[Truncated abstract] Respiratory system impedance (Zrs) is commonly measured at low to medium frequencies (0.5 - 40 Hz) to infer structural and physiological information about the respiratory system. Coupled with the use of mathematical models of the lungs, Zrs has been used to partition the behaviour of the conductive airways and the respiratory tissues. High-frequency (HF) Zrs beyond 100 Hz has been comparatively less studied and understood. Past work has revealed spectral features at high frequencies termed antiresonances, marked by peaks in the real part of Zrs, often coinciding with zero-crossings in the imaginary part. It has been shown that the first occurrence of antiresonance in humans primarily reflects the contribution of the airways, and is a property of sound wave propagation in the airways. Also, the first antiresonance is altered in diseases such as chronic airflow obstruction, and wheeze in infants. The main aim of this project is to shed further understanding about the first antiresonance, via the behaviour of two parameters characterising this feature of the HF spectrum: the frequency at which the first antiresonance occurs, far,1, and the magnitude of the real part of Zrs at this frequency, Rrs(far,1). In our studies, Zrs is measured as an input impedance using the forced oscillation technique with a loudspeaker-in-box and wavetube setup, and employing pseudorandom frequency signals. We studied the effects of altered lung conditions, first in an animal model, then progressed on to humans. v vi In the rat, we found that both far,1 and Rrs(far,1) tended to decrease together with increasing lung volume. With methacholine(MCh)-induced bronchoconstriction, rats showed increases in far,1 and Rrs(far,1) with increasing MCh dose, but these occurred at higher doses compared to increases in airway resistance. The changes in these HF parameters were independent of the changes in tissue properties. ... It was found that in a group of patients with emphysema, VDRrs(far,1) was significantly more negative, potentially due to alterations to airway dimensions and wall properties. Furthermore, VDRrs(far,1) was correlated with extent of obstruction and hyperinflation, suggesting a relationship with severity of emphysema. These results show that the first antiresonance reflect changes in the airways, and its measurement shows promise as a clinical tool, in its potential as an easy-to-perform assessor of conditions in which the airways are altered. Keywords: antiresonance, respiratory input impedance, high frequencies, emphysema

Made available in DSpace on 2014-06-11T19:23:32Z (GMT). No. of bitstreams: 0 Previous issue date: 2007-03-22Bitstream added on 2014-06-13T18:50:44Z : No. of bitstreams: 1 sanchez_ff_dr_botfm.pdf: 1771868 bytes, checksum: 429488c50f3fd192853726c00c1fd7c1 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A doença pulmonar obstrutiva crônica (DPOC) apresenta manifestações sistêmicas e, dentre entre elas, as alterações nutricionais são bastante evidentes. A perda de peso e o índice de massa do corpo (IMC) foram os primeiros indicadores do estado nutricional relacionados ao prognóstico em pacientes com DPOC. Entretanto, estudos recentes ressaltam a maior prevalência da depleção da massa magra do corpo (MMC) nestes pacientes. Embora algumas repercussões da depleção da MMC em pacientes com DPOC sejam conhecidas, as informações sobre a distribuição, mecanismos e características das alterações parecem contraditórios. Alguns estudos sustentam a idéia de que a fraqueza muscular é proporcional à perda de massa muscular. Por outro lado, os resultados de estudos recentes sugerem que as alterações qualitativas ou funcionais são mecanismos, adicionais à atrofia, envolvidos na disfunção muscular de pacientes com DPOC. Outro aspecto contraditório é o envolvimento de diferentes grupos musculares; alguns estudos mostram que a função dos músculos dos membros superiores (MMSS) encontra-se relativamente preservada enquanto outros sugerem a existência de fraqueza muscular generalizada. O impacto da disfunção muscular na endurance e na tolerância ao exercício também é controverso. Os objetivos deste estudo foram avaliar a prevalência e as repercussões da depleção da massa muscular sistêmica e localizada em pacientes com DPOC. Foram avaliados sessenta e dois pacientes com DPOC atendidos no Ambulatório de Pneumologia da Faculdade de Medicina de Botucatu – UNESP; vinte e seis pacientes (VEF1: 49,0±18,0%) com depleção de MMC e trinta e seis pacientes... / Chronic obstructive pulmonary disease (COPD) presents significant systemic manifestations and, among them, the nutritional alterations are very important. Loss of body weight and the body mass index (BMI) were the first indicators of the nutritional status related to the prognosis in patients with COPD. However, recent studies have shown the predominance of the fat-free mass (FFM) depletion in these patients. Although some consequences of FFM depletion are well known, information regarding the distribution, mechanism and characteristics of the modification remains unclear. Some researches support the idea that the muscular weakness is proportional to the loss of FFM. On the other hand, results of recent investigations suggest that either the qualitative or functional alterations are mechanisms, additional to the atrophy, involved in the muscular dysfunction in patients with COPD. Another controversial aspect is related to the involvement of different muscular groups; some findings show that the function of the upper-limb muscles are relatively preserved while others suggest the existence of generalized muscular weakness. The impact of the muscular dysfunction in the endurance function and in exercise tolerance is also controversial. The goals of this research were to evaluate the prevalence and the consequences of the systemic and peripheral FFM depletion in patients with COPD. Sixty-two patients with COPD attending to the respiratory outpatient clinic (Botucatu School of Medicine UNESP) were included in the study; twenty-six (FEV1: 49.0l18.0%) with FFM depletion and thirty-six (FEV1: 59.8l24.4%) without FFM depletion. The depletion was characterized by the presence of FFM index <15 kg/m2, for women, and <16 kg/m2, for men. Patients were, in average, 64.0l9.3 years old and 68% were male... (Complete abstract, access undermentioned eletronic address)

Orientador: Irmã Godoy / Banca: Vitor Zuniga Dourado / Banca: José Alberto Neder / Banca: José Antônio Baddini Martinez / Banca: Sérgio Rupp Paiva / Resumo: A doença pulmonar obstrutiva crônica (DPOC) apresenta manifestações sistêmicas e, dentre entre elas, as alterações nutricionais são bastante evidentes. A perda de peso e o índice de massa do corpo (IMC) foram os primeiros indicadores do estado nutricional relacionados ao prognóstico em pacientes com DPOC. Entretanto, estudos recentes ressaltam a maior prevalência da depleção da massa magra do corpo (MMC) nestes pacientes. Embora algumas repercussões da depleção da MMC em pacientes com DPOC sejam conhecidas, as informações sobre a distribuição, mecanismos e características das alterações parecem contraditórios. Alguns estudos sustentam a idéia de que a fraqueza muscular é proporcional à perda de massa muscular. Por outro lado, os resultados de estudos recentes sugerem que as alterações qualitativas ou funcionais são mecanismos, adicionais à atrofia, envolvidos na disfunção muscular de pacientes com DPOC. Outro aspecto contraditório é o envolvimento de diferentes grupos musculares; alguns estudos mostram que a função dos músculos dos membros superiores (MMSS) encontra-se relativamente preservada enquanto outros sugerem a existência de fraqueza muscular generalizada. O impacto da disfunção muscular na endurance e na tolerância ao exercício também é controverso. Os objetivos deste estudo foram avaliar a prevalência e as repercussões da depleção da massa muscular sistêmica e localizada em pacientes com DPOC. Foram avaliados sessenta e dois pacientes com DPOC atendidos no Ambulatório de Pneumologia da Faculdade de Medicina de Botucatu - UNESP; vinte e seis pacientes (VEF1: 49,0±18,0%) com depleção de MMC e trinta e seis pacientes... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Chronic obstructive pulmonary disease (COPD) presents significant systemic manifestations and, among them, the nutritional alterations are very important. Loss of body weight and the body mass index (BMI) were the first indicators of the nutritional status related to the prognosis in patients with COPD. However, recent studies have shown the predominance of the fat-free mass (FFM) depletion in these patients. Although some consequences of FFM depletion are well known, information regarding the distribution, mechanism and characteristics of the modification remains unclear. Some researches support the idea that the muscular weakness is proportional to the loss of FFM. On the other hand, results of recent investigations suggest that either the qualitative or functional alterations are mechanisms, additional to the atrophy, involved in the muscular dysfunction in patients with COPD. Another controversial aspect is related to the involvement of different muscular groups; some findings show that the function of the upper-limb muscles are relatively preserved while others suggest the existence of generalized muscular weakness. The impact of the muscular dysfunction in the endurance function and in exercise tolerance is also controversial. The goals of this research were to evaluate the prevalence and the consequences of the systemic and peripheral FFM depletion in patients with COPD. Sixty-two patients with COPD attending to the respiratory outpatient clinic (Botucatu School of Medicine UNESP) were included in the study; twenty-six (FEV1: 49.0l18.0%) with FFM depletion and thirty-six (FEV1: 59.8l24.4%) without FFM depletion. The depletion was characterized by the presence of FFM index <15 kg/m2, for women, and <16 kg/m2, for men. Patients were, in average, 64.0l9.3 years old and 68% were male... (Complete abstract, access undermentioned eletronic address) / Mestre

No description available.

Bibliography: pages 103-119. / The aims of this study were (a) to examine the profile of hospital admissions for selected respiratory illnesses for two major hospitals in Cape Town, and (b) to analyse the association of such admissions with air pollution indicators and meteorological variables. The first part of the study investigated the admission patterns of coloured and African children under twelve years of age who were diagnosed as suffering from asthma or acute respiratory infections at two major teaching hospitals in Cape Town. Computerized hospital admission records covering the years 1988-1990 from the overnight holding wards of the Red Cross War Memorial Children's Hospital and Tygerberg Hospital were used to determine patterns with respect to diagnosis, gender, race, age and date of admission. During the three year study period, respiratory admissions at both hospitals accounted for 15 078 (47.3%) out of a total of 31 887 admissions. Acute respiratory infections accounted for 63.6% and asthma 37.4 % of these respiratory admissions. Two factors of interest were noted: (1) Considerably more males than females were admitted with both asthma and acute respiratory infections. (2) Asthma admissions to Red Cross Hospital among African children were proportionally much less than those of coloured children when compared to the proportions of admissions for acute respiratory infections. After removal of the seasonal effect, a multiple linear regression model was fitted to the data to determine the individual associations between admissions and ambient environmental variables. Significant associations were found between: (1) acute respiratory infections and oxides of nitrogen, soiling index, and temperature; (2) asthma and oxides of nitrogen (3) total admissions and soiling index, average temperature and minimum temperature (negative). The study concluded that despite generally low levels of air pollution in Cape Town, childhood respiratory admissions to Red Cross War Memorial Children's Hospital and Tygerberg Hospital were statistically significantly associated with some ambient air pollutants as well as temperature. However, given the nature of both the exposure and admissions databases, these results should be treated with caution. More representative site selections for air pollution monitors, as well as searching and controlling for possible confounding factors (i.e. indoor air pollution, parental smoking, overcrowding), would allow a better understanding of the current air pollution problem and the possible effects on the respiratory health of children in metropolitan Cape Town.

Thesis (PhD (Medicine. Internal medicine))--University of Stellenbosch, 2007. / 1.1. Background Tumors arising from the lung, pleura, or chest wall are a frequent problem in clinical pulmonary medicine. Most lesions are either infectious, neoplastic or granulomatous in nature, but a variety of other differential diagnoses must be considered. An accurate diagnosis is important because the available treatments differ substantially, and because any delay will impair the prognosis in potentially curable patients with lung carcinoma. The investigations involve the disciplines of radiology, pulmonology, surgery, microbiology, and anatomical pathology and consume a respectable amount of resources. The aim of the work covered in this thesis was to optimize the available diagnostic methods for the routine use in a health care setting with limited resources. 1.2. Methods The general idea of this work was to identify conventional sampling methods that could be developed further to become more useful for the diagnosis of chest tumors in a low resource health care setting. The key method was research performed: a) to revise and expand the indication for a sampling method, b) to technically improve the sampling process, and c) to optimize sample transport, preparation and analysis in collaboration with the analytical laboratory. 1.3. Results A list of invasive diagnostic procedures, imaging methods and analytical processes were developed, evaluated and integrated into clinical practice. A) transbronchial needle aspiration, B) transthoracic cutting needle biopsy, C) transthoracic fine needle aspiration, D) transthoracic ultrasound, and E) rapid on-site evaluation of needle aspirates by a cytopathologist. Five studies pertaining to this thesis were published in international peerreviewed journals: â ¢ Safety and yield of ultrasound-assisted transthoracic biopsy performed by pulmonologists (Respiration 2004;71:519-22) This paper established that ultrasound-assisted transthoracic biopsy performed by pulmonologists is feasible, safe, practical, low-cost and has a high yield. â ¢ Utility of rapid on-site evaluation of transbronchial needle aspirates (Respiration 2005;72:182-8) This paper demonstrated the economical advantages of on-site evaluation of transbronchial specimens in a low-resource setting. â ¢ Transbronchial needle aspirates: comparison of two preparation methods (Chest 2005;127:2015-8) This paper demonstrated that preparing smears on-site has a far better yield than pooling samples into a vial. This means that the yield is improved over the current standard at no additional cost. â ¢ Transbronchial needle aspirates: how many passes per target site? (European Respiratory Journal 2007;29:112-6) This paper investigated the most economical and effective approach to serial sampling with transbronchial needle aspiration during flexible bronchoscopy. â ¢ Ultrasound assisted transthoracic biopsy: fine needle aspiration or cutting needle biopsy? (European Respiratory Journal 2007;29:357-62) This paper compared two common methods of sampling and demonstrates that the less expensive method is sufficient in the majority of cases. 1.4. Conclusion This work has impacted on current practice in multiple ways. Conventional methods have been optimized by improving technical factors and with the integration of interdisciplinary collaboration. The initiated research is ongoing with the aim to achieve continued technical and economical improvements in the diagnosis of chest tumors.

Chan, Wai Kiu. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 233-256). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstract and appendix also in Chinese.

Amongst respiratory diseases, inflammatory lung diseases constitute a major part of public <p>health problem. As a consequence, investigating the immune mechanisms that contribute to <p>the pathogenesis of these diseases is essential to identify candidate targets for the <p>development of new therapeutic drugs. Furthermore, over the past 20 years, the growing awareness <p>that purinergic signalling events shape the immune and inflammatory responses to infection and <p>allergic reactions warranted the development of animal models to assess their importance in vivo in <p>acute lung injury and chronic airway diseases. The field of purinergic inflammation formulated the <p>unifying concept that ATP is released as a «danger signal» to induce inflammatory responses upon <p>binding purinergic receptors.<p>According to these elements, we began in 2007 to evaluate lung inflammation in mice deficient for <p>the P2Y2 purinergic receptor in TH2 and TH1 models. The most convincing evidence that the P2Y2<p>receptor is engaged during alarm situations comes from studies related to cystic fibrosis and asthma. <p>Indeed, chronic respiratory diseases are commonly associated with elevated airway ATP <p>concentrations, as reported in cystic fibrosis, but also in idiopathic pulmonary fibrosis and chronic <p>obstructive pulmonary disease (COPD) patients, and they are raised by allergens in asthmatic <p>patients.<p>First, we demonstrated a significant role of the P2Y2R in a TH2-ovalbumin(OVA)-induced asthma <p>model. We observed that eosinophil accumulation, a distinctive feature of lung allergic inflammation, <p>was defective in OVA-treated P2Y2-deficient mice compared with OVA-treated wild type animals. <p>Interestingly, the upregulation of VCAM-1 was lower on lung endothelial cells of OVA-treated P2Y2 <p>knockout mice compared with OVA-treated wild type animals. Adhesion assays demonstrated that <p>the action of UTP on leukocyte adhesion through the regulation of endothelial VCAM-1 was <p>abolished in P2Y2-deficient lung endothelial cells. Additionally, the level of soluble VCAM-1, reported <p>as an inducer of eosinophil chemotaxis, was strongly reduced in the bronchoalveolar lavage fluid of <p>P2Y2-deficient mice.<p>Secondly, we studied the consequences of P2Y2R loss in lung inflammation initiated after pneumonia <p>virus of mice (PVM) infection in collaboration with the group of Pr. Daniel Desmecht (ULg). We <p>demonstrated here that P2Y2<p>-/-<p>mice display a severe increase in morbidity and mortality rate in <p>response to PVM. Lower survival of P2Y2<p>-/-<p>mice was not correlated with excessive inflammation <p>despite the higher level of neutrophil recruiters in their broncho-alveolar fluids. Interestingly, we <p>observed lower numbers of dendritic cells, CD4<p>+<p>T cells and CD8<p>+<p>T cells in P2Y2<p>-/-<p>mice compared to <p>P2Y2<p>+/+<p>infected lungs. Lower level of IL-12 and higher level of IL-6 in broncho-alveolar fluid support <p>an inhibition of Th1 response in P2Y2<p>-/-<p>mice. Quantification of DC recruiter expression revealed <p>comparable IP-10 and MIP-3& / Doctorat en Sciences biomédicales et pharmaceutiques / info:eu-repo/semantics/nonPublished

Chemoattractant agents play a crucial role in the initiation of immune responses, by regulating the traffic and function of leucocyte populations. Their receptors are therefore considered as potential targets for the development of new therapies in the fields of cancer and inflammatory diseases. ChemR23, a previously orphan receptor discovered in the laboratory, is structurally related to receptors for chemoattractant agents. It is expressed on immature myeloid and plasmacytoid dendritic cells (mDCs and pDCs respectively), as well as on adipocytes, macrophages, NK and endothelial cells. Chemerin, the endogenous ligand of ChemR23, is abundant in various human samples originating from inflammatory diseases, including pleural effusions. Chemerin is secreted as an inactive precursor, prochemerin, and is activated by the removal of six or seven amino-acids from its carboxy-terminus by serine proteases, such as as cathepsin G and elastase. Chemerin acts as a chemoattractant agent of low nanomolar potency for macrophages, immature mDCs and pDCs. It is however more active on pDCs, in line with the higher expression of ChemR23 on these cells. pDCs possess important immunoregulatory properties in lung diseases, and their ability to secrete large amounts of type I interferon (IFN) upon viral infection makes them crucial players in anti-viral immunity.<p>According to these elements, and to the role of neutrophils in the physiopathology of many inflammatory lung diseases and in the generation of active chemerin, we began in 2007 to study the role of chemerin and its receptor ChemR23 in inflammatory lung diseases. We first characterized the mouse chemerin/ChemR23 system, and described that this system was very similar to the human one, in terms of distribution, pharmacology and functional properties. We then used wild type mice (WT) and mice invalidated for the receptor (ChemR23-/-) in various models of inflammatory lung diseases, including asthma, lung fibrosis, viral pneumonia, and acute lung injury. <p>Whereas the asthma and lung fibrosis models did not allow to demonstrate a significant role of the chemerin/ChemR23 system (possibly as a result of the lack of production of active chemerin in these models), infection by either the Pneumonia Virus of Mice (PVM), the mouse counterpart of human RSV, or by a murinized H1N1 influenza strain resulted in a significantly higher mortality rate in ChemR23-/- mice as compared to their WT counterparts. Using the PVM-induced pneumonia model, we observed that the excessive mortality of knock-out mice is caused by an inadequate and excessive innate immune response characterized by a massive recruitment of neutrophils to the lungs, associated with a delayed viral clearance and lower type I IFN synthesis. This latter observation suggested an impairment of pDC recruitment, according to the important contribution of pDCs to the production of type I IFNs in viral diseases, and the role of chemerin in the recruitment of these cells. We indeed confirmed a lower recruitment of pDCs in the lung of infected ChemR23-/- mice, as compared to WT mice. However, experiments of adoptive transfert and depletion of pDCs failed to proof a link between impaired pDC recruitment and the excessive morbidity and mortality observed in ChemR23-invalidated mice. <p>In parallel, we studied the role of the chemerin/ChemR23 system in the control of innate immune responses, by using a model of acute lung injury caused by the intra-tracheal instillation of bacterial lipopolysaccharide (LPS). In this model, administration of recombinant chemerin together with LPS in WT mice resulted in a significant (about 50%) reduction of neutrophil recruitment to both lung parenchyma and airways. Assessment of pro-inflammatory cytokines and chemokines in broncho-alveolar lavage fluids confirmed this anti-inflammatory effect of chemerin, which was ChemR23-dependent, as the inflammatory response of ChemR23-/- mice was unaffected by chemerin. In our hands, chemerin does not modulate macrophage functions, in contrast to data recently published by other groups, attributing anti-inflammatory effects of chemerin or chemerin-derived peptide to the modulation of macrophage activation and phagocytosis. Other hypotheses that could take our observations into account are presently investigated, including an immunomodulatory role of chemerin on lung epithelial or endothelial cells, and/or the ChemR23-dependent recruitment of subtypes of macrophages or other myeloid cells endowed with immunosuppressive properties. <p>In conclusion, our studies characterized the mouse chemerin/ChemR23 system and highlighted the role of this system in the physiopathology of some inflammatory lung diseases. Our results suggest that the chemerin/ChemR23 system might be considered as a potential therapeutic target for the development of future anti-infectious and anti-inflammatory therapies, particularly for viral pneumonia, which represent a major public health problem, as well as for acute respiratory distress syndrome (ARDS) following severe acute lung injuries.<p> <p><p>Les agents chimioattractants jouent un rôle fondamental dans l’initiation des réponses immunes en régulant le trafic et la fonction des populations leucocytaires. Leurs récepteurs constituent dès lors des cibles d’intérêt pour le développement de traitements contre les maladies inflammatoires et le cancer. Le laboratoire d’accueil a identifié le récepteur ChemR23, exprimé à la surface des cellules dendritiques myéloïdes (mDCs) et plasmacytoïdes (pDCs) immatures, des macrophages, des cellules NK, des adipocytes, et des cellules endothéliales. Le ligand endogène du récepteur ChemR23, la chémérine, est présent en abondance dans divers échantillons pathologiques d’origine inflammatoire. La chémérine est produite sous la forme d'un précurseur inactif, la prochémérine, qui nécessite pour devenir active le clivage protéolytique de six ou sept acides aminés à son extrémité carboxy-terminale. La chémérine induit le chimiotactisme des macrophages et des DCs immatures, et en particulier des pDCs immatures en accord avec l’expression plus importante de ChemR23 par les pDCs. Les pDCs jouent un rôle immunorégulateur important en pathologie pulmonaire, en particulier dans la physiopathologie des pneumonies virales, par leur capacité à produire d’importantes quantités d’interféron (IFN) de type I.<p>Compte tenu de ces éléments et du rôle des polynucléaires neutrophiles dans de nombreuses pathologies pulmonaires, ainsi que dans la génération de chémérine active à partir de son précurseur, nous avons débuté en octobre 2007, l’étude du rôle de la chémérine et de son récepteur ChemR23 dans le contrôle des pathologies pulmonaires inflammatoires. Nous avons tout d’abord caractérisé le système chémérine/ChemR23 chez la souris et avons montré que ce système présentait des caractéristiques similaires à celles décrites chez l’homme, en termes de distribution, de pharmacologie et de propriétés fonctionnelles. <p>Ensuite, nous avons comparé des souris sauvages et invalidées pour le récepteur ChemR23 (ChemR23-/-) dans divers modèles de pathologies pulmonaires. Les modèles d’asthme et de fibrose pulmonaire induite par instillation de bléomycine ou de silice n’ont pas permis de mettre en évidence un rôle important du couple chémérine/ChemR23, peut-être en raison de l’absence de génération de forme active de chémérine dans ces modèles. En revanche, l’administration de deux agents viraux différents, le PVM (Pneumonia Virus of Mice), l’équivalent murin du RSV humain, et un virus de l’influenza H1N1 murinisé, a résulté en un taux de mortalité 40% plus élevé pour les souris ChemR23-/- par rapport à leurs homologues sauvages. En utilisant le modèle de pneumonie induite par le PVM, nous avons montré que cette différence de mortalité est causée par une réponse immune inappropriée et excessive, associée à une réduction de l’élimination du virus, ainsi qu’à un déficit de synthèse d’IFN de type I. Les pDCs, dans un contexte d’infection virale, sont capables de synthétiser d’importantes quantités d’IFN de type I, et nous avons mis en évidence un déficit relatif de recrutement en pDCs chez les souris ChemR23-/- infectées. Néanmoins, les expériences de transfert adoptif et de déplétion de pDCs n’ont pas permis de lier ce défaut de recrutement à l’excès de morbidité et de mortalité observé chez les souris ChemR23-/- infectées. <p>En parallèle, le rôle de ce couple ligand-récepteur dans le contrôle des réponses immunitaires innées a été étudié dans un modèle de pneumopathie aiguë induite par instillation intra-trachéale de lipopolysaccharide (LPS). Dans ce modèle, l’administration simultanée de chémérine recombinante avec le LPS entraîne chez les souris sauvages une diminution significative (environ 50%) du nombre de polynucléaires neutrophiles recrutés dans les voies aériennes et dans le parenchyme pulmonaire, ainsi qu’une importante diminution de synthèse de cytokines pro-inflammatoires. Cet effet anti-inflammatoire de la chémérine est dépendant de ChemR23, et ne semble pas être secondaire à un effet de la chémérine sur l’activation des macrophages, contrairement à certaines données publiées récemment par d’autres groupes. D’autres hypothèses permettraient cependant de prendre en compte ces observations, notamment un effet de la chémérine sur les cellules épithéliales et/ou endothéliales pulmonaires, ainsi que sur le recrutement de sous-populations de macrophages ou d’autres cellules myéloïdes possédant des propriétés immunosuppressives. Des expériences complémentaires ont été initiées afin de tester ces hypothèses. <p>En conclusion, après avoir caractérisé le système chémérine/ChemR23 chez la souris, nos études ont permis de mettre en évidence le rôle de ce couple ligand/récepteur dans la physiopathologie de certaines pneumopathies inflammatoires, ouvrant ainsi de nouvelles perspectives thérapeutiques, en particulier pour le traitement des pneumopathies virales, qui constituent un problème de santé publique majeur, ainsi que des syndromes de détresse respiratoire aiguë (ARDS). / Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

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