Dissertations / Theses on the topic 'Diffusion pulmonaire'

Ce travail a été consacré à l’étude non invasive de la circulation pulmonaire normale par mise en œuvre de l’échocardiographie Doppler. <p>En intégrant les mesures obtenues dans une approche physiopathologique, et en exploitant les nouvelles possibilités d’échocardiographes portables, techniquement performants, nous avons analysé les effets d’un inhibiteur de la phosphodiestérase-5 et d’une prostacycline, pour tenter d’en identifier d’éventuels effets introtropes intrinsèques, nous avons exploré le concept de réserve vasculaire pulmonaire comme facteur limitant de l’aptitude aérobie et indice potentiel d’une atteinte vasculaire pulmonaire précoce, et obtenu des résultats préliminaires permettant d’identifier une hypertension artérielle pulmonaire (HTAP) latente. Nos principaux résultats peuvent être résumés comme suit :<p>1. Chez le sujet sain, en normoxie ou dans un modèle expérimental d’HTAP induite par l’inhalation d’un mélange gazeux hypoxique, le sildenafil per os ou l’epoprostenol par voie intraveineuse, à des doses utilisées en clinique pour le traitement de l’HTAP, améliorent les indices de la fonction ventriculaire droite en proportion de leurs effets vasodilatatoires pulmonaires, sans effets inotropes intrinsèques détectables.<p>2. La consommation d’oxygène maximale du sujet sain augmente en raison directe de son volume capillaire pulmonaire (calculé à partir de sa capacité de diffusion pour l’oxyde nitrique et le monoxyde de carbone) et en raison inverse de sa résistance vasculaire pulmonaire, non seulement en altitude, mais aussi au niveau de la mer. Ce résultat suggère qu’une plus grande réserve vasculaire pulmonaire est propice aux efforts aérobiques intenses, probablement par moindre postcharge ventriculaire droite.<p>3. Des mesures réalisées chez un petit nombre de sujets suggèrent que la distensibilité vasculaire pulmonaire, calculée à partir d’une relation débit-pression vasculaire pulmonaire, est typiquement réduite chez des porteurs asymptomatiques de la mutation BMPR2, qui est actuellement le facteur de risque le plus élevé connu de l’HTAP. La mutation BMPR2 pourrait aussi être associée à une réactivité vasculaire pulmonaire accrue à l’hypoxie. <p>Nos résultats suggèrent indirectement que l’échocardiographie Doppler, de repos ou de stress, pourrait être davantage développée dans la mise au point de patients à risque d’HTAP./<p><p>Novel advances in echocardiography offer the opportunity to reliably characterize pulmonary circulation in terms of pressure-flow relationship, and to better understand the coupling of right ventricular (RV) function with normal and abnormal pulmonary hemodynamics. Moreover, when combined with the measurement of pulmonary capillary blood volume, this renewed methodological approach may help to understand the concept of pulmonary vascular reserve as a limiting factor of exercise capacity and potential sensitive marker of early vascular disease.<p><p>In the present work we used a model of hypoxic pulmonary vasoconstriction to analyse the effects of two targeted therapies of pulmonary arterial hypertension (PAH) on the RV function. We showed that the beneficial effects of these drugs are mainly driven by a decrease in RV afterload and not an enhanced myocardial inotropic state. Whether this is transposable to abnormal RV-arterial coupling in PAH patients remains to be investigated.<p><p>Echocardiography may be useful to explore the pulmonary vascular reserve as an important limiting factor of exercise capacity. We showed that a higher pulmonary vascular reserve, defined by a decreased PVR and increased lung diffusing capacity, allows for an improved aerobic exercise capacity (as assessed by a higher peak oxygen consumption), at a lower ventilatory cost, at sea level and at high altitude. <p><p>Stress echocardiography may detect an abnormal pulmonary vasoreactivity. We showed that asymptomatic relatives of patients suffering from idiopathic pulmonary arterial hypertension, and who carry a bone morphogenetic protein receptor type 2 mutation (BMPR2) present with a decreased pulmonary vascular distensibility and an enhanced pulmonary vasoreactivity to hypoxia, which are identifiable by echocardiography examination. However, the predictive value of these findings is not known. <p><p>Thus echocardiography may represent, in experienced and dedicated hands, a noninvasive, safe, widely available, applicable at the bed-side as well as in extreme environment (e.g. high altitudes), less expensive alternative for the evaluation of the pulmonary circulation, either by the interrogation of pressure-flow relationship (stress echocardiography), by the investigation of the right ventricle global and regional function in relation to its afterload (standard and Tissue Doppler Imaging), or by a combined approach with the measurement of lung diffusing capacity (DLNO / DLCO) to assess the pulmonary vascular reserve.<p><p>The present data are encouraging for further development and implementation of echocardiography for the detection, but also the diagnosis and follow-up of patients with pulmonary hypertension.<p><p><br>Doctorat en Sciences médicales<br>info:eu-repo/semantics/nonPublished

L'acinus pulmonaire constitue l'unité d'échange gazeux entre l'air et le sang dans les voies aériennes pulmonaires. Dans le cadre de cette thèse, nous nous sommes plus particulièrement intéressés à l'oxygène. Plusieurs mécanismes sont mis en jeu depuis son entrée dans l'acinus jusqu'à sa capture par l'hémoglobine : les mécanismes de transport de l'oxygène dans l'air : convection et diffusion, le transfert par diffusion passive de l'oxygène à travers la membrane alvéolo-capillaire et sa capture par l'hémoglobine. Par la détermination de la capacité diffusive pulmonaire DL, il est possible d'évaluer cliniquement le fonctionnement et l'efficacité de ces mécanismes. Cette mesure est couramment employée pour le diagnostic, notamment pour mettre en évidence les détériorations de la membrane alvéolo-capillaire ou encore les pertes de surface d'échange. Expérimentalement, la DL s'exprime à partir des deux mesures cliniques suivantes: la pression alvéolaire PA et la consommation de gaz V. Plus particulièrement, dans le cas qui nous intéresse ici soit celui de l'oxygène, il s'agit de la pression partielle en oxygène contenue dans les alvéoles pulmonaires PA,O2 et de la quantité d'oxygène échangée en une minute VO2. Il est possible de déterminer une valeur théorique de la capacité diffusive pulmonaire grâce à une formulation classique et empirique très utilisée en médecine. Celle-ci est aujourd'hui encore le sujet de nombreuses publications car elle ne reproduit pas exactement les résultats de l'expérience. Nous avons mis en place un modèle numérique dynamique du transport et du transfert de l'oxygène au sein de l'acinus pulmonaire permettant de restituer les valeurs de PA,O2 et VO2 chez les sujets sains. Ce modèle dépend d'un unique paramètre physique ajustable qu'on appelle la perméabilité $W$. Celle-ci traduit toute la complexité du transfert de l'oxygène vers le sang. Elle se définit comme une conductance équivalente imposée par les trois mécanismes acteurs du transfert vers le sang. Par cette approche numérique, nous avons donc construit un acinus artificiel qui, à partir de la seule détermination de la perméabilité $W$ est capable de reproduire le fonctionnement de l'acinus réel. A partir de ce modèle, nous avons pu étudier l'influence de la géométrie asymétrique de l'acinus pulmonaire sur le transport et l'échange. Cette étude a mis en évidence une forte hétérogénéité de la répartition du flux d'oxygène échangé vers le sang dans l'acinus pulmonaire. Ceci peut s'expliquer grâce à un phénomène physique appelé masquage diffusionnel, responsable du fait que la pression partielle en oxygène dans l'acinus diminue. Ce phénomène est gouverné, notamment, par l'absorption à travers la membrane alvéolaire et la diffusion le long de la structure irrégulière de l'acinus. Cet effet entraîne que les parties profondes de l'acinus sont très peu alimentées en oxygène, la majorité ayant été absorbée dans les premières générations. Au repos, l'influence du masquage est élevée et le flux d'oxygène ne dépend que très peu du volume (proportionnel à la surface alvéolaire). A l'effort, l'effet du masquage est moindre, notamment grâce à la vitesse de convection plus élevée. Ainsi, la quasi-totalité de la surface alvéolaire est utilisée.

La capacité de transfert du monoxyde du poumon (Tlco) est habituellement décrite par l’équation de Roughton et Forster : 1/Tlco = 1/Dmco + 1/0co x Vc. Dans ce modèle, Dm et Vc sont considérés comme indépendants. Tlco dépend de la capacité de la conductance du CO à travers la membrane alvéolo-capillaire, de la vitesse de réaction entre le CO et l’hémoglobine. . . Ainsi que du volume capillaire pulmonaire (Vc). Guénard et al. Ont établi que la capacité de transfert du monoxyde d’azote (Tlno) dépend seulement des caractéristiques de la membrane alvéolo-capillaire. Théoriquement, il existe une relation de proportionnalité entre Vc et Dm car la surface de contact entre l’alvéole et le capillaire est commune. Le rapport Tlno/Tlco est alors inversement proportionnel au produit entre l’épaisseur de la membrane alvéo-capillaire et l’épaisseur du lit capillaire pulmonaire (K). Différentes conditions expérimentales dans lesquelles une augmentation de K était attendue ont diminué le rapport Tlno/Tlco. Dans une seconde étude, des valeurs standard de Tlno ont été établies chez 303 sujets sains. Tlno dépend de la taille, du genre, de la ville d’inclusion et diminue avec l’âge en suivant une relation biphasique dont la pente est plus importante après 60 ans. Le rapport Tlno/VA diminue avec l’âge alors que Tlno/Tlco n’est correlé à aucune variable suggérant que ce rapport est une caractéristique anthropométrique. Dans une dernière étude, la mesure Tlno a été effectuée durant l’exercice. Tlno augmente de moitié à 80% de la puissance maximale aérobie. D’autre part, Vc au repos est supérieur de 25 % chez les sportifs par rapport aux sédentaires, sans modification du rapport Tlno/Tlco. Ces données suggèrent une augmentation du nombre de capillaires pulmonaires avec l’entraînement.

Les pneumopathies acquises sous ventilateur (PAV) sont fréquentes et graves en réanimation. Leur traitement dépend de l’hôte, de la bactérie responsable et de l’antibiotique choisi. L’obtention de concentrations tissulaires et d’indices pharmacocinétiques/ pharmacodynamiques (PK/PD) adéquats tels que T&gt;CMI = 100 % pour les antibiotiques temps-dépendant (β-lactamines), Cmax/CMI  10 ou ASC/CMI &gt;125 pour les antibiotiques concentration-dépendants (aminosides, fluoroquinolones. . . ) semble optimiser l’efficacité des antibiotiques. Ces données sont cependant peu connues en réanimation. Nous avons donc réalisé plusieurs études chez des patients de réanimation atteints de PAV mesurant les concentrations sériques et pulmonaires - après recueil par mini-lavage bronchoalvéolaire (LBA) - d’antibiotiques fréquemment utilisés (pipéracilline/tazobactam, ertapénème, ceftazidime, céfépime, lévofloxacine, linézolide et tobramycine), qui rapportées à la concentration minimale inhibitrice (CMI) des bactéries fréquemment incriminés ont permis de calculer les index PK/PD prédictifs de succès. En outre, certaines de ces études ont permis de valider la technique de prélèvement par mini-LBA comparée au LBA fibroscopique, technique de référence, ainsi que plusieurs méthodes de dosage par chromatographie liquide à haute performance. Nos études montrent que la pharmacocinétique et la diffusion pulmonaire des antibiotiques sont éminemment variables chez les patients de réanimation atteints de PAV et que des dosages individuels sériques voire alvéolaires semblent nécessaires pour optimiser les indices PK/PD en fonction de la CMI du germe en cause. Cependant, seules des études cliniques comparatives bien conduites permettront de déterminer l’impact réel de l’optimisation de l’antibiothérapie des PAV sur le devenir des patients<br>Ventilator-associated pneumonia (VAP) remains frequent and serious in intensive care units (ICU). Treatment of VAP is related to the patient, the involved pathogen and the selected antimicrobial agent. The achievement of adequate tissue concentrations and pharmacokinetic/pharmacodynamic (PK/PD) indexes such as T&gt;CMI = 100 % for time-dependent antibiotics (β-lactams), Cmax/CMI  10 ou ASC/CMI &gt;125 for concentration-dependant antibiotics (aminoglycosides, fluoroquinolones. . . ) is required to optimize the efficacy of antimicrobial agents. However, only few data are available in ICU patients. Therefore, we conducted various studies in critically ill patients with VAP aiming at measuring the serum and pulmonary concentrations – obtained after mini-bronchoalveolar (BAL) sampling – of frequently used antimicrobial agents - (piperacillin/tazobactam, ertapenem, ceftazidime, cefepime, levofloxacine, linezolid et tobramycin), which, once related to the minimal inhibitory concentration (MIC) of pathogens commonly involved in VAP, permitted the calculation of PK/PD indices predictive of success. Moreover, some of these studies have permitted to validate the mini-BAL sampling method in comparison to the gold-standard conventional bronchoscopic BAL, and some high-performance liquid chromatography methods. Our studies show that the pharmacokinetics and pulmonary diffusion of antibiotics exhibit wide variability in ICU patients with VAP and that individual serum or alveolar dosages may be required to optimize the PK/PD parameters in relation to the causative pathogen MIC. However, further well-conducted comparative clinical studies are required to determine the actual impact of the optimization of VAP antimicrobial treatment on patient outcome

L’exposition hyperbare induit des risques sanitaires, en particulier d’accidents de décompression (ADD), dont la probabilité dépend de multiples facteurs, tant externes qu’individuels. Parmi ceux-ci, l’altération de la barrière alvéolo-capillaire est peu ou pas étudiée. Nous avons donc cherché à identifier les effets d’une altération pulmonaire caractérisée par une diminution de la capacité de diffusion alvéolo-capillaire du monoxyde de carbone (DLCO) sur le risque d’ADD. Après un bilan d’aptitude préalable, chaque volontaire a été évalué avant et après la plongée.15 plongeurs professionnels civils répartis en 2 groupes en fonction de leur DLCO, normale (Contrôle) ou diminuée (DLCO), ont réalisé une plongée standardisée à 20 mètres pendant 40 minutes dans le bassin d’eau de mer d’IFREMER. Nous avons mesuré le score de bulles intravasculaires (VGE), la réponse microcirculatoire par débitmétrie laser doppler et les concentrations de différents paramètres biologiques en particulier l’aldostéronémie. Même en l’absence de survenue d’ADD, tous les plongeurs produisent des VGE. Le groupe DLCO est caractérisé par un pic de VGE plus tardif (60 minutes vs 30 minutes) et une tendance à des scores plus importants (Grade IV : 17% vs 11%). Par ailleurs, l’hypoaldostéronémie n’est observée que dans le groupe contrôle (-30.4±24.6%), pas dans le groupe DLCO (+14.8±34.7%). En dehors d’une diminution du risque thrombotique chez tous les plongeurs, les autres paramètres mesurés sont inchangés. Ces résultats évoquent une augmentation du risque d’ADD devant être confirmée par d’autres études<br>Hyperbaric exposure leads to a risk of decompression sickness (DCS). The likelihood of DCS depends on multiple factors, external as well as individual. Among them, the alteration of the blood-air barrier has been poorly studied.Therefore, we measured the effect of pulmonary impairment characterized by a decreased diffusing lung capacity of carbon monoxide (DLCO) on the risk of DCS.15 professional divers were splited into 2 groups according to their DLCO, normal (control) or decreased (DLCO), and enrolled after an initial full “fit-to-dive” clinical check-up. They made a standardized 20 meters/40 minutes SCUBA dive in a sea water pool (IFREMER) Vascular Gas Emboli (VGE) score, micro-circulatory response, inflammatory biomarkers, thrombotic factors, and aldosteron rate were measured pre- and post-dive. Although no DCS occurred, all the divers showed VGE after diving. Compared to the control group, we observed in the DLCO group an increased latency to the VGE peak (60 vs 30 minutes) and a tendency for higher VGE scores (Grade IV: 17% vs 11%). A significant decrease (-30.4±24.6%) of aldosteron rate was observed in control and not in the DLCO group (+14.8±34.7%). Most of the biological parameters and microvascular response remained unchanged while all divers had a lowered post-dive thrombotic risk.These results imply that divers with a decreased DLCO might be exposed to an increased DCS risk.Further studies are required to confirm the implication and significance of pulmonary impairment in DCS

L'étude du facteur de transfert pulmonaire au CO (TLCO) et de la capacité résiduelle fonctionnelle (CRF) chez le nourrisson est du domaine de la recherche. Les études qui portent sur CFR sont nombreuses alors que seulement quelques-unes analysent TLCO. Dans ce travail nous avons perfectionné un système instrumental mis en place au départ pour mesurer uniquement VA chez le nouveau-né et le nourrisson. Pour cela, nous avons utilisé un modèle mathématique basé sur celui de Prisk et McKinnon (1987) qui décrit les variations des fractions de CO et He au cours d'une manœuvre de rebreathing. Les parties transitoires des fractions End-Tidal et inspirée de CO et He sont utilisées par la suite dans les équations du modèle pour mesurerTLCO et CRF. Une partie du travail a été consacrée à la conception d'une valve respiratoire composée de deux éléments solidaires. Un pneumotachographe avec un espace mort instrumental de 1,8 ml et une valve électrique en Y. L'espace mort instrumental de l'électrovalve est de 2,8 ml et le temps de commutation de son clapet est d'environ 30 ms. Nous avons exploré 26 nourrissons âgés de 1 à 12 mois répartis en deux groupes, l'un de 14 nourrissons (groupe de référence ou N) et l'autre de 12 nourrissons obstructifs (groupe P). Le rapport Tptef/TE, utilisé comme indice de l'obstruction bronchique, est diminué chez les nouveau-nés du groupe P indiquant une persistance de la limitation des débits expiratoires. Les valeurs de TLCO et CFR du groupe N sont similaires à celles reportées dans la littérature. TLCO n'est pas différent entre les groupes N et P. Ainsi l'obstruction bronchique n'influence pas la mesure de TLCO. Nous avons observé une augmentation de CRF, VT et VA dans le groupe P comparé à N. Cependant, l'indice VA/CRF est identique pour les groupes. Ces résultats suggèrent que les nourrissons du groupe P compensent l'obstruction bronchique en ajustant leur ventilation afin d'assurer un renouvellement alvéolaire et des échanges gazeux efficaces.

<p>Chronic obstructive pulmonary disease (COPD) is in up to 90 % of all cases caused by</p><p>smoking. COPD often has negative effects on circulation, effects that first and foremost can be</p><p>observed as respiratory insufficiency. Reduced function of the right ventricle of the heart is</p><p>common in patients suffering from chronic obstructive pulmonary disease, especially if they</p><p>also have hypoxemi; insufficient levels of oxygen in blood or tissue. The incidence of this</p><p>cardiac complication reduces the survival time. It is possible in chronic obstructive pulmonary</p><p>disease that the pressure in the pulmonary circulation gradually increases resulting in</p><p>pulmonary hypertension followed by a slow adaptation of the right ventricle by hypertrophy of</p><p>the myocardium.</p><p>To investigate a correlation between COPD and pulmonary hypertension COPD patients</p><p>were subjected to spirometry and ultrasound on heart.</p><p>Of 14 examined patients 5 had developed pulmonary hypertension. A correlation between</p><p>obstruction in the COPD- patients and an increase in left ventricular diameter was found.</p><p>DLCO (diffusion capacity) of the lungs is directly connected to PA (pulmonary arterial</p><p>pressure). The lower DLCO, the higher risk to develop pulmonary hypertension. However, we</p><p>could not find a significant correlation between COPD and pulmonary hypertension in this</p><p>study even if most patients had a decreased DLCO.</p>

The goal of the present investigation was to evaluate the role of the pulmonary diffusion capacity (as measured by DLco) in relation to exercise-induced hypoxemia in elite athletes working at near maximal exercise intensities. Twenty-four elite cyclists were submitted to a direct measurement of VO$ sb2$ max on cycle ergometer which permitted classification into one of two groups. "Desaturaters" (N = 13) if oxyhemoglobin saturation (SaO$ sb2$%), as determined by finger oxymetry, fell below 91% or "non-desaturaters" if SaO$ sb2$% remained above 91%. Subsequent determinations of the transfer capacity for CO (DLco) were made using a 3 second breath-hold technique (Gould 2400/2450), at rest as well as at 60% and 90% of previously determined VO$ sb2$ max ($>$4.0 1/min). The results show an increase in DLco from rest to the first exercise intensity (desat: 41.7 $ pm$ 5.7 to 55.1 $ pm$ 4.7; non-desat: 41.1 $ pm$ 5.8 to 57.2 $ pm$ 6.9 mlsCO/mmHg/min) without much further increase to the maximal workload (desat: 61.0 $ pm$ 6.0; non-desat: 61.4 $ pm$ 9.5 mls CO/mmHg/min). No significant differences in DLco were found between the two groups at rest or either of the two exercise intensities. Significant differences between the desat and non-desat groups were found for FVC, post-exercise FEF$ sb{25-75 %}$, and VE/VO$ sb2$.<br>The present results are in agreement with previous reports showing arterial desaturation in 50% of highly-trained subjects when VO$ sb2$ max $>$4.0 1/min. The present investigation cannot clearly establish the role of DLco in this response. (Abstract shortened by UMI.)

Title from PDF of title page (University of Missouri--Columbia, viewed on Feb 26, 2010). The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file. Dissertation advisor: Dr. Peter Pfeifer. Vita. Includes bibliographical references.

INTRODUÇÃO: Indivíduos com SZ (esquizofrenia) fumam até três vezes mais que a taxa da população em geral. Constatou-se que fumantes com esquizofrenia fumam mais intensamente do que comparados com fumantes não esquizofrênicos. Adicionalmente, existem relatos não sistemáticos de que apesar de alta taxa de tabagismo, os esquizofrênicos apresentam proporcionalmente pouca lesão pulmonar comparado com tabagistas de igual consumo sem esquizofrenia. Esta diferença, se confirmada, poderia sugerir mecanismos diferentes de reação a agentes exógenos nos sistema respiratório, e entre estes mecanismos diferentes poderia estar o sistema de complemento, já evidenciado em estudos do grupo de pesquisa, porém sem controle para tabagismo. Este estudo investigou se a capacidade de difusão pulmonar em SZ é maior que em NSZ, e se o sistema complemento C3 e C4 é diferente entre SZ e NSZ e ao mesmo tempo está associado a difusão pulmonar de forma diferente em SZ e NSZ. OBJETIVOS: comparar a capacidade de difusão pulmonar e complemento C3 e C4 em pacientes fumantes com e sem esquizofrenia e analisar se existe evidência de mecanismos diferentes mediando prejuízo na capacidade de difusão em tabagistas com e sem SZ. MÉTODOS: esse é um estudo caso controle pareado, desenhado para ser multicêntrico, no momento descrevendo resultados de um centro. Recrutados 30 tabagistas sendo 15 SZ e 15 NSZ pareados por sexo, idade e tempo de tabagismo. Foram medidos complemento C3 e C4, espirometria e difusão pulmonar, dependência de nicotina pelo Teste de Fargerstrom e psicopatologia psiquiátrica nos portadores de esquizofrenia pelo Escala Breve de Avaliação Psiquiátrica (BPRS). Os pacientes foram oriundos do centro colaborador do estudo no HCPA. RESULTADOS: C3 foi significantemente maior em SZ quando comparado com controles (p=0,041), e C4 não mostrou diferença. Houve associação negativa entre o C4 e a capacidade de difusão somente no grupo controle (r=-0,692; p=0,009), sem diferença significativa no grupo de esquizofrênicos (r=0,451; p=0,141). Os grupos foram equivalentes em idade, grau de dependência de nicotina, porém foram diferentes em relação a ocupação (p=0,001). O grupo de esquizofrênicos apresenta maior proporção de desempregados e em benefício do que os controles. Desta forma, apesar de C3 mais aumentado em esquizofrênicos, este sistema aparentemente não media perda de difusão pulmonar, enquanto que aparentemente C4 mostra diferença quanto a prejuízo de difusão em esquizofrênicos tabagistas (maior C4 associado a menor capacidade de difusão somente nos tabagistas sem esquizofrenia). CONCLUSÃO: Quanto ao sistema complemento, houve maior ativação do C3 em tabagistas portadores de esquizofrenia comparados com tabagistas sem esquizofrenia, o que corrobora pesquisas anteriores que descrevem ativação do sistema complemento na SZ indicado pelo aumento dos níveis de C3. Curiosamente, somente nos controles tabagistas foi identificada associação entre aumento de C4 e redução da capacidade de difusão pulmonar. Nos pacientes com esquizofrenia não houve relação entre ativação de C4 e prejuÍzo de difusão pulmonar, o que sugere um padrão de ativação do sistema de complemento diferente dos sujeitos normais, preferencialmente pela via C3 e não pela via C4. Este fator não parece estar afetado pela diferença em escolaridade e trabalho, visto que era esperado que o aumento fosse maior nos esquizofrênicos devido a maior gravidade representada por menor índice de trabalho e menor escolaridade. Este estudo, se confirmado em amostras maiores envolvendo os outros centros colaboradores, pode confirmar existência de mecanismos diferentes de reação inflamatória em esquizofrenia.<br>Background: Subjects with SZ (schizophrenia) smoke up to three times the rate of the general population. It was found that smokers with schizophrenia smoke more intensely than smokers compared with non-psychiatric. Additionally, there are no systematic reports that despite high rates of smoking, people with schizophrenia have proportionately less lung injury compared with smokers without schizophrenia equal consumption. This difference, if confirmed, would suggest different mechanisms of response to exogenous agents in the respiratory system, and between these different mechanisms could be the complement system, as evidenced in studies of the research group, but not control for smoking. This study investigated whether the pulmonary diffusion capacity in SZ is higher than in non-SZ, and the complement C3 and C4 is different between SZ and NSZ and if at the same time is associated with pulmonary diffusion differently in SZ and NSZ. OBJECTIVES: To compare the pulmonary diffusion capacity and complement C3 and C4 in smokers with and without schizophrenia and examine whether there is evidence of different mechanisms mediating impaired diffusion capacity in smokers with and without SZ. METHODS: This is a matched case-control study, designed as a multicenter, when describing the results of a center. Recruited 30 smokers and 15 non-schizophrenics and 15 schizophrenics matched for sex, age and duration of smoking. We measured C3 and C4 complement, spirometry and DLCO, nicotine dependence and the test Fargerstrom psychiatric psychopathology in patients with schizophrenia by Brief Psychiatric Rating Scale (BPRS). The patients came from the study's collaborating center at HCPA. RESULTS: C3 was significantly higher in SZ compared to controls (p = 0.041), and C4 showed no difference. There was a negative association between C4 and the ability to broadcast only in the control group (r =- 0.692, p = 0.009), no significant difference in the schizophrenic group (r = 0.451, p = 0.141). The groups were equivalent in age, degree of nicotine dependence, but were different in relation to occupation (p = 0.001). The schizophrenic group has a higher proportion of unemployed and for the benefit of the controls. Thus, although most of C3 increased in schizophrenics, this system apparently did not measure loss of pulmonary diffusion, while C4 shows apparent difference in the loss of diffusion in schizophrenic smokers (greater C4 associated with a lower diffusion capacity in smokers without schizophrenia only) . CONCLUSION: As the complement system, activation of C3 was higher in smokers with schizophrenia compared with smokers without schizophrenia, which corroborates previous studies that describe activation of the complement system in SZ indicated by increased levels of C3. Interestingly, only smokers in controls been identified association between increased C4 and reduction of pulmonary diffusion capacity. In patients with schizophrenia there was no relationship between activation of C4 and prejuízo pulmonary diffusion, which suggests a pattern of activation of the complement system different from normal subjects, preferably through C3 and not via C4. This factor does not seem to be affected by the difference in schooling and work, as it was expected that the increase was greater in schizophrenics because of greater severity represented by lower rates of work and less schooling. This study, if confirmed in larger samples involving other collaborating centers, can confirm the existence of different mechanisms of inflammatory response in schizophrenia.

Ce mémoire rapporte la mise en oeuvre de la technique d'Imagerie par Résonance Magnétique (IRM) de l'hélium-3 hyperpolarisé à 0,1 T puis à 1,5 T, in vivo, chez l'Homme sain. L'utilisation des gaz hyperpolarisés en IRM entraîne deux conséquences majeures : l'absence de régénération de l'aimantation longitudinale et une diffusion très rapide. Prenant en considération ces deux contraintes, différentes stratégies d'acquisition sont comparées à bas champ (0,1 T) : séquences "single-shot" (RARE et EPI) et "multi-shot" (FLASH). On montre ainsi que la séquence RARE permet d'acquérir des images de bonne qualité en moins de 400 ms avec peu de gaz ; la séquence EPI a l'avantage de la rapidité mais entraîne davantage d'artefacts, en particulier en raison du terme de Maxwell ; ces deux séquences sont intrinsèquement limitées en résolution à 5 mm in vivo ; la séquence FLASH, moins efficace en termes de rapport signal sur bruit, permet cependant d'atteindre de meilleures résolutions. Les avantages de l'utilisation d'un bas champ magnétique en régime hyperpolarisé sont discutés : en particulier, le rapport signal sur bruit est, dans une très large gamme, indépendant du champ principal. Des mesures RMN puis IRM de diffusion utilisant la technique CPMG sont présentées et permettent de mettre en évidence la restriction due à la structure alvéolaire des poumons.

Einleitung: Bei Langzeitüberlebenden nach OLT findet sich eine Reduktion der Diffusionskapazität ohne Veränderungen des Lungeninterstitiums (nachweisbar in der high resolution Computertomographie HR-CT) und eine Reduktion der Muskelmasse. Wir untersuchten daher den Pathomechanismus der Diffusionsstörung, den zeitlichen Verlauf der Diffusionskapazität und die Auswirkungen der Lungen- und Atemfunktion auf die kardiopulmonale Belastbarkeit. Methoden: Bei 38 Lebertransplantierten (67.7 Mon. nach OLT) wurden Diffusionskapazität, Membranfaktor, Kapillarvolumen, Atemantrieb, maximaler inspiratorischer Druck (PImax), die maximale O2-Aufnahme (VO2max) und Atemeffizienz bestimmt und ein HR-CT der Lunge sowie eine Echokardiographie durchgeführt. Ergebnisse: Diffusionsstörungen bestanden bei 21% der Patienten. Der Diffusionskoeffizient war gegenüber der Voruntersuchung um 4% angestiegen 4% (p<br>Introduction: In long-term survivors after OLT, a reduction of the diffusion capacity (TLCO) may be noticed in absence of interstitial pulmonary changes (as observed in high resolution computertomography HR-CT). Also a diminution of the body muscle mass may be seen together with an increase in body fat mass. We tried to identify the origin of the pulmonary diffusion impairment as an alteration of the membrane factor or the capillary volume. We analysed the progression of the impairment in the course time and the effects of cardiac and respiratory function on VO2max. Methods: In 38 patients (67.7 month after OLT) we determined TLCO, membrane factor, capillary volume, ventilatory drive, maximal inspiratory pressure (PImax), maximal O2-uptake on exercise and breathing efficiency. Also HR-CT and echocardiography have been performed. Results: Diffusion impairment has been found in 21% of the patients. In the course of 3 years the diffusion coefficient has increased by 4% (p

Introdução: A diferenciação entre saúde e doença do sistema respiratório torna-se mais difícil devido à tendência de envelhecimento populacional e da necessidade de identificação das alterações próprias da senescência. Os testes de função pulmonar constituem ferramentas clínicas importantes para avaliação respiratória e sua interpretação está baseada em equações de referência derivadas de amostra de indivíduos saudáveis, que podem não expressar adequadamente o comportamento nesta faixa etária específica, dada a reduzida representatividade de indivíduos idosos nos estudos que postularam tais equações. Objetivo: Verificar a acurácia das equações de referência disponíveis para testes de função pulmonar e cardiopulmonar de esforço em relação aos valores obtidos em amostra de indivíduos idosos hígidos e o impacto clínico na interpretação funcional baseada nestas equações. Metodologia: Estudo prospectivo observacional transversal, com voluntários saudáveis, com idade igual ou superior a 65 anos, não tabagistas, urbanos. Em uma única visita, foram coletados dados demográficos, antropométricos e clínicos, seguidos da realização de provas de função pulmonar em repouso (espirometria, medidas de volumes pulmonares e difusão) e do teste cardiopulmonar de exercício máximo (TCPE). Os resultados obtidos foram comparados com os valores esperados de acordo com equações de referência rotineiramente utilizadas para a interpretação (teste-T pareado e avaliação de concordância pelo diagrama de Bland-Altman) e a frequência de casos fora das faixas previstas foi determinada. Novas equações de referência foram geradas por regressão linear múltipla. Resultados: Foram incluídos 95 indivíduos (55 mulheres), com idade (anos) 75 ± 6 (feminino) e 74±6 (masculino). Caracterizou-se diferença significativa entre as médias dos parâmetros de função pulmonar em repouso observados e previstos por pelo menos 2 das 3 equações testadas para CVF, VEF1, CPT, VR e difusão para ambos os sexos. O mesmo ocorreu para os parâmetros funcionais ao exercício (carga e VO2 no pico do esforço) para 3 de 4 equações testadas. Não houve homogeneidade de um autor específico em predizer com melhor acurácia os valores observados na amostra testada para todos os parâmetros funcionais em ambos os sexos. A frequência de classificação de parâmetros fora das faixas de referência foi elevada para todas as equações avaliadas. Novas equações de referência foram apresentadas a partir dos dados obtidos. Conclusões: A utilização das equações de referência existentes apresentou aplicabilidade limitada à amostra de idosos saudáveis estudada, gerando elevados índices de valores sub e superestimados, potencialmente comprometendo a sensibilidade e especificidade dos testes. Foram derivadas equações idade-específicas para uma amostra de idosos suadáveis brasileiros, visando contemplar as mudanças fisiológicas nesta faixa etária<br>Introduction: Differentiating between health and disease of the respiratory system becomes more challenging due to the tendency of population aging and the need to identify themselves senescence changes. Pulmonary function tests are important tools for respiratory evaluation. Its interpretation is based on reference equations derived from healthy people studies that possibly not accordingly express the behavior at this particular age group, due to the low representativity of elderly individuals in the studies that postulated such equations. Objective: To verify the accuracy of reference equations available for pulmonary function and cardiopulmonary exercise tests in comparison to values obtained in a sample of healthy elderly subjects and assess the clinical impact on functional interpretation based on these equations. Methodology: Cross-sectional observational prospective study in healthy volunteers, aged over 65 years, non-smokers, urban living. Demographic, anthropometric and clinical data, were collected and pulmonary function tests at rest (spirometry, lung volumes measures and diffusing capacity pulmonary), and the maximal cardiopulmonary exercise test (CPET) were performed. Results were compared to the expected values according to reference equations routinely used for interpretation (paired t-test and evaluation agreement by Bland-Altman plot) and the frequency of cases outside the reference ranges were determined. New reference equations elderly-specific were generated using multiple linear regression. Results: 95 subjects (55 women), age (years) 75 ± 6 (female) and 74 ± 6 (male) were included. Significant difference between the mean lung function parameters observed versus predicted by at least 2 of 3 tested equations for FVC, FEV1, TLC, RV for both sexes were identified. The same occured for exercise measurements (load and VO2 at peak exercise) for 3 of 4 tested equations. There was no homogeneity of a particular author to predict more accurately values observed in the sample tested for all functional parameters in both sexes. There was high rates of out of reference range classification for all evaluated equations. New elderly-specific reference equations were presented from the data obtained. Conclusions: The use of existing reference equations had limited applicability to the sample of healthy elderly studied, generating high rates of under and overestimated values, potentially compromising the sensitivity and specificity of the tests. Age-specific equations were derived from a sample of Brazilian healthy elderly, aiming to represent the physiological changes in this age group

Background: Exercise capacity (EC) is widely recognized as a strong and independent predictor of mortality and disease progression in various diseases, including cardiovascular and pulmonary diseases. Furthermore, it is generally accepted that exercise capacity in healthy individuals and in patients suffering from cardiovascular diseases is mainly limited by the maximum cardiac output. Objectives: This thesis investigated the impact of different lung function indices on EC in healthy individuals, patients with cardiovascular disease (e.g., pulmonary hypertension (PH)) and patients with pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD)). Methods: The present thesis is based on cross-sectional and longitudinal analyses of patients suffering from COPD, attending pulmonary rehabilitation at Uppsala University Hospital (studies I and II), and healthy men enrolled in the “Oslo ischemia study” (study IV). Study III is a cross-sectional study of patients suffering from PH attending the San Giovanni Battista University Hospital in Turin. EC was assessed using a bicycle ergometer in studies I and IV, with 12-minute walk tests (12MWT) in study II and with 6-minute walk tests (6MWT) in study III. Extensive pulmonary function tests, including diffusing capacity of the lung (DLCO), were performed in studies I-III and dynamic spirometry was used to assess lung function in study IV. Results: DLCO is more closely linked to decreased levels of EC than airway obstruction in COPD patients. Furthermore, the decline in 12MWT over a 5-year period was mainly explained by deterioration in DLCO in COPD patients. Spirometric parameters indicating airway obstruction significantly related to EC and exercise-induced desaturation in PH patients. A significant, but weak association between lung function parameters and EC was found in healthy subjects and this association is strengthened with increasing age. Conclusion: DLCO is the strongest predictor of low EC and EC decline in COPD. In PH, airway obstruction is strongly related to reduced 6MWT. Therefore, extensive analysis of lung function, including measurements of diffusing capacity, along with standard assessment of airway obstruction, gives a more comprehensive assessment of the functional exercise capacity in patients suffering from pulmonary hypertension or COPD. Lung function is also significantly linked to EC even in healthy subjects, lacking evident cardiopulmonary diseases.

The inhalation lesion is one of the biggest mortality causes in fire exposed patients at closed places. Medium and long follow-up respiratory consequences are still rarely reported at world literature. Alveolar-capillary membrane commitment caused by inhaled particles can persist during several years and progress to bronchiolitis obliterans. Thereby, the objective of this work was to evaluate the Diffusing Capacity for Carbon Monoxide (DLCO) lung test, at patients that inhaled toxic smoke at a fire in the nightclub Kiss at January 2013, in Santa Maria, parallel 29°, south Brazil, after first year follow-up. Were included 64 patients that were submited to DLCO and 6-minutes Walk Test (WT6) measurements. Dates were obtained by standard formularies including demographic characteristics, respiratory symptoms and inhalatory medication use. DLCO average was 63% (20,95 mL/mmHg/min) from predict and WT6 distance was 505,55 meters. At studied sample, 21,8% were asthmatics and when compared to no-asthmatics, they had better DLCO (p = 0,017). There was no statistical significance when compared other variables how: tracheal intubation, dyspnea, tabagism, dessaturation at WT6, smoke exposure time and intubation duration to DLCO results. Studied patients had a DLCO reduction greater than current literature. Development of chronic pulmonary complications, especially bronchiolitis obliterans, is a concrete possibility and must be better clarified and adequate screened. Late development of this kind of complication makes a prolonged ambulatorial follow-up indispensable.<br>A lesão inalatória é uma das grandes causas de mortalidade em pacientes expostos a incêndios fechados. As consequências respiratórias a médio e longo prazo nos sobreviventes ainda é pouco relatada na literatura mundial. O comprometimento da membrana alvéolo capilar pelas partículas inaladas pode persistir ao longo dos anos e progredir para bronquiolite obliterante. Desta forma, o objetivo deste trabalho foi avaliar o teste de difusão do monóxido de carbono (DLCO), nos pacientes que inalaram fumaça tóxica no incêndio ocorrido na Boate Kiss em Janeiro de 2013, em Santa Maria, paralelo 29°, no Sul do Brasil, após o primeiro ano do incêndio. Ao todo foram incluídos 64 pacientes, os quais foram submetidos à medida da DLCO e ao teste de caminhada de seis minutos (TC6). Os dados foram obtidos através de questionário contendo informações que incluíam características dos pacientes, sintomas respiratórios e uso de medicação inalatória. A DLCO média foi 63% do previsto (20,95 mL/mmHg/min) e a média da distancia no TC6 foi 505,5 metros. Na amostra estudada, 21,8% eram asmáticos e quando comparados a não asmáticos, possuíam melhor DLCO com p 0,017. Não houve significância estatística quando comparados outras variáveis como: intubação orotraqueal, dispneia, tabagismo, dessaturação no TC6, tempo de exposição, dias de intubação ao resultado da DLCO. Os pacientes estudados apresentaram redução na DLCO maior que a encontrada na literatura. O desenvolvimento de complicações pulmonares crônicas, em especial, bronquiolite obliterante, é uma possibilidade concreta e deve ser esclarecida e adequadamente rastreada. A característica tardia dessas complicações torna o seguimento ambulatorial prolongado imprescindível.

Made available in DSpace on 2016-06-02T20:19:26Z (GMT). No. of bitstreams: 1 6645.pdf: 2027088 bytes, checksum: 18fe5648e0835cf1cfcbef303f079520 (MD5) Previous issue date: 2015-02-27<br>Universidade Federal de Sao Carlos<br>In chronic obstructive pulmonary disease (COPD), functional and structural impairment of lung function can negatively impact heart rate variability (HRV); in addition, a reduced exercise capacity is an important independent prognostic marker in COPD patients. However, 1) if the degree of lung impairment negatively impacts HRV responses and 2) whether the injury of the autonomic control may be associated with reduced exercise capacity in patients with COPD remain unclear. Thus, two studies were conducted in order to verify if functional status at rest and during exercise would be related to autonomic impairment in COPD patients. In the first study, entitled "Relationship between linear and nonlinear dynamics of heart rate and impairment of lung function in COPD patients," we investigated whether the impairment static lung volumes and lung diffusion capacity (DL) would be related to HRV indices in moderate-to-severe COPD. Sixteen patients with COPD underwent pulmonary function tests (spirometry, plethysmography and lung diffusion capacity for carbon monoxide - DLCO). The RR interval was registered in the supine, standing and seated positions and during a respiratory sinus arrhythmia maneuver (M-RSA). Our results suggest that responses of HRV indices were more prominent during M-RSA in moderate-to-severe COPD. Moreover, greater lung function impairment was related to poorer heart rate dynamics. Finally, impaired DLCO is related to an altered parasympathetic response in these patients. The second study, entitled "Are linear and nonlinear heart rate dynamics in submaximal exercise related to cardiorespiratory responses during maximal exercise in patients with COPD?", we inquired whether there is a relationship between HRV responses and exercise capacity in patients with COPD. Fifteen patients underwent incremental cardiopulmonary exercise testing and six-minute walk test (6MWT). The RR interval was registered at rest (standing position) and during 6MWT. Our results showed that HRV responses at rest and during simple field tests may reflect functional impairment of COPD patients, providing important information about both ventilatory and hemodynamic inefficiency in these patients.<br>Em pacientes com doença pulmonar obstrutiva crônica (DPOC), as alterações funcionais e estruturais do pulmão podem impactar negativamente na variabilidade da frequência cardíaca (VFC). Além disso, a reduzida capacidade de exercício se traduz como um marcador prognóstico nesses pacientes. No entanto, ainda não estão esclarecidos 1) se o grau de comprometimento pulmonar tem impacto negativo sobre as respostas da VFC, frente a diferentes estímulos autonômicos, e 2) se o prejuízo no controle autonômico pode estar relacionado à reduzida capacidade de exercício nos pacientes com DPOC. Sendo assim, dois estudos foram realizados com o intuito de relacionar as alterações funcionais, no repouso e no exercício, com o grau de prejuízo autonômico em pacientes com DPOC. O primeiro estudo, cujo título é Correlação entre as dinâmicas linear e não linear da frequência cardíaca e o comprometimento da função pulmonar em pacientes com DPOC , teve como objetivo investigar se o comprometimento nos volumes pulmonares estáticos e na difusão pulmonar estaria relacionado aos índices da VFC em repouso e em resposta às mudanças posturais. Dezesseis pacientes com diagnóstico de DPOC foram submetidos à prova de função pulmonar (espirometria, pletismografia e capacidade de difusão pulmonar ao monóxido de carbono DCO) e à coleta da VFC nas posturas supino, ortostatismo e sentado e durante a manobra de arritmia sinusal respiratória (M-ASR). Nossos resultados sugerem que as respostas da VFC frente a um estímulo vagal (M-ASR) são mais evidentes. Ainda, quanto maior o comprometimento da função pulmonar pior a dinâmica da frequência cardíaca. Por fim, a redução da DCO está relacionada à alterada resposta vagal nos pacientes com DPOC. O segundo estudo, intitulado Os índices da dinâmica linear e não linear na frequência cardíaca no exercício submáximo estão relacionados com as respostas cardiorrespiratórias ao exercício máximo em pacientes com DPOC? teve por objetivo avaliar se existe relação entre as respostas da VFC e a capacidade de exercício em pacientes com DPOC. Quinze pacientes foram submetidos aos testes de exercício cardiopulmonar incremental e de caminhada de seis minutos (TC6). A coleta da VFC feita em repouso (ortostatismo) e durante o TC6. Os resultados mostraram que as respostas da VFC no repouso e em testes simples de campo podem inferir o prejuízo funcional de pacientes com DPOC, fornecendo informações importantes acerca das limitações ventilatória e hemodinâmica destes pacientes.

To investigate the relationship between pulmonary diffusion limitation, ventilation-perfusion (VA/Q) mismatch, pulmonary transit times (PTT) and pulmonary gas exchange during exercise, 10 highly trained male athletes (age=26.4±4.4 years, Height=185.5±5.3cms, Weight=78.2±8.6 kg, V 02max=5.15±0.521-min-1) under went exercise testing at rest (R) and 150W, 300W and maximal exercise (372±22W), corresponding to an oxygen consumption (V0₂) of 0.41±0.09, 2.16±0.17, 4.32±0.35 and 5.13±0.50 1-min-1respectively, while trace amounts of six inert gases were infused via a peripheral vein. Arterial blood samples, mixed expired gas samples and metabolic data were obtained. Observed alveolar arterial difference ([A-a]D0₂(0)was calculated according to the alveolar gas equation. Indices of VA/Q mismatch: LogSDi and Log SDa and predicted [A-a]D0₂([A-a]DO₂(p)) were derived from 50 compartment model analysis of retentions and excretions of the inert gases. Additional indices of '/A/I,) mismatch: DISPR*, DISPE and DISPR*_E and inert gas alveolar difference ([A-a]D, R(A-a)D and E(A-a)D) were obtained directly from the inert gas data. One to two weeks later, the subjects underwent first pass radionuclide angiography using a Siemens ZLC wide field of view gamma camera. Following in vitro labeling with 99mTechnecium, 5-10 ml of the subject's blood, containing 10-20 mCi of activity, were injected at rest. First pass and post-static data were obtained on an ADAC 3003 computer and cardiac output was calculated using the Stewart Hamilton equation. PTT was determined using deconvolution and centroid methods. Gated radionuclide angiography was then performed at rest, 150, and 300W. On a separate occasion, first pass cardiac outputs and pulmonary transit times were obtained at maximal exercise. Mean arterial partial pressure of 0₂ (Pa0₂) decreased significantly from rest to 150W , and from 150 to 300W to a low value of 86±9 torn, before increasing to near resting values at maximal exercise. [A-a]D0₂(3) increased across each exercise levels however only the increase from 150 to 300 W was significant. The overall and perfusion-related indices of VA/Q mismatch showed a significant increase with exercise, mainly as a result of increasing perfusion of areas of high VA/Q [A-a]D0₂(0 was greater than predicted, becoming significant during heavy exercise, indicating diffusion limitation. Cardiac output increased from 6.9±0.9 1-min-1 (R) to 25.2±2.5 1-min-1 at 300W and 33.3±3.7 1-min-1 at maximal exercise. End diastolic volume increased from R to heavy exercise (p < 0.001), accompanied by a decrease in end systolic volume (p =0.05). Stroke volume and ejection fraction also increased significantly from R to 300W (p <0.001). Deconvolution PTT decreased from 9.32±1.41 s at rest to 2.91±0.30 s during max exercise and was highly correlated with centroid PTT both at rest (r=0.99, p<0.001) and during maximal exercise (r=0.96, p<0.001). PTT during maximal exercise was significantly correlated with Pa0₂ (1=0.65, p<0.05) and [A-a]D0₂(0)_[A-a]D0₂(p) (r=-0.60, p<0.05). Calculated pulmonary blood volume increased during maximal exercise by 57% over resting values to over 25% of total blood volume and when corrected for body surface area correlated significantly with Pa0₂ (r=0.69, p<0.05). There was a significant correlation between (A-a)D, PTT, the ventilatory equivalent for CO₂ and Pa0₂ during maximal exercise (r=0.94, p<0.01) allowing prediction of over 80% of the variance in Pa0₂ between subjects. These data indicate that highly trained athletes develop VA/Q mismatch accompanied by diffusion limitation during maximal exercise. Observed decrease in Pa0₂2 during high intensity exercise is the result of a complex interaction between VA/Q mismatch, hypoventilation and diffusion limitation secondary to shortened pulmonary transit.

Pulmonary gas transport has not been typically recognized as a limiting factor to physical exercise. Dempsey et al. (1984; 1986) have suggested that the pulmonary system remains unchanged despite chronic aerobic training. Adaptations to other physiological systems may impose metabolic demands which the respiratory system can not meet. In essence, the lung's capacity for gas exchange becomes surpassed by other training adaptations. Supporting evidence is seen as decreases in arterial oxygenation at near maximal work rates in highly trained male endurance athletes (Dempsey et al., 1984; Powers et al., 1988; 1989; Hopkins and McKenzie 1989). Decreased arterial oxygenation has been termed exercise-induced arterial hypoxemia (EIH), and has direct consequences on VO₂max (Lawler et al., 1988; Powers et al., 1989; Martin and O'Kroy, 1993) and maximal performance capacity (Koskolou and McKenzie, 1994). It is estimated that approximately fifty percent of highly trained male endurance athletes exhibit EIH (Powers et al., 1988; 1993; Martin et al., 1992b). One mechanism that has been advanced to explain this phenomenon is a diffusion limitation. Diffusion capacity of the lung (DL) may be depressed during exercise and not allow for complete gas equilibrium to occur. If a structural alteration were present during exercise, it would continue to depress DL during recovery. To investigate the time course of change in pulmonary diffusion capacity for carbon monoxide (DL[sub co]) ten (N=10) highly trained male cyclists (HT) and ten (N=10) moderately (MT) male subjects were selected for this study. Subjects cycled to exhaustion to determine maximal oxygen consumption (VO₂max) on an electronically braked cycle ergometer (Mijnhardt KEM-3) (mean ± SD; HT VO₂max = 68.0 ± 4.9; MT VO₂max = 51.6 ± 4.7 mL-kg⁻¹Emin⁻¹). Percent arterial oxygen saturation (%SaO₂) was monitored by a pulse oximeter (Ohmeda Biox 3740) to determine if subjects demonstrated exercise-induced arterial hypoxemia (defined as %SaO₂ ≤ 91%) (%SaO₂min HT = 91.4 ± 1.6; MT = 94.6 ± 1.1). At a second data collection period, pulmonary function testing was performed. All subjects demonstrated normal pulmonary function. Initial diffusion measurements were made to obtain resting DL[sub CO]. diffusion capacity of the alveolar membrane (DM), and pulmonary capillary blood volume (Vc). Both spirometry and diffusion measurements were made using the same apparatus (Collins PLUS DS II). DM and Vc were calculated by measuring DL[sub CO] at two inspired O₂ concentrations using the technique of Roughton & Forster (1957). Subjects then cycled to fatigue at a workrate that corresponded to the highest workrate attained during the VO₂max test. Expired gases and %SaO₂ data were collected during the time to fatigue cycle test. Five additional measurements of pulmonary diffusion were made at 1, 2, 4, 6 and 24 hours following the cycle test. One hour post-exercise, DL[sub CO] was significantly decreased in both groups compared to baseline. The decrease reached a minimum value at 6 hrs and approached normal values 24 hrs after the exercise. Only HT subjects exhibited EIH yet both groups experienced similar changes in DL[sub CO] The correlation between %SaO₂min and change in DL[sub CO] was low (r=-0.3), implying that EIH can not be explained by post exercise decrease in DL[sub CO]. The change in DL[sub CO] can be explained primarily by a parallel decrease in Vc. Vc decreased below baseline values in both groups, perhaps indicating a compensatory shunting mechanism. A smaller degree of change was observed in DM, and played less of a role in the decreased DL[sub CO]- The results of this study are the first to compare diffusion capacity in two separate groups, based on training status, following maximal exercise. Both moderately trained and highly trained subjects exhibited similar decreases in pulmonary diffusing capacity. This supports the theory that the lung may not adapt to aerobic training and behaves in a similar manner regardless of training status.

Pulmonary diffusing capacity for nitric oxide (DLNO) is a relatively new pulmonary function test to assess gas transfer in the lung. To date, there are no prediction equations made for healthy adult African-American (black) subjects. Thus, the purpose of this study was to create prediction equations for DLNO in this ethnic/racial group. A total of 59 healthy subjects (27 males and 32 females) were recruited to perform pulmonary function testing at Georgia State University. They were diverse in age (18-67 yr), height (140-189 cm), and body mass index (17.2-32.3 kg/m2). All subjects completed single-breath maneuvers at rest inhaling 43 ± 4 ppm NO with a standard diffusion mixture. The breath-hold duration was 5.6 ± 0.6 s. Multiple linear regression predicted DLNO based on the subject’s age, height, and sex. The prediction equation for DLNO (mL/min/mmHg) = 0.92·(height in cm) +38.8·(sex) – 0.012·(age2) – 25, where 1 = male, 0 = female for sex. About 77% of the variance in DLNO was accounted for by sex (67%), age2 (7%), and height (4%). The standard error of the estimate in predicting DLNO was 16.3 mL/min/mmHg. Those with higher resting heart rates had a lower DLNO (r =-0.28, p = 0.03) but it was not included in the regression model as it did not enhance the fit. Black males had a 7-10% lower DLNO and black females had a 12-15% lower DLNO compared to matched white subjects. Black males of the same age and height had a 10% smaller alveolar volume, while black females had a 15% lower alveolar volume compared to matched white subjects. In conclusion, DLNO values and alveolar volumes are reduced in blacks compared to matched whites. The regression model presented best predicts DLNO in African-Americans below 40 years of age.

The purpose of this study was to determine whether a reduced post-exercise pulmonary diffusing capacity (DL) had a physiological effect on subsequent exercise. Thirteen endurance-trained male athletes (age = 27 ± 3 yrs; ht = 179.6 ± 5.0 cm; mass = 71.8 ± 6.9 kg; VChmax = 67.0 ± 3.6 ml‧kg⁻¹‧min⁻¹) performed two consecutive V02max exercise tests, separated by 60 min of recovery. Testing was on an electronicallybraked cycle ergometer (Quinton, Excalibur) using a ramp protocol (30 W-min"1). Arterial oxygen saturation (%SaO₂) was measured via ear oximetry (Ohmeda Biox 3740 pulse oximeter), and resting DL was measured by a single-breath carbon monoxide diffusing capacity test (Collins Survey Tach Pulmonary Function Testing Unit), prior to exercise and 60 min following each exercise bout. In order to partition the membrane diffusing capacity (DM) and pulmonary capillary volume (Vc) from DL, two test gases were used (21% O₂ and 90% O₂ with 0.3% CO). Athletes that exhibited a decrease in %SaO₂ ≤ 91 during exercise were grouped as desaturaters (D) all others were grouped as nondesaturaters (ND). There was a significant difference in %SaO₂ between D and N D (p = 0.0001); however, all other measures between the two groups were not significantly different. There were no significant differences in VO₂max or %SaO₂min between exercise bouts. A 1.7% decrease (p = 0.003) in peak power output occurred during the second exercise test (Ex2). Significant decreases occurred in DL (p< 0.0001), DM (p = 0.02) and Vc (p < 0.0001) post-exercise, as compared to pre-exercise. DL decreased 11% following the initial exercise bout (p < 0.05) and a further 6% (p < 0.05) from post-exercise 1 (Exl) to post-Ex2. Similarly, Vc showed an overall decrease of 20% with a 10% decrease (p < 0.05) between exercise bouts. DM showed a significant (p < 0.05) 11% decrease from pre-exercise to post-Exl and a further 2% decrease (p > 0.05) between post-Ex 1 and post-Ex2. A strong positive linear relationship existed in D between changes in %SaO₂ and changes in D L (r = 0.87, p = 0.03), and between changes in %SaO₂ and changes in DM (r = 0.85, p = 0.03) consequent to Exl. No linear relationship existed for changes in D during Ex2 or during either exercise bout for ND. Rapid shallow breathing (RSB) was observed during recovery (R) following both exercise bouts. No significant differences in breathing pattern existed between Exl - Rl and Ex2 - R2, or between D and ND. The development of RSB and decreases in DM following exercise support the presence of pulmonary edema. Because no further changes were observed following the second exercise bout and no differences existed between D and ND, alternate mechanisms in addition to diffusion limitations, must contribute to the final decrease in %SaO₂.

Pulmonary diffusing capacity for carbon monoxide (Dlco), alveolar-capillary membrane diffusing capacity (Dm), and pulmonary capillary blood volume (Vc) are all significandy reduced following exercise. It is unknown if measurement position affects this impaired gas transfer postexercise. Prior to (baseline) and 15 minutes, 1, 2, and 4 hours following an incremental cycle to fatigue Dlco, Dm, and Vc were recorded in 10 healthy male subjects in both a supine and upright seated position. It was expected that the supine post-exercise measurement position would significantly reduce the decrement in Vc and thus Dlco, by facilitating a return of blood to the thoracic cavity. With removal of the 15 minute data, due to the lack of achievement of a resting cardiovascular state (heart rate, systolic and diastolic blood pressure all significantly different from baseline), a significant reduction in Dlco, Dm, and Vc was observed 1, 2, and 4 hours postexercise, as indicated in Table 1. [TABLE 1] There was a significant difference between positions for Dlco (4.66+0.98 vs. 5.22±0.89, seated vs. supine, p=0.022) and Dm (6.28±1.36 vs. 7.00+1.32, seated vs. supine, p=0.016), but there was no position effect for Vc. Nor was there any significant interaction between the positions over time for Dlco, Dm, or Vc. The change in Dlco appears to be primarily due to a decrease in Vc. The limited decrease in Dm in the supine position was likely due to a redistribution of blood within the lung, due to gravity, enhancing the surface area available for diffusion. Although the mechanism for the reduction in Vc cannot be determined from this data, a passive relocation of blood into the periphery due to gravity can be discounted, indicating that active vasoconstriction of the pulmonary vasculature and/or peripheral vasodilatation maybe occurring post-exercise. This is the first data to indicate that the maintained diffusion impairment is independent of measurement position.