Teses / dissertações sobre o tema "Air exhalé"

La maladie rénale chronique se caractérise par une diminution progressive des fonctions rénales. Elle est cliniquement silencieuse jusqu’à un stade avancé. Au stade ultime de cette pathologie (insuffisance rénale chronique terminale), il est nécessaire de mettre en œuvre une suppléance rénale par dialyse, ou de réaliser une transplantation rénale. Le dépistage de cette pathologie est effectué par des tests sanguins et urinaires. Cependant, ce dépistage reste insuffisamment réalisé et la maladie rénale chronique est souvent découverte de manière trop tardive. Pour améliorer l’acceptabilité d’un dépistage précoce par des méthodes non invasives, il est intéressant de se rapprocher à des techniques d’analyse des composés organique volatils (COV) dans l’air exhalé. De manière préliminaire à une telle approche, cette thèse rapporte, d’abord l’analyse d’une empreinte physico-chimique en COV d’une population avec une MRC au stade de dialyse. La caractérisation de l’exhalome en début et en fin de dialyse a été réalisée en prélevant l’air exhalé de 43 patients hémodialysés. Pour cela, nous avons utilisé un dispositif d’échantillonnage ReCIVA puis une analyse de l’air exhalé par la méthode TD/GC/FID-MS. Les résultats ont mis en évidence que 23 COV de différentes familles chimiques ont des concentrations variables dans l’air exhalé des patients dialysés entre le début et la fin d’une même séance de dialyse. 9 de ces 23 COV sont probablement d’origine exogène émis par le matériel de dialyse. D’autres COV sont probablement des composés endogènes volatils émis dans l’air exhalé. Le second volet de cette thèse concerne la qualification d’un dispositif d’échantillonnage développé au sein de l’IMT NE qui repose sur le prélèvement d’air exhalé en permettant la sélection des différentes phases respiratoires et la collecte de l’air exhalé sur une multiplicité de techniques de caractérisation (supports de collection, analyses en ligne). Le but de ce travail était de vérifier l’inertie chimique de ce dispositif avant de le déployer auprès des patients. D’une part, la caractérisation du potentiel de non-contamination a permis de d’identifier 4 COV à des concentrations comprises entre 5 et 80 µg/m3 et 2 autres (N.N-diméthylacétamide et phénol) entre 100 et 700 µg/m3. Le conditionnement sous étuve du matériau constituant le dispositif a permis de réduire les émissions de ces espèces de manière très importante (> 90 %). D’autre part, le paramètre de non-rétention a été quantifié : 9 COV ont présenté un écart de leurs concentrations inférieur à 15 %. Cependant, pour l’acétone, une perte de 25 % a été quantifiée au niveau du masque qu’il sera nécessaire de réduire ou de prendre en compte durant les prélèvements. En dernier lieu, le stockage dans des sacs de collection a permis de conclure à une bonne stabilité de 9 COV testés (écart < 13 %) durant une semaine. En revanche, deux espèces (acétone et ammoniac) ont révélé des pertes. Au regard de ces résultats, il a été suggéré de stocker l'échantillon au maximum pendant deux heures pour limiter la perte de ces espèces à 20 %, ou au plus tard 2 jours en prenant en compte une perte de 36 % pour l’ammoniac
Chronic kidney disease is characterized by a progressive decline in kidney function. It is clinically silent until an advanced stage. At the final stage of this pathology (end-stage chronic renal failure), it is necessary to perform a renal replacement therapy by dialysis, or a renal transplant. The detection of this pathology is done by blood and urine tests. However, this detection remains insufficiently, and chronic kidney disease is often discovered too late. To improve the acceptability of an early detection by non-invasive methods, it is interesting to approach the techniques for analysis of volatile organic compounds (VOC) in exhaled air. As a preliminary to this approach, this thesis reports first the analysis of a physico-chemical VOC appropriate to CKD population at dialysis stage. The characterization of exhaled air at the beginning and at the end of dialysis was done by sampling it with 43 hemodialysis patients. For this, we used a sampling device ReCIVA and then an analysis of exhaled air by a TD/GC/FID-MS method. The results presented that 23 VOC from different chemical families have varying concentrations in exhaled air of dialysis patients between the beginning and end of the same dialysis session. Nine of these 23 VOC are probably exogenous origin emitted by dialysis equipment. Other VOC are probably endogenous emitted into exhaled air. The second part of this thesis concerns the qualification of a sampling device developed within IMT NE which is based on the sampling of exhaled air by allowing the selection of the different respiratory phases and the collection of exhaled air on a multiplicity of characterization techniques (collection support, online analyses). The purpose of this work was to verify the chemical inertness of this device before deploying it to patients. First, the characterization of the non-contamination potential made it possible to identify 4 VOC at concentrations between 5 and 80 µg/m3 and 2 others VOC (N.N-dimethylacetamide and phenol) between 100 and 700 µg/m3. Conditioning the material constituting the device in an oven reduced the emissions of these species very significantly (> 90 %). In addition, the non-retention parameter was quantified: 9 VOC presented a difference in their concentrations of less than 15 %. However, for acetone, a loss of 25 % was quantified in the mask, which will need to be reduced or considered during sampling. Finally, storage in collection bags allowed to conclude a stability of 9 VOC tested (difference < 13%) for one week. In contrast, two species (acetone and ammonia) revealed losses. In view of these results, it was suggested to store the sample for a maximum of two hours to limit the loss of these species to 20 %, or at the latest 2 days considering a loss of 36 % for ammonia

Un accès direct et non invasif à la pathogénèse par l’évaluation de biomarqueurs volatils (FeNO) ou non volatils de l’air exhalé grâce à la méthode des condensats de l’air exhalé (EBC) est utile pour estimer précocement le degré d’atteinte pulmonaire en rapport avec une exposition professionnelle et surveiller son évolution en regard des mesures correctives mises en place. L’étude du NO exhalé (FeNO) est actuellement bien standardisée et l’augmentation exponentielle des publications concernant les EBC reflètent un intérêt croissant pour le diagnostic non invasif des atteintes pulmonaires. Les marqueurs étudiés dans l’air exhalé sont des produits de l'inflammation tels que le FeNO et les cytokines ainsi que des produits du stress oxydant incluant le peroxyde d'hydrogène, les produits de peroxydation lipidique (8-isoprostane, malondialdehyde) et les oxydes d'azote (NOx). S’agissant d’une technique d’exploration relativement récente, les modalités méthodologiques font encore l’objet de nombreux travaux, les premières recommandations internationales étant apparues en 2005. Les écueils méthodologiques sont nombreux et encore décrits dans la littérature en 2012. Ils concernent toutes les étapes du processus du recueil et d’analyses.Objectifs : L’objectif principal de notre recherche était dans un premier temps de développer la méthode des EBC pour l'étude des composés de l'air exhalé puis de détecter et quantifier des biomarqueurs tels que les protéines totales, les NOx et le 8-isoprostane dans les EBC d’une population d’adultes sains (n= 48) ou atteints de pathologies pulmonaires telles que l'asthme (n=24), la BPCO (n=20), la pneumopathie interstitielle diffuse (n=27) et la sclérodermie (n=27). L’objectif secondaire était la comparaison des niveaux de biomarqueurs dosés dans les EBC et du FeNO chez les sujets malades par rapport aux témoins.Résultats / Conclusion : Notre recherche, soutenue l’ANR et l’ANSES, a permis de standardiser la méthodologie de recueil et d’analyse des EBC avec une optimisation du système de recueil et de l’agent coatant pour la détermination de la concentration nécessaire et compatible avec les analyses. Nous maitrisons le dosage dans les EBC des biomarqueurs tels que les protéines, les NOx et le 8-isoprostane. D'autres biomarqueurs sont encore en cours d'étude tels que le malondialdehyde et les cytokines. Ce travail méthodologique, publié, a permit dans un second temps la détection (> à 95%) et la quantification de ces biomarqueurs dans les EBC des sujets sains et malades de notre population.Perspectives : La constitution des valeurs de référence pour les biomarqueurs dosés dans les EBC est nécessaire à l’interprétation des dosages chez les sujets malades. Il convient également de finaliser la standardisation de la mesure des cytokines et du malondialdehyde et d’explorer de nouveaux biomarqueurs produits lors du stress nitrosant tels que la 3-nitrotyrosine pour compléter les mécanismes physiopathologiques. Enfin le développement de cette méthode non invasive et peu contraignante apparait prometteuse en clinique médicale dans le suivi individuel de la maladie ou son traitement comme lors d’études épidémiologiques respiratoires dans des populations exposées professionnellement ou environnementalement. Dans ce cadre, l’étude de marqueurs d’exposition professionnelle tels que les métaux lourds dans les EBC est en cours de développement
The study of both volatile (FeNO) and non-volatile respiratory biomarkers using the method of exhaled breath condensates can be useful in medical surveillance of exposed workers, the early identification of respiratory diseases or in the monitoring of their development. Studies of exhaled NO (FeNO) is now well standardized and the exponential increase in publications on exhaled breath condensate (EBC) reflects growing interest in a non-invasive diagnosis of pulmonary diseases. The biomarkers studied are products of inflammation, such as FeNO and cytokines, and products of oxidative stress, including hydrogen peroxide (H202), products of lipid peroxydation (8-isoprostane, malondialdehyde) and nitrogen oxides. The first recommendation was published in 2005 but although many recent publications have applied this new method, numerous methodological pitfalls remain and still described in 2012. They concern all the stages of the collection to the analysis.Objectives: The main objective of this research was initially to develop the method of EBC for the study of compounds of exhaled air and then detect and quantify biomarkers such as total protein, NOx and 8-isoprostane in exhaled air in a population of healthy adults (n = 48) or patients with lung inflammatory diseases such as asthma (n = 24), COPD (n = 20), diffuse interstitial pneumonia (n = 27) and scleroderma (n = 27). The secondary objective was to compare levels of biomarkers measured in the EBC and FeNO in patients compared to controls.Results / conclusion: Our research, supported by ANR and ANSES, allowed to standardize the methodology of collection and analysis of EBC with a choice of the collection system and coating which must be effective and compatible with the analyzes. In EBC, we control the dosage of biomarkers such as proteins, NOx and 8-isoprostane. Other biomarkers are still being studied such as malondialdehyde and cytokines. This published methodological study, allowed in a second step the detection (> 95%) and quantification of these biomarkers in EBC of healthy patients in our population.Perspectives: This standardization is a key epidemiological requirement for the task force on the establishment of reference values and the publication of methodological guidelines so as to realize the promise of this approach for clinical studies of lung diseases. We have also to finish the development of biomarkers such as cytokines or malondialdehyde and to investigate new biomarkers to complete the pathophysiological mechanisms. Finally our objective is the widespread use of this noninvasive method in daily epidemiological studies on subjects with professional and/or environmental exposure. In this context, the study of markers of the toxic burden in the lungs such as heavy metals in the EBC is being developed

Introduction. L’Enquête Littoral Souffle Air Biologie Environnement (ELISABET) a pour objectif général l’étude de la santé respiratoire et cardiovasculaire dans les communautés urbaines de Lille (CUDL) et Dunkerque (CUD). Les objectifs spécifiques de cette thèse sont d’étudier : (i) la prévalence et le sous-diagnostic des troubles ventilatoires obstructifs (TVO), (ii) l’évolution de la prévalence des principaux facteurs de risque cardiovasculaire (FDRCV) dans la CUDL entre 1986 et 2013, (iii) les interactions entre deux biomarqueurs de l’asthme (fraction exhalée du monoxyde d’azote (FENO) et taux d’éosinophiles sanguin (S-eos)) et le statut tabagique, (iv) le rôle de médiateur de l’inflammation chronique de bas-grade dans la relation entre diabète et baisse de la fonction pulmonaire, et (v) l’impact à court terme de la pollution atmosphérique sur la fonction respiratoire.Méthodes. Les 3276 participants (âgés de 40 à 65 ans) à l’enquête transversale en ELISABET ont été sélectionnés à partir de listes électorales par échantillonnage aléatoire et inclus entre janvier 2011 et novembre 2013. Un questionnaire détaillé, des explorations fonctionnelles respiratoires et un prélèvement sanguin ont été effectués. (i) Les TVO ont été définis par un rapport du volume expiratoire maximal à la première seconde (VEMS) sur la capacité vitale forcée (CVF) inférieur à 0.70 ou à la limite inférieure de la normale calculée à partir des dernières équations de référence disponibles. (ii) La prévalence des principaux FDRCV a été estimée à partir d’échantillons représentatifs de la population de la CUDL issus des enquêtes MONICA1986-88, MONICA1995-96, MONALISA2005-07 et ELISABET2011-13. (iii) L’asthme allergique a été défini comme un asthme (auto-déclaration, et sifflements dans la poitrine dans les 12 derniers mois ou prise de traitement) avec terrain atopique. (iv) Le diabète était défini par la prise d’un traitement antidiabétique ou une glycémie à jeun ≥ 1.26 g/L ou des valeurs d’hémoglobine A1c ≥ 6.5%. L’inflammation chronique a été mesurée par la Protéine C réactive ultra-sensible (CRPus). Une analyse de médiation a été conduite sur un échantillon de sujets sans pathologie respiratoire ou athérosclérotique. (v) Les valeurs des particules inférieures à 10 µm (PM10) et du dioxyde d'azote (NO2) ont été fournies par les stations de mesures ATMO des CUDL et CUD.Principaux résultats. (i) La prévalence des TVO s’étendait de 9.5% à 16% (dépendant du centre et de la définition utilisée) ; le taux de sous-diagnostic était élevé (environ 75 %). (ii) La prévalence des principaux FDRCV diminuait régulièrement sur une période de 25 ans, à l'exception de l'usage du tabac chez les femmes, du diabète chez les hommes (tous deux stables) et de la surcharge pondérale chez les hommes (augmentée). (iii) Une interaction positive entre le statut tabagique et l'asthme allergique a été observée dans les modèles expliquant le FENO (p = 0,003) et les S-eos (p = 0,001). Ainsi, les participants souffrant d'asthme allergique avaient (comparés à ceux n’en souffrant pas) des valeurs plus élevées de FENO (+ 63,4 %, IC95% = [39; 92]) et de S-eos (+ 63,2 % [38,2; 92,7]) chez les non-fumeurs, mais pas chez les fumeurs actuels. (iv) Le diabète était associé à une diminution des pourcentages prédits du VEMS (-3.5% [-5.8; -1.3]) et de la CVF (-3.6% [-5.9; -1.3]). La force de ces associations diminuait (-3.1% [-5.4; -0.9] pour les deux) après ajustement sur la CRPus. Ainsi, la part médiée de la CRPus valait 12% [2.4; 37] et 13% [3.7; 39.4] pour le VEMS et la CVF, respectivement. (v) Les mesures de PM10 et NO2 semblaient associées à une diminution du débit expiratoire maximal à 25 % de la CVF (résultat préliminaire).Conclusion. Les données de l’enquête ELISABET ont permis l’étude de la prévalence des TVO et des principaux FDRCV au sein de notre population d’étude. Elles ont également permis d’obtenir des résultats originaux à partir d’études cliniques et physiopathologiques
Introduction. The general goal of the ELISABET (Enquête Littoral Souffle Air Biologie Environnement) survey is to study the respiratory and cardiovascular health in two urban areas in northern France (Lille and Dunkirk). The specific objectives of this thesis are to study: (i) the prevalence and underdiagnosis of airway obstruction (AO), (ii) long-term time trends in the prevalence of cardiovascular risk factors between 1986 and 2013 in the Lille urban area, (iii) the relationships between both the fractional exhaled nitric oxide (FENO) and the blood eosinophil count (B-eos) on one hand and asthma and atopy on the other, according to smoking status, (iv) whether low-grade systemic inflammation (as measured by the level of high sensitivity-C-reactive protein, hs-CRP) mediated the relationship between diabetes and lung function, and (v) the short-term impact of atmospheric pollution on lung function.Methods. The 3276 participants (aged from 40 to 64) in the 2011-2013 ELISABET cross-sectional survey were selected from electoral rolls by random sampling, and recruited between January 2011 and November 2013. A detailed questionnaire, lung function tests, and a blood sample collection were performed. (i) AO was defined by a forced expiratory volume in the first second (FEV1) to forced vital capacity (FVC) ratio below 0.70 or below the lower limit of normal calculated by the most recent reference equations of the Global Lung Initiative. (ii) The prevalence of the main cardiovascular risk factors was estimated from representative samples inhabitants of Lille urban area from MONICA1986-88, MONICA1995-96, MONALISA2005-07 and ELISABET2011-13 surveys. (iii) Allergic asthma was defined as asthma (a self-report of physician-diagnosed asthma, and wheezing in the previous 12 months or the use of asthma medications) with atopy. (iv) Diabetes mellitus was defined as ongoing diabetes treatment or a fasting blood glucose level ≥1.26 g/L or a hemoglobin A1c value ≥6.5%. A mediation analysis was performed to assess and quantify the hs-CRP level as a mediator of the relationship between diabetes and lung function from a sample of participants without self-reported pulmonary and atherosclerotic disease. (v) Measurements of particles less than 10 mm in diameter (PM10) and nitrogen dioxide (NO2) were provided by measuring stations ATMO in the two urban areas.Main results. (i) The prevalence of AO in northern France ranged from 9.5 to 16.0%, depending on the centre and definition used; the underdiagnosis rate was high (around 75%). (ii) A steady decline in the prevalence of cardiovascular risk factors over a 25-year period was observed, with the exception of tobacco use in women, prevalence of diabetes in men (both of which remained stable) and prevalence of overweight in men (which increased). (iii) A positive interaction between smoking status and allergic asthma was observed in multivariate models explaining FENO (p=0.003) and B-eos (p=0.001). Thus, compared to those without allergic asthma, participants with allergic asthma had higher FENO values (+63.4%, 95%CI=[39; 92]) and higher B-eos (+63.2% [38.2; 92.7]) in never and former smokers, but not in current smokers. (iv) Diabetes was associated with FEV1 (-3.5% [-5.8; -1.3]) and FVC (-3.6% [-5.9; -1.3]). Strength of both latter associations fell to -3.1% [-5.4; -0.9] after adjustment for hs-CRP. Hence, the proportion of the effect that is mediated by hs-CRP was 12% [2.4; 37] and 13% [3.7; 39.4] for FEV1 and FVC, respectively. (v) Measurements of PM10 and NO2 seemed to be associated with lower values of the expiratory flow at 25% of the FVC (preliminary result).Conclusion. Data from the ELISABET survey have allowed the study of the prevalence of AO and the main cardiovascular risk factors in our population. They also allowed obtaining original results from clinical and pathophysiological studies

Background: Indoor air contaminants generally have a greater impact on health than outdoor air contaminants, which increases the importance of a dependable, accessible, and minimally impactful method for measuring indoor air exchange rates. Objective: Evaluate the use of naturally generated CO2 as a tool to measure indoor ventilation. Methods: Indoor CO2 levels were measured over seven sample intervals in an airtight one-bedroom apartment with two residents. High frequency noise was removed from the measurements with Fourier, Kalman, LOESS, and rolling average filters. Root-mean squared errors (RMSE) between filtered and measured CO2 were calculated and compared for each sample interval and filter pair. A multivariable linear regression was used to assess differences between digital filters. Local minima and maxima were identified to calculate air exchange rates. The R statistical software was used for all data management and analysis. Results: The RMSE for all filter types had geometric standard deviations between one and two, indicating that all filters were stable across sample intervals. Results of the multivariable linear regression indicate that the RMSE of the Fourier filter were significantly lower than those of the Kalman filter with a P-value ofConclusions:The Fourier filter performed best based on visual analysis and RMSE comparisons. All filters except for the rolling average filter identified the majority of primary local minima/maxima effectively.

The purpose of this study was to develop methodology involving the use of biological monitoring of exhaled air to determine respirator protection factors. The concentration of fluorocarbon 113 in breath was correlated to the original exposure concentration while wearing a full facepiece negative pressure respirator. Protection factors calculated from breath sampling were compared to fit factors derived from a negative pressure test device. Although biological monitoring indicated a nearly three fold increase in fluorocarbon 113 penetration rates compared to the negative pressure fit test results, a correlation of 0.86 suggests that this methodology may be used in the design of a workplace protection study. No correlation was found between the biological and quantitative mask sampling methods.

Background: Fraction of exhaled nitric oxide (FENO) is a promising non-invasive index of airway inflammation that may be used to assess respiratory effects of air pollution. We evaluated FENO as a measure of airway inflammation after controlled exposure to diesel exhaust or ozone. Methods: Healthy volunteers were exposed to either diesel exhaust (particle concentration 300 mu g/m(3)) and filtered air for one hour, or ozone (300 ppb) and filtered air for 75 minutes. FENO was measured in duplicate at expiratory flow rates of 10, 50, 100 and 270 mL/s before, 6 and 24 hours after each exposure. Results: Exposure to diesel exhaust increased FENO at 6 hours compared with air at expiratory flow rates of 10 mL/s (p = 0.01) and at 50 mL/s (p = 0.011), but FENO did not differ significantly at higher flow rates. Increases in FENO following diesel exhaust were attenuated at 24 hours. Ozone did not affect FENO at any flow rate or time point. Conclusions: Exposure to diesel exhaust, but not ozone, increased FENO concentrations in healthy subjects. Differences in the induction of airway inflammation may explain divergent responses to diesel exhaust and ozone, with implications for the use of FENO as an index of exposure to air pollution.

L'analyse des composés organiques volatils (COVs) dans l'air expiré est une méthode non invasive prometteuse en médecine pour le diagnostic précoce, le phénotypage, le suivi de la maladie et du traitement et le dépistage à grande échelle. La spectrométrie de masse à temps de vol par réaction de transfert de protons (PTR-TOF-MS) présente un intérêt majeur pour l'analyse en temps réel des COVs et la découverte de nouveaux biomarqueurs. Le manque de méthodes et d'outils logiciels pour le traitement des données PTR-TOF-MS provenant de cohortes représente actuellement un verrou pour le développement de ces approches.Nous avons ainsi développé une suite d'algorithmes permettant le traitement des données brutes jusqu’au tableau des intensités des molécules détectées, grâce à la détection des expirations et des pics dans les spectres de masse, la quantification dans la dimension temporelle, l'alignement entre les échantillons et l'imputation des valeurs manquantes. Nous avons notamment mis au point un modèle innovant de déconvolution des pics en 2 dimensions reposant sur une régression du signal par splines pénalisées, ainsi qu'une méthode permettant de sélectionner spécifiquement les COVs dans l'air expiré. L'ensemble du processus est implémenté dans le paquet R/Bioconductor ptairMS, disponible en ligne. Nous avons validé notre approche à la fois sur des données expérimentales (mélange de COVs à des concentrations standardisées) et par simulation. Les résultats montrent que l'identification des COVs provenant de l’air expiré à partir du modèle proposé atteint une sensibilité de 99 `%. Une interface graphique a également été développée pour faciliter l'analyse des données et l'interprétation des résultats par les expérimentateurs (les cliniciens notamment). Nous avons appliqué notre méthodologie à la caractérisation de l'air expiré d'adultes sous ventilation mécanique atteints de l’infection COVID-19. Les analyses de l'air expiré de 40 patients atteints d’un syndrome de détresse respiratoire aiguë (SDRA) ont été effectuées quotidiennement, de l'entrée à la sortie de l'hôpital. Nous avons d'abord réalisé un modèle de classification pour prédire le statut de l'infection, en utilisant l'acquisition disponible la plus proche de l’admission à l'hôpital.Ce modèle permet de prédire le statut de l'infection avec une précision de 93%. Ensuite, nous avons utilisé toutes les données disponibles pour une analyse longitudinale de l'évolution des COVs en fonction de la durée de l'hospitalisation, en utilisant un modèle à effets mixtes. Après sélection de variables, quatre biomarqueurs de l'infection par le COVID-19 ont pu être identifiés. Ces résultats soulignent la valeur des données PTR-TOF-MS et du logiciel ptairMS pour la découverte de biomarqueurs dans l'air expiré
The analysis of Volatile Organic Compounds (VOCs) in exhaled breath is a promising non-invasive approach in medicine for early diagnosis, phenotyping, disease and treatment monitoring and large-scale screening. Proton Transfer Reaction Time-Of-Flight Mass Spectrometry (PTR-TOF-MS) is of major interest for the real time analysis of VOCs and the discovery of new biomarkers in the clinics. However, there is currently a lack of methods and software tools for the processing of PTR-TOF-MS data from cohorts.We therefore developed a suite of algorithms that process raw data from the patient acquisitions, and build the table of feature intensities, through expiration and peak detection, quantification, alignment between samples, and missing value imputation. Notably, we developed an innovative 2D peak deconvolution model based on penalized splines signal regression, and a method to specifically select the VOCs from exhaled breath. The full workflow is implemented in the freely available ptairMS R/Bioconductor package. Our approach was validated both on experimental data (mixture of VOCs at standardized concentrations) and simulations, which showed that the sensitivity for the identification of VOCs from exhaled breath reached 99 %. A graphical interface was also developed to facilitate data analysis and result interpretation by experimenters (e.g., clinicians).We applied our methodology to the characterization of exhaled breath from mechanically ventilated adults with COVID-19 infection. Analysis of exhaled breath from 28 patients with an acute respiratory distress syndrome (ARDS) and COVID-19 infection, and 12 patients with non-COVID-19 ARDS were performed daily from the hospital admission to the discharge. First, classification models were built to predict the status of the infection, using the closest available acquisition to the entry into hospital, and achieved high prediction accuracies (93 %). Then, all the available data acquired during the hospital stay were used for the longitudinal analysis of the VOCs evolution as a function of the hospitalization time by mixed-effects modeling. Following feature ranking and selection, four biomarkers of COVID-19 infection were identified. Altogether, these results highlight the value of the PTR-TOF-MS data and the ptairMS software for biomarker discovery in exhaled breath

Screening complex biological specimens such as exhaled air, tissue, blood and urine to identify biomarkers in different forms of cancer has become increasingly popular over the last decade, mainly due to new instruments and improved bioinformatics. However, despite some progress, the identification of biomarkers has shown to be a difficult task with few new biomarkers (excluding recent genetic markers) being considered for introduction to clinical analysis. This review describes recent advances in gas chromatographic methods for the identification of biomarkers in the detection, diagnosis and treatment of cancer. It presents a general overview of cancer metabolism, the current biomarkers used for cancer diagnosis and treatment, a background to metabolic changes in tumors, an overview of current GC methods, and collectively presents the scope and outlook of GC methods in oncology.

Background: Carbon monoxide (CO) is a toxic gas, but it is also produced endogenously when haem is degraded. When produced in vivo, CO is believed to have positive biological effects. For example it activates the production of cyclic guanosine mono-phosphate and causes vasodilatation. CO is also believed to have anti-inflammatory properties by binding to Mitogen activated protein (MAP) kinase. Several studies in cells, mice and rats support this opinion regarding both the circulatory as well as the anti-inflammatory properties. However, studies in larger animals regarding circulatory effects have demonstrated contradictory results. The only study in humans regarding anti-inflammatory properties of CO could not demonstrate such effects. Methods: This thesis consists of four different models. In paper I a method for analysis of CO in blood was developed using gas chromatography. In paper II a porcine model was used to investigate the elimination time for CO. The pigs in paper II had a high concentration of CO administered via blood, and CO concentrations were followed over time and kinetically parameters calculated. Circulatory parameters were also measured to evaluate if there were any circulatory changes after CO administration. In paper III CO´s anti-inflammatory properties were investigated in an endotoxin-induced systemic inflammatory model in pigs. Paper III was a randomized study where one group inhaled CO and the other group served as controls. Plasma cytokine concentrations were measured and followed over time as an indication of the inflammatory state. In paper IV, CO concentrations in blood from blood donors at the Blood Centre in Umeå were investigated. The blood donors also completed a questionnaire about age, smoking history and other possible sources for exogenous contamination of CO in the blood. Results and conclusions: In paper I we developed a method suitable for analysis of low concentrations of CO in blood. The half-life of CO at levels of 250 µM in pigs was found to be 60 minutes. CO did not show anti-inflammatory effects after an endotoxin-induced systemic inflammation in pigs. In banked blood CO was present at concentrations up to six times higher than normal concentrations. This could be a risk when transfusing such blood to susceptible patients.

Le Virus Respiratoire Syncytial (VRS) est une des causes les plus fréquentes d'infections respiratoires chez l'enfant. Actuellement les mécanismes de transmission, notamment la part des aérosols, ne sont pas connus. Dans ce contexte, l'objectif de ce travail a porté sur l'étude de l'aérobiocontamination virale des espaces clos. Ainsi, cette recherche a concerné l'étude en laboratoire de l'infectivité du VRS sous forme d'aérosols, la caractérisation des émissions trachéobronchiques ainsi que la recherche d'aérosols de VRS dans différents environnements intérieurs. L'étude d'un aérosol de Virus Respiratoire Syncytial en laboratoire a montré une baisse notable du pouvoir infectieux dans une ambiance humide. Cependant l’approche cinétique montre que l’impact de l'humidité relative peut se révéler très différent selon l’âge de l’aérosol. L'étude des émissions trachéobronchiques, réalisée sur un panel de 81 volontaires, symptomatiques et asymptomatiques, a mis en évidence la proportion importante de particules fines et ultrafines dans ces émissions. De plus, il a été montré que les asymptomatiques ont tendance à émettre moins de particules que les symptomatiques et qu'il n'existe pas de distribution en taille spécifique d'un groupe ou l'autre. Enfin, la recherche d'aérosols de VRS dans les environnements intérieurs a été effectuée à l'aide d'un préleveur cyclonique à haut débit au sein d'un hôpital et d'établissements recevant des enfants. Au total 14 prélèvements ont été effectués et associés à des analyses PCR. Ces prélèvements n'ont pas mis en évidence la présence de virus respiratoires aéroportés dans ces environnements
Respiratory Syncytial Virus (RSV) is a leading cause of respiratory infections in infants. However, the mechanisms involved in the transmission of the disease are not well known. Therefore, the aim of the present study is to study the viral aerocontamination of indoor environments. This research is thus aimed at the study in laboratory of the survival of RSV aerosol, at the characterization of the particles size of exhaled respiratory aerosols and at the research of these RSV aerosols in various indoor environments. The laboratory study of a RSV aerosol revealed a decrease of its infectivity in a humid atmosphere. However, it appeared that the humidity's impact could be different according to the age of the aerosol. The study of exhaled respiratory aerosol made with 81 volunteers, with or without symptom, showed the important proportion of fine and ultra fine particles. Moreover, it has been shown that volunteers without symptom emit fewer particles than individuals with symptoms. Also, this work highlighted the fact that there is not a specific size distribution considering these emissions. Lastly, the research of RSV aerosols in indoor environments has been done using a high flow cyclone sampler in a hospital and various institutions. Fourteen samplings were done, associated with PCR analyses. These samplings did not permit to detect respiratory airborne viruses

Lúpus eritematoso sistêmico juvenil é uma doença inflamatória autoimune multifatorial com elevação de citocinas inflamatórias e com gravidade variável. Estudos observaram associação entre exposição a poluição do ar e aumento do número de internações hospitalares devido à exacerbação das doenças reumáticas pediátricas e aumento no risco de crianças portadoras de lúpus eritematoso sistêmico juvenil apresentarem atividade de doença moderada /grave após exposição a material particulado e dióxido de nitrogênio. Exposição à poluição do ar pode acarretar agravo agudo em doenças reumatológicas pediátricas, incluindo lúpus eritematoso sistêmico juvenil. Objetivos: Avaliar o efeito da exposição real a poluentes atmosféricos sobre biomarcadores inflamatórios em condensado do ar exalado e sobre a fração de monóxido de nitrogênio em ar exalado em pacientes com lúpus eritematoso sistêmico juvenil. Avaliar ainda, a correlação entre os biomarcadores inflamatórios no ar exalado e atividade da doença. Métodos: Estudo longitudinal de painel de medidas repetidas realizado em 108 visitas consecutivas de pacientes com diagnóstico de lúpus eritematoso sistêmico juvenil sem doenças respiratórias. Por 4 semanas consecutivas, medidas diárias individuais de dióxido de nitrogênio, material particulado fino, temperatura ambiental e humidade relativa do ar foram obtidos. Este ciclo foi repetido a cada 2,5 meses ao longo de um ano, além disso, citocinas do condensado do ar exalado (interleucinas 6, 8, 17 e fator de necrose tumoral-alfa), fração exalada de monóxido de nitrogênio e parâmetros de atividade de doença foram coletados semanalmente. Modelos específicos de equação estimada generalizada foram usadas para avaliar o impacto destes poluentes no risco de Systemic Lupus Erythematosus Disease Activity Index 2000 >= 8, citocinas no condensado do ar exalado e fração exalada de monóxido de nitrogênio, considerando o efeito fixo para medidas repetidas. Os modelos foram ajustados para provas de fase aguda, índice de massa corpórea, infecções, medicações e variáveis meteorológicas. Resultados: Efeito positivo nas medidas de desfechos foi observado para um aumento do intervalo interquartil do material particulado fino (18.12 ?g/m3). Um aumento do intervalo interquartil na média móvel de 7 dias no material particulado fino (lag0 to lag6) foi associado a um aumento de 0.1pg/ml (95%IC:0.01;0.19) e 0.9pg/ml (95%IC:0.05;0,12) nos níveis de interleucina 17 e fator de necrose tumoral-? do condensado do ar exalado, respectivamente. Também foi observado um aumento no risco de Systemic Lupus Erythematosus Disease Activity Index 2000 >= 8 de 1.47(95%CI:1.10;1.84) associado ao aumento da média móvel de material particulado fino. Em adição, um efeito a curto prazo na fração exalada de monóxido de nitrogênio foi evidenciado, medida móvel de 3 dias do material particulado fino foi associada com um aumento de 0.75ppb (95%IC:0.38;1.29) na fração exalada de monóxido de nitrogênio. Conclusão: Exposição a partículas finas inaláveis pode aumentar a inflamação das vias aéreas e posterior inflamação sistêmica nos pacientes com lúpus eritematoso sistêmico juvenil
Systemic lupus erythematosus is an inflammatory multisystem, autoimmune disease with elevated inflammatory interleukins levels. Exposure to air pollution may trigger pulmonary inflammation/systemic inflammation. Objective: The objective of this study was to investigate the association between daily individual exposure to air pollutants and airway inflammation and disease activity in childhood-onset systemic lupus erythematosus patients. A longitudinal panel study was carried out in 108 consecutive appointments with childhood-onset systemic lupus erythematosus patients without respiratory diseases. Methods: Over four consecutive weeks, daily individual measures of nitrogen dioxide, fine particulate matter, ambient temperature, and humidity were obtained. This cycle was repeated every 2.5 months along 1 year, and cytokines of exhaled breath condensate (interleukins 6, 8, 17 and tumoral necrose factor-alpha), fractional exhaled nitrogen monoxide, and disease activity parameters were collected weekly. Specific generalized estimation equation models were used to assess the impact of these pollutants on the risk of Systemic Lupus Erythematous Disease Activity Index 2000 >= 8, exhaled breath condensate cytokines, and fractional exhaled nitrogen monoxide, considering the fixed effects for repetitive measurements. The models were adjusted for inflammatory indicators, body mass index, infections, medication, and weather variables. Results: An interquartile range increase in fine particulate matter 4-day moving average (18.12ug/m3) was associated with an increase of 0.05 pg/ml (95% CI 0.01; 0.09, p = 0.03) and 0.04 pg/ml (95% CI 0.02; 0.06, p = 0.01) in interleukin 17 and tumoral necrosis factor-alpha exhaled breath condensate levels, respectively. Additionally, a short-term effect on fractional exhaled nitrogen monoxide was observed: the fine particulate matter 3-day moving average was associated with a 0.75 ppb increase (95% CI 0.38; 1.29, p = 0.03) in fractional exhaled nitrogen monoxide. Also, an increase of 1.47 (95% CI 1.10; 1.84) in the risk of Systemic Lupus Erythematous Disease Activity Index 2000 >= 8 was associated with fine particulate matter 7-day moving average. Conclusion: Exposure to inhalable fine particles increases airway inflammation/pulmonary and then systemic inflammation in childhood-onset systemic lupus erythematosus patients

碩士
國立臺灣大學
環境衛生研究所
93
The objective of this study was to clarify the differences of volatile organic compounds (VOCs) in exhaled air between the asthmatic children and the non-asthmatic children. This article also discusses the correlation between the VOCs and several different indoor environments with questionnaire and statistics. This was a cross-sectional study and purposive selection was taken. All cases came from the out-patient departments of pediatrics and ophthalmology of a medical center in northern Taiwan. There were 60 children total and the range of age was from 4 to 12 years old. 30 of them were asthmatic and others were non-asthmatic. Basic demographic data, life styles, indoor environments and the conditions of asthma were all collected by questionnaire. The exhaled air and the indoor air collected at the out-patient departments of pediatrics and ophthalmology were analyzed by GC/MS and semiquantitative analyses were also done. We focused on 64 kinds of VOCs, such as hydrocarbon, ketone, aldehyde, alcohol, furan, aromatics, sulfur compounds, chlorinate species, nitrogen containing species, etc. The results of the experiment were analyzed by statistical software SPSS13.0. 12 kinds of VOCs showed significant differences in alveolar gradients between the two groups (P＜0.05). 10 out of these 12 kinds of VOCs showed significant differences (P＜0.05) with regard to the means of transport to school, parents smoke, family handiwork, pets, upholsteries, dust, the frequency of cooking, aromatic and mosquito coil incense usage by multiple regression. This research has demonstrated that asthmatic children exhaled 2-methyl-1,3-pentadiene, butanenitrile, 1-methyl-1H-pyrrole and 3-hexanone, but the children in the control group didn’t. Isoprene and 1-(methylthio)-propane are endogenous compounds (proved by positive AG value) and were exhaled in both groups. The AG values of isoprene and 1-(methylthio)-propane were greater in the asthmatic group than in the control group. These compounds may be the candidates for markers of asthma.

碩士
國立臺灣大學
環境衛生研究所
93
This study was aimed to analyze volatile organic compounds (VOCs) in exhaled air of furniture sales department clerks, and to observe the variation of VOCs from occupational exposure. In addition to exhaled air VOCs, formaldehyde and VOCs in the environmental air were also measured, and there relationship together with items in the questionnaire were discussed. The study design was a cross-section study. The furniture sales department clerks were divided into common furniture sales department clerks and systematic furniture sales department clerks. Seventy-four volunteers were participated in this study, including twenty-nine in ordinary furniture sales department、twenty in systematic furniture sales department and twenty-five in control. The VOCs in exhaled air was collected in a Tedlar bag and was analyzed using thermal desorption GC/MS. Each compound was identified based on the mass spectrum using Wiley 275 mass spectra library, and semi-quantitative analysis was used to measure the alveolar gradient of each compound. More than sixty compounds were detected, including alkanes, alkenes, ketones, furans, aromatics, sulfur-containing compounds, chlorine-containing compounds and nitrogen-containing compounds. Statistical analysis indicated that ten compounds in the exhaled air of non-smoking volunteers were significantly different among the three groups (p<0.05). Twenty-six compounds in the air, including ethylbenzene , 1,3-dimethyl-benzene and formaldehyde, were significantly different among the three groups (p<0.05). The alveolar gradient of pentane in non-smoking volunteers was significantly different between the furniture sales department clerks and the control volunteers, and was significantly different with the relative abundance of ethylbenzene and 1,3-dimethyl-benzene in air. Thus, exhaled air pentane abundance may be influenced by ethylbenzene and 1,3-dimethyl-benzene in air.

碩士
國立陽明大學
公共衛生研究所
87
Asthma is a chronic inflammatory disease of the airway. Recently, studies have found that exhaled nitric oxide (eNO) was correlated with airway inflammation. We used eNO measurement and questionnaire to clarify the effect of air pollution on asthma and airway disease in schoolchildren. Our study subjects were third grade students from 石牌國小 in Taipei and 淡水國小 in Tamshui. We recruited 256 students (male: 133, female: 123) from the two schools. Study was performed between October 1998 and Apr 1999. The effect of children''s atopy or airway disease on eNO, and the effect of air pollutants and children''s eNO were analyzed. Finally, We compared the effect of air pollutants on children with or without atopic airway disease. In the study subjects, 10.2% children had physician-diagnosed asthma, 19.1% children had wheezing, 24.6% children had physician-diagnosed allergic rhinitis, and 5.4% children had physician-diagnosed dermatitis. Family factors that influenced eNO: children''s father with higher education, mother with allergic rhinitis, and sibling with allergic rhinitis would increase children''s eNO level. Children''s factors affecting eNO included: physician-diagnosed asthma, wheeze, allergic rhinitis, dermatitis, cough in the past year, and upper airway infection (at the time of examination) would increase children''s eNO level. Air pollution: Ozone concentration, ambient temperature, and particulate matter would decrease eNO level, but ambient nitric oxide concentration would increase eNO level. We also found that eNO level was continually increasing from October 1998 to Mar 1999. And it was decreased from Mar 1999 to Apr 1999. URI, sulfur dioxide, and particulate matter had more pronounced effect on nonatopic students. We also found that atopic students were more sensitive to ambient temperature. We concluded that atopy, airway disease and air pollution were correlated with eNO. The most important factor in air pollution that influenced children''s eNO was ambient temperature. We also found that eNO had a time-dependent trend. In conclusion, ozone concentration, ambient temperature, ambient nitric oxide, URI, and allergic rhinitis were important on eNO level.

碩士
輔仁大學
公共衛生學系碩士班
96
Background： According to the epidemiological studies, it demonstrated that the prevalence and incidence rate of asthma were increasing gradually every year. People spent over 80 % of their time indoors. Indoor and outdoor air pollutants such as particular matter（PM）, volatile organic compounds（VOCs）, sulfur dioxide（SO2）, ozone（O3）had been proved to be significantly correlated with the increased incidence of respiratory symptoms in asthmatic children. Collection of exhaled gas was a simple and noninvasive technique for sampling of nitric oxide（NO）and airway lining fluid that can be used as indicators of exacerbation of respiratory diseases. This study was to evaluate the impaction of indoor and outdoor air pollutants on pulmonary function by measuring NO levels and exhaled breath condensate（EBC）pH in exhaled gas. Methods： This panel study recruited 15 asthmatics and 15 healthy children, aged between 7 and 12 years old, from outpatient department of Chang Gung Memorial Hospital in 2006. Self-reported questionnaires included personal information, family allergic history, blood allergy index, and home/life characteristics. Air quality in domestic environment was measured with the dust monitor（GRIMM particle size analyzer model l.108, Germany）, air quality monitor（I.A.Q, KD Engineerings AirBoxx, USA）, and VOCs monitor（ppbRAE, RAE Systems model PGM-7600, USA）. Exhaled NO levels in schoolchildren were monitored by a chemiluminescence analyzer （CLD 77 AM, ECO Physics, Dürnten, Switzerland）. EBC pH was analyzed after collecting EBC from subjects using an exhaled breath condensate collector（ECoScreen, Jaeger-Toennies, Germany）. Pulmonary function tests were performed every three months to evaluate the variation of lung functions. The concentrations of outdoor air pollutants measured at the ambient air monitoring site operated by Taiwan Environmental Protection Agency（EPA）that located in district of Songshan were also collected. All the data were analyzed by SPSS software. Result： This study was to monitor indoor air quality of domestic environment in schoolchildren with asthma and healthy controls in autumn and winter. Air temperature in domestic environment of asthmatics was higher than the recommended value of indoor air quality guideline. Our results demonstrated that mean eNO concentrations in asthmatics（41.62 ppb in autumn and 48.75 ppb in winter）were significantly higher than those in healthy individuals（14.90 ppb in autumn and 14.94 ppb in winter）（ p＝0.001 in autumn and p＜0.001 in winter）. There was not a statistically significant difference in EBC pH between asthmatics（pH=6.76 in autumn and 6.61 in winter）and healthy children （pH=7.12 in autumn and 6.82 in winter） （ p＝0.112 in autumn and p＝0.412 in winter）, but EBC pH had a lower tendency found in children with asthma than normal controls in this study. In addition, forced expiratory volume time on one second (FEV1), peak expiratory flow (PEF) and forced expiratory flow25% ~ 75%, (FEF25% ~ 75%) in asthmatics had a decreased trend compared to healthy controls in both autumn and winter. From our findings, it was indicated that air pollutants were associated with eNO level, EBC pH and pulmonary function test. NO association was found between eNO level and EBC pH in schoolchildren. Conclusion： Exhaled gas analysis is a noninvasive, duplicated, and safety monitoring technique. Measurements of exhaled NO and EBC pH would react with airway inflammation correlated to indoor and outdoor air pollutants exposure.

碩士
國立臺灣大學
環境衛生研究所
98
Expose to air pollution has been associated with eye and respiratory system irritation, allergic and inflamed effects and cardiovascular disease. These symptoms were observable in susceptible groups. In Taipei metropolis, the asthma incidence rate rise yearly in schoolchildren. Therefore, the objective of this study was to investigate exhaled breath VOCs and lung function relevance of the air pollution in asthmatic children. Besides, the lag effect of exposure to particulate matter would also be studied. The study divided participants into asthmatic and non-asthmatic schoolchildren. Take the exhaled breath and lung function cooperate with the air quality monitor data of EPA Supersite. The thermal desorption GC/MS was used to analyze the exhaled breath and conducted pentane as an indicator of oxidative stress; moreover, the lung function was measured by spirometer. Generalized Estimating Equations (GEEs) was used to examine the repeated measurement of the exhaled breath and lung function affected by air pollution. As the result, the higher oxidative stress and the lower average lung function in asthmatic children (Pentane=0.106 and 0.095, AG) was observed gender, body mass index (BMI), flu, and air pollutant (SO2, CO, NO, NO2, PM2.5) had significant influence in oxidative stress. Lung function were affected by height, weight, BMI, road, dust, vitamins, and air pollutant (SO2, CO, O3, NO, NO2, PM2.5). Lag effect of PM2.5 exhibit the oxidative stress in Lag10, Lag14, Lag30. The lung function (FVC, FEV1) and Lag5, Lag7, Lag10, Lag14, Lag30 in oxidative stress showed the lag effect of PM10. Asthmatic children which are susceptible had higher oxidative stress. The effects of air pollution display in oxidative stress and lung function of schoolchildren. The lag effects in oxidative stress and lung function of particulate matter were significant. This study indicated that oxidative stress is a sensitive factor and can reflect the long-term injury of exposure. In addition, the lag effect of PM10 was observed by lung function.

碩士
國立陽明大學
公共衛生研究所
88
Toluene, xylene and ethylbenzene, three major components in gasoline, are important volatile organic compounds in gasoline station and have been proved as adverse health effects to human. Ten gasoline stations (public and private) in Taipei were randomly selected for study. We investigated the air borne concentrations of toluene, xylene and ethylbenzene of the target stations and the workers’ personal exposure level. Alveolar breath samples of the gasoline station workers after their work shifts were also determined. The samples were analyzed by GC/FID. According to the results, the geometric mean concentrations (geometric standard deviation) of toluene, xylene and ethylbenzene in the ambient air of the public stations are 99.33 (1.44), 27.91 (1.83) and 16.12 (1.49) ppb, respectively. The geometric mean concentrations (geometric standard deviation) in private stations are 113.73 (2.11), 36.86 (2.18) and 16.34 (4.26) ppb. The geometric mean concentrations (geometric standard deviation) of toluene, xylene and ethylbenzene for the personal exposure of the public stations are 153.80 (1.97), 49.18 (2.07) and 24.78 (1.67) ppb. The geometric mean concentrations (geometric standard deviation) of the private stations are 189.19 (2.04), 63.63 (2.13) and 38.13 (2.57) ppb. The alveolar breath geometric mean concentrations (geometric standard deviation) of toluene, xylene and ethylbenzene of the public station workers are 10.56 (1.92), 3.31 (2.22) and 1.39 (2.51) ppb. The geometric mean concentrations (geometric standard deviation) of toluene, xylene and ethylbenzene of the private station workers are 14.22 (1.54), 4.81 (1.28) and 2.36 (1.49) ppb . The concentrations of anmbient air, personal exposure and alveolar breath in public stations were higher than those in private stations, but the differences have not reached significant in statistics. The ambient air concentrations correlated well with personal exposure levels in all of the three compounds, the r values for toluene, xylene and ethylbenzene are 0.569, 0.513, 0.591, respectively. The personal exposure levels correlated well with alveolar breath concentrations in toluene and xylene, the r values for toluene and xylene are 0.683, 0.457, respectively. These findings suggest that alveolar breath is a good biological exposure index for low organic solvents exposure. The matrix of alveolar breath is simple and the collection is non-invasive. The alveolar breath could be a better alternative rather than urine determination for low-level organic solvents exposure monitoring.

碩士
高雄醫學大學
公共衛生學研究所
102
Background: Enterovirus infection is a common source of disease in children and infants and cause HFMD and herpangina outbreaks around the world. Enterovirus infection is usually transmitted via fecal-oral route or airborne route. Previous study had already detected enterovirus in exhaled air and indoor air of hospital. Intrafamilial and kindergarten transmissions were major modes of enterovirus transmission. However, no study evaluated concentration of enterovirus in exhaled air in household members and air samples of household and school. Aim: Detection of enterovirus in exhaled air of child, their family and school classmates. Evalution of intrafamiliy enterovirus transmission in family and school. Method: We used exhaled air sampling method and real-time qPCR for enterovirus detection of infected child, their family and school classmates. Result: There were six index cases of children who had been diagnosed of enterovirus infection, positive rate of exhaled air samples was 83.3%. Positive rate of household members was 42.9%, children of household were 63.3%, adults of household were 44.4%. The mean concentration of exhaled air of children was 9.59x 108copies/ m3, and adults were 4.12x 109copies/ m3. Possitive rate of air samples was 15.8%, the mean concentration of air samples were 4.97x 102copies/ m3.

碩士
國立臺灣大學
環境衛生研究所
92
This study was aimed to utilize the equipment in being to detect volatile organic compounds (VOCs) in exhaled air and apply it in environmental health. VOCs collected from smokers’ and nonsmokers’ exhaled air were identified and compared. The VOCs’ patterns in smokers’ exhaled air before and after smoking were observed. This study employed sampling bags to collect exhaled air and used multi-bed sorbent traps and sampling pump to concentrate VOCs. The VOCs sample was thermal desorbed and focused by a cryogenic trap, then analyzed by GC/MS. In identification, after background or overlapping peak subtraction, mass spectrum of each compound was identified by Wiley 275 library. The ratio of compound peak integrating area and internal standard peak integrating area was used to estimate the relative abundance of the VOCs (semiquantitative). About 170 VOCs were detected, including alkanes, alkenes, ketone, aldehyde, ester, furan, aromatics, sulfur compounds, chlorinate species, nitrogen containing species, and some unidentified species. Comparing smokers’ and nonsmokers’ exhaled air, 7 compounds were detected only in smoker’s sample, and 21 compounds were significantly (P<0.05) different between two groups. When the patterns of VOCs in smokers’ exhaled air before and after smoking were studied, we found that most of the VOCs’ abundance increased in exhaled air immediately after smoking, but rapidly decreased after 10 min.

Introduction: Numerous studies have found associations between exposure to airborne particulate matter and respiratory morbidity and mortality. However, the varying composition, dependant on the different sources of particulate matter, and its effect on processes of inflammation and oxidative stress in the airways has not been completely elucidated. The use of airway biomarkers, fractional exhaled nitric oxide (FENO) and exhaled breath condensate (EBC), can provide valuable insight into processes of inflammation and oxidative stress in the airways. In these studies we sought to characterize the associations between airborne pollutant exposures and their sources and airway biomarkers. Methods:The study population of interest for Chapters III-V is a subset of children currently enrolled in a birth cohort under the Columbia Children's Center for Environmental Health. Chapter III refers to the validation in this population of a method for partitioning FENO contributions from the proximal and distal airways. Chapters IV and V refer to the implementation of this method in the study of ambient metals and residential proximity to relevant sources of particulate matter (PM) and black carbon (BC). Briefly, the children of African-American and Dominican mothers living in low-income NYC neighborhoods had FENO samples collected offline at constant flow rates of 50, 83 and 100 mL/sec at ages 9 and/or 11. Surrogate measures for bronchial flux NO (JNO) and alveolar (Calv) NO concentrations were estimated using a previously validated mathematical model. Wheeze in the last 12 months was assessed by the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Seroatopy was determined by specific IgE at age 9. For Chapter IV, in order to examine the associations between metal fractions of particulate matter and airway inflammation, ambient measures of Ni, V, Zn and Fe were obtained from a local central monitoring site and averaged over nine days based on three 24 hour measures every third day. Seroatopy was determined by specific IgE at age 7. For Chapter V, residential distance to a major road, truck route and bus stop density, area covered by major roads, stationary point sources (SPS), toxic release inventory sites (TRIS) and commercial buildings, and number of buildings burning residual oil within 250-meters of each child's home were determined. These variables were selected a priori as potential important sources or airborne PM and BC. For Chapter VI, the study population was comprised of seven- and eight-year-old children enrolled in an asthma case-control study in New York City. Seven day averages of domestic levels of particulate matter <2.5 microns (PM2.5), BC and environmental tobacco smoke (ETS) were measured. Urea and 8-isoprostane were measured by liquid chromatography tandem mass spectrometry (LC/MS/MS) in EBC collected during home visits. All data were analyzed with SPSS. Results: In our first study, children with seroatopy had significantly higher median JNO p<0.001) when compared to non-seroatopic children; however, median Calv was not significantly different between these two groups (p=0.644). Children with wheeze in the past year had significantly higher median Calv (p<0.001), but not JNO (295 vs. 165 pL/s, p=0.241) when compared with children without wheeze. In our second study, ambient V and Fe concentrations were associated positively with FENO50 (p=0.018, p=0.027). Ambient Fe was associated positively with JNO (p=0.017). Ambient Ni and V concentrations were associated positively with Calv (p=0.004, p=0.018 respectively). A stronger association of Ni concentrations with Calv was observed among the children with seroatopy. In our third study, there were no significant associations between any of the air pollution indicator variables and FENO parameters in adjusted models. In our final study, PM2.5and BC, but not ETS, were significantly associated with increases in 8-isoprostane (p<0.05 for both) after adjustment for covariates. In a co-pollutant model including PM2.5, BC and ETS, only BC remained a statistically significant predictor of 8-isoprostane. Discussion: Recent exposure to airborne pollutants was associated with increased levels of biomarkers of airway inflammation and oxidative stress measured in exhaled breath. The metal and BC fractions of PM might be more relevant to the understanding adverse respiratory outcomes related to air pollution exposure.

碩士
輔仁大學
公共衛生學系碩士班
96
Background： The allergic disease has been markedly increased in recent years in Taiwan. Indoor air pollutants such as suspended particular matter ( SPM ), volatile organic compounds ( VOCs ), carbon dioxide ( CO2 ), carbon monoxide ( CO ), sulfur dioxide ( SO2 ) and ozone ( O3 ) may cause adverse health effects to children with airway hyper-sensitively. Detection of exhale nitric oxide ( eNO ), nasal nitric oxide ( nNO ) and exhaled breath condensate pH ( EBC pH ) is a noninvasive technique to monitor the airway inflammation. The effects of air pollutants exposure on the eNO, nNO, and EBC of allergic children are an important issue in environmental health. Methods： The panel study recruited 28 children, including 10 with asthma and allergic rhinitis ( AS ), 9 children with allergic rhinitis ( AR ) and 9 health children ( HE ). The concentrations of outdoor air pollutants measured at the ambient air monitoring site operated by Taiwan Environmental Protection Agency ( EPA ) which close to the childrens’ home were used to evaluate children exposure of outdoor air pollutants. Indoor SPM ( PM1、PM2.5、PM10 )、VOCs、CO、CO2、NO2/O3、temperature and relative humidity in domestic environments were measure by portable dust monitor ( GRIMM, GRIMM particle size analyzer model l.108, Germany ) , VOCs monitor ( ppbRAE, RAE Systems model PGM-7600, USA ) and air quality monitor ( I.A.Q, KD Engineerings AirBoxx, USA ). Exhaled NO and nasal NO levels in children were monitored by chemiluminescence analyzer ( CLD 77 AM, ECO Physics, Dürnten, Switzerland ). EBC pH was analyzed after collecting EBC from subjects using an exhaled breath condensate collector ( ECoScreen, Jaeger-Toennies, Germany ). Exhaled gas analysis and pulmonary function test were performed in winter and spring. Domestic environment characteristic and severity of the asthma and allergic rhinitis were investigated by using questionnaires and telephone interview, respectively. Result： In winter and spring, the indoor air pollutants of the domestic environments was under the indoor air quality recommended values, outdoor air pollutants concentrations were also lower than the EPA ambient air quality standards. The eNO, nNO level of AS, AR, amd HE children had no significant differences in winter and spring. In spring, the EBC pH in HE children were significantly lower than the AR children. The EBC pH in AS and HE children in spring was lower than the winter significantly. In the lung function parameters, the FVC % of HE children in spring was significantly higher than the winter. The FEV1/FVC % of AS children was significantly lower than the HE children in winter and it was significantly lower than other two groups in spring. No significant correlation was found between the indoor air pollutants and the respiratory tract biomarkers ( eNO、nNO and EBC pH ). In winter, the eNO level of HE children was correlated significantly with the preceding 24 hurs average of ambient SO2, CO, NO2, and O3 concentration. The nNO level of AR children was correlated significantly with preceding week average of ambient PM10 concentration. Conclusion： The correlations between respiratory tract biomarkers and air pollutants didn’t reveal consistent trends in AS, AR, and HE children. The effects of different air pollutants and exposures on the respiratory tract were variable, and may cause the exacerbation of allergic children respiratory tract inflammation. The season change also may affect the respiratory tract biomarkers. The results of this research may provide a useful reference for researchers to apply the noninvasive and safe exhaled biomarkers to evaluate the respireable effects of air pollutants.

impacto da poluição ambiental na saúde tem sido, nas últimas décadas, um recorrente objetivo de estudo, não só numa perspetiva de investigação científica mas, igualmente, numa lógica de implementação de políticas de saúde pública. São enumeras as evidências dos efeitos, a curto e a longo prazo, que se associam com maiores índices de morbilidade e mortalidade decorrentes da exposição à poluição. Do ponto de vista da saúde respiratória, estão disponíveis dados que demonstram que a exposição ambiental é a causa para o desenvolvimento e/ou agravamento de doenças respiratórias nomeadamente, doença pulmonar obstrutiva crónica (DPOC), asma, fibrose pulmonar idiopática e cancro do pulmão. A investigação sobre os efeitos da poluição ambiental na saúde começou por ser dirigida para o impacto dos contaminantes do ar exterior, sendo o estudo relativo aos efeitos dos poluentes no ar interior relativamente recente. Na perspetiva da qualidade do ar interior (IAQ), os idosos são entendidos como uma população mais vulnerável. Por um lado, é sabido que têm um sistema imunitário mais comprometido decorrente do envelhecimento, por outro lado também se apresentam mais tempo confinados aos espaços interiores, devido a eventuais limitações nas suas atividades diárias. O estudo geriátrico dos efeitos na saúde da qualidade do ar interior em lares da 3ª idade de Portugal (GERIA) foi o primeiro, a nível nacional, com o objetivo de estudar os efeitos da IAQ de equipamentos residenciais para pessoas idosos (ERPI) na saúde e qualidade de vida dos idosos institucionalizados. O presente trabalho foi realizado no âmbito do projeto GERIA e os dados utilizados correspondem a uma subamostra de idosos que integraram o referido projeto. O objetivo geral deste trabalho é descrever o impacto da exposição ambiental do ponto de vista da IAQ na saúde respiratória de uma amostra de idosos, residentes em ERPI, avaliados através da espirometria e do condensado brônquico do ar exalado (EBC).
The health impact of environmental pollution has been recurrently studied over the last few decades, not only in a scientific research perspective, but also in the context of implementing public health policies. In fact, the evidence of short and long-term effects due to pollution exposure is associated with higher morbidity and mortality rates. In terms of respiratory health, data available demonstrates that environmental exposure is the cause for the development and / or worsening of respiratory diseases, as chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis and lung cancer. In fact, the research about the health effects of environmental pollution started to focus, primarily, on the impact of external air pollutants. However, in turn, the study on the effects of indoor air pollutants is relatively recent. In a perspective of indoor air quality (IAQ), the elderly are a vulnerable population. On the one hand, as a consequence of the ageing process, they have a more compromised immune system; on the other hand, they also tend to spend more time confined to indoor spaces, due to possible limitations in their daily activities. The geriatric study on the health effects of indoor air quality in Portuguese elderly households (GERIA) was the first, at a national level, to study the effects of IAQ found on residential equipment for the elderly (ERPI) and, thus, its consequences in health and quality of life of the institutionalized ones. The present work was carried out within the GERIA project framework and the data used correspond to a subsample of the elderly who integrated the project. The main objective of this study is to describe the impact of environmental exposure from the point of view of IAQ in the respiratory health in a sample of elderly people living in ERPI. The elderly were evaluated through spirometry and exhaled bronchial condensate (EBC).