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1

Madouri, Fahima. "Asthme allergique induit par un allergène d’acarien, House Dust Mite (HDM) : rôles de la caspase-1 et de la protéine kinase C thêta (PKC-θ)." Thesis, Orléans, 2014. http://www.theses.fr/2014ORLE2055/document.

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Des études menées au laboratoire avaient démontré un rôle critique de l’inflammasome NLRP3 dans l’asthme allergique en réponse à l’ovalbumine en absence d’adjuvant. Mes travaux de thèse ont porté sur le rôle de NLRP3 et de la caspase-1 dans un modèle murin d’inflammation pulmonaire induite par l’allergène d’acarien HDM. Nous avons montré un rôle régulateur de la caspase-1 dépendant de l’inflammasome NLRP3 et la molécule adaptatrice ASC mais pas de l’inflammasome NLRC4. Cette régulation de la réponse allergique se caractérise par une augmentation de l’infiltration des éosinophiles, de l’hyperréactivité bronchique et de la production des cytokines de type Th2 telles que l’IL-4, l’IL-5, l’IL-13 et l’IL-33 dans les poumons. Nous avons montré que les mécanismes responsables de cette régulation sont associés à l’IL-33 produite par les macrophages et que la neutralisation de l’IL-33 par administration locale de la protéine de fusion au récepteur ST2 (muST2-Fc) atténue les caractéristiques de l’asthme allergique. Ces résultats suggèrent que l’activation de la caspase-1 réduit la production d’IL-33 in vivo et régule ainsi la réponse l’inflammation pulmonaire induite par HDM et la réponse Th2. D’autre part, nous nous sommes intéressés au rôle de la Protéine Kinase C thêta (PKC-θ) dans ce même modèle d’inflammation pulmonaire. Nous avons démontré que PKC-θ joue non seulement un rôle protecteur dans l’asthme allergique mais également un rôle critique pour la prolifération et l’activation des cellules lymphoïdes innées (ILC2). D’autre part, l’inhibition de PKC-θ in vivo par administration orale de son inhibiteur spécifique C20 (BIX02656) atténue l’inflammation pulmonaire et la production d’IL-5 et d’IL-13. Nous suggérons que PKC-θ est impliquée dans la différenciation des Th2 et des ILC2 via un mécanisme dépendant des facteurs de transcription IRF4 et NFAT-1. Au total, mes travaux de thèse mettent en exergue deux molécules IL-33 et PKC-θ qui pourraient constituer des cibles thérapeutiques potentielles
Studies from our laboratory have shown a critical role of NLRP3 inflammasome in response to ovalbumin allergen. In the present study we investigate the role of NLRP3 and caspase-1 in a mouse model of pulmonary inflammation induced by HDM. We have shown a regulatory role of caspase-1 dependant of the NLRP3 inflammasome and the adaptator molecule ASC but not NLRC4. The regulation of the allergic response is characterized by an increase of eosinophilia, bronchial hyperreactivity and Th2 cytokines production (IL-4, IL-5, IL-13 and IL-33) in lungs. We have shown that mechanisms responsible of this regulation are associated with IL-33 production by macrophages and that neutralization of IL-33 by local administration of a fusion protein of the ST2 receptor (muST2-Fc) reduce characteristics of asthma. These results suggest that caspase-1 activation reduce IL-33 production in vivo regulating lung inflammation and Th2 response induced by HDM. Moreover, we investigate the role of the Protein Kinase C theta (PKC-θ) in allergic airway inflammation. We have demonstrated that PKC-θ plays a protective role in allergic asthma but is critical for the activation and proliferation of innate lymphoid cells (ILC2). In addition, in vivo inhibition by oral administration of PKC-θ specific inhibitor C20 (BIX02656) reduces pulmonary inflammation with IL-5 and IL-13 production. We suggest that PKC-θ is implicated in Th2 and ILC2 differenciation by a mechanism dependant on transcription factors IRF4 and NFAT-1. Finally, my thesis projects describe IL-33 and PKC-θ as potential therapeutic targets for allergic lung inflammation
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2

Ullah, MD Ashik. "Novel mechanisms of airway inflammation in mouse models of allergen and virus-induced asthma." Thesis, The University of Sydney, 2014. http://hdl.handle.net/2123/12830.

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Asthma is a heterogeneous disorder encompassing distinct clinical phenotypes thought to be mediated by distinct mechanisms. The Receptor for Advanced Glycation End products (RAGE) is a pattern-recognition receptor capable of ‘sensing’ exogenous and endogenous molecules; and there is evidence that ligand-RAGE axis is activated in asthma. We investigated the role of RAGE and its ligand high-mobility group box-1 (HMGB1) in the inception and progression of allergen and virus-induced asthma using mouse models. We demonstrate that RAGE is a critical mediator of allergic airway sensitization induced by house dust mite (HDM) and cockroach (CR) allergens. Our studies suggest that RAGE is engaged secondary to the release of HMGB1 by airway epithelial cells; and that HMGB1-RAGE signalling drives type 2 immunity and airway inflammation. RAGE is also required for anti-viral immunity to pneumonia virus of mice (PVM) (equivalent to human respiratory syncytial virus). PVM infection in RAGE-deficient mice led to increased HMGB1 expression in the airways; this contributed to the development of an asthma-like pathology characterised by airway smooth muscle remodelling, airways hyperresponsiveness and the absence of granulocytic inflammation, representing a pauci-granulocytic phenotype of human asthma. In separate studies we investigated whether an anti-IL-6 receptor (IL-6R) antibody protects against allergic airway inflammation. Intriguingly, anti-IL-6R protected against CR-induced airway inflammation but exacerbated the airway inflammatory response to HDM. This differential response was related to differential activation of IL-6 signalling mechanisms in response to CR and HDM. The studies herein expose novel molecular mechanisms that may explain the development of specific phenotypes of human asthma in response to viral or allergic triggers. Selective targeting of these pathways in appropriate patient sub-groups may lead to better outcomes in asthma management.
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3

Glass, Emmett V. "Environmental control of house dust mites : strategies for limiting exposure to house dust mites and their allergens /." The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1486461246818192.

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4

Hill, Michael Richard. "Studies on house dust mites and atopic disease." Thesis, University of Oxford, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.306515.

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5

Folisi, Caterina. "Oxidative stress and anti-oxidant response in allergen, virus, and corticosteroids withdrawal-induced asthma exacerbation." Doctoral thesis, Università di Catania, 2015. http://hdl.handle.net/10761/3871.

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Si stima che oltre 300 milioni persone di tutte le età e razze, soffrono di asma.1 L'onere di questa malattia per i governi, le famiglie, e i pazienti è in aumento a livello globale. L'asma è una condizione eterogenea e complessa causata da una combinazione di fattori genetici e ambientali. L'asma è caratterizzata da tosse ricorrente, respiro sibilante, senso di costrizione toracica, e responsività ai broncodilatatori. Iper-reattività bronchiale, infiammazione cronica, alterazioni strutturali delle vie aeree, e iper-secrezione ghiandolare sono altre caratteristiche dell asma. Lo stress ossidativo svolge un ruolo centrale nella patogenesi dell asma.2 Esso si verifica quando la produzione di specie ossidanti supera la capacità dei sistemi biologici di detossificazione o di riparo. La presenza di un alterato status ossidante è ben stabilita in pazienti asmatici. Tuttavia, non è stata ancora eseguita alcuna analisi sistematica del danno ossidativo e sulle risposte cellulari anti-ossidanti negli asmatici. Questa tesi è stata incentrata sulla valutazione dello stress ossidativo e risposta anti-ossidante nell'asma e durante la sua riacutizzazione. La presente tesi ha avuto lo scopo di valutare le conseguenze ossidative che le riacutizzazioni hanno sulle proteine cellulari e di individuare i principali meccanismi anti-ossidanti coinvolti nella risposta cito-protettiva. La tesi ha studiato la relazione tra stress ossidativo, stato anti-ossidante, e sintomi da riacutizzazione asmatica. Una valutazione bio-chimica completa dello stato ossidativo e delle risposte anti-ossidanti è necessaria per identificare la natura e la portata di eventuali deficit anti-ossidanti associati con l'asma e la sua riacutizzazione. Una piena comprensione dello stato ossido-riduttivo nelle riacutizzazioni dell'asma potrebbe sostenere lo sviluppo di nuovi interventi terapeutici sicuri ed efficaci. La popolazione che ha partecipato negli studi inclusi in questa tesi è composta da 4 gruppi di asmatici. Il primo gruppo di nove asmatici è stato esposto al Rhinovirus-16. Il secondo gruppo comprendeva venti asmatici atopici esposti all acaro della polvere. Il terzo trentasette individui sani impiegati in laboratori ed esposti ad allergeni da roditori per un periodo di due anni; alcuni di loro sono diventati allergici. Il quarto gruppo comprendeva ventitré asmatici in trattamento con corticosteroidi la cui sospensione è stata eseguita allo scopo di studiare la riacutizzazione asmatica indotta dalla sospensione di questi farmaci. Sono stati condotti diversi esperimenti in vivo, ex vivo e in vitro per chiarire la relazione tra stato ossidativo e la riacutizzazione asmatica. L ossidazione delle proteine cellulari è stata valutata come stabile indice biologico di stress ossidativo e il livello di espressione è stato misurato per diverse proteine anti-ossidanti nel plasma e nell espettorato indotto. È stata anche determinata la produzione di mediatori pro-infiammatori. I pazienti durante la riacutizzazione dell'asma, come previsto, mostravano livelli più alti di stress ossidativo. L entità del danno ossidativo risultava associata alla severità della sintomatologia. È stato interessante riscontrare che i pazienti durante una riacutizzazione asmatica erano anche più suscettibili a danni ossidativi delle proteine cellulari; questo è stato associato ad una riduzione della capacità anti-ossidante cellulare, ridotta traslocazione nucleare del principale fattore di trascrizione anti-ossidante, e maggiore produzione di mediatori pro-infiammatori. Inoltre, i livelli basali di stress ossidativo sono stati in grado di predire quali pazienti erano più inclini a sviluppare sintomi di riacutizzazione. Questi risultati suggeriscono che il rafforzamento dei meccanismi anti-ossidanti locali e sistemici in asmatici può attenuare l'infiammazione delle vie aeree e il suo aggravamento durante le fasi di riacutizzazione.
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6

Lawson, Alan. "The domestic hygro-thermal environment, house dust mites and asthma." Thesis, University of Strathclyde, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.401343.

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7

Lassiter, Mark Timothy. "A Survey of House Dust Mites in the Williamsburg Area." W&M ScholarWorks, 1985. https://scholarworks.wm.edu/etd/1539625296.

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8

Hay, David B. "Ecology of the house dust mite Dermatophagoides pteronyssinus (Trouessart)." Thesis, University of Oxford, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302975.

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9

Rockwood, Jananie. "House Dust Mite Induced Gene Expression and Cytokine Secretion by Human Dermal Fibroblasts." Wright State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=wright1347976529.

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10

Shaw, Stephen Charles. "The immune response in canine atopy : hypersensitivity to house dust mites (Dermatophagoides spp.)." Thesis, Open University, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340709.

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11

Cheung, Heidi How-Moy. "The role of indoor air pollutants and house dust mites in childhood asthma." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393736.

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12

Newman, Aaron Mathew. "The Response of Vascular Dermal Enodethial Cells to House Dust Mite Extracts." Wright State University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=wright1205717763.

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13

Traherne, James Arnold. "The T cell receptor genes and the specific immunoglobulin E response." Thesis, University of Oxford, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365752.

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14

Andes, Glenda Gilmore. "The Effect of Carpet Fiber on the Growth of Dermataphagiodes farniae in a Controlled Environment." Thesis, Virginia Tech, 2000. http://hdl.handle.net/10919/36256.

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Mites are endemic and allergy to mite excreta and parts is one of the most common allergies. Health care practitioners have recommended the removal of carpets from homes of people with mite allergies. Little, if any, consideration is given to the fact that some persons may benefit directly from the presence of carpet in their homes. In the allergen and mite research literature, carpets are rarely described as having unique characteristics and are generally referred to as a generic entity. Carpets, however, do have unique characteristics that define their construction, appearance, wearability, and cleanability. Seventy-two pieces of commercially available, residential flooring materials were inoculated with identical numbers of mites, Dermatophagiodes farinae, and placed in the Textiles Conditioning Lab at Virginia Tech. The mites and carpet pieces were maintained in the lab, under identical, environmentally controlled conditions for 6 weeks, then the mites were extracted and counted. On the basis of the results of statistical tests run on the study data, the null hypothesis, that there is no difference between the numbers of mites grown on the different flooring conditions, was rejected. Statistically significant differences exist between the hard floor and the nylon carpet, between hard floor and olefin carpets, but no difference between hard floor and wool carpet. Nylon was the carpet fiber that was most supportive of the growth of house dust mites, olefin was the second most supportive, and wool carpet and hard floor were similar in being the least supportive.
Master of Science
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15

Joseph, Karen Elizabeth. "The effect of providing bedding encasings on adherence to dust mite control procedures in pediatric asthma patients." Morgantown, W. Va. : [West Virginia University Libraries], 2000. http://etd.wvu.edu/templates/showETD.cfm?recnum=1605.

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Thesis (M.A.)--West Virginia University, 2000.
Title from document title page. Document formatted into pages; contains viii, 123 p. Includes abstract. Includes bibliographical references (p. 63-68).
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16

Ucci, Marcella. "The psychrometric control of house dust mites : testing the validity in UK dwellings of two combined hygrothermal population models for beds." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1445682/.

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Beds are a crucial source of house dust mite (HDM) allergens, which play a major role in allergic disease, particularly asthma. HDM require a specific combination of hygrothermal conditions to thrive. These bed conditions depend on a number of interacting factors, such as: external climate; building characteristics; heating, ventilation and moisture-producing habits; mattress properties; etc. Because of the complexity of the many interacting factors occuring in real dwellings, a modelling approach is required, whereby the models' predictions have to be consistent with field results. This thesis tested the hypothesis that a combined HDM population-hygrothermal model for beds can adequately predict field data and that the model can be a valuable tool for scenario modelling and intervention studies focused on the psychrometric control of house dust mites in UK housing. Two combined models were considered: a simple steady-state one-dimensional model (BED/MPI), and a complex transient three-dimensional mode (Lectus/Popmite). A combination of fieldwork and scenarios modelling was carried out, which involved hygrothermal and mite monitoring of 25 beds, utilising a novel technique whereby live mites were caged in mite bags and installed in monitored beds and bedrooms (82 sets of mites bags). The work was carried out as part of a multidisciplinary project aimed at developing and testing the models. Good agreement was found between field data and the models predictions, particularly when the uncertainties due to input variables and measurements were taken into account. The results showed that under borderline conditions for HDM growth, simple steady-state predictions may not be accurate. Temperature, not only RH, is a critical variable for HDMs. Areas for model improvement were also identified. In particular, factors other than hygrothermal conditions may be crucial for a beds mite carrying capacity, requiring further investigation: food, space availability, and mite movement. Despite these uncertainties, it can be concluded that greater ventilation, increased thermostat settings and reduced moisture rates can decrease mite levels in beds. The ventilation rates provided by some mechanical ventilation with heat recovery systems may be inadequate to sufficiently control moisture and reduce mite growth. Scenarios modelling suggests that there is considerable potential for the psychrometric control of house dust mites in UK dwellings.
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Poola, Swetha Avula. "INFLUENCE OF DIET ON POPULATION GROWTH AND ALLERGEN PRODUCTION IN CULTURED HOUSE DUST MITES - DERMATOPHAGOIDES FARINAE AND DERMATOPHAGOIDES PTERONYSSINUS." Wright State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=wright1247665992.

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18

Yella, Lakshmi. "The Influence of Temperature on Population Growth and Allergen Production in Cultured House Dust Mites – Dermatophagoides pteronyssinus and Dermatophagoides farinae." Wright State University / OhioLINK, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=wright1260772254.

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19

Taylor, Rebecca Chantelle. "Effects of toll-like receptor 2 ligands on T-cell responses to mite allergen in humans." University of Western Australia. School of Paediatrics and Child Health, 2007. http://theses.library.uwa.edu.au/adt-WU2007.0107.

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[Truncated abstract] The last few decades have witnessed an increase in the prevalence, morbidity and economic burden associated with asthma and allergic disease. This rising incidence cannot be completely explained by changes in genetic factors or by improvements in diagnostic procedures. Environmental factors, particularly those associated with a westernised lifestyle, are considered to be involved in this increase. In the late 1980’s Strachan was the first to link environmental factors with allergic disease, this theory became to be known as the ‘hygiene hypothesis’. This hypothesis links the “cleaner” more “healthy ” environment we now live in, with an increased risk of developing allergic disease. This effect is highlighted by studies linking farm and animal exposure (rich in microbial compounds) during early life with a decrease in allergic disease. Since then numerous studies have been undertaken to ascertain the factors present in the microbe rich environment, which elicit this protective effect. Many studies have revolved around endotoxin, however microbial components (mainly from Gram-positive bacteria) which signal through Toll-like receptor 2 (TLR2), have also shown that they can alter the allergic immune response. In mice models TLR2 has been shown to both exacerbate and inhibit allergic disease. The above research highlights the need for further studies into the effect of TLR2 ligands, and to define the mechanisms by which they exert their effects in human allergic disease. These mechanisms will be relevant to understanding the pathogenesis of allergy, but also might provide novel ways to treat allergy. The aims of the study outlined in this thesis were to determine whether in vitro exposure to TLR2 ligands could modify the established immune response to house dust mite allergen (HDM), and to examine the mechanisms by which this occurs. ... The addition of glucocorticoids to LTA enhanced the ability of this TLR2 ligand to inhibit IL-5 and IL-13 production by HDM-activated blood mononuclear cells. In conclusion, this study shows that TLR2 ligands have the ability to inhibit the Th2 response to mite allergen in previously sensitized individuals by an as yet unknown mechanism. However the findings described herein do provide an impetus for future studies designed to uncover novel mechanisms by which allergic responses can be ameliorated, and may open new treatment modalities.
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20

Pereira, Desydere Trindade. "Estudo da sensibilização de cães com dermatite atópica na região central do Rio Grande do Sul." Universidade Federal de Santa Maria, 2015. http://repositorio.ufsm.br/handle/1/10196.

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Canine atopic dermatitis (CAD) is a common dermatosis, defined as a genetic-based disease, which predisposes to cutaneous inflammation and pruritus, mediated by class IgE immunoglobulins directed against specific antigens in most cases. Clinical diagnosis may be later complemented by skin allergic and/or serological tests (ELISA). The aim of these tests is to identify possible allergens in order to enable the clinicians to select candidate antigens for allergen specific immunotherapy. This work aimed to identify the sensitization profile of 58 dogs with atopic dermatitis diagnosis. All animals were submitted to intradermic test (IDT) and screened for the presence of antibodies against different allergens using a serologic test. House dust mites are described as the most frequent allergens in all continents. However, the positivity to C. dactylon is not commonly described and may be characteristic for the region. With this work it was possible to identify the main allergens involved in the immunologic response of atopic dogs residing in Rio Grande do Sul, pointing to the importance to include C. dactylon in screening tests for allergy.
A dermatite atópica canina (DAC) é uma dermatose comum, definida como uma doença de cunho genético que predispõe à inflamação e ao prurido cutâneo, mediada por imunoglobulinas da classe IgE dirigidas contra antígenos específicos na maior parte dos casos. O diagnóstico da DAC é clínico e pode ser posteriormente complementado por testes alérgicos cutâneos e/ou sorológicos. O objetivo desses testes é identificar possíveis alérgenos e, com isso, possibilitar ao clínico a seleção de antígenos candidatos para a imunoterapia alérgeno-específica. No presente trabalho buscou-se identificar o perfil de sensibilização de 58 cães diagnosticados com dermatite atópica. Todos os animais foram submetidos ao teste intradérmico (TID) e à detecção de anticorpos específicos para diferentes alérgenos através de teste sorológico (ELISA). Os ácaros domiciliares são descritos como os alérgenos mais frequentes em todos os continentes. Entretanto, a positividade ao C. dactylon não é usualmente descrita e pode ser característica da região. Com esse trabalho foi possível identificar os principais alérgenos envolvidos na resposta imunológica de cães atópicos residentes no Rio Grande do Sul, ressaltando-se a importância da inclusão do extrato de C. dactylon em testes alérgicos.
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Gunnbjörnsdóttir, María Ingibjörg. "Asthma and Respiratory Symptoms in Nordic Countries, Environmental and Personal Risk Factors." Doctoral thesis, Uppsala University, Department of Medical Sciences, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-7076.

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The overall aims of our studies were to identify risk factors for respiratory symptoms and asthma in indoor environment but even to look at some personal risk factors such as body mass index and gastroesophageal reflux. The study population is based on participants of the European Community Respiratory Health Survey I and II.

In the first study, water damage and visible moulds were reported in 7.4% and 17% of the homes respectively. The combination of water damage and visible moulds was independently associated with attacks of breathlessness when resting and after activity and also to long term cough. In the second study, the prevalence of nocturnal GER increased with higher BMI and the same pattern could be seen for habitual snoring. Reported onset of asthma, wheeze and night-time symptoms increased in prevalence along with the BMI gradient. In the multivariable analysis, obesity and nocturnal GER were independent risk factors for onset of asthma, wheeze and night-time symptoms. Habitual snoring was an independent risk factor for onset of wheeze and night-time symptoms, but not for onset of asthma. In the third study, a total of 18% of the subjects reported indoor dampness in the last 12 months and 27% of the subjects reported indoor dampness since the previous survey. Respiratory symptoms and asthma were significantly more prevalent in individuals exposed to indoor dampness and indoor dampness was a risk factor for respiratory symptoms and asthma after adjusting for possible confounders. Indoor dampness was an independent risk factor for onset of respiratory symptoms but not for asthma onset. Remission of respiratory symptoms was less likely to occur if subjects reported indoor dampness. In the fourth study, the lowest prevalence of atopy and the lowest levels of all indoor allergens, bacteria and moulds were found in Iceland. A positive association was found, between cat allergen exposure and asthma symptoms and between bronchial hyperresponsiveness and the amount of viable mould in indoor air.

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Naegele, Alexandre. "Impact des acariens et des micro-organismes de l'habitat dans le développement de l'asthme et de la broncho-pneumopathie chronique obstructive (BPCO)." Thesis, Besançon, 2015. http://www.theses.fr/2015BESA3019/document.

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Notre volonté d'économiser l'énergie nous pousse à vivre dans un environnement confiné favorisant les acariens et les micro-organismes. L'objectif de la thèse est de caractériser la contamination en acariens et en micro-organismes des logements de patients présentant des pathologies respiratoires, d'évaluer l'influence des interactions acariens/moisissures sur l'exposition aux allergènes et de comprendre les facteurs favorisant la pollution biologique de l'air intérieur. Afin de disposer d'un outil commun aux acariens et aux micro-organismes, un modèle innovant de quantification des acariens pas qPCR a été mis au point. Les acariens de stockage sont sous-estimés et les mesures d'éviction doivent être appliquées à l'ensemble de l'habitat. L'observation des interactions acariens/moisissures a montré une vraie relation symbiotique: dispersion des moisissures et apports des nutriments essentiels aux acariens. La contamination des logements de producteurs laitiers atteint de BPCO a été comparée à celle de producteurs laitiers sains, de patients BPCO non­-agriculteurs et de sujets sains non-agriculteurs. L'exposition agricole est abondante et spécifique à certains micro­organismes caractéristiques de la ferme et la sensibilité IgG à Wallemia sebi est spécifique des producteurs laitiers BPCO Le suivi de l'impact du compostage sur la qualité biologique de l'air intérieur a démontré une augmentation des concentrations en acariens de stockage et certaines moisissures circonscrite au bio-seau. De nouveaux indicateurs communs aux acariens, aux moisissures et aux bactéries devraient nous permettre de progresser dans la détermination de la relation dose/effet
Our will to save energy leads us to live in a confined environment providing the ideal conditions to mites and microorganisms development. The aim of the thesis is to characterize mites and microorganisms contamination of dwellings from patients suffering respiratory diseases, to estimate the influence of the interactions between various organic communities on the allergens exposure and to understand the factors increasing the biological pollution ofindoor air. To evaluate our exposition, we needed to quantify mites and microorganisms with a common tool and an innovative quantification mode! of domestic mites by qPCR was developed. The presence of storage mites is overemphasized in dwellings of allergie patients and the eviction measures of mites should be applied into any rooms of dwellings. The contamination of dairy fanners' dwellings suffering from COPD was compared with that ofhealthy dairy fanners, COPC patients non-farmers and healthy non-fanners. In dwellings, the dairy fanners' exposure was important and specific ofth1 fanning environment. The lgG sensitivity to Wallemia sebi was significantly specific of dairy fanners suffering from COPD. The impact of the composting on the biological air quality was evaluated and the concentrations in storage mites and some molds increased significantly only in a confined area around the waste bin. New common indicators of domestic mites, molds and bacteria should allow us to progress in the determination of the dose-response relationship for the different allergens and their possible synergie effects
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Rigaux, Peter. "Evaluation des propriétés immunomodulatrices de la bactérie lactique Lactobacillus plantarum NCIMB8826 dans le cadre de l'allergie aux acariens." Doctoral thesis, Universite Libre de Bruxelles, 2008. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/210414.

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Les effets anti-allergiques des bactéries lactiques sont suggérés par plusieurs études épidémiologiques, des essais cliniques et des modèles expérimentaux d’allergie. Cependant, les propriétés immunomodulatrices des bactéries lactiques sont sous-exploitées par les stratégies vaccinales développées pour combattre l’allergie et les mécanismes empruntés par ces bactéries pour moduler l’allergie restent peu caractérisés.

Dès lors, nous avons caractérisé les propriétés immunomodulatrices qu’exerce Lactobacillus plantarum NCIMB8826, une bactérie lactique modèle, sur la cellule dendritique étant donné le rôle déterminant de cette cellule sur la réponse allergique. Nous montrons que L. plantarum induit une forte sécrétion d’IL-12 p40, d’IL-12 p70, de TNF-a mais une faible production d’IL-10. Cette faculté à induire la sécrétion de cytokines polarisantes dépend de TLR2, de TLR9, de MyD88, de NF-kB, des MAPKs (en particulier JNK, p38 et ERK 1/2), de la composition de l’acide lipotéichoïque de L. plantarum et de CD14. Nous montrons aussi que l’ADN génomique de L. plantarum est un agoniste de TLR9 et que CD14 et CD36 facilitent la liaison de la cellule dendritique avec L. plantarum.

Ensuite, nous avons évalué le potentiel vaccinal d’une coadministration L. plantarum + Der p 1 dans un modèle murin d’allergie à Der p 1. Cette formulation vaccinale prévient la production d’IgE Der p 1-spécifique et atténue l’éosinophilie pulmonaire tout en stimulant une forte production d’anticorps IgG2a Der p 1-spécifiques et d’IFN-g par les cellules spléniques. Ces effets bénéfiques nous ont conduit à élaborer une bactérie lactique recombinante dérivée de L. plantarum produisant Der p 1 pour la vaccination contre l’allergie aux acariens. La forme antigénique que nous avons réussi à faire produire par L. plantarum correspond à une protéine de fusion entre la Maltose Binding Protein de E. coli et ProDer p 1 (le zymogène de Der p 1), la présence de ce partenaire de fusion étant indispensable à la production de ProDer p 1. En prophylaxie, la vaccination par cette bactérie recombinante prévient la production d’anticorps IgE-Der p 1-spécifiques et stimule la production d’anticorps IgG2a spécifiques, reproduisant les effets de la coadministration L. plantarum + Der p 1. Elle réduit de manière drastique la production d’IL-5 des cellules spléniques et des cellules ganglionnaires médiastinales et prévient l’éosinophilie pulmonaire mais n’a pas d’effet sur l’hyperréactivité bronchique. Der p 1 étant un des allergènes d’acarien les plus immunodominants, cet ensemble de données montre donc que cette bactérie recombinante constitue un vaccin prophylactique prometteur pour la prévention de l’allergie aux acariens. Des résultats préliminaires obtenus à partir de cellules dendritiques humaines et lymphocytes T autologues montrent la forte capacité de cette bactérie recombinante à induire le développement d’une réponse Th1 fortement polarisée (production d’IFN-g en l’absence de production d’IL-4 et d’IL-5), ce qui suggère que l’utilisation de cette bactérie recombinante pourrait être envisagée pour le traitement de l’allergie chez l’homme.


Doctorat en Sciences agronomiques et ingénierie biologique
info:eu-repo/semantics/nonPublished

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24

Audousset, Camille. "Implication du récepteur NOD1 dans l’asthme allergique aux acariens & Impact fonctionnel des bouchons de mucus dans les voies aériennes de patients asthmatiques sévères selon leur statut tabagique." Thesis, Université de Lille (2018-2021), 2021. https://pepite-depot.univ-lille.fr/ToutIDP/EDBSL/2021/2021LILUS050.pdf.

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L’asthme est une maladie inflammatoire chronique des voies aériennesresponsable d’une morbi-mortalité significative et définie par une association entre dessymptômes cliniques et une obstruction bronchique variable. Les caractéristiques cardinalesde l’asthme sont une hyper-réactivité des voies aériennes, une inflammation bronchiqueassociée à une modification de la structure des bronches dont une hyperproduction demucus.L’ensemble de ces caractéristiques aboutit à de nombreuses présentations cliniques,appelées des phénotypes asthmatiques, qui sont la conséquence de multiples mécanismesphysiopathologiques distincts. Le phénotype asthmatique le plus fréquent est l’asthmeallergique dont les acariens représentent l’un des principaux pneumallergènes.L’hétérogénéité de cette pathologie requiert une approche globale incluant des travauxfondamentaux et une approche clinique translationnelle. Ces deux approches ont étédéveloppées dans cette thèse.Dans la première partie, l’implication d’un récepteur de l’immunité innée, lerécepteur Nod1, dans l’asthme allergique aux acariens a été investiguée. Ce récepteurreconnaît des fragments de peptidoglycanes bactériens et participe à la réponse immune. Ilest également impliqué dans la régulation du microbiote digestif. Chez les souris Nod1-/-, lesparamètres allergiques asthmatiques induits par les acariens sont réduits comparativementaux souris sauvages. Cette atténuation de la réponse allergique asthmatique n’est pas liée àune modification de la flore digestive des souris Nod1-/-. En revanche, les extraits d’acarienscontiennent une flore microbienne, principalement composée de bacille gram négatif,susceptible d’activer directement le récepteur Nod1 au niveau de l’épithélium des voiesrespiratoires. Cette activation participe à l’exacerbation de la réponse allergique asthmatiqueinduite aux acariens et offre une nouvelle perspective thérapeutique dans le traitement del’asthme allergique aux acariens.La deuxième partie de ce travail est consacrée à l’impact fonctionnel de bouchons demucus présents dans les voies aériennes de patients asthmatiques en fonction de leur statuttabagique en utilisant des outils précédemment développés. La présence de bouchons demucus est fréquente quel que soit le statut tabagique des asthmatiques. Une corrélationinverse a été retrouvée entre le nombre de segments pulmonaires présentant au moins unbouchon de mucus et l’obstruction des voies aériennes. Cette caractéristique clinique estcorrélée au pourcentage de polynucléaires éosinophiles dans les expectorations. Chez lespatients ayant un antécédent de tabagisme, la présence d’occlusions des voies aériennesest associée au pourcentage de neutrophiles. Les bouchons de mucus apparaissent commeun marqueur de sévérité de l’asthme et sont corrélés à différents types d’inflammationbronchique selon le statut tabagique.Cette thèse a contribué à faire avancer les connaissances fondamentales et clinicofonctionellesdans l’asthme. Ces résultats invitent à poursuivre les investigations dans cesdifférents domaines
Asthma is a chronic inflammatory airway disease responsible for significant morbidityand mortality defined by an association between clinical symptoms and variable airwayobstruction. The cardinal features of asthma are airway hyperresponsiveness, bronchialinflammation associated with changes in the structure of the bronchi including overproductionof mucus. Taken together, these characteristics result in numerous clinical presentations,called asthmatic phenotypes, which are the consequence of multiple distinctpathophysiological mechanisms. The most common asthma phenotype is allergic asthma, ofwhich house dust mites are one of the main pneumallergens. The heterogeneity of thispathology requires a comprehensive approach including fundamental work and translationalclinical approach. These two approaches have been developed in this thesis.In the first part, the involvement of an innate immunity receptor, the Nod1 receptor, inhouse dust mite allergic asthma was investigated. This receptor recognizes fragments ofbacterial peptidoglycans and participates in the immune response. It is also involved in theregulation of the digestive microbiota. In Nod1-/- mice, the mite-induced asthmatic allergicparameters are reduced compared to wild type mice. This attenuation of the allergicasthmatic response is not linked to a change in the digestive flora of Nod1-/- mice. In contrast,mite extracts contain microbial flora, mainly composed of gram-negative bacillus, capable ofdirectly activating the Nod1 receptor in the epithelium of the respiratory tract. This activationcontributes to the exacerbation of the allergic asthmatic response induced by house dustmites and offers a new therapeutic perspective in the treatment of allergic asthma to housedust mites.The second part of this work is devoted to the functional impact of mucus plugspresent in the airways of asthma patients according to their smoking status using previouslydeveloped tools. The presence of mucus plugs was common regardless of the smokingstatus of the asthmatics. An inverse correlation was found between the number of lungsegments with at least one mucus plug and airway obstruction. This clinical feature wascorrelated with the percentage of eosinophils in the sputum. In patients with a history ofsmoking, the presence of airway obstructions was correlated with the percentage ofneutrophils. Mucus plugs appear to be a marker of asthma severity and are correlated withdifferent types of bronchial inflammation depending on smoking status.This PhD has helped advance fundamental and clinical-functional knowledge inasthma. These results invite further investigations in these different fields
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25

Hu, Chung-Yi, and 胡忠怡. "Investigating the allergic immune response toward house dust mite (HDM) and factors associated with the clinical manifestations of HDM-sensitive asthma." Thesis, 2002. http://ndltd.ncl.edu.tw/handle/74073117785997313071.

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博士
國立臺灣大學
微生物學研究所
91
Allergic diseases such as allergic asthma (AS), allergic rhinitis (AR) and atopic dermatitis (AD) affect about 30% of people in northern Taiwan. The prevalence of asthma has rised from 5.8% to 10.2% during the past decade. House dust mite (HDM, Dermatophagides pteronyssinus, Dp) is the most important source of allergens. Der p1 and Der p2 are the major HDM allergens and there are more than 80% of sera from asthmatic children showed Der p1 and Der p2-specific IgE antibodies. It has been demonstrated that Der p2 specific IgE and the Th2 type cytokines produced during T cell immune response is important in the development of allergic bronchial asthma. The first part of the thesis intended to investigate the possible genetic factor(s) that might affect individual’s allergic immune response toward the HDM allergens through a population study. Although HDM allergens are present in the environment, only certain persons with atopy develop allergic diseases. There is familial aggregation of allergic diseases. Twin studies also showed that the concordance rate of asthma is higher in monozygotic than in dizygotic twins. The previous reports suggested certain genetic factors might predispose an individual to allergy. A possible candidate for controlling specific IgE responsiveness toward HDM allergens is the class II human leukocyte antigens (HLA IIs), which shows extensive polymorphism and is implicated in processing and presentation of endocytic peptides to allergen-specific Th cells. For exploring the possible association between HLA IIs and HDM asthma, we recruited 248 unrelated individuals in this population study. The Der p1, Der p2 and Der p5-specific IgE and IgG antibodies were detected by ELISA. Genetic polymorphisms in HLA class II -DRB1, -DQA1, -DQB1 and DPB1 loci were assessed by PCR and sequence-specific oligonucleotide probe hybridzation (SSOPH). The results indicated that there was no significant association between HLA-DRB1, -DQA1, -DQB1 alleles and HDM-specific IgE responsiveness noted except that the DQA1*0103 allele showed positive association with Der p5-specific IgE responsiveness. The HLA-DPB1*0501 and *1301 was weakly associated with the IgE responsiveness to HDM Der p1 and Der p5. There was a strong negative association between HLA-DPB1*0201 allele and IgE responsiveness to Der p1, Der p2 and Der p5 (Odd’s ratio/Pc were 0.3/0.001, 0.46/0.056, 0.35/0.01 respectively). As all the subjects showed positive HDM allergen-specific IgG antibodies irrespective of the presence of allergen-specific IgE, the HLA-DPB1 alleles were associated with HDM allergens-specific IgE but not IgG responsiveness. It is interesting to note that a single HLA-DPB1 allele was found to be associated with IgE responsiveness toward three HDM allergens of completely different biochemical characteristics, indicating that HLA-DP antigens might serve as restriction elements in allergen priming process and to determine the dichotomy of HDM allergen-specific Th response. In addition, it is possible that other genetic loci closely linked to HLA-DPB1 might predispose subjects to IgE-responsiveness toward HDM allergens. The HLA-DMB gene, which is involved in peptide loading in MHC II and antigen presentation, is located between HLA-DPB1 and HLA-DOB loci. Polymorphism of HLA-DMB gene was analyzed by PCR/SSOPH and correlated to IgE responsiveness toward HDM allergens. There was no association between HLA-DMB alleles and HDM allergen-specific IgE responsiveness noted. It suggested that there might be other genetic loci that determine the IgE responsiveness to HDM and that should be positioned centromeric to HLA-DPB1 gene. The second part of the thesis investigated the immunological parameters associated with the clinical manifestation of asthma. Although allergen-specific Th2 cells, the Th2 cytokines, and allergen-specific IgE are important in the pathogenesis of the development of asthma. Some of the asthmatic children grow out of the disease after adolescence. The immunological basis underlying the improvement of asthmatic clinical manifestation remained undefined. For investigation of the possible factors contribute to the improvement of clinical manifestation of asthma, we recruited 49 adult subjects with history of HDM-sensitive asthma and studied their T cell response to Der p2. Among these subjects, Twenty three (46.9%) had improved clinical manifestation (group AS/N) with no asthmatic attack for at least 24 months, whereas 26 (53.1%) of them had recurrent asthmatic attacks (group AS/Y) and had at least one asthmatic attack within 12 months. The level of sera Der p2-specific IgE and IgG antibodies did not show correlation with the clinical manifestation. To investigate the Der p2-specific Th cytokines IFNγ/IL4 production, PBMCs were collected and stimulated with rDer p2 or rDer p2 plus PMA/Ionomycin and subjected to intracellular cytokine staining. It revealed that the proportion of IFNγor IL4-producing PBLs in response to Der p2 stimulation did not differ between asthmatic subjects with different clinical manifestation. Studies in this thesis indicated that polymorphisms in certain HLA-class II genes did affect the outcome of Th dichotomy and the immune response toward HDM allergens. However, to investigate the role that allergen-specific IgE/IgG and Th cytokines played in the progression of the adulthood mite-sensitive asthma, we were not able to find serum allergen-specific IgE/IgG and Th cytokines produced by peripheral blood lymphocytes correlated to clinical manifestations of asthma. As the serum antibody as well as the cytokines produced in PBLs might not reflect the actual status within the inflammatory airway. It indicated that investigation in other cell types, cytokines, or chemokines involved in the airway inflammation in allergic asthma would be the future trend of research.
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Mueller, Geoffrey Andrew. "The molecular and antigenic structure of the major house dust mite allergen Der p 2 /." Diss., 1998. http://wwwlib.umi.com/dissertations/fullcit/9916261.

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27

Liao, En Chih, and 廖恩慈. "House Distribution and Seasonal Abundance of Dust Mites in Three Cities in Taiwan and the Sequence Analyses of the Internal Transcribed Spacers of Ribosomal DNA in four species of Dust Mites." Thesis, 2001. http://ndltd.ncl.edu.tw/handle/76671785761533871166.

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碩士
國立陽明大學
寄生蟲學研究所
89
From November, 1999 through October, 2000, house dust mites were surveyed in three urban areas of Taiwan, Taipei, Taoyaun and Taichung. Thirty-three households of healthy inhabitants and seventeen households with patients suffering from allergic hypersensitivity were included in this study. Data indicated that the density of house mites positively correlated with room temperature and relative humidity. Dermatophagoides pternyssinus and D. farinae appeared to be the most dominant species among seven species of mites. These mites appeared mostly in collections from pillow, bed covering and mattress within the bedroom. Statistical analyses was made to test the significance among mite densities for different parameters, which included nature of materials of household items, frequency of onset of air condition and dehumidifier, and the weekly clean effect. Data revealed that woolen carpet and bed covering carried more mites than other materials. They also suggested that increasing use of air condition and dehumidifier, and increasing of cleaning activity significantly lowered population. Polymerase chain reaction was used to amplify the DNA fragment containing ITS-1, 5.8S and ITS-2 for four species of mites that usually collected from house dust. These mites included colonies of D. farinae, D. pteronyssinus, two collected colonies of Tyrophagus putrescentiae and Chelytus eruditis. These fragments were cloned and sequenced. Sequence data indicate that ITS-1 appears to be longer than that of ITS-2 in these four mites. Because the length of the ITS-1 and ITS-2 differed among with species, it could be regarded as a molecular marker for species identification. Homology of nucleotide sequence homology was higher revealed between closely related species of D. farinae and D. pteronyssinus and lower among distantly related ones. Moreover, one EcoR1 cutting site exists in the sequence of D. farinae but not in D. pteronyssinus. A ratio of 1% variation was found within the sequences of two colonies of T. putrescentiae.
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Nkala, Bongani Alphouse. "Toxicological analysis of house dust collected from selected Durban residental buildings." Thesis, 2009. http://hdl.handle.net/10413/7492.

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Indoor air quality is described as the chemical, physical and biological characteristics of air in a residential or occupational indoor environment. In residential settings, there are many contributions to indoor pollution levels namely; human activities, biological sources and outdoor air. There has been increased focus on house dust due to its potential to contain biological and chemical pollutants in indoor environments. These have the potential to cause harm to human health. The purpose of this study was to conduct toxicological analysis of house dust collected from inside selected Durban residential buildings. The objectives of this study were to isolate, identify and quantify mould occurrence in house dust samples; to measure the occurrence of heavy metals (arsenic, lead and mercury) in house dust; and to analyse the cytotoxicity of house dust on human lung bronchus carcinoma epithelial line (A549) and human lung bronchus virus transformed epithelial cell line (BBM). One hundred and five house dust samples were obtained from households that participated in the South Durban Health Study. In each home, a sample of settled dust was collected, using standardized protocols, then sieved and individually packed into polystyrene bags. The samples were taken from three surface areas namely; living room couches, bed mattresses, and carpets. Well documented methods were used for the isolation, identification and quantification of mould. The samples for heavy metals analysis were sent to Umgeni Water (chemistry laboratory, Pietermaritzburg) where standardised methods were used. Human cell lines were treated with five different dilutions of each house dust extract. Cell viability was assessed using the MTT assay. Toxic effects of house dust extract were analyzed, following house dust extract treatment and cells were stained with double dye (annexin-V- and propidium iodide) and analysed with flow cytometry, and fluorescent microscope. Cytokines were analysed by Microbionix (Neuried, German) using a Luminex®100 plate reader for multiplex human cytokines analysis. There were (n=128) mould types isolated and (n=105) were identified, of which (n=10) were predominately isolated moulds. This was further confirmed by Allerton Provincial Laboratory in Pietermaritzburg. Among the isolated genera in all three surface areas, Rhizopus spp and Penicillium spp were widely distributed throughout surface areas in greater proportion. The overall highest mean which was reported in this study and expressed in colony forming unit per gram (CFU/g) for Penicillium spp ranged (3400 - 62316 CFU/g) obtained from living room couches, followed by Rhizopus spp (5200 - 15990 CFU/g). The mould results were compared with the South African Occupational Health and Safety Act (OHSA) 85 of 1993 as amended suggested guidelines of 1,000, 000 CFU/g. The findings of this study suggest the moulds in the homes studied were below the suggested guideline. However, this does not imply that the indoor conditions are unsafe or hazardous. Instead, the findings act as an indicator of moulds presence indoors. The type of airborne mould, its concentration and extent of exposure and the health status of the occupants of a building will determine the health effects on an individual. Heavy metals were detected in the dust in the following ascending order: arsenic (As) ranged from 1.3 ug/g -18.4 ug/g (mean, 4.26 ug/g), lead (Pb) ranged from 28.0 - 872 ug/g (mean 171.66 ug/g), and mercury (Hg) ranged from 0.6 -19.0 ug/g (mean, 2.22 ug/g). The mean concentration of lead in the dust was within the range of Canadian National Classification guidelines on residential contamination (500 ug/g). There was numerous numbers of samples in this study that exceeded these guidelines. The mean concentration of arsenic was within residential soil guidelines (20 ug/g). Mercury was within limits when compared with Global Hg project guidelines of soil/residential (6.6 ug/g), thought some of samples were notably above this mean. The ability of house dust extract to lower the cell viability which was slightly above 80% (prior treatment) to less than 50% (post treatment) in both cells was observed in this study. The findings in this study showed that dust extract are toxic to human cell lines, and cells undergone a degree of apoptosis and necrosis 62% (A549) and 99% (BBM). The cytokines serve an important role in the non-specific defence external against insults. It was observed that A549 cells up-regulated the release of IL-6 and IL-8 pro-inflammatory cytokines and under-regulated the release of other cytokines analysed (IL-4, IL-13, and TNF-a). BBM cells released IL-4, IL-8 and IL-13 within limit of detection. The presence of moulds in these sampled indoor household dusts, which is comparable with findings elsewhere indoors, show that moulds act as an indicator for building conditions such as dampness, which supports mould growth. Individuals, whether they are sensitized or not, may develop allergic reactions towards spores, thus the elevated numbers of spores quantified in this study are of concern. Some of the heavy metals reported in this study were higher or marginally higher than international norms and guidelines. The findings in this study strongly suggest that house dust extract is toxic to human lung cell lines. It must be noted, however, that this study may not reflect all that happens when a human lung is exposed to house dust. The findings of this study could contribute to the development of South African indoor air guidelines. In conclusion further study needed to be undertaken with respect to air pollution disease such as allergic; the reason being this study shown the reduced expression of cytokines that are involved in allergic inflammation.
Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2009.
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Boor, Brandon Emil. "Studies on particle resuspension, infant exposure, and the sleep microenvironment." Thesis, 2015. http://hdl.handle.net/2152/31356.

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Understanding the transport of particulate and gaseous indoor air pollutants from source to exposure is paramount to improve our understanding of the complexities of the built environments in which we spend the majority of our time. This dissertation offers new insights on particle resuspension from indoor surfaces, infant exposure to organic contaminants released from crib mattresses, and the dynamics of pollutant transport and human exposure while sleeping. Particle resuspension is the physical process by which settled particles detach from a surface and become airborne through application of various aerodynamic and mechanical removal forces. Resuspension is an important indoor source of coarse mode particles (> 1 µm in diameter) and can be a source mechanism for biological matter and organic contaminants that accumulate in house dust. Settled dust deposits on indoor surfaces can vary considerably in their structure and mass loading, yet little is known as to how these parameters affect resuspension. Through wind tunnel experiments, this research demonstrates that the deposit structure (monolayer or multilayer) can have a significant impact on the number of particles that aerodynamically resuspend. Furthermore, this dissertation presents the first full-scale experimental chamber study to show that human body movements in bed can resuspend settled mattress dust particles. An indoor aerosol model was utilized to provide a mechanistic understanding of the impact of movement intensity, surface vibrations, bedroom ventilation rate, and dust loading on the resuspension flux and intake fraction of resuspended particles. Infants spend most of their time sleeping and are likely to be exposed to elevated concentrations of chemicals released from their crib mattresses. Through a combination of chamber experiments and solvent extractions, this research shows that infant crib mattresses can emit a variety of volatile organic compounds (VOCs) and contain numerous chemical additives, including phthalate and alternative plasticizers, flame retardants, and unreacted isocyanates. Additionally, this study discovered that infants are exposed to approximately twice the concentrations of VOCs in their breathing zones as compared to the bulk bedroom air, due to their close proximity to the source.
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