Dissertations / Theses on the topic 'Pulmonary function tests'

The lungs are an incredibly complex pair of organs, whose function is strongly driven by both shape and structure. However, in standard clinical practice lung function is assessed through analysis of 'at-the-mouth' measurements, which by their nature represent a smoothing of behaviours throughout the lungs. Due to this there is a lack of precision in the understanding of how different pulmonary function test outputs respond to different types of lung disease. Within this thesis we apply mathematical and computational modelling to analyse and improve understanding of these responses, and to generate hypotheses that are suitable for further clinical investigation. In the early chapters physics-based models of ventilation, gas transport and frequency propagation within the lungs are developed, and then implemented in efficient computing environments. These models are then applied to the exploratory analysis of indices derived from three pulmonary function tests: the multiple-breath washout; the forced oscillation technique; and magnetic resonance imaging, under a variety of bronchoconstrictive patterns. Following preliminary analysis, we provide a detailed validation of the washout and frequency propagation models, and then show how these models can help create clinical insight as to how different test indices can be most effectively interpreted. In the later chapters we extend upon earlier models, to incorporate flow and gas transfer processes throughout the pulmonary bloodstream. By embedding these models in high-performance computing environments, we create a tractable way to simulate function of the entire pulmonary system. Following implementation of the pulmonary model, we apply it to analyse how gas choice may affect the multiple-breath washout. Finally, we close the thesis with a discussion of the role of mathematical modelling in clinical medicine, of the clinical relevance of results within this thesis, and of the potential for future work.

Lung spirometry data from three working-class industry populations were analyzed using logistic and linear regression to see if seasonality adversely affected test outcomes. Populations included emergency responders, general industry, and shipwrights. The data was organized into allergy and non-allergy seasons using NOAA meteorological data and regression and logistic analysis was run on these separate populations to test for demographic and seasonal effects on lung spirometry test outcomes. The American Thoracic Society gold standard was as a point for determining impaired lung function (FEV1/FVC > 0.80). It was found that seasonality imparted a slight linear effect on the predictive values of FEV1 and FVC for determining impaired lung function FEV1 and FVC values were Pr > 0.0003 and Pr > 0.0002, respectively. For demographic variables, age imparted the greatest linear effect for FEV1 and FVC, with significant p-values of 0.0002 and

Objective: To investigate the adverse effect of welding exposure on pulmonary function test and respiratory symptoms in welders. Design: Cross-sectional study Setting: Guangzhou, China Subjects: 350 male welders in an automobile assembly factory and 350 controls in MTR corporation who had no exposure to welding fumes and toxic gases. Methods: The data was collected from Guangzhou No.12 People’s Hospital. This inclusion and exclusion criteria for subjects and controls were set. The relationship between pulmonary function, respiratory symptoms and welding exposure was investigated by comparing the prevalence of abnormal pulmonary function and respiratory symptoms among welders and non-welders. Chi-square was used for comparison of categorical variables. Logistic regression was performed to estimate odds ratios after adjustment for age, working duration and smoking habits. Results: After accounting for age, working years and smoking habit, the adjusted OR (95% C.I.) of pulmonary function among welders and non-welders was 1.425 (0.916, 2.215), suggesting that welders was associated with a 1.43 times as high the odds of being tested abnormal pulmonary function as non-welders. However, there was no significant (P=0.116) difference in odds between welders and non-welders. The differences of respiratory symptoms in odds between welders and non-welders was not significant (P>0.268). But when restricted to smokers, significant difference (p<0.05) in abnormal pulmonary function was found between welders (17.5%) and non-welders (10.6%). Of the respiratory symptoms, only prevalence of cough was found to be statistically higher (p<0.05) among welders (16.1%) who smoked than non-welders (8.0%) who smoked. Conclusion: It is not evident from my study thatwelders who worked in a well-ventilation working environment and well protected by wearing personal protective equipment are subjected to increased prevalence of abnormal pulmonary function and respiratory symptoms. Studies with larger samples and longer period of observation are warranted. Smoking was observed to be the most important factor contributing to the presence of abnormal pulmonary function and respiratory symptoms. Smoking cessation would be needed to carry out in welders.
published_or_final_version
Public Health
Master
Master of Public Health

O objetivo deste estudo foi investigar o grau de correlação entre testes de cabeceira e testes de função pulmonar em quatro grupos de indivíduos: sadios, gestantes (36ª semana), obesos (IMC 40 Kg/m2) e idosos ( 60 anos). Foram estudados 20 indivíduos por grupo. Os testes realizados foram: Teste de ventilação (ventilometria, VVM, Espirometria, Medidas de Pimax e Pemáx) e Testes de Cabeceira (Teste da Vela, Teste de Apnéia, Cirtometrias torácica e abdominal). Para a medida de ventilometria e VVM foi utilizado um ventilômetro e para as medidas de CVF, VEF1, VEF1/CVF% e PFE utilizou-se um espirômetro portátil. Para as medidas de Pimax e Pemáx utilizou-se um manovacuômetro analógico. No Teste da vela considerou-se a distância em que a chama foi apagada. A distância inicial foi de 60 cm e esta foi diminuída de 10 em 10 centímetros até que o sucesso fosse atingido. No teste de apnéia, após 3 testes, foi considerado o maior tempo. No grupo obeso, as correlações do Teste de Apnéia com a VVM, CVF, VEF1, PFE e Pemáx foram estatisticamente significantes. Houve correlação significante do Teste da Apnéia com a VVM, CVF, VEF1, PFE e Pemáx. No teste da vela, os coeficientes foram todos positivos, com exceção do grupo gestante no qual eles foram negativos. Houve correlação significante do torácico inspiratório em quase todos os grupos. Houve correlação do torácico expiratório com a VVM apenas no grupo obeso. No abdominal inspiratório, os coeficientes foram todas positivos, mas sem significância estatística. Na correlação do abdominal expiratório, houve correlação positiva com todos os testes de ventilação, exceto no grupo controle, que mostrou correlação negativa do abdominal expiratório com VVM e PFE. Os testes de cabeceira possuem correlação com os testes espirométricos. .
The objective of this study was to investigate the degree of correlation between bed side tests and tests of pulmonary function in four groups of individuals: healthy, pregnant (36ª week), obese (IMC > 40 Kg/m2) and elderly (> 60 years). Twenty individuals for group had been studied. The carried through tests had been: test of ventilation (ventilometry, VVM, spirometry, Measures of Pimax and Pemáx) and bed side tests (Test of the Candle, Test of Apnea, thoracic and abdominal circunference). For the measure of ventilometry and VVM, a ventilometer was used one and for the measures of CVF, VEF1, VEF1/CVF and PFE one was used portable espirometer. For the measures of Pimax and Pemáx one was used analogical manavacuometer. In the Test of the candle it was considered in the distance where the flame was extinguished. In the distance initial it was of 60 cm and this was diminished of 10 in 10 centimeters until the success was reached. In the apnea test, after 3 tests, were considered the biggest time. In the group obese, the correlations of the Test of Apnea with the VVM, CVF, VEF1, PFE and Pemáx had been statistical significant. It had significant correlation of the Test of the Apnea with the VVM, CVF, VEF1, PFE and Pemáx. In the test of the candle, the coefficients had been all positives, with exception of the pregnant group in which they had been negative. toracic inspiratory in almost all had significant correlation of all the groups. thoracic expiratory with only the VVM in the group had correlation of obese. In abdominal inspiratory, the coefficients had been all positives, but without significance statistics. In the correlation of abdominal expiratory, had positive correlation with all the ventilation tests, except in the group has control, that it showed to negative correlation of abdominal expiratory with VVM and PFE. The bed side tests possess correlation with the spirometrics tests.

Three longitudinal pulmonary function data sets were analyzed by several statistical methods for the purposes of: 1) determining to what degree the conclusions of an analysis for a given data set are method dependent; 2) assessing the properties of each method across the different data sets; 3) studying the correlates of FEV₁ decline including physical, behavioral, and respiratory factors, as well as city of residence and type of work. 4) assessing the appropriateness of modelling the standard linear relationship of FEV₁ with time and providing alternative approaches; 5) describing longitudinal change in various lung function variables, apart from FEV₁. The three data sets were comprised of (1) yearly data on 141 veterans with mild chronic bronchitis, taken at three Canadian centres, for a maximum of 23 years of follow-up; their mean age at the start of the study was 49 years (s.d.=9) and only 10.6% were nonsmokers during the follow-up; (2) retrospective data on 384 coal workers categorized into four groups according to vital status (dead or alive) and smoking behavior, with irregular follow-up intervals ranging from 2 to 12 measurements per individual over a period of 9 to 30 years; (3) a relatively balanced data set on 269 grain workers and a control group of 58 civic workers, which consisted of 3 to 4 measurements taken over an average follow-up of 9 years. Their mean age at first measurement was 37 years (s.d.=10) and 53.2% of the subjects did not smoke. A review of the pulmonary and statistical literature was carried out to identify methods of analysis which had been applied to calculate annual change in FEV₁. Five methods chosen for the data analyses were variants of ordinary least squares approaches. The other four methods were based on the use of transformations, weighted least squares, or covariance structure models using generalized least squares approaches. For the coal workers, the groups that were alive at the time of ascertainment had significantly smaller average FEV₁ declines than the deceased groups. Post-retirement decline in FEV₁ was shown by one statistical method to significantly increase for coal workers who smoked, while a significant decrease was observed for nonsmokers. Veterans from Winnipeg consistently showed the lowest decline estimates in comparison to Halifax and Toronto; recorded air pollution measurements were found to be the lowest for Winnipeg, while no significant differences in smoking behavior were found between the veterans of each city. The data set of grain workers proved most ameniable to all the different analytical techniques, which were consistent in showing no significant differences in FEV₁ decline between the grain and civic workers groups and the lowest magnitude of FEV₁ decline. It was shown that quadratic and allometric analyses provided additional information to the linear description of FEV₁ decline, particularly for the study of pulmonary decline among older or exposed populations over an extended period of time. Whether the various initial lung function variables were each predictive of later decline was dependent on whether absolute or percentage decline was evaluated. The pattern of change in these lung function measures over time showed group differences suggestive of different physiological responses. Although estimates of FEV₁ decline were similar between the various methods, the magnitude and relative order of the different groups and the statistical significance of the observed inter-group comparisons were method-dependent No single method was optimal for analysis of all three data sets. The reliance on only one model, and one type of lung function measurement to describe the data, as is commonly found in the pulmonary literature, could lead to a false interpretation of the result Thus a comparative approach, using more than one justifiable model for analysis is recommended, especially in the usual circumstances where missing data or irregular follow-up times create imbalance in the longitudinal data set.
Graduate and Postdoctoral Studies
Graduate

The possibility that an inadequate response of the pulmonary system might limit high intensity exercise in man has received increasing attention over the past few years. However, very few scientific investigations have focused systematically on pulmonary function during high intensity constant-load exercise. Furthermore, many studies have examined only one part of the pulmonary system during exercise and some have not included blood gas measurements as a measure of the adequacy of pulmonary function. The studies reported in this thesis were designed to investigate the possible failure of the gas exchanging and pump functions of the pulmonary system during high intensity constant-load exercise. In particular, the aim was to determine the extent to which the pulmonary system might be a factor causing fatigue during this form of exercise.

Previously, Whipp et. al. (J. Appl. Physiol.: Respirat. Environ. Exerc. Physiol. 50(1):217-221, 1981) demonstrated the feasibility of determining four parameters of aerobic function, identified as maximum oxygen uptake (μVO_2), VO_2 at anaerobic threshold (θan), the time constant for oxygen uptake kinetics (rVO_2) and work efficiency (η), using a short duration ramped bicycle ergometer exercise test. Because of the importance of being able to measure these parameters on a variety of measurement instruments a short duration ramping treadmill protocol has been developed. The ability of this protocol to determine the four aerobic parameters has been validated against conventional methods. The results of this investigation indicate that μVO_2, θan, rVO_2 and, η may be obtained from a single, short-duration ramping treadmill test.

INTRODUÇÃO: A sobrecarga hemodinâmica pulmonar (SHP) está associada a entidades clínicas de elevada morbimortalidade como: o edema pulmonar pós-pneumonectomia, o tromboembolismo pulmonar, o transplante pulmonar e a situações fisiológicas como o exercício físico. Vários pontos da sua fisiopatologia não estão elucidados. OBJETIVOS: Estudar as alterações fisiopatológicas pulmonares e cardíacas induzidas pela SHP. MÉTODOS: Vinte porcos Large White foram anestesiados, intubados e submetidos à ventilação mecânica a volume seguida por toracotomia bilateral trans-esternal. Os elementos dos lobos pulmonares foram isolados através de dissecção cirúrgica, com reparo das artérias pulmonares do lobo inferior direito, lobo mediastinal e pulmão esquerdo. Os animais foram randômicamente alocados em 4 grupos de estudo (n=5), sendo um controle (C) e três de SHP (LI, LII e LIII) induzida através da oclusão das artérias pulmonares específicas. No grupo C (controle), todos os lobos tiveram sua perfusão mantida. No grupo LI, somente o pulmão direito foi perfundido. No grupo LII, o pulmão direito menos o lobo inferior e no grupo LIII, o pulmão direito menos os lobos mediastinal e inferior, obstruindo a vasculatura pulmonar em 42, 76 e 82% respectivamente. Variáveis de hemodinâmica e de trocas gasosas foram monitoradas durante 60 minutos de SHP. Ao final do regime de SHP o lobo médio foi ressecado para análise de variáveis estruturais: morfometria (alveolar e vascular) e cálculo da relação peso úmido / peso seco. Na análise estatística foram utilizados ajustes de modelos lineares mistos com estrutura de variâncias e covariâncias, ANOVA a um fator, regressão linear simples e regressão linear de efeitos mistos com intercepto e tendência aleatório. RESULTADOS: Nas comparações intergrupos houve diferenças significativas ao longo dos 60 minutos de SHP nas variáveis hemodinâmicas: Frequencia cardíaca (p=0,004), Pressão arterial média (p=0,01), Índice sistólico (p=0,002), Pressão arterial pulmonar (p=0,001) e Pressão capilar pulmonar (p<0,0001). Trocas gasosas: Relação PaO2/FiO2 (p=0,002), PaCO2 (p<0,0001), pH (p<0,0001), Índice de consumo tecidual de O2 (p=0,02), Fração de shunt (p=0,03). Estruturais: Edemas alveolar e perivascular (p<0,0001) em ambos e Relação peso úmido / peso seco (p=0, 005). Nas comparações intergrupos, não houve diferenças significativas das variáveis: Índice cardíaco (p=0,94), HCO3 (p=0,63), Índice de oferta tecidual de O2 (p=0,89) e Taxa de extração tecidual de O2 (p=0,08). CONCLUSÕES: A SHP promoveu disfunção pulmonar significativa em pulmões previamente hígidos com alterações estruturais (edema alveolar e perivascular) e elevação das pressões arterial e capilar pulmonar. A função cardíaca foi preservada apesar de grande redução no leito vascular pulmonar (82% no grupo LIII). No grupo LII houve melhora da disfunção pulmonar ao longo do tempo de SHP
INTRODUCTION: The pulmonary hemodynamic overload (PHO) is associates to high mortality and morbidity clinical entities as: postpneumonectomy pulmonary edema, pulmonary thromboembolism, lung transplantation and physiological situations as physical exercise. Some pathophysiological aspects related to PHO are not elucidated. OBJECTIVES: To study pulmonary and cardiac pathopysiological alterations induced by PHO. METHODS: Twenty Large White pigs were anesthetized, intubated and subjected to volume controlled mechanical ventilation followed to median sternotomy. Pulmonary lobes structures were isolated by surgical dissection and pulmonary arteries of left lung, right lower lobe and mediastinal lobe were completely isolated. The animals were randomized into 4 groups (n=5 each) with one control (C) and three of PHO (LI, LII and LIII) induced by pulmonary arterial occlusions specifics for each group. In the control group (C), all lobes were perfused, ie none of arteries were occluded. In the LI group, only the right lung was perfused; in the LII group, the right lung but the lower lobe; in LIII group, the right lung but the lower and mediastinal lobes, obstructing the pulmonary vasculature in 42, 76 and 82% respectively. Hemodynamics and gas exchange variables were monitored during 60 minutes of PHO. At the end of the study, the middle lobe was resected for analysis of structural variables: morphometry (alveolar and vascular) and calculation of the wet weight / dry weight ratio. Statistical analysis settings were used with mixed linear models of variance and covariance structure, a one-way ANOVA, simple linear regression and mixed effects linear regression with random intercept and trend. RESULTS: In intergroup comparisons there were significant differences during the 60 minutes of PHO in hemodynamic variables: Heart rate (p=0, 004), Systemic arterial pressure (p=0,01), Systolic index (p=0,002), Pulmonary arterial pressure (p=0,001) and Pulmonary capillary pressure (p <0,0001). Gas exchange: for PaO2/FiO2 ratio (p=0,002), PaCO2 (p<0,0001), arterial pH (p<0,0001), O2 consumption index (p=0,02), Shunt (p=0,03). Structural: perivascular and alveolar edema (p<0,0001) in both and the wet weight / dry weight ratio (p=0,005). There were no significant differences in intergroup comparisons of variables: Cardiac index (p=0,94), arterial HCO3 (p=0,63), O2 offer index (p=0,89) and O2 extraction (p=0,08). CONCLUSIONS: The PHO promoted significant pulmonary dysfunction in previously healthy lungs with structural changes (alveolar and perivascular edema) and increased arterial and pulmonary capillary pressures. Cardiac function was preserved despite the large reduction in pulmonary vascular bed (82% in group LIII). In LII group occurred reverse of pulmonary dysfunction with past of PHO time

A acromegalia é uma doença multissistêmica decorrente da hipersecreção do hormônio do crescimento (GH) e do fator de crescimento semelhante à insulina tipo I (IGF-I), o que resulta no crescimento somático exagerado e alterações nas proporções corporais, estando associada à considerável aumento da morbidade e mortalidade. Estima-se ainda que os problemas respiratórios contribuam com 25% de todas as mortes encontradas neste grupo de pacientes. Diferenças metodológicas entre os diversos estudos levaram ao surgimento de dados inconsistentes sobre o papel do crescimento alveolar no desenvolvimento do aumento do volume pulmonar em acromegálicos, o que reforça a importância de novos trabalhos e outras abordagens sobre o tema. Ao mesmo tempo, com o desenvolvimento tecnológico, os métodos de imagem propostos em alguns estudos foram substituídos por outros mais sensíveis como a tomografia computadorizada (TC) multislice (Q-MDCT) que garante adequada mensuração do volume pulmonar, o que proporciona diferentes tipos de comparação e análise e, ainda, permite o estudo anatômico do tórax e vias pulmonares. Nossos objetivos foram identificar os principais achados da tomografia computadorizada (TC) em pacientes acromegálicos, determinar por meio da TC de tórax o volume pulmonar e comparar os achados da densitometria pulmonar com os da função pulmonar entre pacientes acromegálicos com doença ativa e doença controlada e, secundariamente, correlacionar estes achados. Foi realizado um estudo transversal com 29 portadores de acromegalia que tiveram diagnóstico da acromegalia suspeitado por características clínicas e confirmado por níveis elevados de GH não suprimido ou com níveis de IGF-I acima do limite normal. Posteriormente, os pacientes foram subdivididos nos grupos doença ativa(11 indivíduos) e doença controlada(18 indivíduos), segundo os níveis séricos de IGF-I. Houve ainda um grupo controle (17 indivíduos) em que os pacientes, após já terem realizado TC de tórax por alguma razão, foram convidados à realizar os testes de função pulmonar. A Q-MDCT e os testes de função pulmonar apresentaram excelente correlação: o volume total do pulmão (VTP) medido na TC inspiratória apresentou correlação significante com a capacidade pulmonar total (rs=0,742, p=0,0001), enquanto VTP medido na TC expiratória apresentou correlação significante com a capacidade residual funcional (rs=0,606, p=0,0005). Os pacientes acromegálicos com doença ativa apresentaram pulmões mais pesados em relação aos controles [885 (723994) vs. 696 (599769) g, p=0.017]. Os pacientes com acromegalia ativa também apresentaram maiores quantidades de compartimentos pobremente aerados em relação aos outros dois grupos, sendo esta diferença observada em %VTP [3,25 (2,553,46) vs. 2,24 (1,702,56) vs. 1,70 (1,452,15), p = 0,001] e g [82,6 (75,4 100,2) vs. 63,9 (49,180,3) vs. 54,2 (42,259,2), p = 0,0001]. O compartimento pobremente aerado medido na TC inspiratória apresentou correlação significante com os níveis de GH e IGF (rs=0,407, p=0,029; rs=0,467, p=0,011, respectivamente). Em conclusão, a Q-MDCT mostra que os pacientes acromegálicos com doença ativa apresentam pulmões mais pesados e maiores quantidades de compartimentos não aerados e pobremente aerados. Há relações entre os achados da densitovolumetria pulmonar e os parâmetros dos testes de função pulmonar na acromegalia.

Introdução: O teste de apneia respiratória tem sido testado e demonstrou ser de utilidade clínica. Objetivos: Determinar o tempo de apneia voluntária máxima em pacientes com distúrbios ventilatórios obstrutivos (DVO) e em indivíduos normais e correlacionar os tempos de apneia com os testes de função pulmonar. Métodos: Foi realizado um estudo caso-controle incluindo pacientes com DVO (casos) e um grupo controle, composto por voluntários com espirometria normal, recrutados no Hospital de Clínicas de Porto Alegre (HCPA). A espirometria foi realizada com espirômetro computadorizado e o teste de apneia respiratória utilizando-se um sistema eletrônico microprocessado e um pneumotacógrafo ((Hans Rudolph ® – Kansas OH, EUA)– Kansas OH, EUA) como transdutor de fluxo. As curvas de fluxo respiratório foram exibidas em tempo real em um computador portátil e os tempos máximos de apneia voluntária inspiratória e expiratória (TAVIM e TAVEM) foram determinados a partir do sinal adquirido. Resultados: Um total de 35 pacientes com DVO (casos) e 16 controles foram incluídos no estudo. O TAVIM foi significativamente menor nos casos (22,3 ± 11,8 s) do que no grupo controle (31,5 ± 15,7 s) com p = 0,025. O TAVEM também foi significativamente menor nos casos (16,9 ± 6,6 s) do que no grupo controle (22,1 ± 7,9 s) com p = 0,017. Foram encontradas correlações positivas moderadas entre TAVIM e CVF (r = 0,476, p = 0,004) e entre TAVIM e VEF1 (r = 0,383, p = 0,023). Conclusões: As medidas de TAVIM e TAVEM foram significativamente menores nos casos do que nos controles, e o TAVIM teve correlação moderada com a CVF e VEF1. Estes resultados fornecem uma evidência adicional da utilidade clínica do tempo de apneia como teste de função pulmonar.
Introduction: Breath-holding test has been tested in some clinical scenarios and has proved to be of clinical utility. Objectives: To determine the maximum voluntary breath-holding time in patients with obstructive ventilator defects and in normal subjects and to correlate the breathholding times with pulmonary function tests. Methods: We conducted a case-control study including patients with obstructive ventilator defects and a control group consisted of volunteers recruited in the same hospital, with normal spirometry. Spirometry was performed using a computerized spirometer. The Breath-holding test was conducted using an electronic microprocessor and a (Hans Rudolph ® – Kansas OH, EUA)pneumotachograph and flow transducer. Respiratory flow curves were displayed in real time on a portable computer. The maximal voluntary apnea inspiratory and expiratory times (MVAIT and MVAET) were determined from the acquired signal. Results: A total of 35 patients with obstructive ventilatory defects and 16 controls met the inclusion criteria and were included in the analysis. The MVAIT was lower in cases (22.3 ± 11.8 seconds) than in controls (31.5 ± 15.7 seconds) (p=0.025). MVAET was also lower in cases than in controls (16.9 ± 6.6 vs. 22.1 ± 7.9; p=0.017). We found positive and significant correlations between MVAIT and FVC (L) (r=0.476; p=0.004) and between MVAIT and FEV1 (L) (r=0.383; p=0.023). Conclusions: MVAIT and MVAET were significant lower in patients with obstructive ventilatory defects than in controls, and that MVAIT was correlated positively with FVC and FEV1 in cases. Our results provide additional evidence of usefulness of MVAIT as a pulmonary function test.

INTRODUÇÃO: Linfangioleiomiomatose (LAM) é uma doença rara, caracterizada pela proliferação de células musculares lisas atípicas ao redor de vias aéreas, vasos sanguíneos e linfáticos, com formação de cistos pulmonares difusos. Na prova de função pulmonar (PFP), a doença se caracteriza por padrão obstrutivo, aprisionamento aéreo e redução da capacidade de difusão do monóxido de carbono (DLCO), podendo haver resposta positiva ao teste de broncodilatação. No teste de exercício cardiopulmonar (TECP), a menor tolerância ao esforço é frequente e secundária a múltiplas causas, com maior destaque para a limitação ventilatória. Entretanto, nem todos os fatores potencialmente limitantes foram investigados. Os principais objetivos do estudo foram avaliar a prevalência e os preditores de hiperinsuflação dinâmica (HD) em pacientes com LAM, em comparação a mulheres saudáveis (controles), investigando-se adicionalmente a resposta ao broncodilatador. METODOLOGIA: Realizou-se avaliação transversal de 42 pacientes com LAM utilizando-se questionário de qualidade de vida, PFP e TECP incremental no ciclo-ergômetro, com medida seriada da capacidade inspiratória (CI) para definir HD, comparando-se aos controles. As pacientes foram ainda submetidas ao teste de caminhada de seis minutos (TC6M). A seguir, elas foram incluídas em uma avaliação randomizada, cruzada, placebocontrolada, duplo-cega (salbutamol inalatório vs. placebo). PFP e TECP com carga constante, com medida seriada da CI, foram realizadas após cada intervenção. RESULTADOS: Comparando-se aos controles, as pacientes com LAM apresentaram pior qualidade de vida, principalmente nos domínios físico e emocional, e padrão obstrutivo, aprisionamento aéreo e redução da DLCO na PFP. As pacientes demonstraram ainda menor capacidade de exercício, associada com limitação ventilatória, dispneia mais intensa e maior dessaturação no esforço. HD ocorreu em 55% das pacientes, mesmo naquelas com alteração funcional leve, e não foi observada nos controles, correlacionando-se com obstrução ao fluxo aéreo, aprisionamento aéreo, comprometimento da DLCO e dispneia. Em comparação ao subgrupo que não teve HD (subgrupo não HD), as pacientes que desenvolveram HD (subgrupo HD) tinham maior tempo de diagnóstico, caracterizando-se por obstrução ao fluxo aéreo, aprisionamento aéreo e DLCO reduzida. Apesar da capacidade de exercício semelhante, observou-se que o subgrupo HD apresentou limitação ventilatória, além de maior dessaturação e maior grau de dispneia no TECP e no TC6M. Não houve redução da HD ou aumento do tempo de exercício após utilização de salbutamol inalatório, mesmo no subgrupo HD. CONCLUSÕES: HD é frequente nas pacientes com LAM, mesmo naquelas com alteração leve na espirometria, associando-se com duração e gravidade da doença, maior grau de dispneia e menor saturação de oxigênio. Limitação ventilatória e alteração da troca gasosa são importantes fatores para interrupção do exercício em pacientes com LAM. HD também se associa com maior dessaturação e dispneia mais intensa no TC6M. Salbutamol inalatório não reduz HD ou aumenta duração do exercício no ciclo-ergômetro.
BACKGROUND: Lymphangioleiomyomatosis (LAM) is a rare disease that is characterized by the proliferation of atypical smooth muscle cells around the airways, blood vessels and lymphatics, with diffuse pulmonary cyst formation. An obstructive pattern, with air trapping, and a reduction in the diffusion capacity of the lungs for carbon monoxide (DLCO) are found in pulmonary function tests (PFTs), and there may be a positive response to the bronchodilation test. In the cardiopulmonary exercise testing (CPET), a lower exercise tolerance is frequent, secondary to multiple causes, with a greater emphasis on ventilatory limitation. However, not all potentially exercise limiting factors were evaluated. The aims of this study were to evaluate the prevalence and predictors of dynamic hyperinflation (DH) in patients with LAM in comparison with healthy women. The response to bronchodilator was also evaluated. METHODS: A cross-sectional study with 42 patients with LAM was conducted, with evaluation of a quality of life questionnaire, PFTs and a ramp CPET on cycle, with serial measurements of inspiratory capacity (IC) to establish DH. Data were compared with the healthy control subjects. The patients also performed the six-minute walk test (6MWT). Then, the patients were included in a randomized, placebo-controlled, doubleblind, crossover evaluation (inhaled salbutamol vs. placebo). After each intervention, they performed PFTs and endurance CPET with serial measurements of IC. RESULTS: In comparison with the healthy individuals, the patients with LAM experienced an impaired quality of life, mainly in the physical and emotional domains. They also had obstructive pattern, air trapping and lower DLCO in the PFTs. LAM was associated with diminished exercise performance, in association with ventilatory limitation, greater dyspnea intensity and exercise desaturation. DH occurred at a higher prevalence (55%) in patients with LAM, even in those with mild spirometric abnormalities, compared with no occurrence in the normal subjects. DH correlated with airflow obstruction, air trapping, DLCO impairment and dyspnea. The patients who developed DH (DH subgroup) had a longer duration since diagnosis and were characterized by airflow obstruction, air trapping and reduced DLCO, compared with those who did not have DH (non-DH subgroup). Although there was no difference in the exercise performance, DH subgroup had ventilatory limitation, with a higher desaturation and greater dyspnea intensity in the CPET and in the 6MWT. There was no reduction of DH or increase in exercise duration after use of inhaled salbutamol, even in the DH subgroup. CONCLUSIONS: DH is frequent in patients with LAM, even in those with mild spirometric abnormalities, and it is associated with the duration since diagnosis, the severity of disease, augmented dyspnea and lower oxygen saturation. Ventilatory limitation and gas exchange impairment are important reasons for exercise cessation in patients with LAM. DH is also associated with desaturation and greater dyspnea intensity in the 6MWT. Inhaled salbutamol does not reduce DH or improve exercise duration on cycle.

Introdução: A característica clínica principal da DPOC é a intolerância ao exercício físico. O mecanismo dessa limitação é complexo e multifatorial. Os principais mecanismos considerados responsáveis são a hiperinsuflação pulmonar dinâmica (HD) e disfunção muscular periférica. A hipótese principal do presente estudo é que a diminuição da massa livre de gordura (MLG) nesses pacientes, além de diretamente contribuir para redução da capacidade aeróbia, poderia contribuir indiretamente causando acentuação da HD durante o exercício. Objetivo: Investigar se a quantidade de MLG tem efeitos diretos na hiperinsuflação pulmonar dinâmica, durante o exercício em pacientes com DPOC. Métodos: 38 pacientes em estádio moderado a grave realizaram teste de exercício cardiopulmonar incremental até o limite da tolerância com medidas seriadas de capacidade inspiratória (CI). A MLG foi medida pelo teste de bioimpedância elétrica de corpo inteiro. Foram coletados também dados de função pulmonar (espirometria). Resultados: A média de idade dos pacientes foi de 66,5 ± 7,3 anos de idade, com média de VEF1 de 0,98 ± 0.05L (42 ± 15% do previsto). Valores de CI no pico do exercício (uma variável inversamente relacionada com os volumes pulmonares operacionais, ou seja, quanto maior a CI menor é hiperinflação pulmonar) foram significativamente (p <0,05) correlacionados com a CI de repouso (r = 0,78), VEF1 (r = 0,66), CVF (r = 0,56), MLG (r = 0,46) e com o índice de massa livre de gordura (IMLG) (r = 0,39). No entanto, na análise multivariada apenas o VEF1 e a CI em repouso permaneceram preditivos da CI de pico de exercício. A CI de pico foi um preditor significativo da capacidade aeróbia máxima. Conclusão: A MLG apresentou relação direta com as medidas de hiperinsuflação dinâmica durante o exercício. Contudo, a associação não se manteve quando foram feitos ajustes para indicadores de limitação do fluxo aéreo expiratório (VEF1) e hiperinflação pulmonar em repouso (CI de repouso).
Purposes: Investigate if the amount of fat free mass (FFM) has direct effects in dynamic hyperinflation during exercise in COPD patients. Methods: 38 patients with moderate to severe COPD performed treadmill incremental cardiopulmonary exercise test to the limit of tolerance with serial measurements of inspiratory capacity (IC). FFM was measured by whole-body bioelectrical impedance. Results: Patients were 66.5±7.3 years-old with mean FEV1 of 0.98±0.05L (42±15% of predicted). Peak exercise values of IC (a variable inversely related with operational lung volumes, i.e. the greater IC lower is pulmonary hyperinflation) was significantly (p<0.05) correlated with IC at rest (r=0.78), FEV1 (r=0.66), FVC (r=0.56), FFM (r=0.46) and FFM index (r=0.39). However, in multivariable analyzes only FEV1 and IC at rest remained predictive of peak IC. Peak IC was a significant predictor of peak aerobic capacity. Conclusion: FFM was directly related with measurements of dynamic hyperinflation. Nonetheless, this association disappeared when adjustments were made for indicators of expiratory airflow limitation (FEV1) and lung hyperinflation at rest (rest IC).

Orientador: Adyléia Aparecida Dalbo Contrera Toro
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A exposição intra uterina ao vírus da imunodeficiência humana (HIV) pode levar a corioaminionite e déficit no desenvolvimento pulmonar. Há evidências crescentes de que muitas alterações possam persistir até a infância tardia ou mesmo até a idade adulta. Objetivo: Avaliar a função pulmonar de crianças e adolescentes verticalmente expostas ao HIV e não infectados através de Espirometria e Capnografia Volumétrica (CapV), e comparar os resultados obtidos com grupos de crianças e adolescentes saudáveis e de infectados pelo HIV por transmissão vertical. Casuística e métodos: Estudo observacional, analítico, do tipo corte transversal, envolvendo crianças e adolescentes com idade entre 6 à 19 anos de ambos os sexos, que foram expostas verticalmente ao HIV e acompanhadas no Serviço de Imunodeficiência Pediátrica do Hospital de Clínicas da Universidade Estadual de Campinas. Todos os indivíduos realizaram espirometria e CapV. Três comparações foram feitas: pacientes filhos de mães HIV, mas não infectados pelo vírus HIV (Grupo I) pacientes infectados pelos vírus HIV sem doença pulmonar (Grupo II) indivíduos saudáveis (Grupo III). Os testes estatísticos foram: teste exato de Fisher, teste de Mann-Whitney, teste de Wilcoxon, teste de Kruskal-Wallis e o teste de Comparações Múltiplas Não-paramétrico. Em todos os casos adotou-se o nível de significância de 5% (p=0,05). Resultados: Foram incluídos 122 indivíduos, destes, 24 eram pacientes filhos de mães HIV, mas não infectados pelo vírus HIV (Grupo I); 21 pacientes infectados pelos vírus HIV sem doença pulmonar (Grupo II) e 77 indivíduos saudáveis (Grupo III). A idade foi maior no Grupo II (14,9 ± 3,1) quando comparado ao Grupo I e ao Grupo III respectivamente (9,7 ± 2,3; 11,2 ± 1,7) p< 0,001. O z-escore da altura e do IMC foram significativamente menores nos pacientes do Grupo II (-0,72 ± 0,99; -0,50 ± 1,14) quando comparados ao Grupo I (0,65 ± 1,05; 0,56 ± 1,34) p <0,001. As variáveis VEF1% (p=0,007) e FEF25-75% (p=0,007) do Grupo I foram significativamente menores quando comparados ao Grupo III. Os resultados capnográficos não mostraram diferenças estatisticamente significativas entre os grupos estudados.Em relação as variáveis espirométricas pré e pós broncodilatador, o Grupo I não apresentou nenhuma diferença. Já o Grupo II após broncodilatador apresentou maiores valores de VEF1% (p=0,014), de VEF1%/CVF% (p=0,025) e de FEF25-75% (p=0,001) que foram estatisticamente significativos. Houve redução nos valores do Slope 2 (p=0,004 e p=0,025) no Grupo I e no Grupo II respectivamente após broncodilatador. Conclusões: Os pacientes sororeversores (Grupo I), apresentaram valores espirométricos de VEF1, FEF 25-75 menores que os seus controles (Grupo III), porém não apresentaram diferenças significativas quando comparados aos pacientes com HIV (Grupo II). Portanto os pacientes filhos de mães infectadas pelo vírus HIV apresentaram volumes e fluxos alterados que podem ser secundários ao menor calibre da via aérea, mas dentro do padrão da normalidade. Os resultados capnográficos não mostraram diferenças estatisticamente significativas entre os grupos estudados
Abstract: The intra uterine exposure to human immunodeficiency virus (HIV) can lead to corioaminionite and a lung development deficit. There is increasing evidence that many changes may persist until late childhood or even adulthood. Objective: To evaluate pulmonary function in children and adolescents vertically HIV-exposed and not infected by Spirometry and Volumetric Capnography (VC), and compare the results with groups of healthy children and adolescents and vertically HIV-infected. Patients and methods: Observational and analytical transversal cohort study, with children and adolescents aged 6-19 years of both genders who were vertically exposed to HIV and followed at Immunodeficiency Pediatric Clinical Hospital of the State University of Campinas, and a control group of healthy children. All subjects underwent spirometry and VC. Three comparisons were made: uninfected HIV children born of HIV-infected mothers (Group I) vs patients infected by the HIV virus without pulmonary disease (Group II) vs healthy subjects (Group III). The tests used were: Fisher's exact test, Mann-Whitney test, Wilcoxon test, Kruskal-Wallis test and the Test of Nonparametric Multiple Comparisons (TMC). In all cases we adopted the significance level of 5% (? = 0.005). Results: We included 122 individuals. Group I contained 24 patients; Group II contained 21 and Group III, 77 patients. The age was higher in Group II (14.9 ± 3.1) when compared to Group I and Group III respectively (9.7 ± 2.3, 11.2 ± 1.7) p <0.001. The z-score of height and BMI were significantly lower in Group II (-0.72 ± 0.99, -0.50 ± 1.14) when compared to Group I (0.65 ± 1.05; 0, 56 ± 1.34) p <0.001; p = 0,002. As variables FEV1% (p = 0.007) and FEF 25-75% (p = 0.007) in Group I were lower with statistically significant differences when compared to Group III. Capnographic results showed no statistically significant differences between studied groups. In comparison with the pre and post bronchodilator spirometry variables, Group I showed no difference. Group II showed higher FEV1% (p = 0.014), FEV1/FVC% (p = 0.025) and FEF 25-75% values (p = 0.001) which were statistically significant after bronchodilator. There was a reduction in slope 2 values (p = 0.004 and p = 0.025) in Group I and Group II respectively. Conclusions: The seroreverter patients (Group I) had spirometry FEV1, FEF 25-75 lower than their controls (Group III), but not significantly different when compared to HIV-patients (Group II). Therefore patients born to mothers infected with HIV had altered volumes and flows that may be secondary to the lower airway diameter, but within the normality standard. Capnographic results showed no statistically significant differences between the studied groups, because the patients are not sick and they do not show changes in the ventilation-perfusion relationship in the lung
Mestrado
Saude da Criança e do Adolescente
Mestra em Ciências

Orientador: Ilma Aparecida Paschoal
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
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Resumo: Pacientes com defeito obstrutivo podem responder aos broncodilatadores (BD) na espirometria com aumento do volume expiratório forçado no 1° segundo (VEFi) e/ou da capacidade vital forçada (CVF), sendo chamados respondedores de fluxo e/ou de volume, respectivamente. No entanto, ainda acontece debate considerável na definição de resposta ao BD, com a existência de critérios distintos propostos pelas sociedades de pneumologia. Estudos prévios demonstraram que a doença pulmonar obstrutiva crônica (DPOC) grave caracteriza-se por uma maior resposta de volume (RV) e menor resposta de fluxo (RF). Os objetivos principais deste trabalho foram descrever e comparar pacientes portadores de doença obstrutiva grave, com ou sem história prévia de tabagismo (> 10 anos/maço), por meio da análise de seus parâmetros funcionais, de repercussão sistêmica, e estruturais; testar se os respondedores de volume são pacientes mais graves que os respondedores de fluxo e os não respondedores, de acordo com as definições da SBPT (Sociedade Brasileira de Pneumologia e Tisiologia), da ATS/ERS (American Thoracic Society/European Respiratory Society), e de Paré et al. (AVEF1/ACVF > 1 = RF ou < 1 = RV). Sessenta e oito pacientes (idade 55,9 ± 13,7 anos; VEF1 31,9 ± 10,2 % do previsto) realizaram espirometria pré e pós-BD, manovacuometria, bioimpedância, teste de caminhada dos 6 minutos (TC6), radiograma e tomografia de alta resolução do tórax (TCAR), e responderam a um questionário clínico. Dos 68 incluídos, 37 tinham o diagnóstico clínico de DPOC e 31, de bronquiectasias extensas. Comparando os 33 fumantes aos 35 não fumantes, não houve diferença estatisticamente significativa nas variáveis clínicas, funcionais e de repercussão sistêmica, exceto pela capacidade vital, significativamente menor nos não fumantes (p = 0,000). No radiograma, o diafragma rebaixado na incidência em perfil foi mais frequentemente encontrado nos fumantes (p = 0,0470). Na TCAR, bronquiectasias foram encontradas em 48,5% dos fumantes. Os sinais de bronquiolite foram significativamente mais pronunciados nos não fumantes (p = 0,0004), visualizados em 94,3% da amostra. Contudo, eles foram expressivos também nos fumantes, encontrados nas tomografias de 57,6% deles. Encontramos 16, 20 e 29 pacientes com RV de acordo com a SBPT, ATS/ERS e Paré et al., respectivamente. Segundo os critérios de Paré et al., houve 18 pacientes com VEF1 < 30% do previsto entre 29 com RV, e 12 com VEF1 < 30% do previsto entre 39 sem RV (p = 0,0101). Os 32 pacientes com distância caminhada > 350 metros no TC6 apresentaram a mediana da relação massa magra/massa gorda significativamente maior que os 18 com distância caminhada < 350 metros (p = 0,0076). A abordagem conjunta de doenças de via aérea de várias etiologias mostrou-se corroborada por vários dos achados deste estudo. Os critérios de Paré et al. detectaram mais RV entre os pacientes com doença brônquica grave do que os critérios tradicionais. A RV associou-se à maior gravidade da obstrução brônquica quando os critérios de Paré et al. foram empregados. O aumento proporcional da massa gorda, e não somente a perda de massa magra, pode ser um precursor do desenvolvimento de limitação funcional
Abstract: Patients with obstructive disease in spirometry can respond to inhaled bronchodilators (BD) with an increase in forced expiratory volume in the first second (FEVi) and/or in forced vital capacity (FVC) what makes them flow and/or volume responders. However, there is still considerable discordance in the definition of bronchodilator response, with the existence of distinct criteria proposed by the societies of Pulmonology. Previous studies have demonstrated that a large volume response (VR) is accompanied by a small flow response (FR) in patients with severe chronic obstructive pulmonary disease (COPD). The main purposes of this study were to describe and compare patients with severe obstructive disease, with or without previous history of smoking (> 10 pack/years), by means of the evaluation of their functional, systemic and structural features; to test the hypothesis that patients with volume response are more severe than that with flow response or without response, according to the criteria of SBPT (Brazilian Society of Pulmonology and Phthisiology), ATS/ERS (American Thoracic Society/European Respiratory Society) and Paré et al. (AFEV1/AFVC > 1 = FR or < 1 = VR). Sixty-eight patients with stable bronchial disease (age 55.9 ± 13.7 years; FEV1 31.9% ± 10.2 predicted) underwent spirometry before and after BD, manovacuometry, evaluation of body mass composition, six-minute-walk test (6MWT), radiological and thorax high-resolution CT scanning (HRCT), and answered to a clinical questionnaire. Of 68 enrolled patients, 37 had chronic obstructive pulmonary disease (COPD) and 31, extensive bronchiectasis. Comparing 33 smokers to 35 not smokers, there weren't statistically significant differences in clinical, functional and systemic features, except for vital capacity, significantly smaller in non smokers (p = 0.000). A flattened diaphragm in lateral chest radiograms was more frequently found in smokers (p = 0.0470). Eighteen of 37 patients with COPD (48.6%) had bronchiectasis on HRCT. CT signs of bronchiolar disease were more frequently found in not smokers (p = 0.0004), and they were detected in 94.3% of them. However, they were also important in smokers and were found on HRCT of 57.6% of them. There were 16, 20 and 29 patients with VR according to SBPT, ATS/ERS, and Pare et al., respectively. We found 18 patients with FEV1 < 30% predicted among 29 with volume response, and 12 patients with FEV1 < 30% predicted among 39 without volume response (p = 0.0101), considering Pare et al. criteria. The 32 patients with walk distance > 350 meters in 6MWT had median of lean-to-fat body mass ratio significantly higher than the 18 with walk distance < 350 meters (p = 0.0076). The analysis of airway diseases of several etiologies as a whole was supported by many findings of this study. Pare et al. criteria can detect more VR among patients with severe bronchial disease. According to these criteria, a greater degree of airflow obstruction was associated with volume response. The proportional increase of fat mass, and not simply the loss of lean mass, is an important precursor for the development of functional limitation
Mestrado
Clinica Medica
Mestre em Clinica Medica

Les maladies neuromusculaires, sont susceptibles d’évoluer vers un syndrome restrictif. La faiblesse des muscles respiratoires ainsi que les déformations rachidiennes et thoraciques associées font entrer les patients dans un cercle vicieux qui aggrave progressivement le syndrome restrictif et mène les patients vers l’insuffisance respiratoire. À cette insuffisance respiratoire peuvent se rajouter d’autres facteurs comme la réduction chronique des mouvements de la cage thoracique, les perturbations du sommeil, le dysfonctionnement bulbaire et l’inefficacité de la toux. En conséquence, la dysfonction du système respiratoire peut être d’origine multiple et impose une évaluation précise et ciblée sur la compréhension des mécanismes physiopathologiques pour chaque maladie non seulement pour proposer pour chacune un traitement adapté mais également pour apprécier les nouvelles thérapeutiques ciblées sur la réparation musculaire en émergence pour certaines pathologies neuromusculaires. Il parait donc nécessaire de mieux connaitre l’évolution de certaines pathologies, avec et sans les traitements classiques, et d’améliorer la compréhension des mécanismes physiopathologiques de l’insuffisance respiratoire en combinant les outils classiques d’évaluation de la fonction respiratoire avec des nouvelles techniques d’évaluation qui pourraient être complémentaires.Cette thèse a, par conséquent, pour objectif de renforcer les connaissances sur les dysfonctions respiratoires de certaines pathologies neuromusculaires en utilisant des outils classiques d’évaluation et de proposer nouvelles méthodes d’exploration de la fonction respiratoire des patients neuromusculaires. Ainsi, nous avons exploité les données de deux filières de patients neuromusculaires suivies régulièrement : la Dystrophie Facioscapulohumérale (DFSH) et la Dystrophie Musculaire de Duchenne de Boulogne (DDB). L’analyse de la DFSH nous paraissait importante car l’insuffisance respiratoire est très peu connue et décrite dans cette pathologie. Si, au contraire, l’évolution de la DDB est bien connue, l’effet de la ventilation noninvasive (VNI) sur l’évolution de la fonction respiratoire a été, en revanche, très peu décrit alors que de nouveaux essais thérapeutiques vont bientôt être proposés à ces patients, dont certains sont déjà sous VNI. Ensuite, pour mieux prédire le degré d’amélioration du syndrome restrictif qu’une thérapeutique de réparation musculaire pourrait potentiellement apporter, nous avons développé une mesure des volumes pulmonaires à l’aide d’une assistance des muscles inspiratoire et/ou expiratoire. Nous avons aussi développé et validé une méthode non-invasive et non-volitionnelle de mesure indirecte de la force du diaphragme, de manière à obtenir des résultats indépendants de la motivation du patient, à partir d’un examen indolore pour le patient.De ce fait, cette thèse a pu faire progresser les connaissances sur l’évolution de la fonction respiratoire de certaines pathologies neuromusculaires grâce à l’analyse des mesures classiques de la fonction respiratoire. Elle a aussi validé des nouvelles mesures d’explorations fonctionnelles indépendantes de la force volontaire du patient
Neuromuscular disorders are liable to induce a restrictive syndrome. The weakness of respiratory muscles andthe associated spinal deformities lead the patients into a vicious circle, which progressively worsens the restrictivesyndrome and evolves into respiratory failure. This respiratory failure may be associated to additional factors such aschronic reduction of thoracic cage motion, sleep disordered breathing, bulbar dysfunction and ineffective cough. Therefore,dysfunction of respiratory system may have multiples origins and requires precise evaluations targeted on thecomprehension of the physiopathologic mechanisms for each disease, as they may not only allow to adapt specificallytreatment, but also to assess the new therapeutics targeted for muscle restoration that are emerging for some neuromusculardiseases. Accordingly, it is essential to acquire knowledge about the specific evolution of the different disorder, with andwithout classic treatments, and also to improve the understanding of the physiopathologic mechanisms of respiratoryfailure, combining the classic evaluation tools of respiratory function with new evaluation techniques which could provideadditional information.This thesis aims to increase the knowledge of respiratory dysfunction of some neuromuscular disorders using classicevaluation tools and also to propose new exploration methods of respiratory function for neuromuscular patients.Thus, we explored data of two specific neuromuscular disorders patients, regularly followed: FacioscapulohumeralMuscular Dystrophy (FSHD) and Duchenne Muscular Dystrophy (DMD). The analysis of FSHD seemed important asrespiratory failure is not well known and described for this disease. On the other hand, while the evolution of DMD is wellknown, the impact of noninvasive ventilation (NIV) on the evolution of respiratory function has been poorly described,whereas new therapeutic trials will be soon proposed to these patients, some of which are already under NIV.Next, to better predict the improvement of the restrictive syndrome that could be potentially obtained with muscle repairtherapies, we developed a measure of pulmonary volumes, using assistance for inspiratory and/or expiratory muscles.We also developed and validated a painless, noninvasive, non-volitional and indirect method of measurement of thediaphragmatic force, in order to obtain results independent of patients’ motivation.Hence, this thesis was able to advance knowledge of the evolution of respiratory function of some neuromuscular diseases,using traditional evaluation tools of respiratory function. Moreover, it validated new pulmonary function measuresindependent of patient’s voluntary efforts

Base Teórica: O câncer de pulmão é uma doença muito prevalente e altamente fatal. A maioria dos pacientes diagnosticados já se encontra em estágio avançado da doença. Mas existem recursos que contribuem para melhorar a sobrevida destes pacientes, e é necessário avaliar o quão esta doença interfere na qualidade de vida dos mesmos, bem como, na sua funcionalidade. Objetivos: Avaliar a qualidade de vida e função pulmonar de pacientes com câncer de pulmão do Hospital de Clínicas de Porto Alegre que realizaram cirurgia e/ou quimioradioterapia. Métodos: Foi realizado um estudo de coorte, prospectivo, observacional. Foram incluídos no estudo 92 pacientes ambulatoriais/internações com diagnóstico de câncer de pulmão recém diagnosticados e que ainda não tinham iniciado tratamento. Foram submetidos a uma avaliação da QV através do SF-36, espirometria e TC6’ antes de iniciar o tratamento, após 60 dias e 120 dias do início do mesmo. Resultados: No presente estudo, predominou adenocarcinoma e estádio avançado da doença, 27 pacientes cirúrgicos e 60 não cirúrgicos. Não houve diferença na QV entre os 3 momentos, mas um aumento significativo da CVF% nos primeiros 60 dias. Houve correlação significativa entre VEF1 e aspectos físicos e capacidade funcional nos dois grupos, e distância e vitalidade nos não cirúrgicos. A sobrevida foi de 50% nos primeiros 12 meses. Pacientes cirúrgicos tem maior probabilidade de sobrevida do que os não cirúrgicos. Conclusões: Nossos resultados mostraram que pacientes com câncer de pulmão, cirúrgicos e não-cirúrgicos, obtiveram correlações positivas entre VEF1(%) e qualidade de vida em ambos os grupos, assim como, distância da caminhada com vitalidade no grupo não cirúrgico.
Background: Lung cancer is a disease very prevalent and highly fatal. Most patients are already diagnosed with late-stage disease. But there are resources that contribute to improving patient survival, and is necessary to evaluate how this disease affects quality of life of these patients, as well as in its functionality. Objectives: To assess the quality of life and lung function of patients with lung cancer of the “Hospital de Clinicas” of Porto Alegre that underwent surgery and / or chemo-radiotherapy. Methods: We conducted a cohort study, prospective, observational. The study included 92 outpatients / admissions diagnosed with lung cancer at diagnosis and who had not yet started treatment, to undergo assessment of QOL using the SF-36, spirometry and 6MWT before starting treatment, after 60 days and 120 days of start date. Results: It predominated adenocarcinoma and advanced stages disease; totals of 27 surgical and 60 nonsurgical patients. There was no difference in QOL between the three moments, but a significant increase in FVC% in the first 60 days. There was significant correlation between FEV1 and the physical and functional capacity in both groups, and distance and vitality in nonsurgical group. As such, higher chances of survival of surgical patients than nonsurgical. Survival decreased 50% in the first 12 months. Conclusions: Our results demonstrated that patients with lung cancer, surgical and nonsurgical, have obtained positive correlations between FEV1(%) and quality of life in both groups, as well as with walking distance and vitality in nonsurgical group.

Objetivos: Avaliar a percepção da dispneia em pacientes com fibrose cística (FC) comparando com indivíduos normais, durante teste com cargas resistivas inspiratórias e durante teste de caminhada de seis minutos (TC6M). Secundariamente, avaliar a correlação entre os escores de dispneia induzida pelas cargas resistivas e os escores de dispneia provocada pelo TC6M. Métodos: estudo transversal em pacientes com FC (≥15 anos) e indivíduos normais. Os voluntários foram submetidos a teste com cargas resistivas inspiratórias, medida das pressões respiratórias máximas, espirometria, avaliação nutricional e TC6M. Resultados: Foram incluídos no estudo 31 pacientes com FC pareados com 31 indivíduos normais. À medida que a magnitude das cargas resistivas inspiratórias aumentou, os escores de dispneia aumentaram (p<0,001), porém não houve diferença entre grupos quanto ao escore de dispneia (p=0,654) e não houve efeito de interação (p=0,654). SpO2 foi menor em pacientes com FC (p<0,001) e aumentou à medida que a magnitude das cargas aumentou (p<0,001), sem ocorrer efeito de interação (p=,364). Vinte e seis (84%) indivíduos normais completaram o teste com cargas resistivas, comparado com apenas 12 (39%) dos pacientes com FC (p<0,001). Os escores de dispneia foram maiores ao final do TC6M do que no repouso (p<0,001), mas não houve diferença entre os grupos (p=0,080) e não houve efeito de interação (p=0,091). SpO2 foi menor nos pacientes com FC (p<0,001) e diminuiu do repouso ao final do TC6M nos pacientes com FC (p<0,001) com efeito de interação (p=0,004). Os escores de dispneia ao final do TC6M correlacionaram-se significativamente com os escores de dispneia induzidos pelo teste com cargas resistivas. Conclusão: a percepção da dispneia em pacientes com FC induzidos por teste com cargas resistivas inspiratórias e pelo TC6M não diferiu dos indivíduos normais. Contudo, os pacientes com FC descontinuaram o teste com cargas resistivas inspiratórias mais frequentemente. Além disso, houve correlação significativa entre o escore de percepção da dispneia induzida pelas cargas resistivas inspiratórias e pelo TC6M.
Objectives: To evaluate dyspnea perception in cystic fibrosis (CF) patients compared with normal subjects, during inspiratory resistive loading and the six-minute walk test (6MWT). Secondarily, to assess the correlation between dyspnea scores induced by resistive loads and those induced by the 6MWT. Methods: cross-sectional study in patients with CF (≥15 years old) and normal subjects. Volunteers underwent inspiratory resistive loading, measurement of maximal respiratory pressures, spirometry, nutritional evaluation, and the 6MWT. Results: Thirty-one CF patients and 31 paired normal subjects were included in the study. As the magnitude of the inspiratory loads increased, dyspnea scores increased (p<.001), but there was no difference between groups in dyspnea score (p=.654) and no group interaction effect (p=.654). SpO2 was lower in CF patients (p<.001) and increased as the magnitude of the loads increased (p<.001), with no interaction effect (p=.364). Twenty-six (84%) normal subjects completed the whole test, compared to only 12 (39%) CF patients (p<.001). Dyspnea scores were higher post-6MWT than at rest (p<.001), but did not differ between groups (p=.080) with no interaction effect (p=.091). SpO2 was lower in CF patients (p<.001) and decreased from resting to post-6MWT in CF patients (p<.001) with an interaction effect (p=.004). Post-6MWT dyspnea scores were significantly correlated with dyspnea scores induced by resistive loads. Conclusion: dyspnea perception in CF patients induced by inspiratory resistive loading and by 6MWT did not differ from normal subjects. However, CF patients discontinued inspiratory resistive loading more frequently. In addition, there were significant correlations between dyspnea perception score induced by inspiratory resistance loading and by the 6MWT.

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Objetivo: Comparar os valores absolutos da CVF e VEF1 de uma amostra randomizada da populacao de Sao Paulo com mais de 40 anos de idade com os valores previstos das equacoes mais utilizadas no Brasil. Comparar os valores em percentuais do previstos da CVF e VEF1 das equacoes selecionadas com os da equacao PLATINO. Avaliar a mudanca de estadio da DPOC ao se utilizar as diferentes equacoes de referencia. Material e Metodos: Estudo retrospectivo, com 178 pessoas normais da amostra de moradores da regiao metropolitana de Sao Paulo, com idade .40 anos, proveniente do estudo PLATINO. Para a comparacao da CVF e do VEF1, foram subtraidos dos valores previstos a partir de cada equacao os valores absolutos obtidos de cada individuo, considerando uma diferenca de ate 0,15L, como definida pela ATS. Tambem foi realizada a diferenca entre os valores do percentual do previsto da CVF e VEF1 das equacoes com os da equacao PLATINO, com diferenca . 3% (ATS). O diagnostico de DPOC foi definido pela relacao VEF1/CVF < 0,70 pos-broncodilatador e a comparacao do estadiamento foi realizada utilizando a variavel VEF1 em porcentagem do previsto de cada equacao, tendo como referencia o percentual previsto da equacao PLATINO. As equacoes foram aplicadas de acordo com os seus limites de idade e altura. Teste t-student, Qui-quadrado e coeficiente de correlacao intraclasse foram utilizados para avaliar o comportamento da CVF e VEF1 nas diferentes equacoes e os dados foram apresentados em media, desvio padrao, erro padrao e intervalo de confianca de 95%. Resultados: Observamos que as equacoes que apresentam menor diferenca entre o valor previsto e o valor absoluto para CVF e VEF1, em ambos os sexos, foram Roca et al. (n=151), Pereira et al. 2007 (n=176), Enright et al (n=43) e PLATINO (n=178). A equacao Knudson et al (n=177). subestimou os valores absolutos para CVF e VEF1. Na comparacao com a equacao PLATINO, em percentual do previsto para CVF e VEF1, a equacao que apresentou menor diferenca foi a NHANES III (n=172), exceto para CVF masculina, que apresentou grande variabilidade. Foram avaliados 152 pacientes com DPOC, estadiados pelo VEF1, segundo a equacao PLATINO, observando-se mudanca no estadiamento em 29,6% dos pacientes em relacao as equacoes, tendo a equacao Knudson et al. apresentado o maior numero de alteracoes. Conclusao: Existe uma grande variabilidade nos valores previstos entre as equacoes de referencia. As equacoes que apresentaram menor variabilidade e melhor coeficiente de correlacao intraclasse foram Roca et al., NHANES III caucasiano et al., Enright et al. e PLATINO, recomendando-se o seu uso para a populacao brasileira. Existe mudanca no estadio da DPOC quando diferentes equacoes sao aplicadas, sugerindo-se o uso de uma unica equacao durante o tratamento do mesmo paciente para evitar eventuais alteracoes no tratamento.
Objective: To compare the absolute values of FVC and FEV1 found in a random sample of a Brazilian population over 40 years of age with values of equations most used in Brazil. To compare the values in percentage of predicted of FVC and FEV1 of the selected equations with the PLATINO equation ones. To evaluate the change in COPD staying when using different reference equations. Material and Methods: We conducted a retrospective study from a representative sample of residents in the metropolitan region of Sao Paulo, aged .40 years, from the PLATINO study. For comparison of the FVC and FEV1, were subtracted from the predicted values of each equation the absolute values obtained from each individual, considering the equation inadequate wherever there was a difference of up to 0.15 L as defined by ATS. We also evaluated the difference between the values of FVC and VEF1 in percentage of predicted of the equations with the PLATINO equation, considering as a limit a difference .3% (ATS). The diagnosis of COPD was defined as FEV1/FVC <0.70 after bronchodilator, and the comparison of staging was performed using the FEB1 in percentage of predicted in each equation, with reference to the percentage expected from the PLATINO equation. T-student test, chi-squared and the intraclass correlation coefficient were used to evaluate the performance of FVC and FEV1 in different equations and data are presented as mean, standard deviation, standard error and confidence interval of 95%. Results: After evaluating 178 healthy subjects, we observed that the equations that show less difference between the predicted value and the absolute value for both FEV1 and FVC in both sexes were Roca et al., Pereira et al. 2006, Enright et al. and PLATINO. The Knudson et al. equation underestimated the absolute values for both FVC and FEV1. In comparison with PLATINO equation, the percentage of predicted for FVC and FEV1, the equation showing the lowest difference was NHANES III, except for FVC male, who showed a wide variability. We evaluated 152 patients with COPD, observing staging changes in 29.6% in relation to the difference equations, being Knudson et al. the equation that showed the greatest number of changes. Conclusion: There is a great variability among the reference equations. The equations showing less variability and better intraclass correlation coefficient were Roca et al., Caucasian NHANES III et al., Enright et al. and PLATINO, which are the ones that should be recommended to be used for the Brazilian population. There is a change in the COPD staging when different equations are applied, suggesting that the use of a single equation for the treatment of the patient would avoid possible alterations in treatment.
TEDE
BV UNIFESP: Teses e dissertações

This thesis outlines the results of occupational respiratory health surveillance at Minara Resources, Murrin Murrin mine site. The research was conducted as part of a collaborative agreement between Edith Cowan University and Minara Resources, the overarching title of which was ‗Establishing best practice protocols in the management of occupational and environmental health in a high-risk mining and ore-processing environment‘. To form the basis of this research it was hypothesised that although the chemical hazards had been adequately identified, and the occupational exposures in each work area at Murrin Murrin were generally well below their respective occupational exposure levels, it was still possible that additive, or even synergistic biological effects could cause adverse respiratory health effects due to the exposure to a combination of these atmospheric contaminants. This was the perception and a concern voiced by the Murrin Murrin workforce. Therefore, in working through the hypothesis, a literature review concentrating on the gaps in current knowledge and research for the early detection of occupational respiratory diseases was conducted, and the research tool and experiment design determined. The case for using pulmonary function tests in conjunction with a respiratory questionnaire in assessing early respiratory changes due to occupational exposures was established. Over a period between 17 February 2004 and 21 June 2006, a longitudinal study was conducted to ascertain the prevalence of respiratory symptoms and lung function of employees at the Murrin Murrin Operation, and compared with a local control group consisting of catering staff who resided at the accommodation camp approximately eight kilometres from the mine site. Lung function data were also compared to established predicted normal values from a reference population with normal lung function. Lung function data were analysed to determine whether there was an effect due to the area worked, and the employee‘s length of service. The lung function parameters of the study group, corrected for age and height were compared using linear regression analysis with both the control group and the predicted normal values. Repeat lung function tests were conducted on a sample of the original study group approximately two years after the initial study and statistically analysed to determine whether there was an effect on lung function over this time period. In addition, lung function tests were conducted for a cohort of refinery workers at the start and end of their two-week work period to determine whether there was a before-and-after effect due to their working conditions. The prevalence of respiratory symptoms was less in the study group compared to the controls; and these respiratory symptoms were determined to be non-work-related. On statistical analysis, for the ‗presumed healthy‘ workers (minus the smokers and those with known non-work-related respiratory symptoms) there was no overall decrement in lung function. Similarly, there was no overall statistically significant decrement in lung function for the ‗presumed healthy‘ workers in the repeat study conducted approximately two years after the initial study. There was no decrement in lung function associated with area work; nor was there a decrement in lung function for the cohort of refinery workers from the start to completion of their two-week work period. However, there were decrements in lung function for the smokers in the study and control groups. There was a significant difference in FEV1 between non-smokers and smokers with length of service (p

Background: Measurements of lung function are routinely used in patients with cystic fibrosis (CF) to provide information that may be clinically relevant. Spirometry is the conventional lung function measurement used, however young children find spirometry difficult to perform and often cannot achieve the strict acceptability criteria for the test. The forced oscillation technique (FOT) is a lung function measurement that only requires tidal breathing and is easy for young children to perform. However, there is limited information about the utility of this technique in the clinical assessment of young children with CF who are unable to perform spirometry. Aims: The aim of this project was to evaluate the FOT for clinical assessment in 2 to 7 year old children with CF. Specifically this involved: 1. Technical assessment of the FOT in children with CF; 2. Comparisons of lung function using the FOT in children with CF and healthy children; 3. Evaluation of associations with factors known to be associated with lung disease including: i) inflammation ii) infection and iii) structural damage. Methods Lung function was measured in a cohort of 59 children between the ages of 2 and 7 years with CF at the time of quarterly clinic visits. Resistance and reactance at 6, 8 and 10Hz (Rrs6, Rrs8, Rrs10, Xrs6, Xrs8, Xrs10, respectively) were reported and expressed as Z scores. Children were classified as asymptomatic or symptomatic based on a respiratory questionnaire and physical examination at the time of testing. Bronchoalveolar lavage and high resolution computed tomography (HRCT) were performed annually under general anaesthesia annually. BAL fluid was assessed for the presence of micro-organisms and quantification of a range of inflammatory markers and HRCT used to determine the extent of structural abnormalities. Results: The between test repeatability (n=25) for lung function was within limits previously described in healthy children. No systematic bias was observed and repeatability was not affected by the presence of respiratory symptoms. Children with CF (n=57) had significantly increased Rrs6-10 (p<0.0001) and decreased Xrs6-10 (p<0.004) compared to healthy children. Rrs6 and Xrs6-10 were significantly worse in the presence of respiratory symptoms, and Rrs6-10 progressively worsened from an asymptomatic to a symptomatic clinic visit. Children with CF (n=48) had no greater bronchodilator response (BDR) compared to healthy children. BDR was not influenced by the presence of an infection or respiratory symptoms. No relationships between inflammatory markers and lung function (n=39) were identified when the presence of an infection was adjusted for. Children with a current infection (n=20) had increased Rrs6-10 (p<0.01) and decreased Xrs6-10 (p<0.04) compared to children who were uninfected (n=23). These relationships were most marked for children infected with Pseudomonas aeruginosa, with children having a reduced lung function between 0.95 and 1.47 of a Z score. No relationships with the presence or absence of mild structural abnormalities (bronchiectasis, bronchial wall thickening and air trapping) and lung function at the time of HRCT were identified (n=34). Conclusion: The FOT is a repeatable measurement of lung function in children with CF and reliable results can be obtained in children as young as 2 years old. Young children with CF exhibit altered respiratory function which was affected by the presence of factors known to be associated with lung disease. The FOT has the potential to provide useful information about changes in clinical status in young children with CF and may be used to direct management of patient lung disease.

Introdução: O uso de biomassa como combustível para aquecimento e preparação de alimentos vem sendo considerado como um importante fator associado à prevalência aumentada de sintomas respiratórios e à perda de função pulmonar. No presente estudo apresentamos os efeitos respiratórios da exposição crônica à combustão de biomassa (BM) dentro (BMD) ou fora (BMF) do domicílio em uma população do interior do Brasil e comparamos os resultados aos de indivíduos da mesma população que utilizam gás liquefeito de petróleo (GLP). Métodos: Foram incluídos 1402 indivíduos em 260 domicílios divididos em três grupos de acordo com a exposição (GLP, BMD, BMF). Os sintomas respiratórios foram avaliados utilizando questionários validados. O índice de refletância de filtros de papel foi utilizado para avaliar a exposição à biomassa. Em 48 domicílios a concentração de material particulado PM2,5 também foi quantificada. Provas de função pulmonar (PFP) foram realizadas em 120 indivíduos. Resultados: O índice de refletância correlacionou-se diretamente com a concentração de PM2,5 (r=0,92, p<0,001) e foi portanto utilizado para estimar a exposição (ePM2,5). Demonstramos aumento significativo do ePM2,5 no grupo BMD e BMF em comparação com o grupo GLP (p<0,001). Houve ainda aumento significativo da razão de chances (OR) para tosse produtiva, chiado e dispnéia nos adultos expostos à BMD (OR=2,93, 2,33, 2,59, respectivamente) e BMF (OR=1,78, 1,78, 1,80, respectivamente) em comparação com o grupo GLP. As PFP demonstraram que tanto o grupo BM-nãotabagista como GLP-tabagista apresentaram redução no % do VEF1 predito e na relação VEF1/CVF quando comparado com GLP-não-tabagista (p=0,002), o mesmo ocorrendo para o grupo BM-tabagista, em relação a todos os demais (p<0,05). A prevalência de obstrução de vias aéreas encontrada no grupo BM-não-tabagista e GLP-tabagista foi semelhante (20%) e menor do que a observada no grupo BM-tabagista (33%). A PFP correlacionou-se inversamente com o tempo de exposição e a concentração de ePM2,5 (p<0,001). Conclusões: A exposição crônica à combustão de biomassa está associada com o aumento da prevalência de sintomas respiratórios, redução da função pulmonar e desenvolvimento de doença pulmonar obstrutiva crônica. Esses efeitos estão associados com a duração e magnitude da exposição e são potencializadas pelo tabagismo.
Introduction: The use of biomass fuels for cooking and heating is considered an important factor associated with respiratory symptoms and loss of pulmonary function. We report the respiratory effects of chronic exposure to biomass (BM) combustion in a Brazilian population and compared the results with those of individuals from the same community using Liquefied Petroleum Gas (LPG). Methods: 1,402 individuals in 260 residences were divided into three groups according to exposure (LPG, indoor-BM, outside-BM). Respiratory symptoms were assessed using questionnaires. Reflectance of paper filters was used to assess BM. In 48 residences the amount of PM2.5 was also quantified. Pulmonary function tests (PFT) were performed in 120 individuals. Results: Reflectance-index correlated directly with PM2.5 (r=0.92, p<0.001) and was used to estimate exposure (ePM2.5). There was a significant increase in ePM2.5 in Indoor-BM and Outside-BM, compared to LPG (p<0.001). There was a significantly increased odds ratio (OR) for cough with sputum, sneezing and dyspnea in adults exposed to Indoor-BM (OR=2.93, 2.33, 2.59, respectively) and Outside-BM (OR=1.78, 1.78, 1.80, respectively) compared to LPG. PFTs revealed both non-smoker-BM and smoker-LPG individuals to have decreased %predicted-FEV1 and FEV1/FVC as compared to non-smoker-LPG (p=0.022). Reduction was also observed in both parameters between smoker-BM and other groups (p<0.05). The prevalence of chronic obstructive pulmonary disease was 20% for both non-smoker-BM and smoker-LPG and smaller than that observed for smoker-BM (33%). PFT data was inversely correlated with duration and ePM2.5 (p<0.001). The prevalence of airway obstruction was 20% in both non-smoker-BM and smoker-LPG subjects. Conclusions: Chronic exposure to BM is associated with increased prevalence of respiratory symptoms, reduced lung function and development of chronic obstructive pulmonary disease. These effects are associated with the duration and magnitude of exposure and are exacerbated by tobacco smoke.

Orientador: Orlando Petrucci Junior
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: A disfunção pulmonar durante cirurgias cardíacas ocorre pelos efeitos combinados da anestesia geral, circulação extracorpórea (CEC), trauma cirúrgico e isquemia pulmonar. A manobra de recrutamento alveolar (MRA) e a manutenção da pressão positiva no final da expiração (PEEP) durante a CEC são procedimentos que podem reverter o colapso alveolar e melhorar as trocas gasosas no pós-operatório. O objetivo deste estudo foi avaliar o efeito da manobra de recrutamento alveolar e da manutenção da PEEP durante a CEC na mecânica respiratória e nos parâmetros de oxigenação, em pacientes submetidos à cirurgia cardíaca com utilização de CEC. Métodos: Foram incluídos 90 pacientes (57 masculino/ 33 feminino) consecutivos, divididos em três grupos: grupo controle (GC), grupo recrutamento (GR) e grupo PEEP (GP), submetidos à cirurgia cardíaca com utilização de CEC. O GC recebeu ventilação mecânica com volume corrente de 8 ml/kg e frequência respiratória de 12 ciclos por minuto; o GR foi submetido ao mesmo tipo de ventilação mecânica e acrescido ao recrutamento alveolar imediatamente após a saída de CEC, já o GP foi submetido ao mesmo tipo de ventilação mecânica durante o ato cirúrgico, porém no momento da CEC, os pacientes não foram desconectados da ventilação mecânica, onde foi mantido uma PEEP contínua de 8 cmH2O. Os pacientes foram seguidos do momento pré-operatório até a alta hospitalar. Os pacientes foram avaliados quanto a distância caminhada no teste de caminhada de 6 minutos (TC6), complacência e resistência pulmonar, e mecânica respiratória. Resultados: A distância percorrida no TC6 no pós-operatório foi maior no GP comparado aos dois outros grupos no pós-operatório imediato e 2 meses após a cirurgia. A mecânica respiratória avaliada pela pressão inspiratória máxima (PImáx), pressão expiratória máxima (PEmáx) e pico de fluxo expiratório (PFE) variou igualmente nos três grupos não havendo diferença entre eles. A complacência pulmonar foi maior no GP no período pré-extubação comparado aos dois outros grupos. A saturação de oxigênio foi maior no grupo submetido ao recrutamento e no grupo PEEP, logo após a intervenção, mas este efeito não foi duradouro. Conclusão: A manobra de recrutamento alveolar no período intraoperatório e a manutenção de pressão positiva contínua nas vias aéreas durante a CEC proporcionaram melhora da saturação de oxigênio e da complacência pulmonar, mas estes efeitos não foram duradouros. A utilização da PEEP a CEC proporcionou maior distância percorrida no teste de caminhada de seis minutos
Abstract: Introduction: Pulmonary dysfunction related to cardiac surgery may occurs as consequence of several factors such as general anesthesia , cardiopulmonary bypass (CPB) , surgical trauma, and pulmonary ischemia . The alveolar recruitment maneuver (ARM ) or the maintenance of PEEP (Positive Expiratory End Pressure) throughout the CPB period may preclude the alveolar collapse and improve gas exchange at the postoperative period. The aim of this work was evaluate the effects of two different ventilatory strategies on mechanical respiratory physiology and oxygenation parameters in patients undergoing open heart surgeries using CPB. Methods: Ninety patients ( 57 male / 33 female) were allocated to three different groups named: control group (CG ), recruitment group (GR ) and PEEP group ( GP ). The CG were ventilated with a tidal volume of 8 mL/ kg and respiratory rate of 12 breaths per minute, GR were ventilated with the same parameters with additional alveolar recruitment right after weaning from CPB,, and the GP where the patients received a positive airways pressure of 8 cmH2O for the duration of the CPB time. Patients were followed-up up to 2 months of post-operative period. They were evaluated with 6-minute walk test (6MWT), pulmonary compliance resistance and respiratory muscle strength tests. Results: The GP showed longer distance walked in the 6MWT compared to GC and GR groups. The three groups were similar regarding respiratory muscle strength tests. There was an increase of lung compliance in GP at pre-extubation time compared to two other groups. The GR and GP groups showed a slight higher oxygen saturation compared to GC right after the intervention. However, these beneficial effects did not last until first day after surgery. Conclusion: Intraoperative recruitment maneuver and maintenance of PEEP during CPB produced to slight improvements on oxygen saturation and lung compliance, but these effects were not durable. The use of positive pressure during CPB improved the distance walked in six-minute walk test
Mestrado
Fisiopatologia Cirúrgica
Mestre em Ciências

Orientador: Alberto Cliquet Junior
Tese (doutorado) - Universidade Estadual de Campinas. Faculdade de Ciencias Medicas
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Resumo: Pacientes com lesão medular reconhecidamente desenvolvem muitas adaptações sistêmicas. Condições, como fraqueza da musculatura respiratória, paralisia e alterações na função pulmonar e conseqüentemente o aumento do índice de doenças pulmonares, são observadas. Recentemente, o aumento de doenças cardiovasculares também tem ocorrido entre esses pacientes, além das complicações provenientes da osteoporose que já são bem conhecidas. O objetivo deste trabalho foi avaliar as alterações do sistema cardiorrespiratório e esquelético de pacientes com lesão medular em 4 estudos. O estudo 1 avaliou a variabilidade da frequência cardíaca na posição supina e sentada e arritmia sinusal respiratória (ASR) de 37 homens com e sem lesão medular. Os pacientes tetraplégicos apresentaram uma redução dos valores máximos da frequência cardíaca durante ASR. O estudo 2 avaliou a função pulmonar de 23 pacientes com tetraplegia. Os valores de capacidade vital forçada, volume expiratório forçado 1s e ventilação voluntária máxima mostraram que a capacidade pulmonar dos pacientes com lesão medular foi reduzida. O estudo 3 propôs a adaptação do teste de caminhada de 6 minutos para 9 pacientes com paraplegia completa auxiliados por marcha artificial com eletroestimulação neuromuscular e andador. O estudo 4 investigou a densidade mineral óssea e fatores de risco cardiovascular de 44 homens com e sem lesão medular. Os pacientes com lesão medular apresentaram osteoporose e/ou osteopenia e o espessamento da camada íntima-média da carótida, porém os valores do lipidograma e triglicérides foram dentro da faixa de normalidade. A pressão arterial foi menor nos pacientes tetraplégicos. Análise estatística: Os dados foram apresentados em mediana (intervalo interquartil) e/ou média (±DP) e em Box-plot. Diferenças entre grupos foram demonstradas pelo intervalo de confiança da mediana, nível de significância em 5% ou teste t pareado. Conclusões: A atuação simpática e parassimpática no coração alcançou a homeostase, quando os pacientes foram mantidos nas posições supina ou sentada e o teste de ASR mostrou uma diminuição da atuação parassimpática no coração dos pacientes tetraplégicos, possivelmente para compensar uma diminuição ou ausência da atuação simpática, devido ao comprometimento do sistema autonômico pela lesão medular. O teste de caminhada de 6 minutos foi adaptado para avaliar os pacientes com lesão medular completa e se mostrou eficiente. Já a avaliação da função pulmonar dos pacientes mostrou a necessidade de novas equações de predição baseadas em uma população específica e suas características. Por último, os resultados obtidos através da densitometria mineral óssea comprovaram a presença de osteoporose e/ou osteopenia nos pacientes com lesão medular. E um aumento na espessura da camada intima-média da carótida foi observado através da ultrassonografia de carótida. Esses dados reforçam a hipótese de uma possível associação entre essas duas patologias.
Abstract: It is known that individuals with Spinal Cord Injury (SCI) present systemic adaptation. SCI causes respiratory muscle weakness, paralysis and abnormal pulmonary function. Cardiovascular disease is also increased in spinal cord injured subjects and osteoporosis as well. The aim of this study was to assess cardio respiratory and bone diseases in subjects with SCI. Four studies were performed. The first study assessed heart rate variability in supine and seated position and respiratory sinus arrhythmia (RSA) maneuver in 37 subjects with and without SCI. Tetraplegic subjects showed the lowest values of maximal heart rate during RSA. The second study assessed pulmonary function in 23 tetraplegic subjects. Forced vital capacity, maximal voluntary ventilation, forced expired volume showed that the SCI subjects' pulmonary capacity was reduced when compared with able body subjects. The third study adapted the "6 minutes' walk test" to assess complete patients with SCI during gait therapy. The fourth study investigated the clinical presence of osteoporosis and cardiovascular risk factors in 44 subjects with and without SCI. Subjects showed osteoporosis or osteopenia and increased intima-media thickness, although lipids and triglycerides were with normal ranges. Blood pressure in tetraplegic subjects was lower than in paraplegic and control groups. Statistical Analysis: Data are expressed as median (interquartile interval) and presented in box-plot (median, 1st and 3rd quartiles, minimum and maximum). Differences between groups were demonstrated by confidence interval of median, significance level set at ? = 0.05, or mean (±SD) and paired t test. Conclusions: Sympathetic and parasympathetic nervous system allow homeostasis when the subjects are kept in supine or seated position; RSA maneuver showed a reduction in parasympathetic system action in the heart of tetraplegic subjects to compensate a reduction or loss of sympathetic action in spinal cord lesion. "Six minutes walk test" was well adapted and efficient. Pulmonary function showed the necessity to create new predicts equations based on local population characteristics. Finally, bone mineral density showed osteoporosis or osteopenia in paraplegic and tetraplegic individuals as well as increased carotid intima-media thickness measured through ultrasound exam.
Doutorado
Pesquisa Experimental
Doutor em Cirurgia

O objetivo desse estudo foi avaliar a relação da mobilidade diafragmática com a função pulmonar e a força muscular respiratória em indivíduos com DPOC, utilizando a mensuração ultra-sonográfica do deslocamento crânio-caudal do ramo esquerdo da veia porta. Foram estudados 54 pacientes portadores de DPOC com hiperinsuflação pulmonar e 20 sujeitos saudáveis. Os parâmetros avaliados foram: mobilidade diafragmática, função pulmonar e as pressões respiratórias máximas. Pacientes com DPOC apresentaram menor mobilidade do diafragma (36,46 ± 10,90 mm) quando comparados a indivíduos saudáveis (46,33 ± 9,47) (p = 0,001). Nos indivíduos portadores de DPOC foram verificadas uma forte correlação com os parâmetros da função pulmonar que quantificam o aprisionamento de ar (VR: r = -0,60; p < 0,001; VR/CPT: r = -0,72; p < 0,001), uma moderada correlação com a obstrução de vias aéreas (VEF1: r = 0,55, p < 0,001; resistência das vias aéreas: r = -0,32, p = 0,02) e uma fraca correlação com a hiperinsuflação pulmonar (CPT: r = -0,28, p = 0,04). Não foi observada relação entre a mobilidade do diafragma e a força muscular respiratória (PImax: r = -0,11 e p = 0,43; PEmax: r = 0,03 e p = 0,80). Nossos resultados sugerem que a redução da mobilidade do diafragma em pacientes com DPOC ocorre principalmente devido ao aprisionamento de ar, não sendo influenciada pela hiperinsuflação pulmonar ou pela força muscular respiratória.
The purpose of this study was to use ultrasound to measure the craniocaudal displacement of the left branch of the portal vein in order to evaluate the relationship between pulmonary function and diaphragm mobility, as well as that between respiratory muscle strength and diaphragm mobility, in COPD patients. We studied 54 COPD patients with pulmonary hyperinflation, together with 20 healthy subjects. Pulmonary function, maximal respiratory pressures, and diaphragm mobility were evaluated. COPD patients presented less diaphragm mobility than did healthy individuals (36.46 +/- 10.90 mm vs. 46.33 +/- 9.47 mm, respectively) (p = 0.001). In COPD patients, we found that diaphragm mobility correlated strongly with pulmonary function parameters that quantify air trapping (RV: r = -0.60; p < 0.001; RV/TLC: r = -0.76; p < 0.001), moderately with airway obstruction (FEV1: r = 0.55, p < 0.001; airway resistance: r = -0.32, p = 0.02), and weakly with pulmonary hyperinflation (TLC: r = -0.28, p = 0.04). No relationship was observed between diaphragm mobility and respiratory muscle strength (maximal inspiratory pressure: r = -0.11 and p = 0.43; maximal expiratory pressure: r = 0.03 and p = 0.80). The results of this study suggest that the reduction in diaphragm mobility in COPD patients occurs mainly due to air trapping and is not influenced by respiratory muscle strength or pulmonary hyperinflation.

Introdução: O teste de apneia respiratória tem sido testado e demonstrou ser de utilidade clínica. Objetivos: Determinar o tempo de apneia voluntária máxima em pacientes com distúrbios ventilatórios obstrutivos (DVO) e em indivíduos normais e correlacionar os tempos de apneia com os testes de função pulmonar. Métodos: Foi realizado um estudo caso-controle incluindo pacientes com DVO (casos) e um grupo controle, composto por voluntários com espirometria normal, recrutados no Hospital de Clínicas de Porto Alegre (HCPA). A espirometria foi realizada com espirômetro computadorizado e o teste de apneia respiratória utilizando-se um sistema eletrônico microprocessado e um pneumotacógrafo ((Hans Rudolph ® – Kansas OH, EUA)– Kansas OH, EUA) como transdutor de fluxo. As curvas de fluxo respiratório foram exibidas em tempo real em um computador portátil e os tempos máximos de apneia voluntária inspiratória e expiratória (TAVIM e TAVEM) foram determinados a partir do sinal adquirido. Resultados: Um total de 35 pacientes com DVO (casos) e 16 controles foram incluídos no estudo. O TAVIM foi significativamente menor nos casos (22,3 ± 11,8 s) do que no grupo controle (31,5 ± 15,7 s) com p = 0,025. O TAVEM também foi significativamente menor nos casos (16,9 ± 6,6 s) do que no grupo controle (22,1 ± 7,9 s) com p = 0,017. Foram encontradas correlações positivas moderadas entre TAVIM e CVF (r = 0,476, p = 0,004) e entre TAVIM e VEF1 (r = 0,383, p = 0,023). Conclusões: As medidas de TAVIM e TAVEM foram significativamente menores nos casos do que nos controles, e o TAVIM teve correlação moderada com a CVF e VEF1. Estes resultados fornecem uma evidência adicional da utilidade clínica do tempo de apneia como teste de função pulmonar.
Introduction: Breath-holding test has been tested in some clinical scenarios and has proved to be of clinical utility. Objectives: To determine the maximum voluntary breath-holding time in patients with obstructive ventilator defects and in normal subjects and to correlate the breathholding times with pulmonary function tests. Methods: We conducted a case-control study including patients with obstructive ventilator defects and a control group consisted of volunteers recruited in the same hospital, with normal spirometry. Spirometry was performed using a computerized spirometer. The Breath-holding test was conducted using an electronic microprocessor and a (Hans Rudolph ® – Kansas OH, EUA)pneumotachograph and flow transducer. Respiratory flow curves were displayed in real time on a portable computer. The maximal voluntary apnea inspiratory and expiratory times (MVAIT and MVAET) were determined from the acquired signal. Results: A total of 35 patients with obstructive ventilatory defects and 16 controls met the inclusion criteria and were included in the analysis. The MVAIT was lower in cases (22.3 ± 11.8 seconds) than in controls (31.5 ± 15.7 seconds) (p=0.025). MVAET was also lower in cases than in controls (16.9 ± 6.6 vs. 22.1 ± 7.9; p=0.017). We found positive and significant correlations between MVAIT and FVC (L) (r=0.476; p=0.004) and between MVAIT and FEV1 (L) (r=0.383; p=0.023). Conclusions: MVAIT and MVAET were significant lower in patients with obstructive ventilatory defects than in controls, and that MVAIT was correlated positively with FVC and FEV1 in cases. Our results provide additional evidence of usefulness of MVAIT as a pulmonary function test.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
A Amburana cearensis à uma planta nativa do sertÃo nordestino, popularmente conhecida como imburana de cerejeira e cumaru, utilizada empiricamente nas afecÃÃes do trato respiratÃrio. O presente estudo duplo-cego, randomizado, paralelo e controlado por placebo, teve como objetivo avaliar a eficÃcia terapÃutica do xarope de Cumaru como terapia complementar em asmÃticos sob tratamento regular com corticÃide inalatÃrio associado ao broncodilatador nas crises. Os pacientes foram incluÃdos no estudo com base na histÃria clÃnica, exame fÃsico e laboratorial foram randomizados em Grupo teste, que recebeu o Xarope de Cumaru e Grupo Placebo, que recebeu o placebo sendo ambos os grupos compostos por 21 pacientes, que ingeriram o xarope na dose de 15 mL trÃs vezes ao dia durante um perÃodo de 15 dias consecutivos. O estudo teve como desfecho primÃrio a mudanÃa na qualidade de vida avaliada atravÃs do questionÃrio de qualidade de vida em asma com atividades padronizadas - AQLQ(S) distribuÃdos em quatro domÃnios: sintomas, limitaÃÃo das atividades, estimulo ambiental e funÃÃo emocional e como desfechos secundÃrios a avaliaÃÃo das provas de funÃÃo pulmonar e a seguranÃa da formulaÃÃo sob investigaÃÃo mediante exames laboratoriais no perÃodo prÃ-tratamento e no primeiro dia apÃs a finalizaÃÃo do tratamento de 15 dias com o Xarope. Todos os pacientes eram procedentes da cidade de Fortaleza, com 96% pertencentes ao sexo feminino. O grau de escolaridade mÃnimo foi o ensino fundamental completo representado por 94,3% da amostra. A fase prÃ-estudo nÃo evidenciou diferenÃas estatisticamente significativas entre os grupos quanto ao gÃnero, IMC, VEF1, PFE, uso de medicaÃÃo resgate, escore total da qualidade devida mensurado pelo AQLQ (S) e presenÃa de comorbidade (p>0,05), entretanto observou-se diferenÃa estatisticamente significante quanto à mÃdia de idade, onde o grupo Cumaru (46,619  10,351) apresentou resultado significativamente maior que o grupo Placebo (37,238  10,319). A melhora na qualidade de vida foi estatisticamente significante no grupo Cumaru quando comparada ao grupo Placebo tanto no aspecto global como para o domÃnio sintomas, limitaÃÃo das atividades, estimulo ambiental e funÃÃo emocional mensurados pelo AQLQ(S) (p<0,05). No grupo Cumaru a proporÃÃo de pacientes com melhora global da qualidade de vida foi significativamente maior (61,90%) que a verificada no grupo placebo (9,52%), com risco relativo de 6,500. A CVF, VEF1; RelaÃÃo VEF1/ CVF e FEF 25-75% da CVF nÃo sofreram modificaÃÃes significativas nos dois grupos estudados (p>0,05) em nenhuma das etapas estudadas. A anÃlise hematolÃgica e bioquÃmica dos pacientes em ambos os grupos nÃo apresentou diferenÃas estatisticamente significantes entre os mesmos em nenhuma das fases estudadas. O xarope de Cumaru foi bem tolerado pelos pacientes e os efeitos adversos observados foram equivalentes aos do grupo placebo. Conclui-se que a administraÃÃo do xarope de Cumaru, na dose 45mL/dia por 15 dias, como terapia complementar proporcionou melhora significativa da qualidade de vida, sem causar toxicidade sistÃmica embora nÃo tenha modificado os parÃmetros espiromÃtricos representando uma alternativa segura para o tratamento da asma.
Amburana cearensis is a medicinal plant common to the Brazilian Northeastern and empirically used as bronchodilatador in respiratory tract diseases including asthma. A clinical trial double blind, placebo-controlled, randomized, parallel analyzed in the Unit of Clinical Pharmacology, Ceara, Brazil, the therapeutic efficacy of Cumaru syroup as complementar therapy in patients with mild asthma on regular treatment with inhaled corticosteroids. The study had three phases, pre, treatment and post treatment. The patients were included in the study based on clinical history, physical examination and laboratory test and were randomized into group that received Cumaru syrup and the placebo group who received the placebo and both groups consisting of 21 patients who ingested the syrup in the dose 15 mL three times daily for a period of 15 consecutive days. The study had as primary outcome the change in quality of life assessed by questionnaire of quality of life in asthma - with standardized activities - AQLQ (S) distributed in four areas: symptoms, activity limitation, emotional function and environmental stimuli and secondary outcome evaluation made by pulmonary function tests and safety of the formulation under investigation by laboratory tests in the pre-treatment and the first day after completion of treatment for 15 days with the syrup. All patients were from the city of Fortaleza, with 96% belonging to the female and The level of education was the least complete basic education represented 54% of the sample. The pre-study showed no statistically significant differences between groups regarding gender, IMC, FEV1, PEF, use of rescue medication, overall quality score measured by the AQLQ(S) and the presence of hypertension (p> 0.05), however there was statistically significant difference in mean age, where the placebo group showed significantly lower results (37,238 Â 10,319) than the group Cumaru (46,619 Â 10,351). The improvement in quality of life was statistically significant in group Cumaru when compared to the placebo group both in terms of global and for each domain: symptoms, activity limitation, environmental exposure and emotional function measured by the AQLQ(S) (p <0.05). Cumaru group in the proportion of patients with global improvement of quality of life was significantly higher (61.90%) that seen in the placebo group (9.52%), with relative risk of 6500. The FVC, FEV1, for FEV1 / FVC and FEF 25-75% of FVC did not suffer significant changes in both groups (p> 0.05) in any of the stages studied. The Cumaru syrup was well tolerated by patients and adverse events did not show any clinical relevance. The haematological and biochemical analysis of patients in both groups showed no statistically significant differences between them in any of the stages studied. Cumaru syrup was well tolerated by patients and adverse effects observed were equivalent to those in the placebo group. It is concluded that the administration of 45mL/day of Cumaru syrup during 15 days as complementary therapy provided significant improvement in quality of life, without causing systemic toxicity but has not modified the spirometric parameters representing a safe alternative for the treatment of asthma.

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Obesity, as well as impaired lung function, is associated with significant morbidity and mortality. Few studies have evaluated the effect of adiposity on lung function in adolescents. This study was conducted to evaluate the effect of body mass index and sum of skinfolds (triceps and subscapular) on pulmonary function (forced expiratory volume in one second and forced vital capacity) of adolescents in the study there longitudinal live births in 1993, Pelotas - Brazil. Teenagers aged between 14 and 15 years were interviewed (n = 4349), follow-up rate of 85.7% of the original cohort, measured (n = 4110) and their lung function measured (n = 4006). It was observed through a cross-sectional analysis, after controlling for confounding factors during the gestational period, the body mass index presents. Overall direct effect on lung function while the sum of skinfolds opposite effect. The longitudinal analysis allowed us to observe that adolescents, regardless of sex, which remained in the lower tertiles of body mass index during follow-up had lower levels of lung function than those who remained in the middle tercile. The boys who remained in the highest tertile of skinfold thickness had lower lung function values. These findings suggest that low body mass index and the large sum of skinfold thicknesses have negative impact on lung function in adolescents.
A obesidade, assim como a redução da função pulmonar, esta associada à morbidade e mortalidade. Poucos estudos avaliaram o efeito da adiposidade sobre a função pulmonar em adolescentes. Esse estudo foi realizado com objetivo de avaliar o efeito do índice de massa corporal e do somatório das pregas cutâneas (tricipital e subescapular) sobre a função pulmonar (volume expiratório forçado no primeiro segundo e capacidade vital forçada) de adolescentes pertencentes ai estudo longitudinal dos nascidos vivos em 1993, Pelotas Brasil. Os adolescentes com idade entre 14 e 15 anos foram entrevistados (n=4349), taxa de acompanhamento de 85,7% da coorte original, medidos (n=4110) e sua função pulmonar avaliada (n=4006). Observou-se através de uma análise transversal que, após controle para fatores de confusão desde o período gestacional, o índice de massa corporal apresenta de maneira geral efeito direto sobre a função pulmonar ao passo que o somatório de pregas cutâneas efeito inverso. A análise longitudinal permitiu observar que os adolescentes, independentemente do sexo, que permaneceram nos menores tercis do índice de massa corporal durante o acompanhamento apresentaram menores valores de função pulmonar em relação aos que permaneceram no tercil médio. Os meninos que permaneceram no maior tercil de pregas cutâneas apresentaram menores valores de função pulmonar. Esses achados sugerem que o baixo índice de massa corporal e o elevado somatório de pregas cutâneas apresentam impacto negativo sobre a função pulmonar de adolescentes.

Estudos para a avaliação da resistência das vias aéreas de pré-escolares com fibrose cística através da técnica do interruptor (Rint) são escassos. Foi realizado um estudo tranversal, com 38 pacientes acompanhados no ambulatório de Fibrose Cística do Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul. Foram realizadas medida da Rint, seguida da avaliação espirométrica em todos os pacientes, repetindo os testes após o uso de salbutamol para a aferição da resposta ao broncodilatador. Nos resultados, foram encontradas forte correlação entre o inverso da Rint e o volume expiratório forçado no 1º segundo (VEF1), (r=0,8 p<0,001) e moderadas correlações entre o inverso da Rint e o fluxo expiratório forçado entre 25% e 75% da capacidade vital (FEF 25-75), (r=0,74 p<0,001) e entre o inverso da Rint e o índice de massa corporal (IMC), (r=0,62 p<0,001). A acurácia da avaliação da resposta ao broncodilatador pela Rint, foi testada através da curva ROC (Receiver Operator Characteristic Curve),comparando-se com resposta ao broncodilatador na espirometria. Foi obtida uma área de 0,75 para o ponto de corte de -28%, correspondendo a uma sensibilidade de 66% e uma especificidade de 82%. Os achados indicam que a Rint apresenta boa correlação com a espirometria, no entanto a técnica não possui uma acurácia suficiente para substituir a Espirometria na avaliação da resposta ao broncodilatador.
Few studies have been published on airway resistance measurements using the interrupter technique (IT). We performed a cross-sectional study, evaluating 38 children and adolescents with Cystic Fibrosis (CF), followed at the outpatient CF clinic of Hospital São Lucas from Pontifícia Universidade Católica do Rio Grande do Sul. Airway resistance (Rint) was measured by the IT, followed by spirometry in all patients. Measurements were repeated after inhalation of salbutamol in order to evaluate bronchodilator response. There was a strong corelation between inverse Rint and forced expiratory volume in one second (FEV1) (r=0.8, p<0.001) and fair correlations between the inverse Rint and mid expiratory flow (MEF) (r=0.74 p<0.001) and between inverse Rint and body mass index (BMI) (r=0.62 p<0.001). The accuracy of bronchodilator response by the IT was tested through the ROC (reciever operating curve), comparing results with spirometry bronchodilator response. An area of 0.75 under the curve was obtained, for the cutoff point of -28% of Rint, achieving a sensitivity of 66% and a specificity of 82%. The findings suggest that Rint shows good correlation with spirometry parameters, although the IT is not sufficiently acurate to replace spirometry in the evaluation of bronchodilator response.

The overall aim of the research described in this thesis was to evaluate the effect of vitamin A supplementation on respiratory health, assessed by lung function in children aged 6--9 years. It comprises three studies.
The first study determined the magnitude of vitamin A deficiency in the target population in Wukro wereda, Northern Ethiopia. Of the 1339 eligible children identified by house to house surveys, 824 had complete data for vitamin A indicators and anthropometry. Xerophthalmia was detected in 5.8% of the children, 8.4% had serum retinol levels <0.35 mumol/L and 51.1% between 0.35--0.70 mumol/L. Liver vitamin A reserve was also found to be low in 41.0% of the children using the Modified Relative Dose Response (MRDR) and in about 85% of the children, the daily vitamin A intake was below the FAO/WHO basal requirement (<250 RE/day).
The second study found that in comparison with children with adequate vitamin A reserve (MRDR < 0.06), those with low reserve (MRDR ≥ 0.06) had forced expiratory volume in one second (FEV1) 48.8 ml (p = 0.006) lower when unadjusted, 23.1 ml (p = 0.04) when partially adjusted for age, gender and height and 14.1 ml (p = 0.20) when fully adjusted for demographic, general health, lung function and household related characteristics.
The third study describes the results of a randomized controlled trial (RCT) to evaluate the impact of vitamin A supplementation on respiratory health as assessed by change in FEV1 at 4 months. The average change was 53.3 ml (n = 496) and 53.8 ml (n = 501) in the vitamin A and placebo groups respectively. After adjusting for baseline covariates, the difference between them was -3.6 ml (95%CI: -21.6, 14.4). In sub-analysis of the data, gender and vitamin A status subcategories were found to be effect modifiers.
In conclusion, high dose vitamin A supplementation did not show an effect on change in FEV1 at 4 months in children aged 6--9 years with high prevalence of vitamin A deficiency. Sub-analysis findings suggest that the benefits to vitamin A intervention in the study setting can probably be achieved if the other nutritional deficiencies such as zinc are addressed. Moreover, the results also suggest that the effects of vitamin A supplementation on respiratory health status are complex and these need to be taken into account in future studies to assess the clinical and public health implications of vitamin A supplementation in this age group.

Astma i hronična opstruktivna bolest pluća (HOBP) su najčešće hronične nezarazne bolesti respiratornog sistema i predstavljaju značajan zdravstveni problem. U dijagnostici i proceni stepena poremećaja disajne funkcije u ovih bolesnika najčešće se koriste spirometrija i telesna pletizmografija. Impulsna oscilometrija predstavlja novu metodu u dijagnostici poremećaja plućne funkcije. Ova metoda je jednostavna za izvođenje i minimalno zavisi od saradnje pacijenta.Osnovni cilj ove doktorske disertacije bio je da se uporede parametri dobijeni impulsnom oscilometrijom, spirometrijom i telesnom pletizmografijom kod pacijenata sa astmom i hroničnom opstruktivnom bolesti pluća, utvrdi senzitivnost navednih metoda u detekciji opstruktivnog poremećaja ventilacije kao i povezanost parametara impulsne oscilometrije, spirometrije i telesne pletizmografije i stepena težine dispnoičnih tegoba kod odraslih pacijenata sa astmom i HOBP. Korelacijom parametara dobijenih impulsnom oscilometrijom i spirometrijom dobijena je umerena negativna korelacija vrednosti R5 sa FEV1 kod pacijenata sa astmom (r= -0.47, r<0.001) i HOBP (r= -0.50, r<0.001), kao i umerena pozitivna korelacija X5 sa FEV1 (r= 0.54, r<0.001, kod pacijenata sa astmom; r= 0.56, r<0.001 kod pacijenata sa HOBP). Registrovana je dobra korelacija Rt sa vrednostima R5 (r=0.63, r<0.001) i H5 (r= -0.55, r<0.001) kod pacijenata sa astmom, kao dobra korelacija Rt sa R5 (r=0.73, r<0.001) i H5 (r= -0.74, r<0.001) kod pacijenata sa HOBP. Kod pacijenata sa astmom nije registrovana razlika između tri metode u detekciji opstruktivnog poremećaja ventilacije kod pacijenata sa simptomima bolesti, dok se upotrebom sve tri metode povećala se senzitivnost. Sve tri metode bile su u slaboj korelaciji sa stepenom dispnoičnih tegoba kod pacijenta sa astmom. Svi HOBP pacijenti imali su spirometrijski registrovanu opstrukciju disajnih puteva. Senzitivnost impusne oscilometrije raste sa stepenom opstrukcije disajnih puteva, te je sposobnost detekcije opstruktivnog poremećaja ventilacije kod pacijenata sa FEV1%<80 % iznosila 55%, 95% CI 43-67 %, a kod pacijenata sa FEV1%<70 % 61%, 95% CI 47-73%. Registrovana je statistički značajna razlika vrednosti oscilometrijskih parametara u odnosu na spirometrijski stadijum HOBP. Kod pacijenata sa HOBP, sve tri metode bile su u umerenoj korelaciji sa stepenom dispnoičnih tegoba. Zaključujemo da postoji umerena korelacija impulsne oscilometrije sa spirometrijom i telesnom pletizmografijom kod pacijenta sa astmom i HOBP. Impulsna oscilometrija bolje korelira sa telesnom pletizmografijom u poređenju sa spirometrijom. Korelacija tri metode raste sa stepenom opstrukcije disajnih puteva. Komplementarna upotreba tri metode daje sveobuhvatniju sliku respiratorne funkcije kod pacijenata sa astmom i HOBP.
Asthma and chronic obstructive pulmonary disease (COPD) are most common chronic noninfectious diseases of the respiratory system, representing a major health issue. Spirometry and body plethysmography are the procedures which are most often performed to diagnose these diseases and evaluate the lung function impairment of the affected patients. Impulse oscillometry is a novel procedure to establish the lung function impairment. It is easy to perform, and minimally depends on a patient's cooperation. The major objective of this Ph. D. thesis is to compare the parameters obtained by impulse oscillometry, spirometry and body plethysmography in patients with asthma and COPD, establish the sensitivity of these procedures in detecting an obstructive ventilation disorder, and correlate the parameters of impulse oscillometry, spirometry and body plethysmpography to the severity of dyspneic symptoms in adult asthma and COPD patients. Correlating the parameters obtained by impulse oscillometry and spirometry, a moderate negative correlation of R5 values to FEV1 in asthma (r= -0.47, р<0.001) and COPD patients (r= -0.50, р<0.001) has been obtained, as well as a moderate positive correlation of X5 to FEV1 (r= 0.54, р<0.001, in asthmatics; r= 0.56, р<0.001 in COPD patients). A good correlation of Rt to R5 (r=0.63, р<0.001) and Х5 values (r= -0.55, р<0.001) has been registered in asthmatics, as well as a good correlation of Rt to R5 (r=0.73, р<0.001) and Х5 (r= -0.74, р<0.001) in COPD patients. In asthma patients, the three analysed procedures exhibited no difference in detecting an obstructive ventilation disorder in the patients with manifested symptoms, while the sensitivity improved when the procedures were complementary performed. Any of the three procedures correlated poorly to the severity of dyspneic symptoms in asthma patients. All COPD patients had a spirometry-registered airway obstruction. The sensitivity of impulse oscillometry increased with the severity of the airway obstruction, so its capacity to detect an obstructive ventilation disorder in the patients with FEV1%<80 % was 55%, 95% CI 43-67 %, and in the patients with FEV1%<70 %, it amounted to 61%, 95% CI 47-73%. A statistically significant difference in the values of all oscillometry parameters was registered depending on the spirometric COPD stage. In COPD patients, all the three procedures were moderately correlated to the severity of dyspenic symptoms. In conclusion, there is a moderate correlation of impulse oscillometry to spirometry and body plethysmography in asthma and COPD patients. Impulse oscillometry correlates better to body plethysmography than to spirometry. The correlation of the three procedures increases with the severity of the airway obstruction. The complementary application of these three procedures provides a more accurate assessment of the respiratory function in asthma and COPD patients.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
A doença pulmonar obstrução crônica (DPOC) é caracterizada pela limitação de fluxo parcialmente reversível, classificada por níveis de obstrução pós-broncodilatador. Há várias evidências de que o FEV1 sozinho não é capaz de mostrar a broncodilatação de pacientes com DPOC, mesmo naqueles que apresentam melhora clínica. A técnica de oscilações forçadas (TOF) tem mostrado alta sensibilidade na detecção precoce de alterações mecânicas na DPOC, contudo o efeito broncodilatador na impedância respiratória de pacientes com DPOC ainda não está esclarecido. Objetiva avaliar a utilidade da TOF nos diferentes estágios de obstrução das vias aéreas; (2) avaliar a resposta da impedância respiratória ao salbutamol em indivíduos saudáveis ao exame espirométrico e pacientes com DPOC em diferentes graus de gravidade. Foram avaliados 25 indivíduos saudáveis sem história de tabagismo, 24 tabagistas e 151 pacientes com DPOC classificados em graus I, II, III e IV. Todos os sujeitos foram avaliados pela TOF seguida da espirometria, antes e após o uso do salbutamol spray. As curvas de resistência e reatância demonstraram alteração em todos os estágios de obstrução das vias aéreas após o uso do salbutamol. O grupo de risco apresentou alterações mecânicas semelhantes ao grupo leve (p=ns). Os parâmetros R0, Rm, Csr,din e Z4Hz apresentam desempenho diagnóstico adequado (AUC > 0,85) em todos os estágios de gravidade da doença. Todos os parâmetros de TOF e espirometria apresentaram diminuição após uso do salbutamol. Os indivíduos saudáveis apresentaram uma pequena diminuição comparada aos subgrupos de DPOC. A variação em termos absolutos da ΔZ4Hz e das derivadas da resistência, ΔR0, ΔRm, ΔS, apresentaram variação significativa (p<0,0001, p<0,003; p<0,04; p<0,0002, respectivamente) com o aumento da obstrução brônquica. Nas derivadas da reatância o ΔXm aumentou com a gravidade da doença (p<0,0002). Por outro lado, a ΔCrs,dyn não demonstrou diferença significativa com a gravidade da DPOC. Em termos percentuais os parâmetros da TOF apresentaram variação expressiva em ΔRm% (p<0,02), ΔS% (p<0,02) e ΔXm% (p<0,004) com o aumento da obstrução nas vias aéreas. Por outro lado, ΔR0%, ΔCrs,dyn% e ΔZ4Hz% não variaram entre os estágios da DPOC. A associação entre a broncodilatação nas vias aéreas e a impedância pulmonar foi fraca entre ΔXm vs ΔFVC (r=0,32, p<0,0001) e ΔZ4Hz% vs ΔFEV1% vs ΔFVC% (r=0.28, p<0,0005; r=0,29, p<0,0003, respectivamente). A TOF é útil na avaliação das alterações mecânicas nos diferentes níveis de obstrução das vias aéreas na DPOC. Demonstramos o benefício da medicação broncodilatadora, quantificando a melhora da ventilação através da TOF. A impedância respiratória diminui em todos os estágios da DPOC, o estágio leve melhorou tanto quanto o estágio muito grave. Isto sugere que a medida da impedância pulmonar não é dependente do volume como ocorre na espirometria e que a broncodilatação ocorre em todas as fases da progressão da DPOC.
Chronic obstructive pulmonary disease (COPD) is characterized by partially reversible flow limitation, classified by the post-bronchodilator level of airway obstruction. There is abundant evidence that FEV1 alone is not able to show bronchodilation in COPD patients, even in patients with clinical improvement. The forced oscillation technique (FOT) has shown high sensitivity for early detection of mechanical changes in COPD. However, the bronchodilator effect on respiratory impedance is still unclear. Objective to evaluate the utility of FOT in the diagnosis of different stages of airway obstruction, (2) to investigate the response to salbutamol in healthy, smoking and COPD patients in different degrees of severity. We evaluated 25 healthy subjects with no history of smoking, 24 smokers and 151 COPD patients classified into grades I, II, III and IV of severity. All subjects were assessed by the FOT followed by spirometry before and after the use of salbutamol spray. The resistance and reactance curves showed change at all stages of airway obstruction after the use of salbutamol. The smoking group showed similar mechanical changes to the mild group (p=ns). The parameters R0, Rm, Csr,din and Z4Hz presented adequate diagnostic accuracy (AUC>0.85) in all stages of disease severity. All FOT and spirometry parameters showed decreased after salbutamol use. Healthy individuals showed a small decrease compared with the subgroups of COPD. The variations of the impedance module (ΔZ4Hz) and resistance parameters, (ΔR0, ΔRm, Δs) were significant (p<0.0001, p<0.003, p<0.04 and p<0.0002, respectively) with increased bronchial obstruction. Mean reactance (ΔXm) increased with disease severity (p<0.0002). The ΔCrs,dyn showed no significant change with the severity of COPD. In percentage terms, FOT parameters showed significant variation in ΔRm% (p<0.02), Δs (p<0.02) and ΔXm% (p<0.004) with increased airway obstruction. ΔR0% ΔCrs,dyn% and ΔZ4Hz% did not vary between different stages of COPD. The association between bronchodilation in the airways and lung impedance was weak between ΔXm vs ΔFVC (r=0.32, p<0.0001) and ΔZ4Hz% vs ΔFEV1% vs ΔFVC% (r=0.28, p<0.0005, r=0.29, p<0.0003, respectively). The FOT is useful in the evaluation of the mechanical changes at different levels of airway obstruction in COPD. We demonstrate the benefit of a bronchodilator, quantifying the improvement of ventilation through the FOT. The respiratory impedance decreases in all stages of COPD. This suggests that the impedance changes are not dependent on lung volume as in spirometry and that bronchodilation occurs at all stages of the progression of COPD.

In title 12, 22, 11 are in subscript.
Thesis (PhD)--Stellenbosch University, 2002.
ENGLISH ABSTRACT: The aim of this study was to test a synthetic protein-free surfactant preparation, LPM-l, with the same chemical composition as commercially available Exosurf (Glaxo Wellcome), but containing in addition, a sugar, trehalose (TRE). Towards this end, a study was designed to firstly test the hypothesis that the true difference in acute physiological effects between a mixture of oppe, tyloxapol, hexadecanol and trehalose (LPM-l), and Exosurf, (Oppe, tyloxapol and hexadecanol) is zero, in a surfactantdeficient animal model. A second study addressed the physiological effects of oppe, hexadecanol, tyloxapol and trehalose (LPM-l) compared to treatment with trehalose (TRE) or saline, in order to determine (1) the contribution of TRE to the mixture of oppe, hexadecanol and tyloxapol, and (2) to assess the effect of the LPM-l surfactant replacement on the epithelial lining fluid composition by means of analysing bronchoalveolar lavage fluid. Thirdly, the effects of TRE and / or calcium were studied on the surface properties of oppe suspensions, by in vitro analysis using the ring detachment method of Du Nouy The in vivo research comprised of two studies, performed in randomised controlled fashion. In the first study, 24 New Zealand White adult rabbits were randomised into 4 groups, while in the second study, 15 animals were randomised into 3 groups. In the first in vivo study, three synthetic surfactants, LPM-l, Exosurf and LPM-2, and a saline group were tested. LPM-l is a new formulation that consists ofa mixture of Df'PC, TRE, hexadecanol and tyloxapol. LPM-2 is a formulation with a composition equivalent to that of commercially available Exosurf, prepared on site. In both studies animals were subjected to repeated lavage with large volumes of warm saline (25 ml/kg) in order to establish surfactant deficiency and acute lung injury. Five minutes after the last lavage, vehicle, i.e. surfactants LPM-l, Exosurf, or LPM-2, or saline, in the first in vivo study, and LPM-l, TRE or saline in the second in vivo study, was instilled, and the course of the animals followed over the next 3 hours. Ventilator settings were standardized before and after lavage. The effects of surfactant treatment on gas exchange (arterial Pa02, oxygenation index (Ol), arterial-alveolar oxygen (a/A) ratio), percentage calculated shunt, and total dynamic respiratory compliance (CRSdyn), and histopathological changes were compared with changes in saline treated controls. Arterial blood gases in 100% oxygen and CRSdynwere measured before and after lavage, at 15 minute intervals for the first 30 min, then at 60, 90, 120, and 180 min after vehicle instillation. Oxygenation improved to a similar extent after LPM-l and Exosurf instillation, surpassing that of LPM-2 or saline. Overall, intratracheal instillation of both Exosurf and LPM-l, rapidly improved the gas exchange and reduced the intrapulmonary shunt, but did not restore the lung to its pre-lavage condition. From the 2nd in vivo study it was evident that trehalose-only, was inefficient as a lung surfactant, failing to improve oxygenation indices or the calculated percentage shunt, or influencing respiratory compliance. The addition of the sugar, trehalose (TRE), to the on-site 'Exosurf mixture (LPM-2) brought the activity of the resultant LPM-l to the same level as that of commercial Exosurf, but failed to raise the activity above that of Exosurf. These physiological improvements were sustained for up to 3 hours. Saline-treated animals had no improvement in gas exchange despite management with variable PIP (to maintain a tidal volume of -1 0 ml / kg) and constant PEEP of 5 cm H20. In-vitro results, obtained by the Ou Nouy tensiometer, showed higher mean ordinate surface tension values for the OPPC-only and DPPC + TRE mixtures, and the slopes of their respective graphs smaller in magnitude than those of the other formulations, suggesting that these formulations had less surface tension-lowering capability than the other surfactants. At 20°C (20 mg / ml DPPC-surfactants) the mean ordinate values of OPPC and OPPC + TRE, 70.13 and 69.47 dyne / cm, respectively, were not significantly different from each other. The mean ordinate values of LPM-l and the formulation containing OPPC + TRE + tyloxapol + CaCh were lower, but similar, as were the values of LPM-2 (on-site Exosurf) and LPM-2 + CaCho Thus, three internally homogeneous subgroups could be identified which differed significantly, namely: DPPC and DPPC + TRE, LPM-2 and LPM-2 + CaCh, and DPPC + TRE + tyloxapol + CaCh and LPM-l. Similar conclusions apply to the ordinate values of the surfactants at 37°C, and to the mean slope values at 20°C, with the exception that the subgroups, LPM-2 and LPM-2 + CaCh, and LPM-l and OPPC + TRE + tyloxapol + CaCh are not so clearly separated. A similar analysis of mean slope values was performed. Here too a significant difference between substances was found, OPPC alone or in combination with TRE, again being significantly different from the other surfactants. The most prominent light microscopy findings of the lungs of animals included general lymphatic dilatation, congestion and lung polymorphonuclear infiltration, with no difference between study groups. Hyaline membranes were present in all surfactant groups, but significantly more so in the saline treated group. In the first in vivo study, the presence of neutrophils in the lung interstitiwn as well as alveoli, was a common finding in all of the study groups towards the end of the study protocol. A significant increase in the BAL-fluid neutrophil count occurred in all animals, concurrent with a significant decrease in the BAL macrophage count. No significant change occurred in the peripheral neutrophil count during the 3-hour study, suggesting recruitment of neutrophils from storage pools. Treatment with synthetic surfactant (LPM -1) did not have a significant effect on modifying the inflammatory response, since there was no significant difference in the BAL-derived cell counts between the LPM-1 and -saline groups. Epithelial damage was a consistent finding in all groups. The damage was more evident by electron microscopy examination and included hydropic changes, most readily observed in the mitochondria. The airspaces of study subjects showed the presence of oedema fluid. This luminal oedema appeared to be more prominent in the control group and LPM-2 (on site 'Exosurf') group. Organellar debris, probably originating from lysis of epithelial cells, was present, despite treatment with synthetic surfactant. The electron microscopical appearance of the epithelial-lined substance ("hyaline membranes") in the present study showed a marked variability within groups as well as within the same case. The majority of cases showed a mix of membrane types with both granular and fibrillar materials present within the same membrane. In some cases there were layering of the membranes into distinct bands. The instillation of LPM-l resulted in the formation of a slightly different type of epithelial lining fluid after lavage, when compared to the prelavage composition. The most pronounced changes occurred within the fatty acids, whilst the phosphatidylcholine values remained unchanged. Palmitic acid concentrations (C16:0) increased significantly, suggesting enrichment of the epithelial lining fluid after instillation of LPM-l. This increase in C16:0 was concurrent with significant decreases in the percentage C16:1, C18:0, and C18:2. In contrast to previous studies, we describe higher levels for phosphatidyldimethylethanolarnine (PEA). An explanation may be that the lipid identified as PEA, was in fact partly phosphatidylglycerol (PG)-a lipid whose accurate identification was precluded for technical reasons. After surfactant instillation, the PC/SM ratio, a reflection of the lecithin / sphingomyelin (LIS), decreased significantly in the TRE-group between the first and final lavage, but remained statistically unchanged in the animals treated with LPM-l or saline. The change in ratio was mainly accounted for by a decrease in BAL-fluid PC content together with a rise in SM content. A poor correlation existed between the BAL-derived PC/SM ratio and indices reflecting oxygenation status (a/A ratio, Ol), as well as the CRSdynat the time of the final lavage. In conclusion, the primary hypothesis was accepted, LPM-l performed similarly to Exosurf in vivo, improving oxygenation, but not CRSdyn.None was clearly superior to the other. Some questions remain. The reason why LPM-l (LPM-2 + TRE) did not behave in a superior manner, in vivo, to Exosurf, is partly unclear. This finding was somewhat surprising since the chemical composition of Exosurf and LPM-2 did not differ, and the addition of TRE to LPM-2 (on-site Exosurf), did improve the in vivo activity of the resultant LPM-l, above that of LPM-2. A possible explanation for observed differences in performance include methodological issues, i.e. the preparation of the on-site formulations, especially that of LPM-2 (on-site Exosurf), may differ from the way in which true commercial Exosurf is prepared.
AFRIKAANSE OPSOMMING: Die doel van die studie was om 'n sintetiese proteïn vrye surfaktant te ontwikkel en die produk te vergelyk met 'n kunsmatige surfaktant reeds in kliniese gebruik. Die bekende uit die literatuur en die onbekende van die produk wat evalueer sou word, lei op tot die samestelling van die nul hipotese van die PhD naamlik dat geen verskil in longfunksie sou gewys word tussen die toetsproduk en reeds gebruikte kommersiële surfaktant nie. Die hipotese was dat 'n suiker (trehalose), in kombinasie met Dipalmitoiel fosfatidielcholine (DPPC), gaswisseling en longfunksies sal verbeter vir 'n long met 'n lae surfaktant konsentrasie. Vir die studie is jong volwasse wit New Zealand konyne gebruik en is hulle met 'n gestandaardiseerde en menslike manier gebruik in eksperimentele werk. Die diere is onder intraveneuse narkose geplaas en verskillende kardiovaskulêre en pulmonologiese aspekte is gemeet. Die long surfaktant is uitgewas deur middel van fisiologiese soutoplossing wat tot liggaam temperatuur verhit is en daarna is die diere prospektief gerandomiseer tot eksperimentele groepe. Met vooraf bepaalde tydsintervalle is die fisiologiese metings herhaal en was die metings toegespits daarop om longmeganiese funksie en gasoordrag vermoë te evalueer. Lig mikroskopiese en elektron mikroskopiese studies is ook op die longe gedoen en verder is brongoalveolêre vloeistof ook ontleed. Die groepe met ondersoek was: I. oppe, heksadekanol, tyloxapol en trehalose (LPM-I). 2. oppe, heksadekanol, tyloxapol (LPM-2 :. LPM-I sonder trehalose). Hierdie is 'n proteïnvrye surfaktant plaaslik berei ( dieselfde samestelling as Exosurf). 3. Exosurf®. (Kommersiële preperaat reeds in gebruik). Hierdie is 'n proteïnvrye sintetiese surfaktant. 4. Trehalose, 'n non-reduserende disakklaried van glukose. Addisioneel is daar ook in vitro studies gedoen waann die oppervlakte spanmngs aktiwiteite van die verskillende surfaktant oplossings vergelyk is. Die statistiese analise is gedoen in samewerking met Prof. J. Maritz wat 'n unieke metode ontwikkel en gepubliseer het om herhalende veranderlikes op 'n statisties verantwoordbare manier te ontleed. In die eerste van die studies, is LPM-I, Exosurf®, fisiologiese soutoplossing en 'n plaaslik bereide "Exosurf" (LPM-2), met 'n chemiese samestelling identies aan dié van kommersiële Exosurf®, evalueer. In 'n tweede studie is die fisologiese effekte van LPM-I vergelyk met trehalose of fisiologiese soutoplossing om die volgende te ondersoek: 1) Die bydrae van trehalose tot 'n mengsel van oppe, heksadekanol en tyloxapol (LPM-2). 2) Die gevolg van LPM-l surfaktant toediening op die konyn se brongo-alveolêre vloeistof samestelling. 'n Derde, in vitro studie, het die oppervlaktespannings-effekte van trehalose en of kalsiumbyvoegings tot DPPC-oplossings gemeet deur middel van die ring metode van Du Nouy, In die eerste in vivo studie verbeter oksigenasie en persentasie longaftakking tot dieselfde mate na LPM-l en Exosurf® toediening en word die hipotese van die proefskrif bevestig. In die breë gesien, is die tydsprofiele van LPM-l en Exosurf® ten opsigte van oksigenasie en persentasie longaftakking statisties betekenisvol beter en van 'n sneller aard, as die tydsprofiele van dieselfde indekse na die toediening van fisiologiese soutoplossing of LPM-2. Die tydsprofiel van dinamiese longvervormbaarheid, na die toediening van LPM-I of Exosurf®, is dieselfde, maar betekenisvol beter as die vervormbaarheid na toediening van LPM-2 of fisiologiese soutoplossing. Alhoewel die oksigenasie indekse in die geval van LPM-l en Exosurf® betekenisvol verbeter oor die studietydperk, vind volkome herstel tot die basislynwaardes (voor spoeling) nie plaas nie. Bykomend, geen van die surfaktante het na toediening enige noemenswaardige verbetering in longvervormbaarheid tot gevolg gehad nie. Die rede vir die swakker vertoning van LPM-2 en Exosurf is onbekend en sal in opvolg studie ondersoek word. In die tweede in vivo studie is dit duidelik dat trehalose op sy eie, 'n oneffektiewe surfaktant is aangesien die preperaat na toediening geen verbetering teweegbring ten opsigte van oksigenasie indekse, persentasie longaftakking, of long-dinamiese vervormbaarheid nie. Die toevoeging van trehalose tot LPM-2, om LPM-l te lewer, neem wel die aktiwiteit van LPM-l tot dieselfde in vivo vlak as dié van kommersiële Exosurf®, maar slaag nie daarim om 'n hoër fisiologiese in vivo aktiwiteit as dié produk te bereik nie. Die diere wat met fisiologiese soutoplossing behandel is toon geen verbetering in enige fisiologiese parameter nie. Die in vitro resultate wat verkry is deur die Du Nouy tensiometer toon hoër gemiddelde ordinaat oppervlaktespannings waardes vir 'n formule wat slegs uit DPPC bestaan, asook vir 'n mengsel van DPPC + trehalose. Die helling van die grafieke van hierdie oplossings is ook kleiner as die van die ander formulas wat daarop dui dat DPPC op sigself, en DPPC + trehalose, weinig vermoë het om oppervlaktespanning te verminder. Daarteenoor verlaag die volgende oplossings die oppervlaktespanning ten opsigte van gedistilleerde water betekenisvol en wel in In konsentrasie afhanklike manier by beide 21°C en 3rc: LMP-I-, LPM-2-, DPPC + trehalose + tyloxapol + CaCf2-, en LPM-2 + CaCf2. Die prominentste ligmikroskopiese bevindinge van die longe van die diere sluit in: Algemene limfvat dilatasie, stuwing, en long neutrofiel infiltrasie. Betreffende hierdie histologiese bevindinge is daar geen verskille aangetoon tussen die groepe nie. Hialienmembrane was teenwoordig in al die groepe, maar betekenisvol meer in die groep wat fisiologiese soutoplossing ontvang as vervangingsterapie. In die tweede in vivo studie is daar 'n betekenisvolle styging in die neutrofiel- en daling in makrofaagtelling, van die brongoalveolêre vloeistof spoeling in al drie die groep aangetoon. Terselfdertyd vind geen noemenswaardige daling in die perifêre (sistematiese) neutrofieltelling plaas nie. Hierdie bevindinge dui daarop dat die brongoalveolêre selveranderinge toegeskryf kan word aan verwerwing van neutrofiele vanuit 'n longstoringspoel eerder as rekrutering vanuit die sistemiese sirkulatoriese poel. Surfaktant (LPM-l), behandeling het geen betekenisvolle vermindering in long inflammasie teweeggebring nie. Epiteelskade was 'n algemene ligmikroskopiese bevinding in al die groepe. Die samestelling van die brongoalveolêre vloeistof verander na installering van LPM-I. Die prominentste verandering word waargeneem in die vetsuur samestelling terwyl die DPPC waardes onveranderd bly. Die vetsuur, palmitiensuur (palmitic acid), (CI6:0), verhoog betekenisvol na toediening van LPM-l. Daarteenoor verminder die konsentrasie van C16:1, C18:0 en C18:2. In kontras met vorige studies, beskryf die huidige studie hoër konsentrasies van fosfatidieletanolamien, moontlik as gevolg van tegniese verskille in die metingsmetodes. 'n Betekenisvolle verlaging in die fosfatidielcholine:sfingomiëlien (PC/SM) verhouding word waargeneem tussen die eerste en die finale longspoeling van die trehalose-groep, terwyl dit onveranderd bly in die diere wat LPM-1 of fisiologiese soutoplossing ontvang.

Thesis (D. Tech. (Clinical Technology )) - Central University of Technology, Free State, 2013
The HIV pandemic in South-Africa has created a new form of vulnerability for households with regards to food security and nutritional status which are vital components in the general care of HIV-infected individuals. The risk of nutritional deficiencies and malnutrition are predictors of disease progression and treatment in resource limited settings. Furthermore, HIV affects nutritional status by increasing the energy requirements, reducing food intake, affecting nutrient absorption and metabolism inadequacies due to cytokine activity and diarrhea. Several vitamins and minerals are important in fighting HIV infection because they are required by the immune system and major organs to attack infectious pathogens. Many of these micronutrients have been found to be deficient in HIVinfected persons and several studies were launched worldwide to investigate the feasibility of food assistance and nutrient supplementation. Nutritional supplementation has been advocated in HIV-infected persons especially in lowincome countries such as South Africa. Therefore, a study to evaluate the role of nutritional supplementation in HIV-positive patients becomes necessary, especially in a developing country such as South Africa. It is against this background that the present research was initiated to examine the influence of a nutritional supplement on the immune status and health status of HIVpositive/ AIDS adult individuals. The aim of the investigation was to determine if supplementation with a mixture comprised from specific minerals, vitamins and herbs over a period of one year, affected the haematological status, immune status, viral load and pulmonary function in forty (40) HIV-infected individuals living in the Mangaung Metropolitan, RSA. viii A quantitative, open-labeled, before-after clinical trial was conducted at the Central University of Technology, in Bloemfontein, Free State Province in the RSA. Socio-demographic and dietary intake questionnaires were completed. All data pertaining to anthropometric measurements, haematological status, immune status, viral load and pulmonary function were obtained my means of using standard procedures and technological equipment. The data were subjected to parametric and non-parametric statistical analysis. The results of the present investigation show that the eating pattern of this urbanized group of individuals reflects high energy (KJ) and macronutrient intakes coinciding with sub-optimal intake of Vitamin D and iodine. Of all the haematological variables the only statistical significant changes observed were increases in the median erythrocyte sedimentation rate (ESR) (p=0.0219) and mean cell haemoglobin concentration (MCHC) (p=0.0245) after six months of nutritional supplementation. At 12 months a statistical significant decrease in the median CD/CD8 ratio (p<0.0048), median Hematocrit concentration (p<0.0312), median mean cell volume (MCV) (p<0.0359), and median RDW (p<0.0273) accompanied a statistically significant increase in the MCHC (p<0.0003) at 12 months after supplementation. At 6 months 89% (CI95%: 73%; 96%) of the individuals showed a decline in viral load counts with a median percentage decline of 34% (CI95%: 73%; 96%). At 12 months 85% [CI95%: 68%; 94%] of the individuals show a decrease in viral load counts with a median percentage decline of 62.9% (CI95%: 50%; 78.6%) following the intake of the supplement. The main findings of the present investigation reveal that 68% (50%-81%) of the individuals show a statistical median increase (p=0.0302) of 16.9% (11.5%; ix 36.1%) in the Peak Expiratory Flow (PEF) at six months. A significant decrease (p=0.0484) in the median FEF75 of 28.1% (14%; 35.3%) is observed in 70% (53%-83%) of the individuals after 12 months of exposure to the supplement. No statistical significant changes are observed for FVC, FEV1, FEV1/FVC and FEF50 over the entire trial period. The present results suggest that a significant measurable decrease in viral load in HIV-infected individuals can be obtained by means of subjecting individuals to a nutritional fortification supplement strategy for 6 months or more.

Introdução: As alterações da mecânica diafragmática e a alta atividade dos músculos da caixa torácica estão associadas com maior sensação de dispnéia em pacientes com DPOC. Tem sido demonstrado que a respiração diafragmática (RD) aumenta a mobilidade abdominal durante o padrão diafragmático voluntário, porém, até o presente momento, nenhum estudo investigou as mudanças na mobilidade abdominal adotadas naturalmente. O objetivo desse estudo foi investigar os efeitos de um programa de treinamento de respiração diafragmática (PTRD) na mobilidade tóraco-abdominal, mobilidade diafragmática e capacidade funcional de pacientes com DPOC. Método: Trinta pacientes com DPOC (VEF1 42 +/- 13% do predito) foram alocados aleatoriamente para o grupo treinamento (GT) ou grupo controle (GC). O GT completou um PTRD supervisionado de 4 semanas (3 sessões semanais individualizadas). A efetividade do treinamento foi avaliada por meio da mensuração da relação da amplitude de movimento da caixa torácica pelo abdômen (CT/ABD; variável primária) e da mobilidade diafragmática (variável secundária). A relação CT/ABD foi quantificada utilizando a pletismografia respiratória por indutância durante RD voluntária e respiração natural (RN) e a mobilidade diafragmática foi determinada por avaliação ultra-sonográfica. O teste de caminhada em 6 minutos (TC6min) e os fatores de saúde relacionados à qualidade de vida (FSRQV) também foram avaliados. Resultados: Apenas os pacientes do GT apresentaram uma melhora na mobilidade diafragmática (18,8%) e uma redução na relação CT/ABD durante RN (26,1%) e RD voluntária (28,3%), sugerindo que a mobilidade abdominal aumentou em ambas as condições. Também foram observadas melhoras no TC6min e nos FSRQV no GT. Não foi observada diferença no GC para nenhuma variável mensurada. Conclusões: O PTRD para pacientes com DPOC induziu um aumento do recrutamento diafragmático durante a respiração natural resultando em melhora da capacidade funcional
Background: Impairment of diaphragm mechanics and enhanced activity of the chest wall muscles are associated with increased dyspnea in COPD patients. Diaphragmatic breathing (DB) has been suggested to improve abdominal motion but only during voluntarily DB, and no controlled studies have investigated the naturally adopted change in abdominal motion. The aim of this study was to investigate the effects of a diaphragmatic breathing training program (DBTP) on thoracoabdominal motion, diaphragmatic mobility and functional capacity in COPD patients. Methods: Thirty subjects (FEV1 42+/-13% predicted) were randomly allocated to either training (TG) or control group (CG). TG completed a 4-week supervised DBTP (3 individualized weekly sessions). Effectiveness was assessed by amplitude of the rib cage to abdominal motion ratio (RC/ABD ratio; primary outcome) and diaphragmatic mobility (secondary outcome). The RC/ABD ratio was measured using respiratory inductive plethysmography during voluntarily DB and natural breathing (NB). Diaphragmatic mobility was measured by ultrasonography. A 6-minute walk test (6MWT) and health-related quality of life (HRQoL) were also evaluated. Results: Only COPD patients from the TG demonstrated an improvement in diaphragmatic mobility (18.8%) and a reduction of the RC/ABD ratio during both NB (26.1%) and voluntarily DB (28.3%), suggesting that the abdominal motion improved in both conditions. An improvement in the 6MWT and in HRQoL was also observed in the TG. No differences were found in the CG for any measured outcome. Conclusions: We concluded that DBTP for COPD patients induced increased diaphragm recruitment during natural breathing resulting in an improvement in functional capacity

Hronična opstruktivna bolest pluća je jedna od najčešćih hroničnih bolesti pluća i važan uzrok morbiditeta i mortaliteta u svetu. Egzacerbacije predstavljaju značajan događaj u toku bolesti, jer imaju negativan uticaj na mortalitet, kvalitet života, opadanje plućne funkcije i povećanje troškova lečenja. Cilj rada je utvrditi nezavisne faktore rizika za egzacerbaciju i smrtni ishod tokom jednogodišnjeg praćenja obolelih od hronične opstruktivne bolesti pluća i kreiranje prediktivnog modela za neželjeni događaj. U ispitivanje je uključeno 200 pacijenata sa potvrđenom dijagnozom hronične opstruktivne bolesti pluća, koji su lečeni prema preporukama smernice Globalne inicijative za hroničnu opstruktivnu bolest pluća. Pacijenti su praćeni godinu dana, evaluirani na kontrolnim pregledima i beležen je broj egzacerbacija na osnovu vanrednih poseta i eventualni smrtni ishod. Statističkom obradom podataka utvrđeni su nezavisni prediktori egzacerbacije (starost > 65 godina, test procene hronične opstruktivne bolesti pluća > 9, modifikovana skala dispneje > 2, saturacija hemoglobina kiseonikom ≤ 93%) i smrtnog ishoda (starost >65 godina, potreba za primenom antiagregacione terapije, brzina maksimalnog ekspiratornog protoka na 25% vitalnog kapaciteta ≤ 1,16 l, modifikovana skala dispneje >2, puls > 89). Od navedenih nezavisnih faktora su kreirani modeli za predikciju neželjenih događaja. Unutrašnjom validacijom modela dokazana je dobra prediktivna vrednost oba matematička modela, bez statistički značajne razlike opserviranog i očekivanog procenta pojave egzacerbacije i smrtnog ishoda tokom praćenja pacijenata obolelih od HOBP.
Chronic obstructive pulmonary disease is one of the most common chronic lung diseases and is an important cause of morbidity and mortality in the world. Exacerbations are an important event in the course of the disease, as they have a negative impact on mortality, quality of life, lung function decline and increased costs of treatment. The aim of study is to identify risk factors for exacerbation or death during the one-year follow-up of patients with chronic obstructive pulmonary disease, and creation of predictive models for exacerbation and mortality during the follow-up period. The study included 200 patients with a confirmed diagnosis of chronic obstructive pulmonary disease who have had the therapy according to the Global initiative for chronic obstructive airway diseases guidelines. Patients were followed for one year, evaluated the number of exacerbations on the basis of emergency visits and eventual death. With statistical data processing there were identified independent predictors of exacerbations (age > 65 years, COPD Assessment Test > 9, modified Medical Research Council scale >2, oxygen saturation ≤ 93%) and death (age > 65 years, the need for application of antiplatelet therapy, the rate of maximum expiratory flow at 25% of vital capacity ≤ 1,16 l, modified Medical Research Council scale >2, heart rate > 89th). Of these independent factors was created a models for the prediction of adverse events during the one-year mark of COPD patients. Internal validation showed good predictive value of both models. No difference between the observed and the expected percentage of occurrence of exacerbations or death during the the follow-up period.

Introdução: Já se sabe que as alterações na atuação da força da gravidade promovidas pela mudança de postura, influenciam os volumes e capacidades pulmonares, mas o comportamento das propriedades elásticas e plásticas do pulmão ainda não está bem esclarecido na literatura. Objetivo: Avaliar a resistência do sistema respiratório em sujeitos eutróficos e obesos nos diferentes decúbitos. Métodos: Os participantes foram alocados nos diferentes grupos, de acordo com o índice de massa corpórea (IMC Kg/m2 ), sendo eles: 18-25, 25-29, 30-39, 40-49 e >50. As posições foram avaliadas pelo Sistema de Oscilometria de Impulso (IOS) em ordem aleatória: sentada (Se), supina (Su) e decúbitos laterais, esquerdo (DLE) e direito (DLD), sendo obtidos os seguintes parâmetros: resistências total, central e periférica, reatância e frequência de ressonância. A espirometria foi realizada em seguida para a análise das seguintes variáveis: capacidade vital forçada, volume expiratório forçado no primeiro segundo, a relação VEF1/CVF e fluxo expiratório forçado médio. Resultados: Foram recrutados 110 voluntários, 36 com IMC de 18 a 25 Kg/m2 (26,8 anos; 21,7 Kg/m2 ), 19 com IMC de 25 a 29 Kg/m2 (26,1 anos; 26,6 Kg/m2 ), 21 com IMC de 30 a 39 Kg/m2 (30 anos; 34,5 Kg/m2 ), 21 com IMC de 40 a 49 Kg/m2 (35,4anos; 45 Kg/m2 ) e 13 com IMC>50 Kg/m2 (35,5 anos; 54,2Kg/m2 ). Não foram detectados distúrbios ventilatórios pela espirometria (médias acima de 80% do previsto). Os grupos começaram a se diferenciar a partir da faixa de 30-39 Kg/m2 , houve diferenças importantes entre os indivíduos com IMC>50 e 40-49 com aqueles com IMC<25 e 25-29 principalmente em vias periféricas (p<0,0001). A posição supina apresentou maiores valores de resistência para todos os grupos. Essas diferenças frente às mudanças de decúbito são mais frequentes nas faixas de IMC menores (<25 a 29 Kg/m2 ). Conclusão: Há maior impedância do sistema respiratório em sujeitos obesos, com maior contribuição da resistência periférica, porém com menores variações relacionadas à mudança de posição em comparação aos sujeitos eutróficos.
Background: It is known that changes in gravity force action, promoted by change of posture, influence volumes and capacities lung, but the behavior of lung elastic and plastic properties, has not yet well clarified in literature. Aim: To evaluate the effect of different positions on respiratory system resistance. Methods: Participants were allocated to different groups, according to the body mass index (BMI Kg/m2 ). The positions were evaluated by Impulse Oscillometry System (IOS) in a random order: seated (Se), supine (Su), left lateral (LL) or right lateral decubitus (RL) and following parameters was obtained: total, central and peripheral resistance, reactance and resonant frequency. Spirometry was then performed to analyze the following variables: forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), FEV1/FVC and mean forced expiratory flow (FEF25-75%). Results: A total of 110 volunteers were recruited, 36 with BMI<25 kg/m2 (26.8 years, 21.7 kg/m2 ), 19 with BMI between 25-29kg/m2 (26.1 years, 26.6 kg/m2 ), 21 with BMI between 30-39 kg/m2 (30 years, 34.5 kg/m2 ), 21 with BMI between 40-49 kg/m2 (35.4 years, 45 kg/m2 ) and 13 with BMI> 50 kg/m2 (35.5 years, 54.2 kg/m2 ). No ventilatory disturbances were detected by spirometry, all higher than predicted (80%). The groups began to differentiate from the range of 30-39 kg/m 2 , there were important differences between individuals with BMI>50 and 40-49 with those with BMI <25 and 25-29, mainly in peripheral pathways (p<0.0001). The supine position presented higher resistance values for all groups. These differences compared to changes in decubitus are more frequent in the lower BMI ranges (<25 to 29 kg/m 2 ). It was also observed that overweight individuals tend to follow the same pattern as those with BMI within normal range. Conclusion: The respiratory impedance is higher in obese than eutrophic subjects, with more contribution of peripheral resistance, but with smaller variations related to position change when compared to eutrophic ones.

Uma das aplicações básicas da engenharia biomédica se refere aos testes de equipamentos de uso clínico, a avaliação de sua natureza, acessibilidade e/ou suas características. No âmbito da avaliação do sistema respiratório, estão disponíveis diferentes parâmetros de referência (PR) para o teste de espirometria, um dos principais testes de função pulmonar, que permite medir: volumes, capacidades e fluxos pulmonares. Estes PR baseiam-se principalmente em dados étnicos, idade e gênero de indivíduos saudáveis, mas havendo diferenças entre populações avaliadas, como no Brasil com sua grande diversidade de raças e etnias, pode haver erro diagnóstico. Em razão disto, o objetivo deste estudo foi analisar três dos principais PR utilizados nesta população: PR-P (de Pereira e colaboradores de 2007), PR-K ( de Knudson e colaboradores de 1983) e PR-Q (de Quanjer e colaboradores de 2012). Procedeu-se um estudo exploratório descritivo com 683 indivíduos (180 homens e 503 mulheres) entre 24 e 59 anos, em boas condições de saúde, praticantes de exercícios físicos regulares com frequência mínima de duas vezes por semana. Foi aplicada anamnese, coletados dados de massa, estatura e realizada a espirometria forçada (espirômetro bidirecional - Care Fusion MicroLoop) e as variáveis respiratórias avaliadas foram VEF1, CVF, FEF75 e PFE. Como principais resultados verificou-se que a idade média foi de 42 anos (masculino: 40,6 anos; feminino: 44,4 anos); IMC médio de 26 Kg/m² (masculino: 26,26 Kg/m²; feminino: 26,44 Kg/m²); e tempo da prática de exercícios físicos médio de 52 meses (masculino: 66,9 meses; feminino: 37,9 meses). Ao se analisar a variação dos parâmetros de referência para classificação da função pulmonar entre os três protocolos testados, encontrou-se diferença estatisticamente significativa (p<0,05) entre CVF, VEF1, FEF75 e PFE para os valores previstos e atingidos em todos os PR, além de sinais restritivos e obstrutivos. Para o PR-P, mesmo com indivíduos com características assintomáticas e praticantes de exercícios físicos, 17,2% dos indivíduos foram classificados com algum grau de restrição e 17,3% com obstrução, distanciando-se do PR-K e PR-Q que, respectivamente apresentaram valores para restritivo de 7,0% e 12,8% e para obstrutivos de 7,1% e 4,8%. Conclui-se que os respectivos PR podem induzir a erros, levando a classificações diferentes, podendo um mesmo indivíduo ser considerado em estado de normalidade, restritivo ou obstrutivo, a depender do protocolo escolhido. O estado nutricional interferiu na função respiratória no gênero masculino ao se identificar associação significativa entre o estado nutricional e o teste de função pulmonar, x² = 9,80 (p = 0,04). Desta forma, homens acima do peso tiveram 1,9 vezes mais risco de apresentar o teste de função pulmonar insuficiente, mesmo praticando exercícios físicos regulares. Não houve associação significativa em nenhum dos gêneros entre o teste de função pulmonar e o tempo de prática de exercícios físicos. O teste de correlação de Pearson, confirmou a inexistência de correlação entre as variáveis VEF1, PFE e CVF com o tempo de prática para ambos os gêneros.
One of the basic applications of biomedical engineering refers to the testing of clinical use equipment, the assessment of its nature, accessibility and / or its features. In the evaluation of the respiratory system, are available different parameters of reference (PR) for the spirometry test, one of the main pulmonary function tests, which can measure: volumes, capacities and pulmonary flows. These PR based mainly on ethnic data, age and gender in healthy subjects, but with differences between populations studied, as in Brazil with its great diversity of races and ethnic groups, there may be misdiagnosis. Because of this, the objective of this study was to analyze in this population, three of the most used PR: PR-P (Pereira et al., 2007), PR-K (Knudson et al., 1983) and PR-Q (Quanjer et al., 2012). The procedure was a descriptive exploratory study with 683 subjects (180 men and 503 women) between 24 and 59 years, in good health, regular physical exercises practitioners with minimum frequency of twice a week. Anamnesis was applied, collected data of mass and height, performed forced spirometry (bidirectional spirometer - Care Fusion Microloop) and the following respiratory variables were measured, FEV1, FVC, PEF and FEF75. With the main results it was found that the average age was 42 years (male: 40.6 years; women: 44.4 years); BMI average of 26 kg / m² (male: 26.26 kg / m²; female: 26.44 kg / m²); and time the average physical exercises practice 52 months (male: 66.9 months; female: 37.9 months). When analyzing the variation of the reference parameters for pulmonary function classification between the three protocols tested, we found a statistically significant difference (p <0.05) between FVC, FEV1, PEF and FEF75 to the levels required and achieved in all PR, as well as restrictive and obstructive signs. For the PR-P, even with individuals with asymptomatic characteristics and practitioners of physical exercises, 17.2% of subjects were classified with some degree of restriction and 17.3% with obstruction, away from the PR-K and PR-Q which respectively had values for restrictive of 7.0% and 12.8% and for obstruction of 7.1% and 4.8%. We conclude that these PR may induce to errors, leading to different rating, where one individual can be considered in normal state, restrictive or obstructive, depending on the chosen protocol. It was identified that nutritional status interfere with respiratory function, demonstrating significant association between nutritional status and pulmonary function test for males, x² = 9.80 (p = 0.04). Thus, overweight men had 1.9 times more risk to have the insufficient lung function test, even practicing regular physical exercises. There was no significant association in any of the genres between the pulmonary function test and the time of physical activity. The Pearson correlation test confirmed the lack of correlation between the FEV1, FVC and PEF with practice time for both genders.

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The dissertation consisted of two works. The aim of the first study was to evaluate respiratory muscle endurance (RME) in post myocardial infarction (MI) patients without respiratory muscle weakness [maximal inspiratory pressure (MIP)≥60% of predicted] and its correlation with exercise tolerance. Participated in this study ten recent post-MI (<1.5 month post-MI [RIG]), nine late post-MI (>6 months post-MI [LIG]) and twelve healthy (control group [CG]) middle-aged men. They underwent spirometric evaluation, cardiopulmonary exercise test and two RME protocols (incremental [IP] and constant pressure [CP]). There were differences (p0.05) in endurance pressure (PTHMAX) between the RIG and CG. There was a positive correlation for RIG between PTHMAX and maximal voluntary ventilation (MVV) (r=0.67) and peak oxygen consumption (VO2peak) (r=0.59). We conclude that RME seems to be reduced and related to peak exercise tolerance in recent MI patients without inspiratory muscle weakness. Similarly, in the second study, with nine subjects in RIG, ten in LIG and ten in CG, the aim was to characterize the metabolic and ventilatory behavior during testing of RME with IP and CP. In 70 and 80% of MIP (IL) and in the middle and final of CP test, the RIG had lower MET and higher VE/VCO2 compared CG. At 90% of MIP (IL), the RIG had lower VO2 and MET compared to CG. Moreover, RIG achieved lower pressure and product pressure-time using a similar percentage of VO2peak and oxygen consumption at anaerobic threshold (VO2AT) to sustain a 20% lower pressure than the CG. We conclude that the reduced capacity of RME in recent MI patients without inspiratory muscle weakness seems to occur due to lower ventilatory efficiency in the second part of the protocols, even in the presence of lower pressure overload.
A dissertação constou de 2 estudos descritos a seguir. O estudo I teve por objetivo avaliar a resistência dos músculos respiratórios (RMR) de indivíduos pós-infarto do miocárdio (IM) sem fraqueza muscular inspiratória [pressão inspiratória máxima (PIMAX)≥60% do predito] e sua correlação com a tolerância ao exercício. Participaram deste estudo dez homens pós-IM recente (<1 mês e meio pós-IM [GIR]), nove pós-IM tardio (>6 meses pós-IM [GIC]) e doze homens saudáveis (grupo controle [GC]) de meia-idade. Estes foram submetidos a espirometria, teste cardiopulmonar e a dois protocolos de RMR [pressão incremental (RPI) e constante (RPC)]. Houve diferença (p0,05) na pressão de resistência (PTHMAX) entre o GIR e o GC. Houve correlação positiva no GIR entre PTHMAX e ventilação voluntária máxima (VVM) (r=0,67) e o consumo de oxigênio no pico de exercício (VO2pico) (r=0,59). Concluímos que a RMR parece estar reduzida e relacionada a tolerância no pico do exercício em indivíduos pós-IM recente sem fraqueza muscular respiratória. Também foi realizado o estudo II, com nove indivíduos no GIR, dez no GIC e dez no GC, que teve por objetivo caracterizar o comportamento ventilatório e metabólico durante os testes de RPI e RPC. Em 70 e 80% da PIMAx (RPI) e no meio e final do teste de RPC, o GIR apresentou menor MET e maior VE/VCO2 em relação ao GC. Em 90% da PIMAx (RPI), o GIR apresentou menor VO2 e MET em relação ao GC. Além disto, GIR apresentou menor pressão e produto pressãotempo de RMR, utilizando semelhante percentual do VO2pico e do consumo de oxigênio no limiar de anaerobiose (VO2LAV) para pressões 20% menores em relação ao GC. Concluímos que a redução da capacidade de RMR em indivíduos na fase recente pós-IM e sem fraqueza muscular inspiratória parece ocorrer em virtude da menor eficiência ventilatória na segunda metade dos protocolos, mesmo na presença de menor sobrecarga pressórica.

Introdução: O derrame pleural, reduzindo a capacidade funcional pulmonar, torna os pacientes incapacitados para o desenvolvimento de suas atividades habituais. A retirada do líquido pleural através da toracocentese pode reverter este quadro, porém seu impacto especialmente na capacidade ao exercício não foi totalmente estabelecido. Objetivos: Avaliar o impacto da toracocentese de alívio na capacidade funcional ao exercício, no comportamento da função pulmonar e na força dos músculos respiratórios 48 horas pós toracocentese. Casuística e Método: Foram incluídos no estudo 25 pacientes com derrame pleural unilateral, documentado por radiografia de tórax. O teste de caminhada de seis minutos (TC6M), a escala modificada de dispnéia de Borg, as variáveis espirométricas: Capacidade Vital Forçada (CVF), Volume Expiratório Forçado no Primeiro Segundo (VEF1) e as medidas de Pressão Inspiratória Máxima (Pimax) e Pressão Expiratória Máxima (Pemax) foram analisados antes e 48 horas após a retirada de volumes superiores a 600 mL. Resultados: Foram removidos 1564 + 695 mL de líquido pleural. Os valores da distância percorrida, da CVF, do VEF1, da Pimax e da Pemax aumentaram (p < 0,001) enquanto o escore de dispnéia diminuiu (p < 0,001) após o procedimento. Observaram-se correlações estatísticas (p < 0.001) entre a distância percorrida e a CVF (r = 0.725) e VEF1 (r = 0.661) avaliadas 48 horas pós toracocentese e entre a variação da distância percorrida e a variação porcentual da CVF (r = 0,450) e do VEF1 (r = 0,472), corrigidos pelo volume de líquido retirado (p < 0,05). Conclusão: Embora ocorra melhora da função pulmonar após a toracocentese, os benefícios observados são mais evidentes em situações de esforço, o que possibilita melhor readaptação dos pacientes às suas atividades rotineiras.
Introduction: Pleural effusion reducing pulmonary functional capacity hinders patients in carrying out their habitual activities. Pleural fluid removal by thoracentesis reverts the clinical situation but its impact especially on exercise capacity has not yet been determined. Objectives: To evaluate the impact of thoracentesis in functional exercise capacity on pulmonary function and on muscle strength 48 hours after thoracentesis. Methods: Twenty five patients with unilateral pleural effusion documented by chest X-ray were included. The 6 minute walk test (TC6M), Borg\'s modified dyspnea scale, spirometric variables: CVF (forced vital capacity), VEF1 (forced expiratory volume in the first second), Maximum Inspiratory Pressure (Pimax) and Maximum Expiratory Pressure (Pemax) were analyzed before and 48 hours after the removal of volumes greater than 600 mL. Results: The mean of pleural effusion removed was 1564 + 695 mL. After the procedure values of walked distance, CVF, VEF1, Pimax and Pemax covered increased (p < 0.001) while dyspnea decreased (p < 0.001). Statistical correlations (p < 0.001) between the walked distance and FVC (r = 0.725) and VEF1 (r = 0.661) were established noted measured 48 hours post thoracentesis and between the variation of the distance walked and the percentage of variation of CVF (r = 0.450) and VEF1 (r = 0.472), corrected by the volume of fluid removed (p < 0.05). Conclusions: Despite an improvement in lung function after thoracentesis, the benefits noted are more evident in effort situations of exertion, allowing a better readaptation of patients to their routine activities.

Introdução: A DPOC caracteriza-se pela limitação ao fluxo aéreo associada à resposta inflamatória anormal dos pulmões a partículas ou gases nocivos. As alterações mecânicas decorrentes da DPOC estão relacionadas com a disfunção mecânica das fibras do diafragma, já observadas nas fases iniciais da doença. Alguns estudos têm demonstrado o elevado potencial da Técnica de Oscilações Forçadas (FOT) na detecção das alterações mecânicas da DPOC. Contudo, tais aplicações da FOT não permitiam a análise em tempo real das alterações do sistema respiratório, bem como da mobilidade toracoabdominal destes indivíduos. Desta forma, os objetivos desta pesquisa foram analisar, em tempo real, as alterações de impedância do sistema respiratório nas distintas fases do ciclo em portadores de DPOC, assim como avaliar a movimentação toracoabdominal destes indivíduos. Metodologia: Trata-se de um estudo observacional controlado, prospectivo onde foram analisados 48 indivíduos, 23 indivíduos controles e 25 portadores de DPOC com grau de obstrução acentuado. Os indivíduos realizaram exames de FOT para análise da impedância do sistema respiratório e mobilidade toracoabdominal, simultaneamente. Posteriormente aos exames da FOT os indivíduos foram submetidos à Espirometria. Resultados: Os resultados demonstraram aumento da impedância do sistema respiratório nos indivíduos com DPOC em comparação ao grupo controle, em nos parâmetros estudados (Zt, Zi, Ze, Zii, Zie, Zrs e Zpp) (p<0,0001). Em relação às distintas fases do ciclo, os indivíduos deste estudo apresentaram impedâncias maiores na fase inspiratória quando comparadas à fase expiratória (p<0,004). Somente 10% dos portadores de DPOC apresentaram assincronia toracoabdominal (φ ≥ 45), sendo que os valores médios não apresentaram diferença estatística quando comparados ao grupo controle. Discussão: A impedância total do sistema respiratório (Zt) aumentada nos portadores de DPOC confirma o aumento da carga mecânica do sistema respiratório destes indivíduos. Essas alterações são coerentes com o processo fisiopatológico, evidenciado pela obstrução ao fluxo aéreo e destruição do parênquima pulmonar. O aumento da impedância na fase inspiratória quando comparada à fase expiratória, sugere um aumento no trabalho resistivo e elástico. Não foram evidenciados sinais de assincronia na mobilidade toracoabdominal na maior parte dos indivíduos, sugerindo que alguns mecanismos adaptativos atuam na tentativa de evitar a fadiga do músculo respiratório. Conclusões: A DPOC resulta no aumento da carga mecânica do sistema respiratório, alterações identificadas pelo aumento da impedância do sistema respiratório, medida pela FOT em tempo real. Este aumento foi mais evidente durante a fase inspiratória. A mobilidade toracoabdominal não se mostrou alterada na maior parte dos indivíduos com DPOC. Estes resultados são consistentes com publicações prévias e fundamentos fisiopatológicos, confirmando o potencial da FOT monofreqüência na avaliação das modificações relacionadas à DPOC.
Introduction: COPD is carachterized by airflow limitation associated abnormal inflammatory response of the lung to noxious particles or gases. The mechanical alterations associated with COPD have been related with dysfunction of the diaphragm, observed since the initial phases of the disease. Several studies have confirmed the high potential of FOT in the assessment of the mechanics modifications related to COPD. However, such studies did not allow a real-time analysis of the changes in the respiratory system, and the thoracoabdominal mobility of these individuals. Thus, the goals of the present study were to analyze, in real-time, the impedance alterations of the respiratory system in different phases of the respiratory cycle of COPD patients. Methodology: This research consists of a controlled observational study where 48 individuals were analyzed, 23 controls and 25 individuals with COPD and severe airway obstruction. Firstly, they performed simultaneous analysis of impedance of the respiratory system and thoracoabdominal motion. In subsequent examinations, these subjects were submitted to spirometry. Results: The results demonstrated an increase of the respiratory system impedance in individuals with COPD compared with the control group in all of the studied parameters (Zt, Zi, Ze, Zii, Zie, ΔZrs e Zpp) (p<0.0001). Considering the different phases of the respiratory cycle, higher impedances were observed in the inspiratory phase (p<0.004). Only 10% of individuals with COPD showed thoracoabdominal asynchrony (φ≥ 45), and the mean values showed no statistical difference when compared to the control group. Discussions: The total impedance of the respiratory system increased in individuals with COPD, which describes the increase of the mechanic load of the respiratory system in these individuals. These alterations are coherent with the physiopathology of COPD, associated with airflow obstruction and lung parenchyma destruction. The increase of the impedance in the inspiratory phase suggests an increase of the resistive and elastic work. There were not signals of thoracoabdominal asynchrony in the major part of the studied individuals, suggesting that some adaptation mechanisms act to compensate respiratory muscle fatigue. Conclusion: The COPD results in the increase of the mechanic load of the respiratory system. These alterations were identified by the increase of the respiratory system impedance, which was more evidence in the inspiratory phase. The thoracoabdominal asynchrony was not usual in individuals with COPD. Those results are consistent with previously published data and physiopathological fundamentals, confirming the potential of monofrequency FOT in the assessment of the modifications related to COPD.