of weather conditions. This study aims to evaluate the toxicological profile of primary pollutants (emitted directly from the source) and secondary (generated from the weather conditions) through two studies. Objectives: (Study I) Evaluate the acute exposure of diesel and biodiesel exhaust in pulmonary and systemic inflammatory profile. (Study II) Evaluated whether acute exposure to low levels of concentrated ambient particles (CAPs) promotes cardiopulmonary and systemic effects; and whether the magnitude of these observed changes is influenced by periods (cold/dry and warm/humid). Methods: (Study I) Balb/C mice were exposed for two hours to filtered air (FA) and two doses (600 and 1200 ?g/m3) of both diesel (D) and biodiesel (BD) fuels. The PM2.5, NO, and NO2 concentrations, air temperature and humidity were monitored in real time. HRV (time and frequency domain), HR and BP parameters were collected after 30 minutes of exposure. After 24 hours were available the bronchoalveolar lavage (BALf), lung histology, blood and bone marrow for pulmonar and systemic inflammation analysis. The cytokines expression (ET-Ar, ET-Br, INOs, ISO, VCAM, IL-8) were available on peribronchiolar vessels and bronchial epithelium. (Study II) Balb/C mice were exposed to 200 ?g/m3 to concentrated ambient particles (CAPs) and filtered air (FA) in cold/dry and warm/humid periods. Lung hyper-responsiveness, heart rate, heart rate variability and blood pressure were evaluated 30 minutes after the exposures. After 24 hours, blood and tissue sampling were performed. Results: (Study I) Emissions of NO and NO2 were higher in the biodiesel compared to diesel oil exhaust. There was an increase in HRV for the BD600, D600 and D1200 compared to FA, already BP reduced the D1200 compared to FA. There was an increase on the erythrocytes, hematocrit, RDW-SD and reticulocytes in BD1200 and D1200 compared to FA; increase in erythrocytes, lymphocytes and RDW-SD on D600 compared to FA; and reduction of MCHC in BD1200 and D1200 compared to FA. BAL and lung histology was evidenced an increase on the neutrophils BD600 compared to FA. In peribronchiolar vessels there was increased of the expression on ET-Ar and ET-Br on the BD600 compared to FA. In the bronchial epithelium there was increased expression of ET-Br in BD600, BD1200, D600 and D1200 compared to FA, increased VCAM on the BD1200 and D600 compared to FA. (Study II) CAPs generated during both periods (warm/humid and cold/dry) induced alterations in red blood cells and lung inflammation. CAPs during the cold/dry period reduced the mean corpuscular volume (MCV) levels and increased erythrocytes, hemoglobin, mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width coefficient variation (RDW-CV) levels compared to the FA group. Similarly, CAPs during the warm/humid period decreased MCV levels and increased erythrocytes, hemoglobin, haematocrit and RDW-CV levels compared to the FA group. CAPs during the cold/dry period increased the influx of neutrophils in the alveolar parenchyma. No differences were obtained on vasoconstrictors of pulmonary vessels. Conclusion: The exposure to biodiesel caused lung inflammation, bronchoconstriction of the peribronchiolar vessels and bronchial epithelium; already the exposure of the diesel caused systemic inflammation, increased of the parasympathetic stimulation and bronchoconstriction of the bronchial epithelium. Short-term exposures to low concentrations of CAPs elicited modest but significant pulmonary inflammation and, into a lesser extent, changes in blood parameters. In addition, our data support the concept that changes in climate conditions modify slightly particle toxicity, since equivalent doses of CAPS of the cold/dry period produced a more exacerbated response

目的：本研究主要目的是建立預測模型來判定矽肺發生的累積風險從而推薦適宜的胸片照射年限並從而評估常規監測和推薦監測策略的成本效益。此外，本研究還評價了常規診斷和驗證性診斷的符合度以及在驗證性診斷中邀請的三位專家之間的符合度。 / 方法：總計有3492男性接塵工人在1964年1月1日到1974年12月31日期間進入本隊列並隨訪至2008年12月31日。不同閱片專家根據中國最新塵肺病診斷標準 （GBZ70-2009））分別閱片總計9084張。對專家之間閱片結果的兩兩比較和兩種診斷結果的比較均采用Cohen’s Kappa檢驗。應用三種篩選方法（強制所有變量同時進入模型，後退逐步篩選，以及Least Absolute Shrinkage and Selection Operator (LASSO)篩選。LASSO模型作為最優模型，以分數量表的方式來表達。根據分數，把工人分成高、中、低危險組，並估計這三組不同危險水平工人的累積危險度。運用0.1% 累積危險度來判定不同危险的工人及不同期別的矽肺病人的射線照射年限。多狀態Markov模型用於計算矽塵暴露工人不同狀態的年轉移概率，並應用Markov成本效益分析方法來估計每獲得一個生命年的成本效益。 / 結果：截至2008年底，本矽塵暴露隊列共計發現298例矽肺病人（累計發病率為8.53%），死亡1347例（死亡比例為38.57%）。本研究發現常規診斷和驗證性診斷有很好的符合度 （Kappa值為0.89， 95%可信區間為0.88-0.91）。基於LASSO模型的分數量表具有很好的診斷識別能力 （ROC曲線下面積為0.83， 95%可信區間為0.81-0.86）。根據0.1%累積危險度標準，我們判定低危險組工人第一次射線照射的時間為第11年，推薦每兩年隨訪一次；中等危險組工人和高危險組工人的第一次射線照射時間分別為第11年和第5年，推薦每年隨訪一次。矽肺病人未晉級到三期以前均一年隨訪一次。矽塵暴露工人的年轉移概率為：從健康狀態向疑似病例轉移的概率為0.0198，從疑似病例向一期矽肺轉移的概率為0.038，從一期矽肺向二期矽肺轉移的概率為0.0516，從二期矽肺向三期矽肺轉移的概率為0.059，從三期矽肺向死亡轉移的概率為0.18。在1964到2008年間，診斷一例矽肺病例平均花費醫療成本為21853.11美元，非醫療成本為5993.30美元。模擬10,000矽塵暴露工人在未來40年按照當前的狀態轉移概率，應用常規的職業健康檢查為手段獲得一個生命年的成本效益為43.60美元，應用推薦的職業健康檢查為手段獲得一個生命年的成本效益為46.99美元。 / 結論：本研究在最優預測模型的基礎上為不同矽肺危險度的矽塵暴露工人首次提供了科學的證據來判定射線照射的適宜年限，亦為未來矽塵暴露工人的職業健康監測提供了科學理論依據，雖然本研究推薦的監測策略獲得同常規策略相類似的成本和效益。 / Objectives: The primary objective was to develop prediction models for determining the optimal intervals of chest radiographic surveillance for workers exposed to silica dust; the second primary objective is to assess the cost per case identification and compare the cost per life year gained under routine medical surveillance program with that under the recommended program for workers exposed to silica dust in China. In addition, the inter-rater agreement amongst three invited radiologists on rereading the chest radiographs and the agreement between the original diagnoses of silicosis (from routine reports) and the verified diagnoses reassessed by the three experts were also evaluated. / Methods: A total of 3492 male workers exposed to silica dust in an iron ore during the period 1964 - 1974 were recruited into this retrospective cohort study. All cohort members were followed up through the end of 2008 to observe the occurrence of silicosis and overall profile of mortality. All 9084 chest X-ray films were reread by three radiologists who had been qualified as experts at the national level according to the Chinese National Diagnostic Criteria of Pneumoconiosis (GBZ70-2009). The diagnosis of silicosis made by the panel of these three invited experts was referred to the “verified diagnosis“. Cohen’s Kappa test was used to test inter-rater agreements of three invited readers on chest radiographs and the agreement on the diagnosis of silicosis obtained from routine medical surveillance (i.e., the original routine diagnosis) was compared with those verified by the 3 qualified readers (i.e., the verified diagnosis). The multivariate Cox’s proportional hazard regression models were developed to predict the silicosis occurrence based on three selection approaches entry of all predictors at the same time, backward stepwise selection, and Least Absolute Shrinkage and Selection Operator (LASSO) selection. The LASSO model showed the best model fit which was thus regarded as the final model for predicting a score chart. / Based on this practically used score chart, we then classified workers into three groups of different risk levels of silicosis (low, moderate, and high). We estimated the cumulative risk of silicosis over years of follow-up for these three groups of workers at different risk levels. We used 1 per thousand of cumulative risk for developing silicosis as a “benchmark“ to determine the intervals of radiologic surveillance for workers with different risks of silicosis. Multi-state Markov model was used to calculate the transition probabilities of different states of silicosis and the analysis on cost and effectiveness was performed. / Results: By the end of 2008, the cumulative incidence rate of silicosis was 8.53% (298 silicosis cases) and a total of 1347 deaths (38.57%) were observed. / Good inter-rater agreements were observed amongst three invited radiologists for rereading all the chest films. Kappa value for the agreement between the original diagnoses and the verified diagnoses was 0.89 (95% confidence interval [95%CI], 0.88-0.91). / The model with the best fit was LASSO Cox model which showed a good discrimination with an area of 0.83 (95%CI, 0.81-0.86) under the receiver operating characteristic (ROC) curve. We classified workers into 3 risk groups according to the score chart obtained from the LASSO Cox model, and found the observed probabilities matched well to the predictions. According to 1 per thousand “benchmark“, we can determine that the initial interval of radiographic surveillance for workers in the low risk group was 11 years and a subsequent biyearly examination was recommended. The initial examination interval was 11 years and 5 years respectively for workers in the middle and high risk group, and then a yearly examination was recommended. For patients with silicosis, an annual radiological surveillance program was recommended regardless of the stage of pneumoconiosis. / According to results from multi-state model, we estimated that the yearly transition probability was 0.0198 for silica dust exposed workers from healthy state to the suspected silicosis cases (sojourn time = 47 years), 0.0338 from suspected silicosis cases to silicosis stage one (sojourn time = 23 years), 0.0516 from silicosis stage one to stage two (sojourn time = 9 years), 0.059 from silicosis stage two to stage three (sojourn time = 6 years), and 0.18 from silicosis stage three to death (sojourn time = 5 years). / During the period 1964 to 2008, the average direct medical cost spent on identifying one silicosis case was US$ 21853.11 and the non-medical cost for identifying one case was US$ 5993.30 per case. The estimated medical cost regarding per life year gained was US$ 43.60 under the routine medical surveillance program and it would be US$ 46.99 if the newly recommended surveillance program is adopted. / Conclusion: This study is the first to provide scientific evidence on determining the optimal intervals of radiographic surveillance for workers at different risk levels of silicosis based on the ‘best’ prediction model. Although our study revealed similar cost and effectiveness for using the recommended occupational health examination strategy compared with the routine program, this study is the first to provide scientific theory for guiding evidence-based occupational medical surveillance on workers exposed to silica dust in the world. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chen, Minghui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 195-210). / Abstract also in Chinese. / Abstract (English) --- p.i / Abstract (Chinese) --- p.v / Acknowledgements --- p.vii / List of contents --- p.ix / List of tables --- p.xv / List of figures --- p.xviii / List of main abbreviations --- p.xx / Chapter Section I --- Introduction and Literature Review --- p.1 / Chapter Chapter 1 --- Introduction --- p.2 / Chapter Chapter 2 --- Literature Review of Medical Examination, Prediction model and Economic Evaluation in Silicosis --- p.7 / Chapter 2.1 --- The aims of this literature review --- p.7 / Chapter 2.2 --- Search strategies and selection criteria --- p.7 / Chapter 2.3 --- Searching results --- p.8 / Chapter 2.4 --- Critical appraisal criteria and quality of selected studies --- p.9 / Chapter 2.4.1 --- Critical appraisal criteria --- p.9 / Chapter 2.4.2 --- Quality of selected studies --- p.10 / Chapter 2.5 --- Overview of effectiveness of chest radiography in medical surveillance of silicosis for workers exposed to silica dust --- p.15 / Chapter 2.5.1 --- Occupational medical surveillance for workers exposed to silica dust --- p.15 / Chapter 2.5.2 --- Comparison of CT or HRCT and chest radiography --- p.16 / Chapter 2.5.3 --- Comparison of digital radiography (DR) and chest radiography --- p.17 / Chapter 2.5.4 --- Other tests to be relevant to silicosis diagnosis --- p.23 / Chapter 2.5.5 --- The effectiveness of chest radiography in medical surveillance and diagnosis of silicosis --- p.24 / Chapter 2.5.6 --- Comparison between the ILO Classification and the Chinese Diagnostic criteria of pneumoconiosis --- p.25 / Chapter 2.6 --- Overview of application of prediction model in silicosis and a review on methodology in prediction model --- p.32 / Chapter 2.6.1 --- Application of prediction model in occupational diseases --- p.32 / Chapter 2.6.2 --- Overview of application of predicting model in pneumoconiosis including silicosis in China in recent 10 years --- p.34 / Chapter 2.6.3 --- Development of prediction model and the applications from practical perspectives --- p.35 / Chapter 2.7 --- A review on economic evaluation in occupational diseases and the screening interval analyses --- p.42 / Chapter 2.7.1 --- An overview on economic evaluation in pneumoconiosis --- p.42 / Chapter 2.7.2 --- Overview of economic evaluation in occupational health and safety and screening interval analyses --- p.44 / Chapter 2.7.3 --- Overview for methodology of performing CEA --- p.45 / Chapter 2.8 --- Research gaps were found from this literature review --- p.52 / Chapter Section II --- Objectives and Methods --- p.53 / Chapter Chapter 3 --- General aims and objectives --- p.54 / Chapter 3.1 --- General aims --- p.54 / Chapter 3.2 --- Primary objectives --- p.54 / Chapter 3.3 --- Secondary objective --- p.54 / Chapter Chapter 4 --- Methodology and Research Plans --- p.55 / Chapter 4.1 --- Study Design --- p.55 / Chapter 4.2 --- The cohort --- p.55 / Chapter 4.3 --- Follow-up --- p.58 / Chapter 4.4 --- Data Collection --- p.58 / Chapter 4.4.1 --- Baseline information --- p.58 / Chapter 4.4.2 --- Diagnosis of silicosis and the verification --- p.59 / Chapter 4.4.3 --- Occupational hygiene monitoring data --- p.60 / Chapter 4.4.4 --- Cost data of medical examination --- p.61 / Chapter 4.5 --- Data Entry and Data Analyses --- p.62 / Chapter Section III --- Results and Discussions --- p.65 / Chapter Chapter 5 --- Description of the cohort --- p.66 / Chapter 5.1 --- Cohort recruitment --- p.66 / Chapter 5.2 --- Baseline characteristics --- p.69 / Chapter 5.3 --- Change of respirable silica dust concentration over time --- p.71 / Chapter 5.5 --- Occurrence of silicosis --- p.73 / Chapter 5.5.1 --- Basic characteristics of silicosis patients --- p.73 / Chapter 5.5.2 --- Trend of silicosis occurrence with calendar year --- p.78 / Chapter 5.5.3 --- Trend of silicosis occurrence with age of entering the cohort --- p.78 / Chapter 5.5.4 --- Trend of silicosis occurrence with cumulative exposure to respirable silica dust --- p.78 / Chapter 5.6 --- Survival distribution at different respirable silica dust exposure levels --- p.79 / Chapter 5.7 --- A summary of the results in Chapter 5 --- p.82 / Chapter Chapter 6 --- Agreement between the routine diagnosis of silicosis and the verified ‘new panel’ diagnosis --- p.83 / Chapter [Summary] --- p.83 / Chapter 6.1 --- Background --- p.85 / Chapter 6.2 --- Methodology --- p.86 / Chapter 6.2.1 --- The routine and the verified diagnosis of silicosis --- p.86 / Chapter 6.2.2 --- Inter-rater agreement --- p.87 / Chapter 6.3 --- Results --- p.89 / Chapter 6.3.1 --- Technical quality of chest X-ray films --- p.89 / Chapter 6.3.2 --- Inter-rater agreement amongst readers --- p.89 / Chapter 6.3.3 --- Agreement between the routine and the verified diagnosis of silicosis --- p.93 / Chapter 6.3.4 --- Agreement of the progression of silicosis between the routine and verified diagnosis --- p.95 / Chapter 6.4 --- Discussion --- p.97 / Chapter Chapter 7 --- Developing prediction model for determining the optimal intervals of chest radiographic examinations for workers at different risks of silicosis --- p.100 / Chapter [Summary] --- p.100 / Chapter 7.1 --- Background --- p.102 / Chapter 7.2 --- Methods --- p.104 / Chapter 7.2.1 --- The cohort and outcome determination --- p.104 / Chapter 7.2.2 --- Developing prediction models for silicosis --- p.107 / Chapter 7.2.3 --- Coding of Predictors --- p.113 / Chapter 7.3 --- Results --- p.118 / Chapter 7.3.1 --- Model Specifications --- p.118 / Chapter 7.3.2 --- Stepwise Selection and LASSO selection --- p.119 / Chapter 7.3.3 --- Model Validations: Stability and Optimism --- p.119 / Chapter 7.3.4 --- Model Presentations --- p.126 / Chapter 7.3.5 --- Cut-off point of follow up year for determining examination intervals --- p.130 / Chapter 7.4 --- Discussions --- p.136 / Chapter Chapter 8 --- Transition probabilities of multi-states for workers with silica dust exposure --- p.141 / Chapter [Summary] --- p.141 / Chapter 8.1 --- Background --- p.143 / Chapter 8.2 --- Methodology of multi-state model --- p.145 / Chapter 8.2.1 --- Survival data and multi-state model --- p.145 / Chapter 8.2.2 --- Markov model and transition states --- p.151 / Chapter 8.2.3 --- Model assessment --- p.153 / Chapter 8.3 --- Results --- p.154 / Chapter 8.3.1 --- Initial values specification and estimates of intensity matrix --- p.154 / Chapter 8.3.2 --- Transition probability matrix, mean sojourn times, and survival situation --- p.159 / Chapter 8.3.3 --- Observed and expected prevalence of each state for Model assessment --- p.163 / Chapter 8.4 --- Discussion --- p.165 / Chapter Chapter 9 --- Cost effectiveness analysis of occupational medical surveillance for workers exposed to silica dust --- p.168 / Chapter [Summary] --- p.168 / Chapter 9.1 --- Background --- p.170 / Chapter 9.2 --- Methodologies --- p.171 / Chapter 9.2.1 --- Costs and effectiveness --- p.171 / Chapter 9.2.2 --- Cost per silicosis identification estimation in the iron ore during 1964 to 2008 --- p.172 / Chapter 9.2.3 --- Cost effectiveness analysis in the Markov model --- p.173 / Chapter 9.3 --- Results --- p.176 / Chapter 9.3.1 --- Cost estimation and cost per silicosis identification in the iron ore cohort --- p.176 / Chapter 9.3.2 --- Cost effectiveness analysis in the Markov model --- p.181 / Chapter 9.4 --- Discussion --- p.187 / Chapter Section IV --- Conclusions and Implications --- p.191 / Chapter Chapter 10 --- Conclusions, implications, and recommendations --- p.192 / Chapter 10.1 --- Conclusions --- p.192 / Chapter 10.2 --- Implications and recommendations --- p.193 / Reference list --- p.195 / Chapter Appendix I --- Chest Radiographic Imaging of Different Diagnostic Criteria for Pneumoconiosis in China --- p.211 / Chapter Appendix II --- Diagnosis Stages among Different Diagnostic Criteria for Pneumoconiosis in China --- p.212 / Chapter Appendix III --- Publications in journals and international conferences during the PhD study --- p.213 / Chapter Supplement I --- Syntax for test proportionality of Cox model in R survival package and LASSO model in R penalized package --- p.215 / Chapter Supplement II --- Guideline of applying the prediction model in practice --- p.216 / Chapter Supplement III --- Syntax for multi-state model in R msm package --- p.221 / Chapter Supplement IV --- An example for cost estimation of adjusting inflation and exchanging --- p.222 / Chapter Supplement V --- Cost estimation of workers, suspected silicosis cases and silicosis patients in the iron ore during 1964 - 2008 --- p.223 / Chapter Supplement V (Continued) --- Cost estimation of workers, suspected silicosis cases and silicosis patients in the iron ore during 1964 - 2008 --- p.224 / Chapter Supplement VI --- Number of deaths for all cause of death in the iron ore cohort until 2008 --- p.225 / Chapter Supplement VII --- Decision tree of Markov model in the study --- p.226 / Chapter Supplement VII (Continued) --- Decision tree of Markov model in the study --- p.227

Introdução: Muitos dos efeitos nocivos sobre a saúde humana são provocados por poluentes atmosféricos como as partículas menores que 10 micrômetros de diâmetro (material particulado - PM10). Essas partículas se originam principalmente das emissões de veículos automotores em áreas urbanas. Uma porção significativa do material particulado é constituída por sulfatos, nitratos, metais, hidrocarbonetos e outras substâncias adsorvidas em suas moléculas. A poluição do ar relacionada a emissões de fontes veiculares é um importante problema de saúde pública dos grandes centros urbanos sendo as crianças e adolescentes suscetíveis aos efeitos nocivos dessa poluição. No entanto, existem poucos estudos que avaliaram a associação entre a exposição à poluição do ar e doenças autoimunes nessa população, e para nosso conhecimento, nenhum estudo avaliou a influência dos poluentes atmosféricos sobre a atividade do lúpus eritematoso sistêmico juvenil (LESJ). Objetivos: (1). Avaliar a presença de associação entre variações agudas nas concentrações dos poluentes atmosféricos da Região Metropolitana de São Paulo (RMSP) e o risco de atividade da doença através do Índice de Atividade do Lúpus Eritematoso Sistêmico (SLEDAI-2K) em crianças e adolescentes com LESJ e (2). Avaliar a influência da exposição à poluição atmosférica dos 21 dias anteriores a cada consulta (estrutura de defasagem) sobre risco de atividade da doença através do SLEDAI-2K em crianças e adolescentes com LESJ. Métodos: Estudo longitudinal retrospectivo de painel realizado com base em 409 visitas consecutivas de pacientes com LESJ (critérios do American College of Rheumatology - ACR) que vivem na Região Metropolitana de São Paulo. A atividade da doença foi avaliada de acordo com o Índice de Atividade do Lúpus Eritematoso Sistêmico revisado em 2000 (SLEDAI-2K), e os valores de cada consulta foram divididos em dois grupos: SLEDAI 8. Concentrações diárias de material particulado (PM10), dióxido de enxofre (SO2), dióxido de nitrogênio (NO2), ozônio (O3) e monóxido de carbono (CO) foram avaliados nos 21 dias que antecederam as consultas médicas. Um modelo de equação de estimativa generalizada (EEG) foi utilizado para avaliar o impacto dessas medidas sobre o SLEDAI-2K, considerando os efeitos fixos para medições repetitivas. Os modelos foram ajustados para a velocidade de hemossedimentação (VHS), uso de corticosteróides (prednisona e dose cumulativa de prednisona), anti-maláricos, agentes imunossupressores, presença de infecção nos 20 dias anteriores à consulta médica, temperatura mínima e umidade relativa do ar. Resultados: PM10, NO2 e CO foram fatores de risco para a atividade do LESJ (SLEDAI-2K > 8) aproximadamente duas semanas após a exposição. Um aumento de 13,4 ?g / m3 na média móvel de PM10 (do lag12 ao lag15) foi associado a um aumento de 34% (95% intervalo de confiança - 7,0 - 68,0) no risco de SLEDAI-2K acima de 8. Conclusões: (1). Exposição à poluição atmosférica pode aumentar o risco de atividade da doença nos pacientes com LESJ que residem em grandes cidades e (2). Efeito da exposição à poluição do ar sobre o aumento da atividade do LESJ foi observado 13 dias após a exposição / Introduction: Many of the harmful effects on human health caused by atmospheric pollutants have been linked to particles smaller than 10 micrometers in diameter (PM10). These particles mainly originate from automotive vehicle emissions in urban areas. A significant portion of the particulate matter is composed of sulfates, nitrates, metals, hydrocarbons and other substances adsorbed in these molecules. Air pollution related to vehicular emission sources is an important public health problem in large cities, and children and adolescents are susceptible to the harmful effects of this pollution. However, there are few studies evaluating the association between exposure to air pollutants and autoimmune diseases in this population and to our knowledge, no study has assessed the influence of atmospheric pollutants on disease activity of childhood-onset systemic lupus erythematosus (C-SLE) patients. Objectives: (1). Evaluate the presence of association between acute variations in the concentrations of atmospheric pollutants in the Metropolitan Region of São Paulo (MRSP) and the risk of disease activity through the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) in children and adolescents with C-SLE and (2). Evaluate the influence of exposure to air pollution of 21 days prior to each consultation on risk of disease activity through the SLEDAI-2K in children and adolescents with C-SLE. Methods: A longitudinal panel retrospective study was carried out based on 409 consecutive visits of C-SLE patients (American College of Rheumatology - ACR criteria) living in the Metropolitan Region of São Paulo. Disease activity was evaluated according to Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), and the patients were divided in two groups: SLEDAI 8. Daily concentrations of inhaled particulate matter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), ozone (O3) and carbon monoxide (CO) were evaluated on the 21 days preceding the medical visits. A generalized estimation equation (GEE) model was used to assess the impact of these measurements on the SLEDAI-2K score, considering the fixed effects for repetitive measurements. The models were adjusted for erythrocyte sedimentation rate (ESR), corticosteroid use (prednisone use and cumulative dose of prednisone), antimalarials, immunosuppressive agents, presence of infection 20 days preceding the medical appointment, minimum temperature and relative humidity. Results: PM10, NO2 and CO were risk factors for C-SLE activity (SLEDAI-2K > 8) approximately two weeks after exposure. A 13,4 ug/m3 increase in PM10 moving average (from lag 12 to lag 15) was associated to a 34 % (95% confidence interval - 7,0 - 68,0) increase in the risk of SLEDAI-2K above 8. Conclusions: (1). Exposure to atmospheric pollution may increase the risk of disease activity in patients with C-SLE residing in large cities and (2). Effect of exposure to air pollution on increasing JSLE activity was observed 13 days after exposure

Chan Pui-Ling. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 169-182). / Text in English; abstracts in English and Chinese. / Chan Pui-Ling. / Acknowledgements --- p.i / Abstracts --- p.ii / Table of Contents --- p.v / List of Plates --- p.ix / List of Figures --- p.xii / List of Tables --- p.xiv / Abbreviations --- p.xviii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Indoor Air Quality (IAQ): An overview --- p.1 / Chapter 1.1.1 --- Importance of indoor air quality --- p.2 / Chapter 1.1.2 --- Common indoor air pollutants --- p.2 / Chapter 1.1.3 --- Airborne bacteria --- p.4 / Chapter 1.1.3.1 --- Possible sources of airborne bacteria --- p.4 / Chapter 1.1.3.2 --- Health effects of the airborne bacteria --- p.5 / Chapter a. --- Sick building syndromes --- p.5 / Chapter b. --- Building-related illness --- p.7 / Chapter 1.1.4 --- Importance of studying airborne bacteria --- p.12 / Chapter 1.2 --- Situation in Hong Kong --- p.13 / Chapter 1.2.1 --- Outdoor air quality --- p.14 / Chapter 1.2.2 --- Indoor air quality --- p.14 / Chapter 1.2.2.1 --- Hong Kong studies --- p.16 / Chapter 1.2.3 --- Air quality objectives in Hong Kong --- p.18 / Chapter 1.3 --- Different sampling methods --- p.18 / Chapter 1.4 --- Identification of bacteria --- p.24 / Chapter 1.5 --- Site selection --- p.26 / Chapter 2 --- Objectives --- p.28 / Chapter 3 --- Materials and methods --- p.29 / Chapter 3.1 --- Samples collection --- p.29 / Chapter 3.1.1 --- Sampling site --- p.29 / Chapter 3.1.2 --- Complete Biosampler System --- p.29 / Chapter 3.1.3 --- Sampling preparation --- p.33 / Chapter 3.1.4 --- Sampling procedures --- p.33 / Chapter 3.2 --- Recovery of the airborne bacteria --- p.36 / Chapter 3.2.1 --- Cultural medium --- p.36 / Chapter 3.2.2 --- Recovery procedures --- p.36 / Chapter 3.2.3 --- Frozen stocks --- p.37 / Chapter 3.3 --- Indentification of bacterial strains --- p.37 / Chapter 3.3.1 --- Gram stain --- p.37 / Chapter 3.3.1.1 --- Chemical reagents --- p.37 / Chapter 3.3.1.2 --- Gram stain procedures --- p.38 / Chapter 3.3.2 --- Oxidase test --- p.38 / Chapter 3.3.2.1 --- Chemical reagents --- p.38 / Chapter 3.3.2.2 --- Oxidase test procedures --- p.41 / Chapter 3.3.3 --- Midi Sherlock® Microbial Identification System (MIDI) --- p.41 / Chapter 3.3.3.1 --- Culture medium --- p.41 / Chapter 3.3.3.2 --- Chemical reagents --- p.41 / Chapter 3.3.3.3 --- MIDI procedures --- p.41 / Chapter 3.3.4 --- Biolog MicroLogTM system (Biolog) --- p.41 / Chapter 3.3.4.1 --- Culture medium --- p.41 / Chapter 3.3.4.2 --- Chemical reagents --- p.44 / Chapter 3.3.4.3 --- Biolog procedures --- p.44 / Chapter 3.3.5 --- DuPont Qualicon RiboPrinter® Microbial Characterization System (RiboPrinter) --- p.46 / Chapter 3.3.5.1 --- Culture medium --- p.46 / Chapter 3.3.5.2 --- Chemical reagents --- p.46 / Chapter 3.3.5.3 --- RiboPrinter procedures --- p.46 / Chapter 4 --- Results --- p.50 / Chapter 4.1 --- Sample naming system --- p.50 / Chapter 4.2 --- Interpretation of results --- p.50 / Chapter 4.2.1 --- Midi Sherlock® Microbial Identification System (MIDI) --- p.51 / Chapter 4.2.2 --- Biolog MicroLog´ёØ System (Biolog) --- p.51 / Chapter 4.2.3 --- DuPont Qualicon RiboPrinter® Microbial Characterization System (RiboPrinter) --- p.52 / Chapter 4.3 --- Sample results --- p.53 / Chapter 4.3.1 --- Sample 1 (Spring) --- p.53 / Chapter 4.3.2 --- Sample 2 (Summer-holiday) --- p.62 / Chapter 4.3.3 --- Sample 3 (Summer-school time) --- p.71 / Chapter 4.3.4 --- Sample 4 (Autumn) --- p.81 / Chapter 4.3.5 --- Sample 5 (Winter) --- p.90 / Chapter 4.4 --- Bacterial profile of the student canteen --- p.100 / Chapter 4.5 --- The cell and colony morphology of the dominant bacteria --- p.100 / Chapter 4.6 --- Comparison between samples --- p.121 / Chapter 4.6.1 --- Spatial variation --- p.121 / Chapter 4.6.1.1 --- Spatial effect on bacterial abundance --- p.121 / Chapter 4.6.1.2 --- Spatial effect on species diversity --- p.121 / Chapter 4.6.2 --- Daily variation --- p.126 / Chapter 4.6.2.1 --- Daily effect on bacterial abundance --- p.126 / Chapter 4.6.2.2 --- Daily effect on species diversity --- p.126 / Chapter 4.6.3 --- Seasonal variation --- p.126 / Chapter 4.6.3.1 --- Seasonal effect on bacterial abundance --- p.126 / Chapter 4.6.3.2 --- Seasonal effect on species diversity --- p.130 / Chapter 4.7 --- Temperature effect on individual airborne bacterial population --- p.130 / Chapter 4.7.1 --- Gram positive bacteria --- p.130 / Chapter 4.7.2 --- Gram negative bacteria --- p.130 / Chapter 4.8 --- Effect of relative humidity on individual airborne bacterial population --- p.137 / Chapter 4.8.1 --- Gram positive bacteria --- p.137 / Chapter 4.8.2 --- Gram negative bacteria --- p.137 / Chapter 5 --- Discussion --- p.143 / Chapter 5.1 --- Bacterial profile --- p.143 / Chapter 5.1.1 --- Bacterial diversity --- p.143 / Chapter 5.1.2 --- Information of the identified bacteria from the student canteen --- p.144 / Chapter 5.1.3 --- Pathogenicity --- p.153 / Chapter 5.1.4 --- Summary on the bacterial profile --- p.153 / Chapter 5.2 --- Comparison between samples --- p.160 / Chapter 5.2.1 --- Spatial variation (Sampling point 1 against Sampling point 2) --- p.160 / Chapter 5.2.2 --- Daily variation (Morning against Afternoon) --- p.161 / Chapter 5.2.3 --- Seasonal variation --- p.162 / Chapter 5.2.4 --- Summer holiday against Summer school time --- p.163 / Chapter 5.2.5 --- Summary on the factors affecting the bacterial content --- p.164 / Chapter 5.3 --- Summary on indoor air quality of the student canteen in terms of bacterial level. --- p.166 / Chapter 6 --- Conclusions --- p.168 / Chapter 7 --- References --- p.169 / Appendix 1 --- p.183 / Appendix 2 --- p.187

Introdução: Em ambientes urbanos, a exaustão dos carros a diesel é uma importante fonte de partículas e gases que afetam diretamente a saúde das pessoas. Como a adição do biodiesel ao diesel é recente, torna-se necessário avaliar o perfil toxicológico dessas emissões e os possíveis efeitos adversos a saúde. Além do mais, a concentração dos poluentes atmosféricos e sua composição físico-química sofrem influências diretas das condições meteorológicas. Esse estudo tem como foco avaliar o perfil toxicológico dos poluentes primários (emitidos diretamente da fonte) e secundários (gerados a partir das condições atmosféricas) por meio de dois estudos. Objetivos: (Estudo I) Avaliar a exposição aguda da exaustão do diesel e biodiesel no perfil inflamatório pulmonar e sistêmico; (Estudo II) Avaliar se a exposição aguda a baixos níveis de partículas ambientais concentradas (PACs) promovem efeitos cardiopulmonares e sistêmicos; e se a magnitude dessas alterações observadas é influenciada pelos períodos (frio/seco e quente/úmido). Métodos: (Estudo I) Camundongos Balb/C foram expostos ao ar filtrado (AF) e a duas concentrações de MP2,5 (600 e 1200 ?g/m3) tanto da exaustão do combustível diesel (D) quanto do biodiesel (BD). As emissões dos poluentes (MP2,5, NO e NO2), temperatura e umidade foram monitorados em tempo real. Os registros da variabilidade da frequência cardíaca (VFC), frequência cardíaca (FC) e da pressão arterial (PA) foram obtidas 30 minutos após a exposição. Após 24 horas os animais foram eutanasiados e foram coletados o lavado broncoalveolar (LBA), o pulmão, o sangue e a medula óssea para avaliar a inflamação pulmonar e sistêmica. A expressão das citocinas (ET-Ar, ET-Br, INOs, ISO, VCAM, IL-8) foram analisadas nos vasos peribronquiolares e no epitélio brônquico. (Estudo II) Camundongos Balb/C foram expostos ao ar filtrado e as PACs na concentração de 200 ?g/m3 geradas no período frio/seco e quente/úmido. A hiperresponsividade pulmonar, VFC, FC, PA foram mensurados 30 minutos após a exposição. Após 24 horas, os animais foram eutanasiados e foram coletados o pulmão e o sangue para avaliar a inflamação pulmonar e sistêmica. Resultados: (Estudo I) As emissões do NO e NO2 foram maiores na exaustão do biodiesel comparado ao diesel. Houve aumento da VFC no BD600, D600 e D1200 comparado ao AF, já a PA reduziu no D1200 comparado ao AF. Houve aumento dos eritrócitos, hematócrito, RDW-SD e reticulócitos no BD1200 e D1200 comparado ao AF; aumento dos eritrócitos, RDW-SD e linfócitos no D600 comparado ao AF; e redução do MCHC no BD1200 e D1200 comparado ao AF. No LBA e na histologia pulmonar foram evidenciados aumento dos neutrófilos no BD600 comparado ao AF. Nos vasos peribronquiolares, houve aumento da expressão da ET-Ar e ET-Br no BD600 comparado ao AF. No epitélio brônquico, houve aumento da expressão da ET-Br no BD600, BD1200, D600 e D1200 comparado ao AF, aumento do VCAM no BD1200 e D600 comparado ao AF. (Estudo II) As PACs geradas nos períodos frio/seco e quente/úmido, induziram alterações nos parâmetros sanguíneos e inflamação pulmonar. PACs geradas no período frio/seco reduziram o volume corpuscular médio (VCM) e elevaram os eritrócitos, hemoglobina, MCHC e o RDW-CV comparado ao AF, no parênquima pulmonar houve um influxo de neutrófilos. Similarmente, as PACs geradas no período quente/úmido reduziram o VCM e elevaram os eritrócitos, hemoglobina, hematócrito e RDW-CV comparado ao AF. Conclusão: A exposição ao biodiesel causou inflamação pulmonar, broncoconstrição dos vasos peribronquiolares e do epitélio brônquico; já a exposição ao diesel desencadeou uma inflamação sistêmica, aumento do estímulo parassimpático e broncoconstrição do epitélio brônquico. Curtas exposições a baixos níveis de PACs induziram modesta, porém, significante inflamação pulmonar e alterações nos parâmetros sanguíneos. Em adição, nossos dados suportam o conceito de que alterações nas condições climáticas modificam levemente a toxicidade das partículas, já que a dose administrada de PACs geradas durante o período frio/seco produziram uma resposta mais exacerbada / Background: In urban environments, the exhaust of diesel cars is an important source of particles and gases that directly affect people\'s health. As the addition of biodiesel to diesel is recent, it is necessary to evaluate the toxicological profile of these emissions and the possible adverse health effects. Moreover, the concentration of air pollutants and their physico-chemical composition suffer direct influences of weather conditions. This study aims to evaluate the toxicological profile of primary pollutants (emitted directly from the source) and secondary (generated from the weather conditions) through two studies. Objectives: (Study I) Evaluate the acute exposure of diesel and biodiesel exhaust in pulmonary and systemic inflammatory profile. (Study II) Evaluated whether acute exposure to low levels of concentrated ambient particles (CAPs) promotes cardiopulmonary and systemic effects; and whether the magnitude of these observed changes is influenced by periods (cold/dry and warm/humid). Methods: (Study I) Balb/C mice were exposed for two hours to filtered air (FA) and two doses (600 and 1200 ?g/m3) of both diesel (D) and biodiesel (BD) fuels. The PM2.5, NO, and NO2 concentrations, air temperature and humidity were monitored in real time. HRV (time and frequency domain), HR and BP parameters were collected after 30 minutes of exposure. After 24 hours were available the bronchoalveolar lavage (BALf), lung histology, blood and bone marrow for pulmonar and systemic inflammation analysis. The cytokines expression (ET-Ar, ET-Br, INOs, ISO, VCAM, IL-8) were available on peribronchiolar vessels and bronchial epithelium. (Study II) Balb/C mice were exposed to 200 ?g/m3 to concentrated ambient particles (CAPs) and filtered air (FA) in cold/dry and warm/humid periods. Lung hyper-responsiveness, heart rate, heart rate variability and blood pressure were evaluated 30 minutes after the exposures. After 24 hours, blood and tissue sampling were performed. Results: (Study I) Emissions of NO and NO2 were higher in the biodiesel compared to diesel oil exhaust. There was an increase in HRV for the BD600, D600 and D1200 compared to FA, already BP reduced the D1200 compared to FA. There was an increase on the erythrocytes, hematocrit, RDW-SD and reticulocytes in BD1200 and D1200 compared to FA; increase in erythrocytes, lymphocytes and RDW-SD on D600 compared to FA; and reduction of MCHC in BD1200 and D1200 compared to FA. BAL and lung histology was evidenced an increase on the neutrophils BD600 compared to FA. In peribronchiolar vessels there was increased of the expression on ET-Ar and ET-Br on the BD600 compared to FA. In the bronchial epithelium there was increased expression of ET-Br in BD600, BD1200, D600 and D1200 compared to FA, increased VCAM on the BD1200 and D600 compared to FA. (Study II) CAPs generated during both periods (warm/humid and cold/dry) induced alterations in red blood cells and lung inflammation. CAPs during the cold/dry period reduced the mean corpuscular volume (MCV) levels and increased erythrocytes, hemoglobin, mean corpuscular hemoglobin concentration (MCHC) and red cell distribution width coefficient variation (RDW-CV) levels compared to the FA group. Similarly, CAPs during the warm/humid period decreased MCV levels and increased erythrocytes, hemoglobin, haematocrit and RDW-CV levels compared to the FA group. CAPs during the cold/dry period increased the influx of neutrophils in the alveolar parenchyma. No differences were obtained on vasoconstrictors of pulmonary vessels. Conclusion: The exposure to biodiesel caused lung inflammation, bronchoconstriction of the peribronchiolar vessels and bronchial epithelium; already the exposure of the diesel caused systemic inflammation, increased of the parasympathetic stimulation and bronchoconstriction of the bronchial epithelium. Short-term exposures to low concentrations of CAPs elicited modest but significant pulmonary inflammation and, into a lesser extent, changes in blood parameters. In addition, our data support the concept that changes in climate conditions modify slightly particle toxicity, since equivalent doses of CAPS of the cold/dry period produced a more exacerbated response

Uma das principais externalidades dos transportes na dimensão urbana é a emissão de poluentes locais e a geração de gases de efeito estufa (GEE). O estudo tem por finalidade quantificar as emissões da frota de ônibus urbano de uma cidade brasileira e propor um mecanismo de mitigação de GEE. Para atingir o objetivo, o estudo apresenta os combustíveis e tecnologias disponíveis no Brasil, e através de uma meta-análise identifica as combinações de combustível e tecnologia que proporcionam a maior redução das emissões de CO, HC, NOx, MP e CO2e. Os resultados da análise mostram que algumas das opções de combustível e tecnologia que apresentam melhor desempenho são: B100 associado ao DPF e SCR, GNV associado ao 3WC, B20 associado ao DPF e SCR, e D15 associado ao DPF e SCR. A seguir, as contribuições dos mecanismos de mitigação de GEE para o setor de transportes são analisadas. O impacto do Mecanismo de Desenvolvimento Limpo (MDL) no setor é limitado, e não há muitas perspectivas de atuação. As Ações de Mitigação Nacionalmente Apropriadas (NAMAs), têm potencial para atuar na redução de GEE, e devem proporcionar apoio financeiro oriundo dos fundos climáticos para as ações implantadas nos países em desenvolvimento. Um estudo de caso foi desenvolvido para avaliar a possibilidade de elaboração de uma NAMA para a renovação da frota de ônibus urbano de uma cidade. Os resultados obtidos na meta-análise foram aplicados para avaliar o combustível e tecnologia que proporcionam maior redução das emissões. Os resultados mostram que a renovação da frota tem potencial de desenvolvimento de uma NAMA, visto que reduz emissões de GEE e proporciona co-benefícios; contudo, deve-se estabelecer um sistema de MRV (Monitorar, Reportar, Verificar) capaz de quantificar as emissões na mitigação. / One of the main externalities from urban transportation is the emission of local pollutants and greenhouse gases (GHG). The study aims to quantify the emissions from the urban bus fleet of a Brazilian city and propose a GHG mitigation mechanism. First, the study presents the fuels and technologies available in Brazil, and through a meta-analysis identifies combinations of fuel and technology that provide the greatest reduction in emissions of CO, HC, NOx, PM and CO2e. Results show the fuel and technology that perform best are: B100 associated with DPF and SCR, CNG associated with 3WC, B20 associated with DPF and SCR, and D15 associated with DPF and SCR. The contribution of GHG mitigation mechanisms for the transport sector was analyzed. The impact of the Clean Development Mechanism (CDM) in the sector is limited, and there are not many perspectives for the future. The Nationally Appropriate Mitigation Actions, named NAMAs, have the potential to act in reducing GHG in transport sector, and should provide financial cooperation through climate funds for implementation of actions in developing countries. A case study was developed to evaluate the possibility of developing a NAMA for the renewal of the fleet of urban buses in a Brazilian city. The results obtained in the meta-analysis were applied to evaluate which fuel and technology provide greater reductions in emission. The results show that the renewal of the fleet has the potential for developing a NAMA, since it reduces greenhouse gas emissions and provide co-benefits; however it requires a serious MRV (Monitor, Report, Verify) capable of quantifying the mitigation of emissions.