Law Tsui Ying. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 64-70). / Abstracts in English and Chinese. / Acknowledgments --- p.ii / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Structure of Bronchus --- p.3 / Chapter 1.2 --- Existing Systems --- p.4 / Chapter 1.2.1 --- Virtual Endoscope System (VES) --- p.4 / Chapter 1.2.2 --- Virtual Reality Surgical Simulator --- p.4 / Chapter 1.2.3 --- Automated Virtual Colonoscopy (AVC) --- p.5 / Chapter 1.2.4 --- QUICKSEE --- p.5 / Chapter 1.3 --- Organization of Thesis --- p.6 / Chapter 2 --- Three Dimensional Visualization in Medicine --- p.7 / Chapter 2.1 --- Acquisition --- p.8 / Chapter 2.1.1 --- Computed Tomography --- p.8 / Chapter 2.2 --- Resampling --- p.9 / Chapter 2.3 --- Segmentation and Classification --- p.9 / Chapter 2.3.1 --- Segmentation by Thresholding --- p.10 / Chapter 2.3.2 --- Segmentation by Texture Analysis --- p.10 / Chapter 2.3.3 --- Segmentation by Region Growing --- p.10 / Chapter 2.3.4 --- Segmentation by Edge Detection --- p.11 / Chapter 2.4 --- Rendering --- p.12 / Chapter 2.5 --- Display --- p.13 / Chapter 2.6 --- Hazards of Visualization --- p.13 / Chapter 2.6.1 --- Adding Visual Richness and Obscuring Important Detail --- p.14 / Chapter 2.6.2 --- Enhancing Details Incorrectly --- p.14 / Chapter 2.6.3 --- The Picture is not the Patient --- p.14 / Chapter 2.6.4 --- Pictures-'R'-Us --- p.14 / Chapter 3 --- Overview of Advanced Segmentation Methodologies --- p.15 / Chapter 3.1 --- Mathematical Morphology --- p.15 / Chapter 3.2 --- Recursive Region Search --- p.16 / Chapter 3.3 --- Active Region Models --- p.17 / Chapter 4 --- Overview of Centerline Methodologies --- p.18 / Chapter 4.1 --- Thinning Approach --- p.18 / Chapter 4.2 --- Volume Growing Approach --- p.21 / Chapter 4.3 --- Combination of Mathematical Morphology and Region Growing Schemes --- p.22 / Chapter 4.4 --- Simultaneous Borders Identification Approach --- p.23 / Chapter 4.5 --- Tracking Approach --- p.24 / Chapter 4.6 --- Distance Transform Approach --- p.25 / Chapter 5 --- Automated Extraction of Bronchus Area --- p.27 / Chapter 5.1 --- Basic Idea --- p.27 / Chapter 5.2 --- Outline of the Automated Extraction Algorithm --- p.28 / Chapter 5.2.1 --- Selection of a Start Point --- p.28 / Chapter 5.2.2 --- Three Dimensional Region Growing Method --- p.29 / Chapter 5.2.3 --- Optimization of the Threshold Value --- p.29 / Chapter 5.3 --- Retrieval of Start Point Algorithm Using Genetic Algorithm --- p.29 / Chapter 5.3.1 --- Introduction to Genetic Algorithm --- p.30 / Chapter 5.3.2 --- Problem Modeling --- p.31 / Chapter 5.3.3 --- Algorithm for Determining a Start Point --- p.33 / Chapter 5.3.4 --- Genetic Operators --- p.33 / Chapter 5.4 --- Three Dimensional Painting Algorithm --- p.34 / Chapter 5.4.1 --- Outline of the Three Dimensional Painting Algorithm --- p.34 / Chapter 5.5 --- Optimization of the Threshold Value --- p.36 / Chapter 6 --- Automatic Centerline Determination Algorithm --- p.38 / Chapter 6.1 --- Distance Transformations --- p.38 / Chapter 6.2 --- End Points Retrieval --- p.41 / Chapter 6.3 --- Graph Based Centerline Algorithm --- p.44 / Chapter 7 --- Experiments and Discussion --- p.48 / Chapter 7.1 --- Experiment of Automated Determination of Bronchus Algorithm --- p.48 / Chapter 7.2 --- Experiment of Automatic Centerline Determination Algorithm --- p.54 / Chapter 8 --- Conclusion --- p.62 / Bibliography --- p.63

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

Liu Kin Hang. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (leaves 88-98). / Abstracts in English and Chinese. / Abstract (in English) --- p.i / Abstract (in Chinese) --- p.iii / Acknowledgement --- p.v / Table of Contents --- p.vi / List of Tables --- p.ix / List of Figures --- p.x / Glossary of Terms and Abbreviations --- p.xi / Chapter Section I: --- Overview --- p.1 / Chapter Chapter 1: --- Introduction --- p.2 / Chapter 1.1 --- Asthma and Assessment of A irway Inflammation --- p.2 / Chapter 1.1.1 --- Assessment of A irway Inflammation --- p.4 / Chapter 1.1.2 --- Invasive and Noninvasive Methods --- p.4 / Chapter 1.1.3 --- Exhaled Nitric Oxide as a Diagnostic Marker and Its Correlation with Other Markers of Inflammation --- p.6 / Chapter 1.1.4 --- Normal Reference Studies of Exhaled Nitric Oxide --- p.8 / Chapter 1.2 --- Aim of Study --- p.10 / Chapter Chapter 2: --- Plan of Study --- p.11 / Chapter Section II: --- Literature Review --- p.13 / Chapter Chapter 3: --- Nitric Oxide Biology --- p.15 / Chapter 3.1 --- Exhaled Nitric Oxide Production in Airway --- p.15 / Chapter 3.2 --- Nitric Oxide Production and Function --- p.16 / Chapter 3.3 --- Nitric Oxide Synthase Pathway --- p.18 / Chapter 3.4 --- Factors Affecting Exhaled Nitric Oxide Level --- p.21 / Chapter 3.4.1 --- Procedure-related Factors --- p.22 / Chapter 3.4.1.1 --- Nasal Nitric Oxide Contamination --- p.22 / Chapter 3.4.1.2 --- Exhalation Procedure 226}0´ؤؤStarting Lung Volumes --- p.23 / Chapter 3.4.1.3 --- Exhalation Procedure 226}0ؤ Flow --- p.23 / Chapter 3.4.1.4 --- Circadian Rhythm --- p.25 / Chapter 3.4.2 --- Patient Factors --- p.26 / Chapter 3.4.2.1 --- Sex --- p.26 / Chapter 3.4.2.2 --- Upper Respiratory Tract Infection --- p.26 / Chapter 3.4.2.3 --- Diet and Exhaled Nitric Oxide --- p.27 / Chapter 3.4.2.4 --- Effect of Spirometry and Exercise --- p.28 / Chapter 3.4.3 --- Environmental Factors --- p.28 / Chapter Chapter 4: --- Exhaled Nitric Oxide in Asthmatics and Its Relationship to Anti-inflammatory Treatment --- p.31 / Chapter Chapter 5: --- Relationship of Exhaled Nitric Oxide with Other Inflammatory Markers --- p.33 / Chapter 5.1 --- Correlation of Findings from Biopsy and Bronchoalveolar Lavage with Exhaled Nitric Oxide --- p.33 / Chapter 5.2 --- "Exhaled Nitric Oxide, Induced Sputum Analysis and Sputum Eosinophil Cationic Protein" --- p.35 / Chapter Section III: --- Original Study --- p.37 / Chapter Chapter 6: --- Methodology --- p.38 / Chapter 6.1 --- Study Population --- p.38 / Chapter 6.2 --- The International Study of Asthma and Allergies in Childhood --- p.40 / Chapter 6.3 --- ISAAC Questionnaires --- p.42 / Chapter 6.4 --- Standardized Approach for Answering Questions in the Field --- p.44 / Chapter 6.5 --- Anthropometric Measurements --- p.45 / Chapter 6.6 --- Exhaled Nitric Oxide Measurement --- p.46 / Chapter 6.6.1 --- "NIOY® (Aerocrine AB, Stockholm, Sweden)" --- p.46 / Chapter 6.6.2 --- Calibration Procedures --- p.47 / Chapter 6.6.3 --- Exhaled Nitric Oxide Measurement --- p.48 / Chapter 6.7 --- Classification of Subjects --- p.51 / Chapter 6.8 --- Statistical Analysis --- p.53 / Chapter Chapter 7: --- Results --- p.54 / Chapter 7.1 --- Subjects and Demography --- p.54 / Chapter 7.2 --- Exhaled Nitric Oxide in Chinese Children --- p.58 / Chapter 7.3 --- Exhaled Nitric Oxide in Caucasians and Other Ethnic Groups --- p.66 / Chapter Chapter 8: --- Discussion --- p.69 / Chapter Chapter 9: --- Conclusion and Further Studies --- p.76 / Appendix 1 Questionnaires (Chinese Version) --- p.80 / Appendix 2 Questionnaires (English Version) --- p.84 / References --- p.88

INTRODUÇÃO: A inflamação desempenha um papel central no desenvolvimento da asma, que é considerada uma doença alérgica com um perfil inflamatório clássico Th2. No entanto, as citocinas de perfil IL-17 tem sido estudadas para melhor compreender sua participação na fisiopatologia desta doença. Pacientes asmáticos graves apresentam exacerbações freqüentes, sendo a causa infecciosa um dos principais desencadeantes e que podem perpetuar as respostas inflamatórias. A resposta Th17 pode estar claramente associada a esses eventos. OBJETIVO: Este estudo avaliou os efeitos da terapia com anticorpo monoclonal anti-IL-17 nas alterações presentes nos septos alveolares em um modelo experimental de inflamação pulmonar alérgica crônica exacerbado por LPS. MÉTODOS: Foram utilizados 60 camundongos macho da espécie BALB/c, sendo sensibilizados com ovoalbumina intraperitoneal e repetidamente expostos à inalação com ovoalbumina, seguidos por tratamento com ou sem anti-IL-17. Vinte e quatro horas antes do final do protocolo experimental de 29 dias, dois grupos receberam LPS intratraqueal (0,1 mg/ml, sendo os grupos OVA-LPS e OVA-LPS anti-IL-17). Posteriormente, avaliamos o fluido do lavado broncoalveolar (FLBA), por morfometria quantificamos o recrutamento das células apresentadoras de antígenos (FOXP3 e células dendríticas), de eosinófilos, a expressão celular de citocinas próinflamatórias (TNF-alfa, IL-2, IL-4, IL-5, IL-6, IL13 e IL-17), anti-inflamatórias (IL-10), quimiocina (TARC), além da quantificação de IL-6 por RT-PCR. Avaliamos também elementos da matriz extracelular (fibras colágenas tipo I e III, MMP-9, MMP-12, TIMP-1, TGF-beta, actina, decorina, lumicam, biglicano, fibronectina e integrina), edema dos septos alveolares, resposta das vias de estresse oxidativo através dos marcadores iNOS e 8-iso-PGF2alfa e as vias sinalizadoras NF-kB e Rho quinase, além da avaliação do diâmetro alveolar médio. RESULTADOS: Os animais do grupo OVA-LPS apresentaram uma potencialização de todas as respostas (p < 0,05) comparativamente ao grupo OVA, exceto para: expressão de IL-17, TNF-alfa, NF-kB, TIMP-1 e na fração de volume de fibras colágenas tipo I, decorina, lumicam e actina. No grupo OVA-anti-IL17 houve atenuação de todos os parâmetros quando comparado ao grupo OVA (p < 0,05). Nos animais do modelo de inflamação alérgica crônica exacerbado pelo LPS e tratado com anti-IL-17 (grupo OVA-LPS anti-IL-17) houve diminuição comparativamente ao grupo OVA-LPS dos seguintes parâmetros: número de células totais do lavado broncoalveolar, de células positivas para FOXP3 e células dendríticas, número de CD4+ e CD8+, de células positivas para IL-10 anti-inflamatória e citocinas pró-inflamatórias (TNF-alfa, IL-2, IL-4, IL-5, IL-6, IL-13 e IL-17); quimiocinas (TARC), expressão gênica de IL-6, edema nos septos alveolares; elementos da matriz extracelular (fração de volume de fibras colágenas tipo I e III, actina, decorina, biglicano, lumicam, fibronectina, integrina e expressão de células positivas para TGF-beta, MMP-9, MMP-12 e TIMP-1), da resposta das vias de estresse oxidativo: (células positivas para iNOS e fração de volume de isoprostano PGF-2alfa; da expressão celular de NF-kB, e das proteínas Rho quinase 1 e 2 (p < 0,05). Não houve diferenças no diâmetro alveolar médio entre todos os grupos experimentais. CONCLUSÃO: Esses dados sugerem que a inibição da IL-17 pode ser uma via terapêutica promissora para o tratamento da inflamação alérgica crônica, mesmo durante uma exacerbação e pode contribuir para o controle da inflamação Th1/ Th2/Th17, da expressão de quimiocinas, do remodelamento da matriz extracelular e do estresse oxidativo. As vias sinalizadoras de NF-kB e Rho-quinase estão envolvidas no controle dessas respostas neste modelo de inflamação alérgica crônica exacerbado pelo LPS / INTRODUCTION: Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, IL-17 profile cytokines have been studied to better understand their involvement in the pathophysiology of this disease. Severe asthmatic patients have frequent exacerbations, the infectious cause being one of the main triggers and that can perpetuate the inflammatory responses. The Th17 response may be clearly associated with these events. OBJECTIVE: This study evaluates the effects of anti-IL-17 monoclonal antibody therapy on alveolar septa in an experimental model of chronic allergic lung inflammation of asthma exacerbated by LPS. METHODS: Sixty male BALB / c mice were used, being sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours before the end of the 29-day experimental protocol, two groups received intratracheal LPS (0.1 mg / ml, OVA-LPS and anti-IL-17 OVA-LPS groups). Afterwards, we evaluated bronchoalveolar lavage fluid (BALF), by morphometry we quantified the recruitment of antigen-presenting cells (FOXP3 and dendritic cells), eosinophils, the cellular expression of proinflammatory cytokines (TNF-alpha, IL-2, IL IL-5, IL-6, IL-13 and IL-17), anti-inflammatory cytokines (IL-10), chemokine (TARC), and quantification of IL6 by RT-PCR. We also evaluated elements of the extracellular matrix (collagen fibers type I and III, MMP-9, MMP-12, TIMP-1, TGF-beta, actin, decorin, lumicam, biglican and fibronectin), alveolar septum edema, oxidative stress through the marker iNOS and 8-iso-PGF2? and the signaling pathways NF-kB and Rho kinase. In addition, we evaluated of the mean alveolar diameter. RESULTS: The animals of the OVA-LPS group presented a potentiation of the all responses compared to OVA (p < 0.05), except for: expression of IL-17, TNFalpha, NF-kB, TIMP-1 and in the volume fraction of type I collagen fibers, decorin, lumicam and actin. Treatment with anti-IL-17 (OVA-anti-IL17 group) attenuated all parameters compared to OVA group (p < 0.05). The animals of the chronic allergic inflammation model exacerbated by LPS and treated with anti-IL-17 (OVA-LPS anti-IL-17 group) had a decreased of the following parameters compared to OVA-LPS: total bronchoalveolar lavage cells number, FOXP3 and dendritic positive cells, CD4 + and CD8 + numbers, of cells positive for IL-10 antiinflammatory, and pro-inflammatory cytokines (TNF-alfa, IL-2, IL-4, IL-5, IL-6, IL- 13 and IL-17); chemokine (TARC), genic expression IL6; edema in the alveolar septum; extracellular matrix elements (volume fraction of collagen fibers type I and III, actin, decorin, biglican, lumicam, fibronectin, and expression of TGF-beta, MMP-9, MMP-12 and TIMP-1 positive cells) of the oxidative stress pathways response (iNOS positive cells and isoprostane volume fraction 8-isoPGF-2alfa) NFkB and Rho kinase 1 and 2 positive cells (p < 0.05). There were no differences in mean alveolar diameter among all experimental groups. CONCLUSION: These data suggest that inhibition of IL-17 may be a promising therapeutic pathway for the treatment of chronic allergic inflammation, even during an exacerbation, and may contribute to the control of Th1 / Th2 / Th17 inflammation, chemokine expression, extracellular matrix remodeling and oxidative stress. Signaling pathways of NF-kB and Rho-kinase are involved in the control of these responses in this model of chronic allergic inflammation exacerbated by LPS

Por serem as manifestações pulmonares de etiologia infecciosas muito freqüentes e potencialmente graves nas crianças com aids, o diagnóstico deve ser precoce para uma rápida e efetiva intervenção terapêutica. A proteína C reativa (PCR), um dos marcadores das provas de fase aguda, tem sido usada na prática clínica como um recurso diagnóstico na diferenciação entre patologias sistêmicas de etiologia viral e bacteriana, bem como na monitorização da eficácia da terapêutica antimicrobiana frente a uma infecção. Apesar da proteína C reativa ser um exame inespecífico e poder estar aumentada em diferentes situações clínicas (infecções sistêmicas, doenças inflamatórias e neoplásicas, isquemias, queimaduras), a infecção bacteriana é a causa mais freqüente para o seu aumento. A PCR eleva-se rapidamente após a injúria tecidual, atingindo valores 10 a 1000 vezes superiores a seu nível basal: em virtude de sua curta meia vida, retorna em pouco tempo aos valores prévios após o fim da agressão. Com o objetivo de encontrar um método laboratorial auxiliar para as infecções pulmonares nas crianças com infecção pelo HIV foi estudada a proteína C reativa, pela técnica de nefelometria, em dois momentos distintos: na ausência de quadro infeccioso concomitante (grupo 1) e na vigência de pneumonia aguda (grupo 2). O grupo 1 envolveu o estudo de 66 crianças com infecção pelo HIV, resultando em 84 amostras de PCR coletadas na ausência de quadro infeccioso concomitante.No grupo 2 foram analisadas 6 crianças com infecção pelo HIV com 9 episódios de pneumonia aguda. As crianças com infecção pelo HIV foram classificadas de acordo com as categorias clínicas e imunológicas da classificação do CDC para infecção pelo HIV em crianças. Dentre as 66 crianças incluídas no grupo 1, 6 pertenciam à categoria N, 11 à categoria A, 27 à categoria B e 22 à categoria C. Das 84 amostras de PCR coletadas no grupo 1, 76 (90,48%) encontravam-se abaixo de 5 mg/l, 7 amostras entre 5 a 20 mg /l e, apenas 1 amostra entre 20 a 40 mg/l (1,15%). No grupo 2, todas as crianças eram pertencentes às categorias B3 (1/6) ou C3 (5/6), refletindo um estágio mais avançado da doença. Das 9 amostras de PCR, 6 apresentavam valores maiores que 40 mg/l, 1 entre 20 e 40 mg/l e as 2 amostras restantes, entre 5 e 20 mg/l. Os dados sugerem portanto que a infecção pelo HIV por si só não é acompanhada de aumento da PCR, bem como não existe relação com a classificação imunológica em que o paciente se encontre. Pacientes com infecção pelo HIV na vigência de pneumonia aguda apresentam níveis aumentados de PCR. Neste estudo, o ponto de corte que diferenciou os grupos 1 e 2 foi PCR = 28,9 mg/l com sensibilidade de 77,8% e especificidade de 100% (IC 95%) / As pulmonary infection is a common and potentially serious condition in HIV-infected children, effectiveness of treatment of this kind of affection depends to a large extent on the promptness of accurate diagnosis. The C-Reactive Protein (CRP), a reasonably well-established acute phase marker, has long been used to differentiate bacterial from viral infections. Despite its lack of specifity, that is, the fact that other conditions like inflammatory diseases, neoplasms, ischemia and burns may also increase CRP levels, Bacterial infections are the most frequent cause of increased CRP found in daily clinical practice. Shortly after any tissular injury, CRP increases considerably, reaching up to 10-1000 times its previous levels. Due to its short half-life, its decrease after the end of the affection is quick as well. This study aimed at evaluating the CRP (assessed by nephelometry) as an auxiliary tool to diagnose pulmonary infection in HIV-infected children. Two groups of patients were considered in this study: group 1 was constituted by 66 HIV-infected children with no clinical signs of concomitant infection (amounting to 84 CRP samples) and group 2 was constituted by 6 HIV-infected children with pneumonia (amounting to 9 CRP samples). All the subjects were assigned to categories according to the pediatric HIV classification system (CDC, 1994). Among the 66 children from group 1, 6 were assigned to categories N, 11 to A, 27 to B and 22 to C. Regarding the levels of CRP in group 1 it was found: 76 samples (90.48%) < 5 mg/l, 7 (8.33%) in the range between 5 and 20 mg/l and 1 sample between 20 and 40 mg/l. In the group 2, all the children were assigned either to category B3 (1/6) or C3 (5/6) and the CRP level distribution was the following: 6 (6/9) > 40 mg/l, 1 (1/6) between 20 and 40 mg/l and 2 (2/6) between 5 and 20 mg/l. These results suggest that 1.HIV infection by itself does not increase the levels of CRP, regardless the immunologic classification of the patient; 2.HIV-infected children with pneumonia present increased levels of CRP 3.In this study, the cut-off point to differentiate groups 1 and 2 was 28,9 mg/l, with sensitivity of 77,8% and specificity of 100% (p < 0.05)

<p>Uvod: Značajno mesto u morbiditetu nedono&scaron;čadi predstavljaju plućne bolesti. Ultrazvučnim (UZ) pregledom pluća može se smanjiti ukupna doza jonizujućeg zračenja kojoj su nedono&scaron;čad izložena u svakodnevnom kliničkom radu. Cilj: Ispitati povezanost između UZ nalaza na plućima i RTG nalaza i kliničkih parametara respiratornog statusa kod nedono&scaron;čadi. Utvrditi da li se UZ-om detektovane subpleuralne konsolidacije mogu morfolo&scaron;ki diferencirati. Utvrditi da li UZ nalaz na plućima pomaže neonatologu u proceni efekta terapije tokom lečenja nedono&scaron;čadi. Materijal i metode: Prospektivnim tipom jednogodi&scaron;njeg istraživanja obuhvaćeno je 100 nedono&scaron;čadi kojoj je nakon prijema na Odeljenje intenzivne nege i terapije (OINT) bio indikovan RTG snimak pluća. Za izvođenje UZ pregleda pluća kori&scaron;ćeni su Siemens Sonoline Adara i Siemens Sonoline Sienna UZ aparati. Kori&scaron;ćena je siva skala i konveksna sonda (5 MHz) i linearna sonda (7,5 MHz). Za ispitivanje korelacije između UZ nalaza na plućima i kliničkih parametara respiratornog statusa (FiO2, PCO2, SaO2) kori&scaron;ćen je Pearson-ov koeficijent korelacije. Posebno je ispitivana korelacija kod nedono&scaron;čadi koja su bila na mehaničkoj ventilaciji (MV) i kod nedono&scaron;čadi koja su bila na oksigenoterapiji (OxTh). Utvrđivanje razlika između UZ-om uočenih konsolidacija i RTG-om uočenih konsolidacija, urađeno je prebrojavanjem ukupnog broja uočenih konsolidacija svakom od dve navedene radiolo&scaron;ke metode i poređenjem prosečnog broja uočenih konsolidacija UZ-om, odnosno RTG-om. U svim statističkim testovima je kori&scaron;ćen je nivo značajnosti p&lt;0,05 i interval poverenja (CI) 95%. Rezultati: Kod nedono&scaron;čadi koja su bila na MV, kao i kod nedono&scaron;čadi na OxTh, postoji statistički značajna korelacija između UZ nalaza na plućima i kliničkih parametara respitatornog statusa (p&lt;0,001). Kod bolesnika na MV procenat podudaranja, odnosno nepodudaranja UZ nalaza i FiO2 iznosio je 81%, odnosno 19%. Procenat podudaranja, odnosno nepodudaranja UZ nalaza i PCO2 je bio 80%, odnosno 20%, dok je u slučaju SaO2 procenat podudaranja sa UZ nalazom bio 80%, a nepodudaranja 20%. Kod nedono&scaron;čadi na MV, procenat podudarnosti UZ nalaza na plućima i sva tri klinička parametra zabeležen je u 68%, sa dva klinička parametra u 21%, dok je u 11% zabeležena podudarnost samo sa jednim kliničkim parametrom. Kod nedono&scaron;čadi koja su bila na OxTh procenat podudaranja, odnosno nepodudaranja UZ nalaza i FiO2 iznosio je 94%, odnosno 6%. Procenat podudaranja, odnosno nepodudaranja UZ nalaza i PCO2 je bio 94%, odnosno 6%, dok je u slučaju SaO2 procenat podudaranja sa UZ nalazom bio 93%, a nepodudaranja 7%. Kod nedono&scaron;čadi na OxTh procenat podudarnosti UZ nalaza na plućima i sva tri klinička parametra zabeležen je u 85%, sa dva klinička parametra u 10%, dok je u 5% zabeležena podudarnost samo sa jednim kliničkim parametrom. Prosečan broj UZ-om uočenih konsolidacija po svakom pojedinačnom UZ pregledu pluća je bio 0,80, dok ih je na pojedinačnom RTG snimku uočeno 0,25. U 29% slučajeva konsolidacije su istovremeno uočene i UZ i RTG pregledom pluća, dok je u 71% slučajeva konsolidacije bilo moguće otkriti samo UZ pregledom pluća. Od ukupno 304 subpleuralnih konsolidacija koje su uočene UZ-om, u 172 slučaja (56,58%) je na osnovu prethodno klinički i/ili laboratorijski postavljene dijagnoze indirektno utvrđeno poreklo konsolidacije: u 125 slučajeva (72,67%) uzrok je bio atelektaza, u 39 slučajeva (22,67%) neonatalna pneumonija i u 8 slučajeva (4,66%) plućna hemoragija. Zaključci: Postoji statistički značajna korelacija između ultrazvučnog nalaza na plućima nedono&scaron;čadi i kliničkih parametara respiratornog statusa - FiO2, PaCO2 i SaO2, kako kod nedono&scaron;čadi na MV, tako i kod nedono&scaron;čadi na OxTh, zbog čega ultrazvučni nalaz na plućima može biti od pomoći neonatologu u praćenju efekta primenjene terapije. Na osnovu karakteristika ultrazvučno uočenih subpleuralnih konsolidacija nije moguće utvrditi njihovu etiologiju, već samo u korelaciji sa kliničkim i laboratorijskim nalazima. Ultrazvuk pluća je senzitivnija metoda za uočavanje subpleuralnih konsolidacija u odnosu na radiografiju pluća.</p> / <p>Introduction: Lung diseases play a major role in morbidity of premature neonates. Using lung ultrasound (LUS) as a diagnostic tool lowers the dose of ionizing radiation of prematures in every day clinical work. Objectives: To assay the interconnection between LUS and chest X ray (CXR) and clinical parameters of respiratory status (FiO2, PCO2 i SaO2) in prematures. To investigate the possibility of sonographic determination of etiology of subpleural consolidations based on their appearance. To determine whether LUS can be of clinical benefit to the neonatologist in assessing the effect of therapy used in treating prematures. Material and methods: Prospective one year study included 100 premature neonates who underwent a CXR exam after the admission in the Intensive care unit (ICU). Siemens Sonoline Adara i Siemens Sonoline Sienna US machines were used, as well as the gray scale, convex probe (5 MHz) and linear probe (7,5 MHz). Pearson correlation coefficient was used to test the interconnection between LUS and clinical parameters of respiratory status (FiO2, PCO2, SaO2). The test was performed separately for both prematures on mechanical ventilation (MV) and prematures on oxygen therapy (OxTh). Determination of differencies between consolidations seen on LUS and those seen on CXR was done by counting the number of consolidation detected with each method and by comparing the average number of consolidations detected with LUS and by CXR. The assessment of statistical significance was done using the p value, and the p value&lt;0,05 and the confidence interval (CI) of 95% was considered as statistically significant. Results: Statistically significant correlation (p&lt;0,001) was established between clinical parameters of respiratory status and LUS both in prematures on MV and on OxTh. The percentage of concurrence, or nonconcurrence of LUS and FiO2 was 81% and 19% (respectively). The percentage of concurrence, or nonconcurrence of LUS and PCO2 was 80% and 20% (respectively), while in case of SaO2 the percentage of concurrence with LUS was also 80% and the percentage of nonconcurrence was 20%. In the group of prematures on MV the percentage of concurrence of LUS with all three clinical parameters was in 68%, with two parameters the concurrence was evident in 21% and with a single clinical parameter in 11%. In prematures on OxTh, the percentage of concurrence, or nonconcurrence of LUS and FiO2 was 94% and 6% (respectively). The percentage of concurrence, or nonconcurrence of LUS and PCO2 was also 96% and 4% (respectively), while in case of SaO2 the percentage of concurrence with LUS was also 93% and the percentage of nonconcurrence was 7%. In the group of prematures on OxTh the percentage of concurrence of LUS with all three clinical parameters was in 85%, with two parameters the concurrence was evident in 10% and with a single clinical parameter in 5%. The mean number of subpleural consolidations detected by LUS per exam was 0.80. The mean number of consolidations detected on each CXR was 0.25. In 29%&nbsp; consolidations were detected both with LUS and CXR, but in 71% consolidations were only detected using LUS. 304 subpleural consolidations were seen on LUS, but only in 172 cases (56.58%) it was possible to determine the etiology of consolidations and this was done indirectly, in concordance with previously clinically and/or laboratory diagnosis: in 125 cases (72.67%) the origin was atelectasis, in 39 cases (22.67%) neonatal pneumonia and in 8% (4.66%) pulmonary haemorrhage. Conclusion: Statistically significant interconnection between LUS and clinical parameters of respiratory status &ndash; FiO2, PaCO2 i SaO2 exists both in MV prematures and prematures with oxygen supplementation. Previously mentioned suggests that LUS can be of use to neonatologist in following the effect of administred therapy in prematures. The origin of subpleural consolidations cannot be determined on the basis of their appereance or features seen on LUS. The etiology of sonographic subpleural consolidations can only be indirectly determined in correlation with clinical and laboratory findings. LUS is more sensitive than CXR in detecting subpleural consolidations.</p>

<p><strong>Aim:</strong> The aim of this study was to describe the total energy expenditure (TEE) and physical activity levels (PAL) within a group of children with cystic fibrosis (CF) and to compare the results with a control group with healthy children. The aim also was to compare the rated activity levels between the groups as well comparing the difference between boys and girls within the groups. <strong>Method:</strong> The study included 30 participating children, divided into two groups with 15 participants in each group. One of the groups was a CF-group and the other a group of controls, matched for gender and age. Activity diaries were studied and data were presented decrepitly and analyzed with Wilcoxon rank sum test. <strong>Result:</strong> The result showed no difference between the groups while comparing TEE and PAL. Half of the participants in both groups (53,34 % and 46,67 %) reached a moderate or high physical activity level during the registration. No significance was proved between the groups as they rated their activity level, numbered 6-9, in their activity diaries. Neither could any differences be proved significant in rated activity between the boys and girls within the groups. <strong>Conclusion:</strong> The conclusion was that no significant differences appeared regarding TEE or PAL between the CF-group and the control group participating in this study. Neither were there any differences in activity level between boys and girls within the groups.</p> / <p><strong>Syfte:</strong> Syftet med studien var att beskriva energiomsättning och fysisk aktivitetsnivå hos en grupp barn med cystisk fibros (CF) och jämföra resultatet med friska barn i en kontrollgrupp. Syftet var också att jämföra skattade aktivitetsnivåer mellan grupperna samt mellan flickor och pojkar inom de båda grupperna. <strong>Metod:</strong> I studien deltog 30 barn, indelade i två grupper om 15 deltagare. Grupperna var en CF-grupp och en kontrollgrupp matchad efter kön och ålder. Aktivitetsdagböcker granskades och data sammanställdes och data presenterades deskriptivt och analyserades med Wilcoxsons rangsummetest. <strong>Resultat:</strong> Resultatet visade att det inte fanns skillnad mellan de båda grupperna vid jämförelse av TEE och PAL. Ungefär hälften av alla deltagare (53,34 % resp. 46,67 %) nådde moderat eller hög aktivitetsnivå under de registrerade dagarna. Det förekom ingen signifikant skillnad mellan grupperna med avseende antal skattade 6-9:or i aktivitetsdagboken. Inte heller någon skillnad mellan könen inom de båda grupperna kunde påvisas. <strong>Slutsats:</strong> Slutsatsen var att det inte fanns någon signifikant skillnad beträffande energiomsättning eller fysisk aktivitet mellan barn med CF och friska barn som deltog i denna studie. Inte heller kunde någon skillnad i aktivitetsnivå mellan könen inom grupperna påvisas.</p>

In chronic inflammatory diseases like asthma or rheumatoid arthritis, erroneous and exaggerated accumulation of leukocytes in a tissue inadvertently causes the body harm. Several efficient anti-inflammatory drugs exist, for example corticosteroids and cyclo-oxygenase inhibitors. However, these drugs have potent and diverse effects and often act by inhibiting events subsequent to initiation of the inflammatory response, leading to more or less severe side-effects, especially when used in high doses for long periods of time. For this reason, strategies aimed at early inhibition of recruitment and activation of leukocytes have been suggested as safer and more specific approaches to reduce inflammation. Leukocyte adhesion to activated endothelium is a prerequisite to the following activation and extravasation, and takes place in the initial phase of inflammation. By using a model that allows leukocytes to adhere to tumour necrosis factor (TNF)-activated endothelial cells, thus mimicking aspects of an inflammatory reaction, we found that uridine, 4-thiouridine and isomaltitol could all reduce adhesion. This suggested that they may have anti-inflammatory potential. We therefore tried the three substances in a Sephadex-induced lung inflammation model and found that uridine and 4-thiouridine have several anti-inflammatory effects, such as being able to reduce leukocyte accumulation, decrease TNF protein levels and partly inhibit the oedema induced by Sephadex. Isomaltitol turned out to have immunomodulating, rather than anti-inflammatory, effects, which could be of interest in diseases where inadequate inflammatory responses are a problem.

The overall aim of this thesis was to describe subjects with chronic obstructive pulmonary disease (COPD) from different perspectives. Focus was on patients at the time of diagnosis, impact of the disease in comparison to other chronic diseases, factors associated with good health and quality of life (QoL), and diagnostic spirometry in clinical practice. Methods: Qualitative method, grounded theory, was used to analyse patients´ perspectives at the time of diagnosis in a primary care setting (n=10). Public health surveys in the general population were used to compare chronic diseases (n=10,755) and analyse factors associated with health outcomes in COPD (n=1,475). Medical records and spirometry reports, from primary and secondary care, were analysed to assess diagnosis of COPD in clinical practice (n=533). Results: In clinical practice, 70% of patients at the time of diagnosis of COPD lacked spirometry results confirming the diagnosis. Factors related to consequences of smoking, shame and restrictions in physical activity (PA) in particular, were described by patients at the time of diagnosis of COPD. In general subjects with COPD (84%), rheumatoid arthritis (74%) and diabetes mellitus (72%) had an activity level considered too low to maintain good health. In COPD, the most important factor associated with good health and quality of life was a high level of PA. Odds ratios (OR (95%CI)) varied from 1.90 (1.47-2.44) to 7.57 (4.57-12.55) depending on the degree of PA, where subjects with the highest PA level had the best health and QoL. Conclusions: Subjects with COPD need to be diagnosed at an early stage, and health professionals should be aware that feelings of shame could delay patients from seeking care and thus obtaining a diagnosis. The use of spirometry and the diagnostic quality should be emphasised. In patients with COPD greater attention should be directed on increasing the physical activity level, as patients with a low level of physical activity display worse health and quality of life.

Bakgrunden till studien bygger på ett samarbete mellan sjukgymnastprogrammet på Mälardalens högskola och ett sjukhus i Sörmlands läns landsting. Syftet var att utvärdera om behandling bestående av fyra veckors KOL-skola haft effekt på patienternas hälsa, välbefinnande och fysiska kapacitet. KOL-skolan bestod utav fyra tillfällen under vilka olika vårdprofessioner gav patienterna information om bl.a. symptompåverkan, känslomässiga upplevelser och vikten av fysisk aktivitet. Det var tio patienter med kronisk obstruktiv lungsjukdom (KOL) i stadium två till fyra som deltog i interventionen. Utvärderingsinstrument som användes var The St George’s Respiratory Questionnaire och sex minuters gångtest. Resultaten visade att ingen signifikant skillnad i enkäten eller sex minuters gångtest förelåg efter intervention för gruppen. Tidigare forskning har visat att de psykosociala faktorerna har en stor inverkan på patienter med KOL och deras välbefinnande. Författarna anser därför att framtida forskning och verksamhetsutveckling bör utforma behandlingsstrategier för patienter med KOL utifrån den biopsykosociala modellen. / The background of this study is based on a cooperation between the physiotherapy program at Mälardalen University and a hospital in the county of Södermanland. The aim of the study was to evaluate whether a four week treatment of COPD-school have had an impact on patient health, well being and physical capacity. The COPD-school consisted of four occasions in which different health care professionals gave patients information on subjects including; symptom impact, emotional experiences and the importance of physical activity. There were ten patients with chronic obstructive pulmonary disease (COPD) in stage two to four who participated in the intervention. The instruments for evaluation that were used were The St. George's Respiratory Questionnaire and six minute walk test. The results showed no significant difference in the survey or six minute walk test for the group after the intervention. Previous research has shown that psychosocial factors have a profound effect on patients with COPD and their wellbeing. The authors therefore believe that future research should focus on designing treatment for patients with COPD based on the biopsychosocial model.