L’asthme et la maladie pulmonaire obstructive chronique (MPOC) se classent au premier rang parmi les maladies respiratoires les plus fréquentes au Québec. Une mauvaise maîtrise de l’asthme et de la MPOC entraîne d’importantes répercussions sur la santé et la qualité de vie des patients et sur les coûts associés au système de santé canadien, dues à de fréquentes consultations médicales, des visites à l’urgence, des hospitalisations et des décès précoces. Il est donc très important d’évaluer l’usage optimal des médicaments dans le traitement de ces maladies afin de réduire la morbidité et la mortalité Cette thèse vise à comparer dans un premier temps l’efficacité des médicaments en situation réelle dans le traitement de la MPOC sur le taux d’exacerbations et la mortalité puisque les études observationnelles publiées à ce sujet comportaient des biais majeurs dus à une mauvaise mesure de l’exposition au traitement. Ainsi, dans le cadre de cette thèse, deux banques de données administratives québécoises ont été appariées pour créer une cohorte de 36 492 patients âgés de 50 ans ou plus atteints de MPOC (1995-1999) Dans cette cohorte, la théophylline diminuait davantage les exacerbations que les β2-agonistes à longue durée d’action (BALA, RR = 0,89; IC 95 % : 0,84-0,95), mais elle était moins efficace en situation réelle que les corticostéroïdes inhalés (CSI, RR = 1,07; IC 95 % : 1,04-1,10). Un devis cas-témoins niché dans cette cohorte a permis de vérifier que les CSI seuls ou combinés avec un BALA étaient plus efficients pour réduire la mortalité comparativement aux BALA seuls (RR = 0,69; IC 95 % : 0,53-0,88 et RR = 0,73; IC 95 % : 0,56-0,96, respectivement). L’efficacité des CSI dans le traitement de l’asthme pour réduire les exacerbations et la mortalité n’est plus à prouver, cependant la non-adhésion et la non-persistance aux CSI sont grandement problématiques. À notre connaissance, aucune étude n’a évalué l’impact du type d’assurance médicaments sur l'adhésion et la persistance des Québécois aux CSI en raison de l’absence des personnes qui ont une assurance médicaments privée dans la banque de données des services pharmaceutiques de la Régie de l’assurance maladie du Québec. Afin de combler ce manque, une des parties intégrantes de cette thèse a été de développer le registre reMed. Par la suite, une cohorte d’utilisateurs de CSI âgés de 20 à 64 ans a été sélectionnée à partir de reMed (2008-2010) et ces sujets ont été appariés à des utilisateurs de CSI sélectionnés à partir de la banque de données des services pharmaceutiques de la Régie de l’assurance maladie du Québec (RAMQ). Les résultats de cette dernière étude indiquent que même si l’adhésion était faible dans les deux cohortes, les patients ayant une assurance médicaments privée étaient moins adhérant que les patients couverts par l’assurance médicaments publique de la RAMQ (différence moyenne d’adhésion de -9,7 %; IC 95 % : -13,2 % à -6,5 %). De plus, ces patients couverts par une assurance médicaments privée étaient aussi 52 % plus susceptibles d'arrêter leur traitement de CSI au cours d’une année (HR = 1,52; IC 95 % : 1,16-2,00). En conclusion, selon les travaux de cette thèse, la théophylline peut être considérée comme une thérapie efficace en situation réelle pour prévenir les exacerbations aiguës de la MPOC d’autant plus qu’elle est moins dispendieuse que les traitements en inhalations et que sa formulation orale procurerait, selon la littérature, une meilleure adhésion que les médicaments en inhalation. Quant aux CSI, ils ont un rôle important dans le traitement de l’asthme, mais aussi dans le traitement de la MPOC, puisque selon les résultats de cette thèse, ils procureraient une plus grande diminution du risque d’exacerbations aiguës de la MPOC et de la mortalité par rapport aux autres traitements. Par contre, il a aussi été démontré que l'adhésion et la persistance aux CSI étaient très faibles, particulièrement dans le traitement de l’asthme. Le type d’assurance médicaments serait un facteur déterminant de l’adhésion et de la persistance aux CSI. D’autres études seront nécessaires pour évaluer si les différences d’adhésion et de persistance observées dans cette étude se traduisent par des différences sur l’utilisation et les coûts des soins de santé. De plus, il sera nécessaire d’étudier si les différences observées se limitent aux CSI ou si le type d’assurance médicaments a impact sur la prise d’autres médicaments indiqués dans le traitement des maladies chroniques. / Asthma and chronic obstructive pulmonary disease (COPD) are the most prevalent respiratory diseases in Quebec. Poor control of asthma and COPD has a significant economic impact on the health care system, but also on patient’s quality of life, due to frequent medical visits, emergency department visits, hospitalizations and early death. Therefore, it is very important to assess the optimal usage of medications in the treatment of these diseases in order to reduce morbidity and mortality. The first aim of the present thesis was to compare the effectiveness of medications in the treatment of COPD on the rate of exacerbations and mortality because observational studies published on this subject included major bias due to inaccuracy in the treatment exposure measurement. Thus, in the context of this thesis, two Québec administrative databases were matched to select a cohort of 36 492 COPD patients aged 50 years or older (1995-1999). In this cohort, the rate of exacerbations was lower among theophylline users than long-acting β2-agonists (LABA) users (RR = 0.89, 95% CI: 0.84 -0.95), but theophylline was less effective than inhaled corticosteroids (ICS, RR=1.07, 95% CI: 1.04 -1.10). From this cohort, a nested case-control found that ICS alone or in combination with LABA were more effective in reducing mortality compared with LABA alone (RR = 0.69, 95% CI: 0.53-0.88 and RR = 0.73, 95% CI: 0.56 to 0.96, respectively). The efficacy of ICS in the treatment of asthma to reduce exacerbations and mortality is well proven, however, non-adherence and non-persistence with ICS are highly problematic. To our knowledge, no study has evaluated the impact of the type of drug plan insurance on the adherence and persistence with ICS among Quebecers due to the lack of information on prescribed medications for people with private drug insurance in the Régie de l' assurance maladie du Québec (RAMQ) pharmaceutical database. In order to circumvent the lack, the reMed registry was developed as part of this thesis. Thereafter, a cohort users of ICS aged between 20-64 years was selected from reMed (2008-2010) and then matched to users of ICS selected from the RAMQ pharmaceutical database. The results of this study suggest that although adherence was low in both cohorts, patients privately insured were less adherent than patients publicly with the RAMQ (mean difference of adherence -9.7%; 95% CI: -13% to -6.5%). Moreover, patients privately insured were also found to be 52% more likely to stop their ICS during the first year (HR = 1.52; 95% CI: 1.16 to 2.00). In conclusion, based on the work of this thesis, theophylline may be considered as an effective therapy to prevent acute COPD exacerbations. Furthermore, theophyllines are less expensive than inhaled medications and its oral formulation would provide, according to the literature, better adhesion than inhaled medications. ICS are important in the treatment of asthma, but also in the treatment of COPD, since according to the results of this thesis, they would provide a greater reduction on the rate of acute COPD exacerbations and mortality compared to other treatments. However, it was also demonstrated that adherence and persistence with ICS were very low in the treatment of asthma particularly. The type of drug insurance plan is a determinant of adherence and persistence with ICS. Further studies are needed to assess whether differences in adherence and persistence observed in this study result in differences in the use of health services and health care costs. In addition, it will be necessary to investigate whether the observed differences are limited to ICS or if the type of drug insurance has an impact on medications for other chronic diseases.

Chronic obstructive pulmonary disease (COPD) describes a range of lung conditions including emphysema, chronic bronchitis and small airways disease. While COPD is a major cause of death and debilitating illness, current clinical assessment methods are inadequate: they are a poor predictor of patient outcome and insensitive to mild disease. A new imaging technology, hyperpolarised xenon MRI, offers the hope of improved diagnostic techniques, based on regional measurements using functional imaging. There is a need for quantitative analysis techniques to assist in the interpretation of these images. The aim of this work is to develop these techniques as part of a clinical trial into hyperpolarised xenon MRI. In this thesis we develop a fully automated pipeline for deriving regional measurements of lung function, making use of the multiple imaging modalities available from the trial. The core of our pipeline is a novel method for automatically segmenting the pulmonary lobes from CT data. This method combines a Hessian-based filter for detecting pulmonary fissures with anatomical cues from segmented lungs, airways and pulmonary vessels. The pipeline also includes methods for segmenting the lungs from CT and MRI data, and the airways from CT data. We apply this lobar map to the xenon MRI data using a multi-modal image registration technique based on automatically segmented lung boundaries, using proton MRI as an intermediate stage. We demonstrate our pipeline by deriving lobar measurements of ventilated volumes and diffusion from hyperpolarised xenon MRI data. In future work, we will use the trial data to further validate the pipeline and investigate the potential of xenon MRI in the clinical assessment of COPD. We also demonstrate how our work can be extended to build personalised computational models of the lung, which can be used to gain insights into the mechanisms of lung disease.

Maladies fréquentes, l’asthme touche 8,4% de la population canadienne âgée de 12 ans et plus et la maladie pulmonaire obstructive chronique (MPOC) touche de 5 à 15% de la population âgée entre 35 et 79 ans. L’asthme et la MPOC peuvent coexister chez un patient. Ce phénomène appelé syndrome de chevauchement de l’asthme et de la MPOC (ACOS) toucherait environ 10% à 55% des patients MPOC. Afin de mieux caractériser l’ACOS et les effets indésirables des médicaments utilisés pour traiter la MPOC, deux études ont été mises en place. Une première étude réalisée auprès de pneumologues a permis de décrire les méthodes de diagnostic, de traitement et d’évaluation de la maitrise de l’ACOS dans la pratique clinique. Les pneumologues rapportent que le diagnostic devrait être basé sur les caractéristiques cliniques, les tests de fonction pulmonaire et l'intuition clinique du médecin. De plus, un corticostéroïde inhalé en combinaison et un bronchodilatateur inhalé à longue durée d’action devraient être introduits rapidement dans le plan de traitement. La deuxième étude a permis d’évaluer la fréquence des effets indésirables chez les patients MPOC/ACOS traités avec un bronchodilatateur inhalé à longue durée d’action. Cette étude démontre que les effets indésirables sont fréquents chez les patients MPOC/ACOS et que la sécheresse buccale et la gorge sèche sont les plus rapportés. Ces résultats démontrent que la mise en place de lignes directrices pour l’ACOS ainsi qu’une meilleure connaissance du profil de tolérance des bronchodilatateurs inhalés à longue durée d’action seraient bénéfiques pour les patients / Asthma and chronic obstructive pulmonary disease (COPD) are frequent in Canada with a prevalence of 8.4% among Canadians aged 12 and over for asthma and a prevalence of 5 to 15% among Canadians aged 35 to 79 years. Asthma and COPD can coexist in a patient and this Asthma-COPD overlap syndrome (ACOS) affects about 10% to 55% of COPD patients. To better understand this syndrome, two studies were designed and conducted. First, focus groups evaluated how pulmonologists diagnose and treat ACOS, and how they assess its control in routine clinical practice. The pulmonologists reported that the diagnosis must be based on clinical characteristics, pulmonary function tests, and clinical intuition. They also agreed that the treatment should target the features of both asthma and COPD. The second study assessed the prevalence of adverse events in COPD/ACOS patients on long-acting inhaled anticholinergics (LAAC) and β2-agonists (LABA) in a real-world setting. This study demonstrates that side effects are common among COPD/ACOS patients. Dry mouth and dry throat were the most reported side effects. These results demonstrate that more explicit guidelines for ACOS and a better understanding of the safety profile of long-acting bronchodilators would be beneficial for patients.

Pacientes portadores de doença pulmonar obstrutiva crônica (DPOC) podem apresentar assincronia toracoabdominal (ATA). Existem diversos métodos de estimativa da ATA, porém, não há um consenso sobre qual é o mais adequado. O objetivo deste estudo foi comparar dois métodos de estimativa da assincronia toracoabdominal e avaliar a ineficiência ventilatória em pacientes DPOC no repouso e durante o exercício. Foram avaliados 22 pacientes com DPOC (VEF1 40,2±10,5% predito) e 13 indivíduos controle (GC) pareados por idade, gênero e índice de massa corpórea. A cinemática toracoabdominal foi avaliada utilizando pletismografia optoeletrônica no repouso e durante o exercício leve e moderado (70% da carga máxima) no ciclo ergômetro. A ATA foi calculada entre a caixa torácica superior (CTS) e inferior (CTI) e o abdome (ABD) utilizando os métodos de ângulo de fase (AF) e relação de fase (RF). A ineficiência ventilatória foi calculada em cada compartimento como a diferença entre o volume máximo (VM) e o volume calculado (VC) de acordo com o ciclo respiratório (determinado pela soma de volume dos três compartimentos) dividida pelo volume máximo (VM-VC)/VM. Os pacientes com DPOC foram classificados como assíncronos (grupo AT) ou não assíncronos (grupo NA) utilizando como referência os valores do GC. Foi utilizado o teste qui-quadrado ou de Fisher para avaliar a discriminação de pacientes entre os métodos e o ANOVA de dois fatores para comparações entre os grupos. O nível de significância foi ajustado para 5%. O método AF determinou maior número de pacientes com ATA quando comparado com RF no repouso (respectivamente, 15 vs. 7) e no exercício leve (11 vs. 3) e moderado (14 vs. 8). Os valores de assincronia no grupo AT entre CTS-CTI e CTI-ABD foram maiores no repouso (AF: 35,7±45,4° e -42,2±42,5° e RF: 61,8±29,1° e -66,9±27,4°, respectivamente) e no exercício leve (AF: 53,3±35,6° e -55,8±40,4°; RF: 106,1±40,3° e - 124,8±17,2°) e moderado (AF: 61,6±55,1° e -75,9±44,8°; RF: 85,9±23,6° e -81,8±42,2°) quando comparados com os grupos NA (p < 0,05) e GC (p < 0,05). Na análise entre CTSABD não houve diferença entre os grupos. Observou-se que o grupo AT apresentou menor contribuição e maior ineficiência ventilatória da CTI em todos os momentos de avaliação e, durante o exercício moderado, menor volume corrente quando comparado com os grupos NA e GC. Os nossos resultados sugerem que o ângulo de fase apresenta maior detecção de ATA nos pacientes com DPOC. A presença de assincronia parece ocorrer principalmente na caixa torácica inferior e associada com menor contribuição e maior ineficiência ventilatória deste compartimento / Chronic obstructive pulmonary disease (COPD) patients can present thoracoabdominal asynchrony (TAA). There are several TAA estimation techniques, however, there is no consensus about which is the most appropriate. The aim of this study was to compare two thoracoabdominal asynchrony quantification techniques and to assess chest wall ventilatory inefficiency in COPD patients at rest and during exercise. We evaluated 22 COPD patients (FEV1 40,2±10,5% predicted) and 13 healthy controls (CG) matched by age, gender and body mass index. Thoracoabdominal kinematics was assessed via optoelectronic plethysmography at rest and during mild and moderate exercise (70 % maximum workload) in a cycle ergometer. TAA was calculated among upper (URC) and lower ribcage (LRC) and abdomen (ABD) by using the phase angle (PA) and phase relation (PR) approaches. Ventilatory Inefficiency was estimated in each compartment as the difference between the maximal volume (VM) and the volume (VC) calculated according to respiratory timing (sum of volume in the 3 compartments) divided by the maximal volume (VM-VC)/VM. COPD patients were classified as asynchronous (AT group) or not (NA group) by using as reference the values on the controls. Chi-square or Fisher\'s exact test was used for assessing the patients differentiation between the two TAA quantification approaches and two-way ANOVA was used to compare respiratory parameters among groups (CG, AT and NA). Statistical significance was set at 5% level. PA approach determined more patients as asynchronous when compared to RF at rest (respectively, 15 vs. 7) and during mild (11 vs. 3) and moderate (14 vs. 8) exercise. Asynchrony values in AT group among URC-LRC and LRC-ABD were greater at rest (respectively, 35.7±45.4° and -42.2±42.5° with PA and 61.8±29.1° and -66.9±27.4° with PR) and during mild (PA: 53.3±35.6° and -55.8±40.4°; PR: 106.1±40.3° and -124.8±17.2°) and moderate exercise (PA: 61.6±55.1° and - 75.9±44.8°; PR: 85.9±23.6° and -81.8±42.2°) when compared to NA (p < 0.05) and CG (p < 0.05). Analysis among URC-ABD presented no difference between groups. It was observed that AT group presented a smaller LRC contribution and greater ventilatory inefficiency during all assessing moments and, during moderate exercise, had a lower tidal volume when compared to NA and CG. Our results suggest that phase angle approach presents larger TAA detection in COPD patients. This asynchrony seems to occur mainly in the lower ribcage and be associated with decreased contribution and increased ventilatory inefficiency of this compartment

Avaliamos as mudanças no padrão respiratório, movimento toracoabdominal e ventilação em portadores de DPOC e indivíduos sadios. Estudou-se 45 indivíduos entre 45 e 75 anos conforme o VEF1. Utilizou-se sistemas de pletismografia respiratória por indutância, análise metabólica de gases em posição semi-sentada ao repouso e radiografia de tórax para a mobilidade diafragmática. Os grupos DPOC apresentaram redução do TI, TTOT, aumento do VC/TI, f, VE, das relações VEM/VC, VE/VO2, VE/VCO2 e diminuição da SpO2. Redução da mobilidade do diafragma e aumento da VEM/VC associaram-se à ineficiência da ventilação e a alterações no modelo ventilatório utilizado, sem alterações no movimento toracoabdominal. / We assessed changes in breathing patterns, thoracoabdominal movement and ventilation in COPD sufferers and healthy individuals. Forty-five individuals between 45 and 75 were grouped by FEV1. Inductive plethysmographic equipment, respiratory metabolism measuring (with subject at rest in semi-recumbent position), and radiographic measurement of diaphragm mobility were used. The COPD groups presented reduction in TI and TTOT and increased VT/TI, f, VE, and VD/VT, VE/VO2, VE/VCO2 and decreased SpO2. Reduction in diaphragm mobility and increase of VEM/VC were associated with ventilatory inefficiency and alterations in the ventilatory model used. No alterations in thoracoabdominal movement

INTRODUÇÃO: Pacientes com doença pulmonar obstrutiva crônica (DPOC) tem atividade física reduzida. Barreiras que limitam a atividade física e a medida objetiva da limitação ainda são pouco estudadas nesta população. Conhece-las permite um planejamento adequado para incremento da atividade de vida diária (AVD). OBJETIVO: Comparar a AVD de portadores de DPOC e controles com um sensor de movimento, identificar barreiras que impedem a AVD e correlaciona-los à gravidade da dispneia, ao teste de caminhada de 6 minutos (TC6) e um escore de limitação da AVD. MÉTODOS: O número de passos, a distância percorrida em quilômetros e o tempo de caminhada foram registrados por um acelerômetro de bolso e um pedômetro durante 7 dias consecutivos. Um questionário de barreiras percebidas e a escala AVD (LCADL) foram utilizados para qualificar fatores que impedem a AVD. A dispneia foi medida por duas escalas distintas e a capacidade física submáxima pelo TC6. RESULTADOS: Foram avaliados 40 sujeitos com DPOC e 40 controles saudáveis. Os pacientes com DPOC realizaram tempo menor de caminhada (68,5 ± 25,8 minutos/dia vs. 105,2 ± 49,4; p < 0,001), menor distância (3,9 ± 1,9 km/dia vs. 6,4 ± 3,2; p < 0,001) e menor número de passos/dia. A falta de estrutura, influência social e falta de vontade foram as principais barreiras referidas para realização de AVD. O TC6 correlacionou-se com os resultados do acelerômetro, mas o LCADL não. CONCLUSÃO: Portadores de DPOC são menos ativos quando comparados a adultos saudáveis. Sedentarismo e as barreiras para atividade física tem implicação imediata na prática clínica indicando medidas de intervenção precoce / INTRODUCTION: Patients with chronic obstructive pulmonary disease (COPD) have reduced physical activity. Barriers that limit physical activity and objective measures of limitation are poorly studied in this population. The knowledge of them allows a proper planning for increased physical activity. OBJECTIVES: To compare ADLs in COPD patients and controls using a motion sensor, identify perceived barriers that prevent AVD and correlate them to the severity of dyspnea, to the 6-minute walk test (6MWT) and a score of AVD limitation. METHODS: An pocket accelerometer and a pedometer recorded the number of steps, distance in Km and walking time for seven consecutive days. A survey of perceived barriers and the ADL scale (LCADL) were used to describe factors that prevent AVD. Dyspnea was measured by two different scales and submaximal exercise capacity by 6MWT. RESULTS: 40 subjects with COPD and 40 healthy controls were evaluated. Patients with COPD performed less time walking (68.5 ± 25.8 minutes / day vs. 105.2 ± 49.4; p < 0.001), shorter distance (3.9 ± 1.9 km / day vs. 6.4 ± 3.2; p < 0.001) and a smaller number of steps/day. The lack of infrastructure, social influences and unwillingness were the main barriers to performing ADLs. The 6MWT correlated with the results of the accelerometer, but not LCADL. CONCLUSION: Patients with COPD are less active compared to healthy adults. Sedentary and barriers to physical activity has immediate implications in clinical practice indicating early intervention measures

Embora a utilização do corticóide oral não seja indicada no tratamento de manutenção na doença pulmonar obstrutiva crônica, identificamos em nosso ambulatório, um grupo de pacientes que fazem uso desta medicação de forma continuada e, nos quais, todas as tentativas anteriores de retirada da medicação, havia resultado em exacerbação dos sintomas. O objetivo deste estudo foi o de analisar os fenômenos inflamatórios associados à tentativa de redução progressiva do corticóide oral nesses doentes. Avaliamos o escarro induzido de 14 pacientes usuários crônicos de corticóide. Após a avaliação basal, realizada enquanto os pacientes faziam uso de sua dose habitual da medicação (V0), procedemos ao aumento da prednisona a 40 mg por dia, por duas semanas (V1). A seguir, reduzimos progressivamente a dose até que ocorresse uma exacerbação (EXAC), quando a dose de 40 mg de prednisona foi re-introduzida por duas semanas (APÓS). Comparamos os resultados deste grupo aos de um grupo de pacientes portadores de DPOC não-usuários de corticóide oral. Esses pacientes foram avaliados na condição basal (V0), quando exacerbaram (EXAC) e após o tratamento com 40 mg de prednisona, por duas semanas (APÓS). As variáveis analisadas no escarro foram: % de neutrófilos, % de eosinófilos, % de macrófagos, número total de células, interleucinas 4, 6 e 8. Constatamos que o grupo corticóide apresentou um aumento significativo na porcentagem de eosinófilos na exacerbação em relação a V0, e uma redução significativa em APÓS, em relação a EXAC. Isto não ocorreu no grupo não-corticóide. Ao compararmos os dois grupos, observamos que a concentração das interleucinas 4, 6 e 8, foi significativamente mais alta no grupo corticóide em V0 e na exacerbação em relação ao grupo não-corticóide. Quando analisamos o comportamento das interleucinas nas avaliações seqüenciais, dentro de cada grupo, observamos que a interleucina 4 tendeu à elevação na exacerbação, no grupo corticóide, sem atingir, entretanto, significância estatística. As interleucinas 6 e 8 aumentaram significativamente no grupo corticóide na visita APÓS. Concluímos que a retirada progressiva de corticóide oral induz a exacerbação em pacientes com DPOC corticóide-dependentes com um processo inflamatório eosinofílico, que tende à reversão após o aumento da dose do corticóide / Although in chronic obstructive lung disease the use of oral corticoid is not indicated in the maintenance treatment, we identified a group of patients that make use of this medication continuously. The objective of this study was to analyze the inflammatory phenomena associated to the attempt of progressive reduction of oral corticoids in these patients. We evaluated induced sputum of 14 patients on long-term use of oral corticoids. After the basal evaluation, accomplished while the patients made use of their habitual dose of the medication (V0), we increased the dose of prednisone to 40 mg daily for two weeks (V1). To proceed we reduced the dose progressively until an exacerbation occurred (EXAC), when the dose of prednisone 40 mg daily was reintroduced for two weeks (AFTER). We compared the results to a group of patients with COPD not on use of oral corticoids, that were appraised in the basal condition (V0), when they exacerbated (EXAC) and after the treatment with prednisone 40 mg daily for two weeks (AFTER). The variables analyzed in the sputum were:, % of neutrophils, % of eosinophils, % of macrophages, total number of cells, interleukins 4, 6 and 8. We verified that the corticoid group presented a significant increase in the percentage of eosinophils at the exacerbation in relation to V0, and a significant reduction in AFTER in relation to EXAC. This didn\'t happen in the non corticoid group. When we compared the two groups we observed that the concentration of the interleukins was significantly higher in corticoid group in V0 and at the exacerbation in relation to the non corticoid group. When we analyzed the behavior of the interleukins along the evaluations in each group we observed that interleukin 4 tended to an elevation at the exacerbation in the corticoid group, without reaching statistical significance. Interleukins 6 and 8 increased significantly in the corticoid group in the visit AFTER. We concluded that the progressive reduction of oral corticoid induces exacerbation in patients with COPD on long-term use of prednisone with an eosinophilic inflammatory process that tends to reverse after the increase of the dose of the corticoid

Made available in DSpace on 2016-01-26T12:51:40Z (GMT). No. of bitstreams: 1 joabatistasalomao_dissert.pdf: 485965 bytes, checksum: a1e9ad096dff68d92c37d5033056c5f6 (MD5) Previous issue date: 2001-06-12 / Objective Evaluate, social competence and behavior disorders in children with moderate to severe asthma according to parental perception. Casuistics: Sixty-two patients were studied, 36 male and 26 female, ages ranging from 7 to 16 years (MA: 10.94; SD: 2.28), with clinical diagnosis of moderate to severe asthma, without comorbidity, seen at the Pediatric Pneumology Service and the Allergy and Immunology Service at a University Hospital, from March to September, 2000. A control group was simultaneously studied and included 62 patients, 37 male and 25 female, ages ranging from 7 to 16 years (MA: 10.26; SD: 2.37), seen at the Orthopedics and Ophthalmology Outpatient Wards at the same hospital, without symptoms of asthma, respiratory allergy and no chronic diseases. Material and method An Identification Form, a Clinical Data Form and the CBCL (Child Behavior Checklist), a tool to evaluate social competence and behavior disorders, were used. Results Results were evaluated by the proportional tests, Student s t test and ANADEP and ANADEPMU and a significance level of 0.05 was chosen. Patients were classified according to the clinical manifestations of asthma: 42 had moderate asthma and 20 had severe asthma, most of them (93.55%) had been diagnosed since 3 years of age. There was no significant difference in age and gender between the group with asthma and the control group. There was a marked association between overall social competence and asthma (with p=0.000) and between social competence associated to activities (with p=0.001) and school (with p=0.01). There was no difference between children with asthma and the control group for social markers (with p=0.23). There was no correlation between gender and age when evaluating social competence, or overall social competence specific parameters: activities, school and social activities. The evaluation of social competence and type of asthma did not show a correlation. There was a strong association between the presence of behavior disorders and asthma (p=0.005), specially internalizing disorders (p=0.001). There was no association between the externalizing disorders and the disease. Behavior disorders were not associated to gender, age and type of asthma. Conclusions Children with asthma showed alterations in overall social competence and social competence related to activities and school, when compared to the control group. They also showed overall and internalizing disorders, which may be harmful to their development, their quality of life, compliance with the treatment and adequate management of the disease. The integration of biological, psychological and social factors is essential to establish adequate programs for the treatment of children with asthma and their families. / Objetivo - avaliar competência social e transtornos comportamentais em crianças com asma moderada e grave, a partir de percepção dos pais. Causística: foram estudados 62 pacientes, 36 do sexo masculino e 26 do sexo feminino, com idade entre 7 e 16 anos (im:10,94; dp:2,28), com diagnóstico clínico de asma moderada e grave, sem comorbidade, atendidos nos serviços de pneumologia infantil e alergia e imunologia de um hospital escola, no perído de março e setembro de 2000. Um grupo de controle foi estudado no mesmo período, composto de 62 pacientes, 37 do sexo masculino e 25 do sexo feminino, com idade entre 7 e 16 anos (im: 10,26; dp: 2,37), atendidos nos ambulatório de ortopedia e oftalmologia do mesmo hospital, sem qualquer sintomatologia de asma, de alergia respiratória e sem qualquer doença crônica. Material e método - foram utilizados na obtenção dos dados uma ficha de identificação, uma ficha de dados clínicos e um instrumento que avalia competência social e transtornos comportamentais - child behavior checklist (cbcl). Resultados - os resultados foram analisados com testes proporção x (ao quadrado), teste t de student, anadep e anadepmu, adotando-se nível de significância de 0,05. Os pacientes foram classificadossegundo manifestações clínicas da asma: 42 com asma moderada e 20 com asma grave, sendo que 93,55% receberam o diagnóstico da doença antes dos 3 anos de idade. Não houve diferença significante em termos de idade e sexo entre os grupos com asma e controle. Houve associação entre competência social e global e asma (p=0,000) e entre competência social associada a atividades (p=0,001) e escola (p=0,01). Não houve diferença entre crianças com asma e o grupo controle em relação ao aspecto social (p=0,23). Não houve relação entre sexo e idade na análise da competência social, nem quanto à competência social global nem quanto aos aspectos específicos: atividades, escola e social. A análise entre competência social e tipo de asma também não mostrou associação. Houve associação entre presença de transtornos comportamentais e asma (p=0,005), principalmente os transtornos internalizantes (p=0,001). Não houve associação dos externalizantes com a doença. Os transtornos comportamentais não se mostraram associados ao sexo, idade da amostra e tipo de asma. Conclusões - as crianças com asma apresentaram alterações na competência social e global e competência social relacionada a atividades e escola, quando comparadas ao grupo controle. Apresentaram ainda transtornos globais e internalizantes, que podem prejudicar o seu desenvolvimento, sua qualidade de vida, a adesão ao tratamento e o manejo adequado da doença. A integração dos aspectos biológicos, psicológicos e sociais é imprescindível para o delineamento de programas adequados de atendimento à criança portadora de asma e a seus familiares.

Embora a utilização do corticóide oral não seja indicada no tratamento de manutenção na doença pulmonar obstrutiva crônica, identificamos em nosso ambulatório, um grupo de pacientes que fazem uso desta medicação de forma continuada e, nos quais, todas as tentativas anteriores de retirada da medicação, havia resultado em exacerbação dos sintomas. O objetivo deste estudo foi o de analisar os fenômenos inflamatórios associados à tentativa de redução progressiva do corticóide oral nesses doentes. Avaliamos o escarro induzido de 14 pacientes usuários crônicos de corticóide. Após a avaliação basal, realizada enquanto os pacientes faziam uso de sua dose habitual da medicação (V0), procedemos ao aumento da prednisona a 40 mg por dia, por duas semanas (V1). A seguir, reduzimos progressivamente a dose até que ocorresse uma exacerbação (EXAC), quando a dose de 40 mg de prednisona foi re-introduzida por duas semanas (APÓS). Comparamos os resultados deste grupo aos de um grupo de pacientes portadores de DPOC não-usuários de corticóide oral. Esses pacientes foram avaliados na condição basal (V0), quando exacerbaram (EXAC) e após o tratamento com 40 mg de prednisona, por duas semanas (APÓS). As variáveis analisadas no escarro foram: % de neutrófilos, % de eosinófilos, % de macrófagos, número total de células, interleucinas 4, 6 e 8. Constatamos que o grupo corticóide apresentou um aumento significativo na porcentagem de eosinófilos na exacerbação em relação a V0, e uma redução significativa em APÓS, em relação a EXAC. Isto não ocorreu no grupo não-corticóide. Ao compararmos os dois grupos, observamos que a concentração das interleucinas 4, 6 e 8, foi significativamente mais alta no grupo corticóide em V0 e na exacerbação em relação ao grupo não-corticóide. Quando analisamos o comportamento das interleucinas nas avaliações seqüenciais, dentro de cada grupo, observamos que a interleucina 4 tendeu à elevação na exacerbação, no grupo corticóide, sem atingir, entretanto, significância estatística. As interleucinas 6 e 8 aumentaram significativamente no grupo corticóide na visita APÓS. Concluímos que a retirada progressiva de corticóide oral induz a exacerbação em pacientes com DPOC corticóide-dependentes com um processo inflamatório eosinofílico, que tende à reversão após o aumento da dose do corticóide / Although in chronic obstructive lung disease the use of oral corticoid is not indicated in the maintenance treatment, we identified a group of patients that make use of this medication continuously. The objective of this study was to analyze the inflammatory phenomena associated to the attempt of progressive reduction of oral corticoids in these patients. We evaluated induced sputum of 14 patients on long-term use of oral corticoids. After the basal evaluation, accomplished while the patients made use of their habitual dose of the medication (V0), we increased the dose of prednisone to 40 mg daily for two weeks (V1). To proceed we reduced the dose progressively until an exacerbation occurred (EXAC), when the dose of prednisone 40 mg daily was reintroduced for two weeks (AFTER). We compared the results to a group of patients with COPD not on use of oral corticoids, that were appraised in the basal condition (V0), when they exacerbated (EXAC) and after the treatment with prednisone 40 mg daily for two weeks (AFTER). The variables analyzed in the sputum were:, % of neutrophils, % of eosinophils, % of macrophages, total number of cells, interleukins 4, 6 and 8. We verified that the corticoid group presented a significant increase in the percentage of eosinophils at the exacerbation in relation to V0, and a significant reduction in AFTER in relation to EXAC. This didn\'t happen in the non corticoid group. When we compared the two groups we observed that the concentration of the interleukins was significantly higher in corticoid group in V0 and at the exacerbation in relation to the non corticoid group. When we analyzed the behavior of the interleukins along the evaluations in each group we observed that interleukin 4 tended to an elevation at the exacerbation in the corticoid group, without reaching statistical significance. Interleukins 6 and 8 increased significantly in the corticoid group in the visit AFTER. We concluded that the progressive reduction of oral corticoid induces exacerbation in patients with COPD on long-term use of prednisone with an eosinophilic inflammatory process that tends to reverse after the increase of the dose of the corticoid

La Enfermedad Pulmonar Obstructiva Crónica (EPOC), presenta signos y síntomas sistémicos que se han venido explorando desde hace algún tiempo. La presente Tesis Doctoral estudia la disfunción que presentan los músculos respiratorios y periféricos, específicamente el cuádriceps de los pacientes con EPOC. Esta disfunción muscular afecta las actividades de la vida diaria, la tolerancia al ejercicio, limita la calidad de vida y disminuye la expectativa de vida de estos pacientes. Una de las posibles causas de disfunción muscular en los pacientes con EPOC puede ser la pérdida de masa muscular; por eso nos dedicamos a evaluar, los datos antropométricos de los pacientes con EPOC que asistieron durante 2 años a nuestro Laboratorio de Función Respiratoria del Hospital del Mar de Barcelona. La prevalencia de bajo peso en pacientes con EPOC en un hospital con predominante población mediterránea con, índice de masa corporal (IMC) por debajo de 20 Kg/m2, fue de tan sólo 6,6%, cifra que se reducía al 3,1% si el dintel escogido era de 18 Kg/m2. Estas cifras van claramente en oposición a la prevalencia referida en el mundo anglosajón y del norte-centro europeo, que muestra una prevalencia de bajo peso en pacientes con EPOC que oscila entre el 25 y el 35%. Teniendo en cuentas estos datos de baja prevalencia de bajo peso en nuestros pacientes con EPOC, no se explica la alta prevalencia de disfunción muscular en ellos. Por ello evaluamos variables de función muscular en pacientes con EPOC grave, específicamente del músculo cuádriceps y encontramos que los pacientes con EPOC tenían una disminución tanto de la fuerza muscular (43%), como de la resistencia muscular (77%), al compararlos con controles del mismo grupo etáreo.Tratando de profundizar en la causa de la disfunción muscular periférica en los pacientes con EPOC, hicimos a continuación otro estudio donde evaluamos el daño sarcoplásmico y sarcomérico mediante inmunohistoquímica y microscopía electrónica. Este trabajo demostró por primera vez que los pacientes con EPOC presentan mayor daño a nivel del músculo cuádriceps que los controles sanos.Debido a que en la EPOC los músculos periféricos, específicamente los de las extremidades inferiores, pudieran estar afectados por el sedentarismo, decidimos estudiar otras causas de disfunción muscular en un grupo de músculos en que este factor se hallara ausente, como son los músculos respiratorios. Estos mantienen su nivel de actividad normal o incluso aumentada. Para ello tomamos un músculo como el intercostal externo, que es fácilmente accesible a la biopsia, siguiendo un modelo mínimamente invasivo descrito por nuestro grupo. Como en trabajos precedentes ya habíamos valorado el daño sarcomérico, el estrés oxidativo o la actividad enzimática, en esta ocasión el trabajo se centró en la evaluación de la actividad inflamatoria. En él se ha demostrado que las citocinas proinflamatorias TNF-&#945; e IL-6 se encuentran aumentadas en los músculos intercostales externos de los pacientes con EPOC al compararlo con los controles sanos. / Chronic Obstructive Pulmonary Disease (COPD), shows systemic sign and symptoms that have been studied for some time. The present Doctoral Thesis studies the dysfunction shown by the respiratory and peripheral muscles, specifically the quadriceps muscle of patients with COPD. This muscle dysfunction affects the activities of daily living, tolerance to exercise, limits quality of life and diminishes life expectancy of these patients. One of the possible causes of muscle dysfunction in the patients with COPD could be the loss of muscle mass; for that reason we evaluated, the anthropometrics data of the patients with COPD that attended during 2 years our Respiratory Function Laboratory, Hospital del Mar of Barcelona. The prevalence of low weight in patients with COPD in a hospital with a predominantly Mediterranean population with an Body Mass Index (BMI) below 20 Kg/m2, was only 6.6%, a figure that was reduced to 3.1% if the chosen threshold was 18 Kg/m2. These numbers starkly contrast to the prevalence in Northern Europe, with a low weight in patients with COPD raging from 25 to 35%. Considering these data of low prevalence of low weight in our patients with COPD, the high prevalence of muscle dysfunction is not explained. We evaluated variables of muscle function in patients with severe COPD, specifically the quadriceps muscle and we found that the patients with COPD had a decreased muscle strength (43%), and muscle endurance (77%), when comparing with healthy age matched. To study the cause of the peripheral muscle dysfunction in patients with COPD, we began another study where we assessed sarcoplasmic and sarcomeric damage by immunohystochemical methods and electronic microscopy. This work demonstrated for the first time that patients with COPD show greater muscle injury at the quadriceps muscle level that healthy age matched controls.Because in COPD, peripheral muscles, specifically those of the lower limbs, could be affected by sedentarism, we decided to study other causes of muscle dysfunction in a muscle group in which this factor was absent, as they are the respiratory muscles. These maintain their level of normal activity or activity is even increased. For this we chose a respiratory muscle like the external intercostal muscle, that is easily accessible by biopsy, following a minumum invasive model described by our group. As in preceding works of our group we evaluated the sarcomeric damage, oxidative stress or the enzymatic activity, the present work was focused in the inflammatory activity evaluation. We demonstrated that proinflammatory cytokines such as TNF-&#945; and IL-6 are increased in the external intercostal muscles of patients with COPD when comparing with healthy age matched controls.