No description available.

Universiẗat, Diss., 2006--Giessen.

Zugl.: Giessen, Univ., Diss., 2006

Afecções do sistema respiratório estão entre as mais frequentes em equinos, sendo uma das principais causas de baixo desempenho em animais atletas. Dentre essas doenças pode-se citar as afecções inflamatórias das vias aéreas, que apresentam uma prevalência considerável e afetam a saúde e vida atlética do animal. Um dos principais meios de atuação terapêutica no tratamento dessas doenças é a administração de medicamentos corticoides, sendo a dexametasona um dos principais fármacos dessa classe utilizados na medicina equina. No tratamento de doenças semelhantes em humanos preconiza-se a administração dos fármacos por via inalatória, otimizando assim o seu efeito terapêutico e diminuindo os efeitos colaterais. Em equinos existem trabalhos que mostram a deposição pulmonar de medicamentos quando administrados por via inalatória, no entanto, não foram encontrados estudos nesse sentido utilizando a dexametasona. O objetivo desse estudo foi avaliar a deposição pulmonar de dexametasona quando administrada por via inalatória em equinos, bem como fatores que possam interferir no seu nível de deposição e a concentração plasmática do fármaco quando administrada por essa via. Para isso foram utilizados seis equinos que foram submetidos à inalação com dexametasona duas vezes, cada uma utilizando um veículo diferente (aquoso ou oleoso) na formulação do fármaco, e quatro animais foram utilizados para o grupo controle, sendo submetidos à inalação somente com o veículo. Após cada inalação foi realizado um lavado broncoalveolar (LAB) e coletas sanguíneas seriadas para quantificação da dexametasona. Após a inalação o fármaco foi identificado nas amostras de LAB dos animais nos grupos tratados. Não houve diferença significativa entre os veículos utilizados e houve diferença entre os animais agitados e os animais calmos, sendo que os primeiros apresentaram uma concentração significativamente maior de dexametasona no LAB. O fármaco não foi identificado no plasma dos animais. A dexametasona quando administrada via nebulização pneumática atinge a região de bronquíolos e alvéolos respiratórios em equinos, principalmente os de comportamento agitado, e não atinge níveis plasmáticos significativos / Disorders of the respiratory system are among the most frequent deseases in horses and one of the main causes of low performance in athletic animals. Inflammatory diseases of the airways should be mentioned due to its considerable prevalence and to affect the health and athletic life of the animal. One of the main ways of therapeutic action of these diseases is the administration of corticosteroid drugs, being dexamethasone one of the main drugs used in equine medicine. In the treatment of similar diseases in humans it is recommended the administration of drugs by inhalation, which optimizes its therapeutic effect and reduces side effects. In horses, there are studies that show the pulmonary deposition of drugs when administered by inhalation, however, there are no studies using dexamethasone. The aim of this study was to evaluate the pulmonary deposition of dexamethasone when administered by inhalation in horses, as well as factors that may interfere with their level of deposition and the plasma concentration of the drug when administered by inhalation. To that, it was used six horses that were submitted to inhalation of dexamethasone twice, each one using a different vehicle (aqueous or oily) in the drug formulation, and four animals were used as control group, being submmited to inhalation just with the vehicle. After each inhalation a bronchoalveolar lavage (BAL) and serial blood collections for quantification of dexamethasone were performed. After the inhalation, the drug was identified in BAL samples from the animals of the treated groups. There was no significant difference between the vehicles used and there was difference between the agitated animals and calm animals, and the first ones had a significantly higher concentration of dexamethasone in the BAL. The drug was not identified in the plasma of animals. Dexamethasone, when administered via nebulization air, reaches the bronchioles region and respiratory alveoli in horses, especially the agitated behavior ones, and it does not affects plasma levels

No description available.

The objective of this study was to purify IgG from commercially available hyperimmune Rhodococcus equi plasma and to assess the delivery of IgG as an aerosol to the equine lung. IgG was purified from plasma, and the IgG concentration of both the plasma and the purified IgG was determined by ELISA. The purified IgG was aerosolized using a vibrating mesh nebulizer and aerosol characterization was performed using cascade impaction. The purified IgG was nebulized to six healthy adult horses in order to assess the efficacy of pulmonary delivery and safety of administration. Bronchoalveolar fluid was retrieved endoscopically using a low volume technique prior to aerosolization (time 0) and at 0.5, 4 and 24 hours post aerosolization. The BAL fluid IgG concentration was determined and cytologic analysis was performed. The IgG concentrations of the plasma and purified IgG were 2,175 mg/dL and 1,145 mg/dL, respectively. The MMAD of the purified IgG aerosol was 4.7 microns. The mean BAL fluid IgG concentration increased 61% from 19.33 µg/dL at time 0 to 31.5 µg/dL at 0.5 hours, but this increase was not significant (P=0.603). No significant change was observed in inflammatory cell numbers over time or at any time point during the study. This study demonstrated that IgG antibodies were purified at a concentration acceptable for nebulization, and that the nebulization unit generated aerosol particles from the IgG solution of appropriate size for pulmonary delivery. Nebulization of purified IgG to adult horses was well tolerated and caused no local or systemic adverse effects. / Master of Science

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 5 uppsatser.

Actinobacillus pleuropneumoniae est l’agent étiologique de la pleuropneumonie porcine. La bactérie se transmet par voies aériennes et contacts directs. Plusieurs facteurs de virulence ont été identifiés, nommément les polysaccharides capsulaires, les lipopolysaccharide, les exotoxines ApxI à IV et de nombreux mécanismes d’acquisition du fer. Aucun vaccin efficace contre tous les sérotypes de la bactérie n’a encore été élaboré. Afin de mieux comprendre de quelle façon A. pleuropneumoniae régule la transcription de ses nombreux facteurs de virulence et de découvrir de nouvelles cibles potentielles pour l’élaboration de vaccins efficaces, le profil transcriptomique de la bactérie a été étudié dans des conditions simulant l’infection ainsi qu’à la suite d’une infection naturelle aiguë chez l’animal. Des biopuces de première et de seconde génération (AppChip1 et AppChip2) comportant respectivement 2025 cadres de lecture ouverts (ORF) de la version préliminaire du génome d’A. pleuropneumoniae sérotype 5b souche L20 et 2033 ORF de la version finale annotée du même génome ont été utilisées. Dans un premier temps, des expériences réalisées dans des conditions de concentration restreinte en fer ont permis d’identifier 210 gènes différentiellement exprimés, dont 92 étaient surexprimés. Plusieurs nouveaux mécanismes d’acquisition du fer ont pu être identifiés, incluant un système homologue au système YfeABCD de Yersinia pestis, impliqué dans l’acquisition du fer chélaté, ainsi que des gènes homologues aux composantes du système HmbR de Neisseria meningitidis impliqué dans l’acquisition du fer à partir de l’hémoglobine. Dans des conditions de culture permettant la formation de biofilms, les gènes tadC et tadD d’un opéron tad (« tight adherence locus ») putatif, les gènes pgaBC impliqués dans la synthèse d’un polysaccharide de la matrice du biofilm ainsi que deux gènes présentant de fortes homologies avec un gène codant pour l’adhésine auto-transporteur Hsf retrouvée chez Haemophilus influenzae ont montré une surexpression significative. Plusieurs de ces gènes ont également été retrouvés lors d’expériences réalisées avec des cellules épithéliales d’origine pulmonaire en culture, qui ont permis d’identifier 170 gènes différentiellement exprimés après la croissance planctonique au-dessus des cellules, et 131 autres suite à l’adhésion à ces cellules. Parmis les gènes surexprimés, les gènes tadB et rcpA de l’opéron tad putatif, les gènes pgaBC ainsi que le gène codant pour l’homologue d’Hsf ont été retrouvés. En présence de liquide de lavage broncho-alvéolaire (BALF), 156 gènes ont montré un profil d’expression modifié, et le gène apxIVA, identifié comme étant surexprimé, a pu être détecté pour la première fois dans des conditions de croissance in vitro. Finalement, des expériences visant à déterminer les gènes utilisés directement chez l’animal en phase aiguë de la pleuropneumonie porcine ont permis d’identifier 150 gènes qui étaient différentiellement exprimés. En plus d’identifier des gènes d’un possible opéron codant pour un fimbriae de type IV, 3 des 72 gènes surexprimés sont conservés chez tous les sérotypes d’A. pleuropneumoniae et codent pour des protéines ou lipoprotéines de surface. Nos expériences ont permis d’identifier plusieurs nouveaux facteurs de virulence potentiels chez A. pleuropneumoniae ainsi que plusieurs nouvelles cibles potentielles pour l’élaboration de vaccins efficaces contre tous les sérotypes. / Actinobacillus pleuropneumoniae is the etiological agent of porcine pleuropneumonia. Transmission of the disease occurs through direct contact or aerosols. The bacteria possess many virulence factors, namely capsular polysaccharides, lipopolysaccharides, four Apx toxins and iron acquisition mechanisms. To this day, an efficient cross-serotype vaccine has yet to be developed. In order to investigate regulation mechanisms in A. pleuropneumoniae and to identify new potential targets for the synthesis of subunit vaccines, the transcriptomic profile of the bacteria under conditions that simulate the infection and following a natural acute infection in vivo were studied. The experiences relied on first and second generation microarrays (AppChip1 and AppChip2) designed using 2025 ORFs of the draft version of the A. pleuropneumoniae serotype 5b strain L20 genome and 2033 ORFs of the final and annotated version of the same genome respectively. First, experiments were conducted under iron-restricted conditions and 210 genes were deemed differentially expressed, 92 of which were up-regulated. Some new putative iron acquisition mechanisms were identified, including genes homologous to those of the Yersinia pestis YfeABCD chelated-iron acquisition system, as well as other genes homologous to components of the HmbR iron uptake from hemoglobin system of Neisseria meningitidis. When cultured in conditions promoting biofilm production, genes tadC and tadD from a putative tad (« tight adherence locus ») operon, genes pgaABC involved in the biosynthesis of a polysaccharide of the biofilm matrix as well as two ORFs encoding a putative autotransporter adhesins similar to the Haemophilus influenzae Hsf adhesin were all significantly overexpressed. Many of these genes were also overexpressed when lung epithelial cells were infected with A. pleuropneumoniae. While 170 genes were differentially expressed after planktonic growth in the culture medium above the cells, another 131 were identified following direct adhesion to the cells. Genes tadB and rcpA of the tad locus, as well as genes pgaBC and an ORF coding for the Hsf homolog where all found among overexpressed genes. When A. pleuropneumoniae was cultured in contact with broncho-alveolar lavage fluids (BALF), 156 genes were significantly differentially expressed and gene apxIVA, which was up-regulated, was detected for the first time during in in vitro growth conditions. Finally, experiments were conducted in vivo in animals naturally infected with A. pleuropneumoniae in the late stage of the acute phase in order to identify genes that are expressed during the infection of the natural host. While 150 genes were deemed differentially expressed, genes apxIVA as well as two genes from an operon coding for a putative type IV fimbriae were up-regulated. Out of those 72 genes that were overexpressed, 3 encode proteins or lipoproteins of the outer membrane which are conserved among all serotypes of the bacteria. Overall, we were able to identify several new potential virulence factors for A. pleuropneumoniae in the course of our experiments, as well as several new potential targets for the elaboration of an efficient cross-serotype vaccine.

Die Rationale für immuntherapeutische Ansätze zur Behandlung maligner Neoplasien geht davon aus, daß Tumore über spezifische Tumorantigene verfügen. Dendritische Zellen als die wichtigsten antigenpräsentierenden Zellen sind in der Lage, Tumorantigene naiven T-Zellen zu präsentieren und spezifische zytotoxische T-Zellen zu stimulieren. In der vorliegenden Arbeit wurden dendritische Zellen durch Stimulation mit Interleukin-4 (IL-4) und Granulozyten/ Makrophagen Koloniestimulierender Faktor (GM-CSF) aus peripheren mononukleären Blutzellen gesunder Spender und an Tumoren des gastroenteropankreatischen Systems erkrankter Patienten generiert. Mit den dendritischen Zellen cokultivierte immunologische Effektorzellen (Zytokin- induzierte Killerzellen, CIK-Zellen) wurden im Zytotoxizitätstest gegen kolorektale und pankreatische Karzinomzellen eingesetzt. CIK-Zellen sind zytototoxische Zellen, die durch Stimulation mit Zytokinen aus peripheren Blutlymphozyten erzeugt werden. Durch die Cokultivierung der Effektorzellen mit dendritischen Zellen konnte eine signifikante Steigerung der unspezifischen zytotoxischen Wirkung der CIK-Zellen bewirkt werden. Zur Steigerung der spezifischen Zytotoxizität wurden dendritische Zellen mit dem Gesamtprotein der tumor- assoziierten Antigene cancer associated antigen (CA 19-9) und carcinoembryonic antigen (CEA) gepulst. Effektorzellen zeigten nach der Cokultur mit gepulsten dendritischen Zellen zytotoxische Wirkung gegen Targetzellen, die das zum Pulsen verwendete Tumorantigen auf der Zelloberfläche exprimieren. Die Antigenspezifität der zytotoxischen Wirkung konnte durch eine signifikant verminderte Zellyse nach Blockade des Tumorantigens auf den Targetzellen belegt werden. Erstmals beschrieben ist hier das Pulsen dendritischer Zellen mit sowohl autologen als auch allogenen Seren von Patienten mit erhöhten Tumormarkerspiegeln. Eine Kultivierung dendritischer Zellen in tumormarkerhaltigem Serum bewirkte dosisabhängig eine verstärkte zytotoxische Wirkung cokultivierter Effektorzellen gegen Tumorzellen. Die verstärkte Zellyse zeigte sich unabhängig vom allogenem oder autologem Charakter des Serums. Der immunstimulierende Effekt des Patientenserums konnte durch eine vorhergehende Hitzeinaktivierung des Serums neutralisiert werden. Die höchsten Zellysen wurden durch eine Kultivierung dendritischer Zellen in tumormarkerhaltigem Serum und zusätzlichem Pulsen mit exogenem Tumorantigen erreicht. Untersuchungen an komplett autologen Systemen reproduzierten die an Zellkulturen erhobenen Befunde. Hierfür wurden erfolgreich Primärkulturen kolorektaler Tumore etabliert.Aus dem Blut von Tumorpatienten wurden dendritische Zellen generiert, die mit autologem Serum kultiviert wurden. Die cokultivierten autologen Effektorzellen erwiesen sich im Zytotoxizitätstest gegen autologe Tumorzellen als zytotoxisch. Die Cokultivierung der Effektorzellen mit den dendritischen Zellen bewirkte bei beiden Zellpopulationen Veränderungen. Dendritische Zellen zeigten nach der Cokultur eine verstärkte Expression antigenpräsentierender und costimulatorischer Moleküle. Bei den CIK-Zellen kam es zu einem Anstieg der Proliferationsrate. Bei Untersuchungen zur Antigenspezifität von T-Zellrezeptoren konnte vermehrt antigenspezifischer T-Zellrezeptor nachgewiesen werden. Des weiteren stieg das Verhältnis zwischen zytotoxischen T-Zellen und T-Helferzellen zugunsten der zytotoxischen T-Zellen. In ELISpot-Untersuchungen wurde eine Zunahme Interferon-gamma sezernierender CIK-Zellen nachgewiesen. Dendritische Zellen ließen sich erfolgreich mit inaktiviertem Adenovirus, an das kovalent Poly-L-Lysin gekoppelt ist, transfizieren. Die für den adenoviralen Gentransfer benötigten Oberflächenstrukturen konnten auf dendritischen Zellen nachgewiesen werden. Zur Verbesserung der Zytotoxizität wurden dendritische Zellen erfolgreich mit dem Gen für den Transaktivator CIITA transfiziert. CIITA- transfizierte dendritische Zellen exprimierten vermehrt MHC Klasse II-Moleküle. Die transduzierten dendritischen Zellen induzierten bei cokultivierten Effektorzellen eine erhöhte unspezifische Zytotoxizität. Mit Tumorantigen gepulste dendritische Zellen können bei der Entwicklung immuntherapeutischer Protokolle bei malignen Neoplasien von Bedeutung sein. / The immunotherapeutic approach against malignant neoplasias appreciates that tumours encode tumour rejection antigens, that enable them to induce protective immunity. Dendritic cells are major antigen-presenting cells and are able to present tumour antigens to naive T-cells and stimulate cytotoxic T-cells in a specific manner. In the present graduation-manuscript dendritic cells were generated in the presence of Interleukin-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) from peripheral mononuclear blood cells of healthy donors and tumour-patients. Immunological effector cells termed cytokine-induced killer cells (CIK cells) were co-cultured with dendritic cells and tested for their cytotoxic capacity against colorectal and pancreatic cancer cell-lines in a LDH-release assay. CIK cells are cytotoxic lymphocytes generated by incubation of peripheral blood lymphocytes with different cytokines. Co-culture of effector cells with dendritic cells led to a significant increase of the cytotoxic effect of CIK cells. For a further increase of specific cytotoxicity dendritic cells were pulsed with total protein of the tumour-associated antigens cancer associated antigen CA 19-9 and carcinoembryonic antigen (CEA). Co-cultured effector cells showed an increase in cytotoxicity against tumour-antigen expressing target cells, after co-culture with pulsed dendritic cells. The specificity of the cytotoxic effect could be shown by blocking the tumour-antigens with a monoclonal antibody. Autologous and allogenec untreated serums from patients with elevated tumour-marker levels were also used for pulsing of dendritic cells. Similar to the results when using total protein for pulsing, a cultivation in serum of patients with elevated tumour marker levels caused an intensified cytotoxic effect of effector cells against tumour cells in a dose-dependent manner. The intensified cytotoxicity was seen independent of the allogenec or autologous character of the serum. The immuno-stimulating effect of the patient serum could be neutralized by preceding heat inactivating. The highest cytotoxicity was achieved by a cultivation of dendritic cells in serum from patients with elevated tumour marker levels and additional pulsing with exogenous tumour antigen. Experiments with completely autologous systems reproduced the results made with cell-lines. Primary cultures of colorectal tumours were established. Dendritic cells were generated from the blood of tumour patients and were cultivated in autologous serum. Co-cultured autologous effector cells showed cytotoxicity when used against autologous tumour cells. Co-culturing of effector cells with dendritic cells caused modifications at both cell populations. Dendritic cells showed an increase expression of antigen-presenting and co-stimulatory molecules. CIK cells showed a higher proliferation-rate when co-cultured. They express more antigen-specific T-cell receptor, and the cytotoxic T-cells to T-helper cells ratio increased. ELISpot-assays showed an increase of interferon gamma producing cells. Dendritic cells were successfully transduced by using an inactivated adenovirus, which covalently binds poly-L-lysine. Dendritic cells express the molecules that enables adenoviral gene delivery on their surface. For the improvement of cytotoxicity dendritic cells were transduced with the gene encoding for the transactivator CIITA. CIITA transduced dendritic cells increases expression of MHC class II molecules. Cytotoxicity experiments with transduced dendritic cells resulted in an increased induction of non-specific cytolysis from co-cultured effector cells. DC pulsed with tumour-antigens may have a major impact on immunotherapeutic protocols for cancer patients.

Poor athletic performance of racehorses is a major and significant problem in the racing industry. Determining the definitive reason for poor-performance is however a real diagnostic challenge since many of the causative conditions are multifactorial and may only be manifested during exercise. A retrospective study, including various breeds of horses, confirmed musculoskeletal, cardiovascular and upper respiratory tract clinical problems to be the most frequently implicated in reducing athletic performance. Evaluation of the lower respiratory tract was though not performed in this study. The aim of the first part of this work were thus to determine the prevalence of different sub-clinical diseases in a population of poorly-performing Standardbred trotters, and to evaluate the sportive repercussions by comparing their physiological response to exercise with control horses. Fifty horses underwent thorough clinical and ancillary examinations, including haematological et biochemical evaluation, Doppler echocardiography, standardised exercise tests on treadmill et racetrack, treadmill video-endoscopy et collection of respiratory fluids. Most of the poorly-performing horses exhibited many concomitant diseases. The most frequently diagnosed sub-clinical problems involved the lower and upper respiratory tract. Poor-performers also exhibited higher values of blood lactate and heart rate, as well as lower values of haematological parameters and anti-oxidants, compared to control horses. Inflammatory airway disease being mostly present in poorly-performing horses, the second part of this work will mainly focus on this syndrome. The negative impact of inflammatory airway disease, as diagnosed by cytological evaluation of bronchoalveolar lavage fluid, has previously been described on respiratory function using either forced expiration or forced oscillations techniques. Sedation or bronchoprovocation were however usually required. On the other hand, the clinical significance of tracheal inflammation remains currently controversial. The aim was therefore to exhibit and define the respiratory dysfunctions present in horses subclinically suffering from inflammatory airway disease. Respiratory function was evaluated at rest by IOS in 34 Standardbred trotters, whereas tracheal mucus score, and both tracheal and bronchoalveolar lavages were performed 60 min post-exercise. According to the cytology of bronchoalveolar lavage fluid, the inflammatory group included 19 horses and 15 horses were used as control. A significant correlation was found between both cytological evaluations concerning neutrophil counts, whereas no association was found between tracheal mucus and any cytology. A significant increase of respiratory resistance at the lower frequencies (1 10 Hz) as well as a significant decrease of respiratory reactance beyond 5 Hz was observed in inflammatory compared to control horses. Both parameters were also significantly different between inspiration and expiration in the inflammatory group only. Both eosinophil and mast cell counts of the bronchoalveolar lavage fluid were significantly correlated with respectively respiratory resistance and reactance. The present work involved intensive clinical and functional evaluation of control and asymptomatic poorly-performing horses. The different studies allowed establishing the prevalence of medical subclinical diseases in these latter and evaluating its sportive impact considering the associated physiological responses to exercise. The presence of respiratory dysfunctions in horses with lower airway inflammation, the major trouble associated with disappointing performance, were also exhibited by impulse oscillometry./ La contre-performance est un problème majeur dans lindustrie des courses. En déterminer la cause exacte reste néanmoins un défi diagnostic puisque la plupart des affections présentes sont souvent subcliniques, multifactorielles et peuvent ne se manifester que pendant lexercice. Une étude rétrospective, incluant des chevaux de différentes races et disciplines, a ainsi confirmé les affections cliniques des voies respiratoires supérieures, musculo-squelettiques et cardiovasculaires comme étant les plus fréquemment impliquées dans la réduction des performances athlétiques. Cependant, lévaluation des voies respiratoires profondes navait pas été effectuée chez ces différents chevaux. Lobjectif de la première partie de ce travail était donc de déterminer la prévalence des différentes affections sub-cliniques induisant une contre-performance chez des Trotteurs Français, et den évaluer les répercussions sportives par la comparaison des réponses physiologiques à lexercice avec celle de chevaux contrôles. Cinquante chevaux ont respectivement été soumis à un examen clinique complet, une prise de sang pour analyse hémato-biochimique au repos et 60 minutes après chaque test deffort, une échocardiographie Doppler, des tests deffort standardisés sur piste et tapis roulant, une endoscopie à leffort, une évaluation locomotrice à grande vitesse, ainsi quun lavage trachéal et broncho-alvéolaire réalisés 60 minutes post-effort. La plupart des chevaux contre-performants ou intolérants à leffort présentaient plusieurs affections concomitantes. Les troubles sub-cliniques les plus fréquemment diagnostiqués concernaient respectivement les voies respiratoires profondes et supérieures. Ces chevaux présentaient par ailleurs des paramètres hématologiques (taux dhémoglobine et volume globulaire moyen) et anti-oxydants significativement inférieurs, et des paramètres pro-oxydants significativement supérieurs aux chevaux contrôles. De plus, les valeurs de fréquence cardiaque et lactatémie étaient, lors des différents tests deffort, significativement supérieures à celles des chevaux contrôles, Linflammation des voies respiratoires profondes étant majoritairement présente chez ces chevaux présentant des performances décevantes, la deuxième partie de ce travail se concentre plus spécifiquement sur ce syndrome. Limpact négatif sur la fonction respiratoire de cette affection, telle que diagnostiquée par lévaluation cytologique du liquide de lavage broncho-alvéolaire, a précédemment été décrite à laide de techniques dexpiration forcée ou doscillations forcées. Une sédation ou une bronchoprovocation étaient cependant généralement requises pour la réalisation de ces tests. Parallèlement, la signification clinique de linflammation trachéale reste actuellement controversée. Lobjectif était ainsi de mettre en évidence et définir les dysfonctions respiratoires présentes chez des chevaux souffrant sub-cliniquement de maladie inflammatoire des voies respiratoires. La fonction respiratoire a été évaluée au repos par oscillométrie à impulsions chez 34 Trotteurs Français asymptomatiques, alors que le score de mucus trachéal et les différents lavages ont été évalués 60 minutes post-effort. Sur base de la cytologie broncho-alvéolaire, le groupe inflammatoire comprenait 19 chevaux et 15 ont été utilisés comme contrôles. Une corrélation significative était observée entre les cytologies concernant le taux de neutrophiles, alors quaucune association nétait présente entre score de mucus trachéal et cytologies des différents lavages. Une augmentation significative de la résistance respiratoire aux faibles fréquences (1 à 10 Hz) et une diminution de la réactance respiratoire au-delà de 5Hz a été observée chez les chevaux inflammatoires comparativement aux contrôles. Ces deux paramètres étaient également significativement différents entre inspiration et expiration dans le groupe inflammatoire uniquement. La résistance et la réactance respiratoire étaient par ailleurs respectivement corrélées aux taux déosinophiles et de mastocytes du lavage broncho-alvéolaire. Ce travail comprenait une évaluation clinique et fonctionnelle intensive chez des chevaux contrôles et des chevaux contre-performants. Les études menées ont permis détablir la prévalence des affections médicales sub-cliniques chez ces derniers et den évaluer limpact sportif par lintermédiaire des réponses physiologiques à lexercice. La présence de dysfonctions respiratoires chez les chevaux avec inflammation des voies respiratoires profondes, premier trouble associé à des performances décevantes, a également pu être mise en évidence à laide de loscillométrie à impulsion.