The overall aim of this thesis was to assess measurement properties of methods suitable for screening or monitoring of physical capacity and physical activity in subjects with chronic obstructive pulmonary disease (COPD), and to explore factors associated with physical activity levels. Methods: Four observational studies were conducted. Participants in studies I-III (sample sizes) (n=49, n=15, n=73) were recruited from specialist clinics, and in study IV from a population-based cohort (COPD n=470 and Non-COPD n=659). Psychometric properties of methods assessing physical capacity (study I) and physical activity (study II) were investigated in laboratory settings. Daily physical activity and clinical characteristics were assessed with objective methods (study III) and with subjective methods (study IV). Results: Physical capacity as measured by walking speed during a 30-metre walk test displayed high test-retest correlations (ICC>0.87) and small measurement error. The accuracy for step count and body positions differed between activity monitors and direct observations. In study III 92% of subjects had an activity level below what is recommended in guidelines. Forty five percent of subjects’ activity could be accounted for by clinical characteristics with lung function (22.5%), walking speed (10.1%), quadriceps strength (7.0%) and fat-free mass index (3.0%) being significant predictors. In study IV, low physical activity was significantly more prevalent in COPD subjects from GOLD grade ≥II than among Non-COPD subjects (22.4 vs. 14.6%, p = 0.016). The strongest factors associated with low activity in COPD subjects were a history of heart disease, OR (CI 95%) 2.11 (1.10-4.08) and fatigue, OR 2.33 (1.31-4.13) while obesity was the only significant factor in Non-COPD subjects, OR 2.26 (1.17-4.35). Conclusion: The 30 meter walk test and activity monitors are useful when assessing physical capacity and physical activity, respectively in patients with COPD. Impaired physical activity in severe COPD is related to low lung function, low walking speed, low muscle strength and altered body composition, whereas comorbidities and fatigue are linked to insufficient physical activity in patients with moderately severe COPD.

Systemic inflammation is associated with impaired lung function. Inflammation is part of asthma and chronic obstructive pulmonary disease (COPD), but the local and systemic inflammatory pattern differs. The overall aim was to evaluate systemic inflammatory markers in obstructive lung diseases and more specifically: To determine if CRP is related to respiratory symptoms, asthma, atopy and bronchial responsiveness (paper I), in a population sample from three countries (paper I and II); to evaluate if CRP is related to COPD, lung function and rate of lung function decline (paper II); to investigate the association of serum MMP-9 and TIMP-1 with lung function in a cross-sectional population based study (paper III); and finally, to study possible gender differences in the longitudinal association between CRP and lung function in a prospective population based study (paper IV). In the first study we reported that CRP was related to non-allergic asthma but not allergic asthma, and that CRP was related to respiratory symptoms such as wheeze, nocturnal cough and breathlessness after effort, but not associated with atopy or bronchial responsiveness. In the second study we found that COPD was more common in subjects in the highest CRP quartiles and higher CRP levels were associated with lower FEV1 values in both men and women, but the negative association between CRP and FEV1 was larger in men than women. The FEV1 decline was larger in men with high CRP levels, whereas no such association was found for women. In the third study we reported that lower FEV1 was associated with higher levels of MMP-9, TIMP-1 and their ratio MMP-9/TIMP-1. After stratification for gender this association was significant in men but not women. In the fourth study we found that CRP levels were associated with change in both FEV1 and FVC in men but not women. This association was found for both baseline CRP and change in CRP, confirming a stronger association between systemic inflammation and lung function decline in men than women. In conclusion, systemic inflammation is associated with non-allergic asthma but not allergic asthma. Our findings of a stronger association between the systemic inflammation and lung function impairment in men, but not women, may indicate a gender difference in the mechanisms of lung function decline.

Η ΧΑΠ είναι νόσος με πολλούς φαινοτύπους, με παθοφυσιολογία που διαφέρει σε κάθε έναν από αυτούς, με κοινό χαρακτηριστικό την πτώση του λόγου FEV1/FVC. Παρόλα ταύτα πολύ πρόσφατες μελέτες δείχνουν πως δεν υπάρχει σαφής συσχέτιση μεταξύ της προσεκτικά μετρούμενης φλεγμονής στους αεραγωγούς και της πτώσης της FEV1 σε ομάδες ασθενών με ΧΑΠ, κάτι που δυνητικά μπορεί να ανατρέψει βιβλιογραφία 40 ετών [Roy K, et al 2009]. Στόχος όλων των γενετικών μελετών στη ΧΑΠ είναι ο διαχωρισμός των φαινοτύπων και η δημιουργία του γενετικού προφίλ της νόσου. Γνωρίζοντας πως η ΧΑΠ είναι πολυγονιδιακή νόσος και σε συνδυασμό με τη μεγάλη ποικιλότητα των φαινοτύπων της, οι γενετικές αλλοιώσεις φαίνεται πως οδηγούν σε διαφορετικό φαινότυπο, που τώρα ολιστικά ορίζεται ως νόσος «ΧΑΠ», αλλά σίγουρα στο εγγύς μέλλον θα διαχωριστεί σε επιμέρους ομάδες στα πλαίσια μιας πιο αποτελεσματικής και εξατομικευμένης θεραπευτικής προσέγγισης. Η παρούσα μελέτη μεταξύ άλλων, συνέβαλε στα εξής: α. Σχεδιασμός και αξιολόγηση εκκινητών και ιχνηθέτων για τον +134InsA/DelA πολυμορφισμό, με υψηλή διακριτική ικανότητα έναντι των αλληλίων 3Α και 4Α. β. Ανέδειξε την εμπλοκή των πολυμορφισμών+134InsA/DelA και G198T στην εμφάνιση αλλά και στη βαρύτητα της ΧΑΠ (όπως αυτή αξιολογείται με την FEV1), ενώ σκιαγραφήθηκε και το γενετικό προφίλ του ευαίσθητου στον καπνό του τσιγάρου καπνιστή, με λεπτομερή συσχέτιση των απλοτύπων των πολυμορφισμών της ΕΤ-1 που εμπλέκονται στη ΧΑΠ. γ. Ανέδειξε πιθανή εμπλοκή του +134InsA/DelA πολυμορφισμού στην στατική υπερδιάταση και στις αυξημένες αντιστάσεις στη ροή του αέρα στους πνεύμονες δ. Σκιαγράφησε τη σχέση των +134InsA/DelA και G198T με την ανοχή στην άσκηση και συνέκρινε τα αποτελέσματα αυτά με όσα ήδη υπάρχουν στη βιβλιογραφία. Η παρούσα μελέτη είναι η πρώτη που συσχετίζει πολυμορφισμούς με πολλαπλές αξιολογήσεις της αναπνευστικής λειτουργίας, πέραν της FEV1, κάτι που σκιαγραφεί με λεπτομέρεια το φαινότυπο της ΧΑΠ. / Chronic Obstructive Pulmonary Disease (COPD) is an entity with many phenotypes, different pathophysiological characteristics, that exhibits in all cases a diminished FEV to FVC ratio. Nevertheless, recent studies show that there is not a strict relationship between airway inflammation and FEV1 decline in patients with COPD, contrasting a 40 year literature [Roy K, et al 2009]. The aim of all recent studies dealing with genetics in COPD is the distinction of different phenotypes and the elucidation of the genetic profile of the disease. COPD is a multi-gene disorder, and knowing that it is composited by many phenotypes, one can say that, in the near future, “holistic COPD phenotype” will be unraveled in many distinguished phenotypes, leading to a personalized and patient-targeted diagnostic and therapeutic approach. The current study contributed in: a. Designing primers and probes for the +134InsA/DelA polymorphism, that could clearly distinguish both 3A and 4A alleles. b. Exhibiting that both +134InsA/DelA & G198T polymorphisms are implicated in COPD progression and severity (as defined by FEV1 values). At the same time, we managed to highlight the genetic profile of the susceptible to smoke smoker, associating haplotypes and polymorphisms of Endothelin-1 (ET-1) gene (+134InsA/DelA & G198T ) with COPD. c. Showing the implication of the +134InsA/DelA polymorphism with static lung hyperinflation and increased airway resistance. d. Revealing the association of +134InsA/DelA & G198T polymorphisms with exercise tolerance. According to our knowledge, the current study is the first in the literature showing association of ET-1 gene with lung function deterioration.

Recent statistics show that approximately 415 million people worldwide have diabetes. Glycated haemoglobin (HbA1c) measurements were introduced many years ago as the gold standard tool for detecting and monitoring treatment as well as making management decisions for diabetic patients. Glycated haemoglobins are formed by the non-enzymatic glycation of haemoglobin molecules. This non-enzymatic glycation process has been strongly related to pathogenesis of chronic complications associated to diabetes. It was suggested that this glycation process may be moderated by an enzymatic deglycation process thought to involve a deglycating enzyme known as Fructosamine-3-kinase (FN3K), an enzyme that deglycates the glycated haemoglobin in erythrocytes and other glycated proteins in other tissues. FN3K acts through phosphorylation of fructosamines on the third carbon of their sugar moiety, making them unstable and consequently causing them to detach from the protein. The degree of deglycation is thought to depend on the activity of the FN3K enzyme. Moreover, variation in the activity of FN3K between individuals is hypothesised to lead to apparent differences in glycated haemoglobin levels: some individuals have high rates of deglycation so that they tend to have lower average glycaemia than actually the case, while others with low rates of deglycation appear to have higher than actual glycaemia (known as the glycation gap, G-gap). The G-gap has been reported to be associated with alteration of diabetic complications risk. The G-gap reflects the discrepancy between average glycaemia as determined from glycated haemoglobin (measured as HbA1c) and that from the determination of fructosamine. The positive G-gap is defined as a higher level of glycation of proteins than expected whereas a negative G-gap means a lower level of glycation than expected. To explore the role of FN3K in diabetes and other associated morbidities, we decided to divide our research into 3 studies. Each study was categorised according to the type and the source of samples involved. The first study explored the correlation between FN3K activity and protein level with G-gap data; it involved 148 diabetic patients who were recruited at New Cross Hospital, Wolverhampton, selected as having a consistent positive G-gap > +0.5 and a consistent negative G-gap > -0.5 over a minimum of 2 estimations. Age, gender, race and BMI were collected from patients in this study. Blood samples were also 3 collected to measure FN3K activity, protein levels, and markers of CVD in relation to G-gap. The second study involved 23 AECOPD patients who were recruited from St George’s Hospital (London) and were treated with either metformin or a placebo. Serum samples were collected from these patients for a larger study: we assayed those 23 serum samples for FN3K protein levels to explore any possible correlation between FN3K with metformin therapy in COPD patients. The third study utilised 36 human peripheral lung samples from healthy individuals, asymptomatic smokers and stable COPD patients (GOLD 2) who were recruited at The Section of Respiratory Medicine, University Hospital of Ferrara, Italy. Those samples were assessed for FN3K expression by means of immunohistochemistry to explore the difference in FN3K activity between those three categories. It was found that the intracellular activity and protein expression of the FN3K enzyme in diabetic patients negatively correlated with the values of G-gaps where FN3K activity was high in patients with negative G-gap. FN3K serum protein levels were shown to be enhanced with metformin administration in COPD diabetic patients, suggesting a protective role for FN3K enzyme against protein damaged caused by the non-enzymatic glycation of proteins. Therefore, patients with positive G-gap have lower FN3K activity than those with negative G-gap, and in turn they are more susceptible to diabetes related complications. Our data also indicate that metformin has a beneficial effect in reducing damage caused by carbonyl stress from cigarette smoking in COPD patients by the action of FN3K. Our research has demonstrated that FN3K contributes to the protein repair system which protects against damage caused by non-enzymatic glycation. The high activity for the FN3K enzyme was associated with low levels of AGEs and low carbonyl stress levels in observed among patients with diabetes and COPD. In contrast, COPD patients tend to have low FN3K-mediated protection against protein damage in comparison to the normal population. These patients tend to be at risk for developing more complications, particularly CVD complications, than normal, healthy individuals. Treatment with metformin enhances FN3K action in COPD diabetic patients, possibly as a protective enzyme against the damaged caused by the non-enzymatic glycation.

La Bronchopneumopathie Chronique Obstructive (BPCO) associe inflammation et hypoxie, vraisemblablement à l’origine d’altérations du tissu musculaire des patients dont l'état est corrélé au pronostic vital. Bien que justifiée, la réhabilitation par l'exercice n'est pas efficace dans 1/3 des cas, sans que les mécanismes à son origine n’aient été identifiés. Cette non-réponse pourrait impliquer un contrôle épigénétique de l'expression des gènes en lien avec la croissance musculaire via leurs profils d'acétylation. Pour étudier les effets de l'exercice sur le muscle BPCO, nous avons développé un modèle murin d'hypertrophie musculaire induite utilisé dans un contexte d'hypoxie (HC) et d'inflammation pulmonaire chronique (IP). Dans ce contexte, en comparant soléaire et plantaire, il apparaît que l’hypertrophie du soléaire est altérée par l’IP alors que celle du plantaire est fortement inhibée par l’HC. L'administration d'un inhibiteur des Bromodomaines et domaines Extra-Terminaux (i-BET), éléments impliqués dans la lecture des niveaux d’acétylations des histones, restaure leurs capacités d'hypertrophie. Cette altération de la croissance musculaire est associée à des perturbations des voies de protéosynthèse (Akt, S6k1, Erk) et de protéolyse (MuRF-1) muscles dépendantes. Dans le soléaire, l’acétylation des lysines des histones H3 et H4 est augmentée par l’IP ainsi que la transcription d’Histones Déacétylases (HDAC) est diminuée. Ces modifications associées à la restauration de l’hypertrophie du soléaire par l’i-BET malgré la présence d’une IP, suggèrent fortement l’implication des mécanismes épigénétiques dans l‘inhibition de la croissance musculaire. L’augmentation de l’acétylation des histones H3 et H4 du plantaire soumis à une HC tend à confirmer l'implication de mécanismes épigénétiques dans l’altération de la réponse de ce muscle. Toutefois des travaux supplémentaires seraient nécessaires pour confirmer cette hypothèse. Pour finir, les mesures de paramètres hémodynamiques cardiaques nous ont montrés que l’i-BET était également à l’origine d’une diminution de l’Hypertension Artérielle Pulmonaire (HTAP), de l’hypertrophie du ventricule droit et de l’hématocrite lors de l’exposition de nos animaux à une HC.Ces travaux suggèrent que la non-réponse au réentrainement d’un tiers des patients BPCO pourrait être liée à la présence d’une IP associée à une hypoxémie. La restauration des capacités adaptatives du muscle par un traitement à l’iBET pourrait constituer une perspective thérapeutique prometteuse, permettant à ces patients de retirer les importants bénéfices d’une telle prise en charge. Toutefois, la réduction de l’hématocrite de nos animaux traités avec l’i BET en HC, implique une prise en charge parallèle à, ce traitement pour maintenir l’adaptation à l’HC des patients BPCO hypoxémiques. / The Chronic Obstructive Pulmonary Disease (COPD) associates inflammation with hypoxia, likely causing deterioration of muscle tissue whose status is tightly correlated to vital prognosis. Although justified due by its anabolic effects, rehabilitation through exercise which progressively became a key medical care in COPD is inefficient in 1/3 of the patients. This non-response could involve epigenetic control of gene expression via alterations of the acetylation profile induced by pulmonary Inflammation (PI) and Chronic Hypoxia (CH). To study this, we used a murine model of either soleus or plantaris muscle hypertrophy induced by a functional overload, in PI and CH conditions. Results show that soleus hypertrophy is diminished by PI while plantaris hypertrophy is inhibited by CH. These specific responses are associated with alterations in proteosynthesis (Akt, S6k1, Erk) and proteolysis (MuRF-1) in a muscle-dependent manner. With PI, acetylation of lysines of histones H3 and H4 is increased in soleus muscle while transcription of Histone Deacetylases (HDACs) is decreased. Inhibiting the proteins in charge of reading the acetylations (BET) is able to restore the hypertrophic capacities of the soleus when exposed to PI, reinforcing the hypothesis of an involvement of epigenetic regulatory mechanisms in the problem of muscle response to a hypertrophic stimulus. Moreover, the use of the BET inhibitor (i-BET) prevents the development of pulmonary arterial hypertension, of the right ventricle hypertrophy and the increase in hematocrit in animals exposed to CH. Restoring the muscle adaptive capacities using i-BET led us to consider new promising therapeutic perspectives in COPD patients who present limited or no response to exercise rehabilitation.

O teste de exercício cardiopulmonar incremental (TECP) tem sido utilizado para avaliar o impacto global da doença em pacientes com DPOC. Considerando que as avaliações de exercício em laboratório são demoradas, caras e muitas vezes indisponíveis, o teste de caminhada de seis minutos (TC6min) não exige equipamentos caros e sofisticados, e pode ser facilmente realizado. Embora, a principal medida comumente utilizada no teste de caminhada seja a distância percorrida durante os 6 minutos (D), esta medida não leva em conta as diferenças de peso corpóreo, que podem influenciar o desempenho do exercício. Além disso, estudos anteriores correlacionaram o trabalho realizado durante o TC6min com TECP incremental pedalando, modalidade de exercício comumente associada a fadiga de quadríceps e menor consumo de oxigênio de pico ( O2) do que o TECP caminhando. O principal objetivo desse estudo foi avaliar a correlação entre a distância percorrida no TC6min (D) e o produto distância percorrida - peso corporal (DxP), uma estimativa do trabalho realizado durante o TC6min, com o O2 de pico obtido durante o TECP incremental em esteira ergométrica. Foram estudados trinta pacientes (19 homens), apresentando média (± DP) de idade de 66,3 ± 7,5 anos, com DPOC estável de moderada a grave intensidade (VEF1 médio de 1,1 ± 0,4L e 39 ± 13% predito) que realizaram TECP incremental em esteira ergométrica até o limite máximo de tolerância e o TC6min. Os testes foram realizados com pelo menos 48 horas de intervalo. A correlação de Pearson foi utilizada para avaliar o nível de associação entre o O2 pico, a distância e o trabalho executado durante o TC6min. Os pacientes percorreram 425,1 ± 78,6 m e realizaram um trabalho de 28166,4 ± 8368,4 Kg-m durante o TC6min, enquanto que o O2 de pico atingido foi 965,6 ± 370,1 mL/min (68,7 ± 17,4% do previsto) no TCPE. Ao final do exercício, em ambos os testes, a dispnéia foi a principal queixa e maior percepção de dispnéia e maior frequência cardíaca foi observado ao final do TECP comparativamente ao TC6min. O trabalho da caminhada (DxP) durante o TC6min demonstrou maior correlação com o O2 pico do que a distância (D) isoladamente. O mesmo ocorreu para VEF1, CVF, CI, DLCO, CO2, E e duplo produto (uma estimativa do trabalho do miocárdio), (r = 0,57; r = 0,57; r = 0,73; r = 0,7; r = 0,75; r = 0,65; r = 0,51; r = 0,4 respectivamente, todos com p <0,05). Dessa forma, esse estudo corrobora a melhor associação entre o trabalho estimado a partir da TC6min e o O2 pico atingido durante TECP, neste caso em esteira ergométrica, em comparação à distância isoladamente. / Incremental cardiopulmonary exercise testing (CPET) is increasingly used to evaluate the overall impact of the illness in patients with COPD. Whereas laboratory tests of exercise performance are often time-consuming, costly and frequently unavailable, the six-minute walk test (6MWT) does not require expensive or sophisticated equipments, and can be easily performed. Although, the main outcome measure commonly used in this field test is the distance walked during the predetermined 6 minutes (6MWD), this measure does not account for differences in body weight that are known to influence exercise performance. Furthermore, previous studies correlated the working performed during 6MWT with incremental cycling CPET, an exercise modality more associated with quadriceps fatigability and lower peak oxygen consumption ( O2) than incremental walking tests. The main objective of this study is to evaluate the correlation between 6MWD and its derivative walking distance-body weight product, an estimation of the work performed during 6MWT, with peak O2 obtained during a treadmill incremental CPET. The study enrolled thirty patients (19 males), with a mean (± SD) age of 66.3 ± 7.5 years and a stable moderate-to-severe COPD (ie, mean FEV1 1.1 ± 0.4L and 39 ± 13 % predicted) performed a ramp incremental CPET to the limit of tolerance on a treadmill and 6MWT. Tests were performed at least 48 h apart. Pearson´s correlation was used to assess the level of association between peak O2 and the distance and work executed during 6MWT. The patients walked 425.1 ± 78.6 m and performed a work of 28,166.4 ± 8368.4 (Kg-m) during the 6MWT while achieved a peak O2 of 965.6 ± 370.1 mL/min (68.7 ± 17.4% of predicted) in the treadmill CPET. They mainly stopped exercise due to dyspnea in both tests and reported a greater perception of dyspnea and higher heart rate was observed at the end of the CPET. The work of walking during the 6-MWT (DxW) provided greater and more frequent significant correlation with peak O2 than that observed with 6MWD.This was the case for FEV1, FVC, IC, DLCO, CO2, E, and double product (an estimate of myocardial work) (r=0.57; r=0.57; r=0.73; r=0.7; r=0.75; r=0.65; r=0.51 and r= 0.4, respectively; all p<0.05). This study provides evidence to corroborate the better association between the work estimated from the 6MWT and peak O2 achieved during CPET, in this case with a treadmill, than the 6MWD on isolation.

Introdução: A doença pulmonar obstrutiva crônica (DPOC) se caracteriza por limitação crônica ao fluxo aéreo, dispneia e redução da capacidade de exercício. Na doença avançada o desempenho das atividades de vida diária (AVDs) pode estar comprometido. Objetivo: Estudar a relação entre atividades de vida diária, capacidade funcional e gravidade em pacientes com DPOC. Material e Métodos: Estudo transversal, com realização de dois questionários (London Chest Activity of Daily Living - LCADL e International Physical Activity Questionnaire – IPAQ), exames de função pulmonar e teste de caminhada de 6 minutos (TC6m). A dispneia foi avaliada pela escala Modified Medical Research Council (MMRC) e a gravidade da doença pelo VEF1 e pelo índice BODE. Resultados: Dos 95 pacientes avaliados, 62 eram homens (65,3%). O VEF1 médio foi de 1,05±0,43 litros (DP), 40,7±15,9% do previsto. A distância percorrida no TC6m foi de 386±115 m. A média do MMRC foi de 2,5±1,3, do índice BODE 4,3±2,3, do LCADL foi de 23,4±12,2 e do IPAC 837 (0 - 3.493). Em 47,4% dos pacientes o nível de atividade física medido pelo IPAC foi baixo. A pontuação total do LCADL mostrou correlação negativa com a distância caminhada (r=-0,51; p<0,001) e positiva com o MMRC (r=0,50; p<0,001) e com o índice BODE (r=0,46; p<0,001). A melhor correlação entre IPAC e índice BODE e domínios do LCADL foi com o lazer. A associação do LCADL com as demais variáveis funcionais pulmonares foi fraca ou inexistente. Conclusões: Nosso estudo demonstrou uma importante redução do nível de atividade física em pacientes com DPOC e um impacto significativo da doença sobre as AVDs. Houve uma correlação moderada entre o escore total do LCADL e a distância caminhada, a dispneia e o índice BODE. / Introduction: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation, dyspnea, and reduced exercise capacity. In advanced disease, the performance of activities in daily life (ADLs) can be reduced. Aim: To investigate the relationship between ADLs, functional capacity and disease severity in patients with COPD. Material and Methods: Cross-sectional study. Two questionnaires (London Chest Activity of Daily Living - LCADL and International Physical Activity Questionnaire – IPAQ), lung function testing and six-minute walk test (SMWT) were performed. Dyspnea was evaluated by the Modified Medical Research Council (MMRC) scale and the COPD severity by FEV1 and BODE index. Results: Out of the 95 patients studied, 62 were men (65.3%). Mean FEV1 was 1.05±0.43 liters (SD), 40.7±15.9 % of predicted. The walked distance on SMWT was 386±115m. Mean MMRC value was 2.5±1.3, BODE index was 4.3±2.3, LCADL score was 23.4±12.2 and IPAC was 837 (0 - 3.493). In 47.4% of patients the activity level evaluated by IPAC was low. There was negative correlation between total score of LCADL and walked distance (r=-0.51; p<0.001) and positive with MMRC (r=0.50; p<0.001) and BODE index (r=0.46; p<0.001). The best correlation scores of IPAC and BODE index were seen with the leisure time domain of LCADL. Associations of LCADL with other lung function variables were weak or inexistent. Conclusions: Our study demonstrated an important reduction on physical activity level in COPD patients and a significant impact of the disease on ADLs. There was a moderate correlation between total score of LCADL and walked distance, dyspnea and BODE index.

Melhor sincronia entre os compartimentos da caixa torácica tem sido identificada como um dos fatores para a redução da dispnéia e aumento da capacidade de exercício após a cirurgia de redução de volume pulmonar (CRVP).Para elucidar os efeitos da CRVP nas variações de volume da caixa torácica em repouso e durante exercício, seis pacientes (VEF1% 26,5 ± 5,5 e VR 224,6 ± 30,2%) foram avaliados antes CRVP, 1 e 3 meses após a cirurgia. Provas de função pulmonar e teste de caminhada de 6 minutos, mudanças de volume da caixa torácica pulmonar (RCp), caixa torácica abdominal (RCa) e abdome (AB) foram registradas pela Pletismografia Opto-Eletrônica (POE) em repouso e durante um teste de exercício incremental em esteira. Após a CRVP, todos os valores espirométricos, os volumes pulmonares, escores de dispnéia e teste de caminhada de 6 minutos melhoraram significativamente. Antes da cirurgia, volume expiratório final da caixa torácica tendeu a diminuir no início do exercício e aumentar depois. Por outro lado, após a cirurgia, o aumento do volume expiratório final foi significativa a partir de 1 mph para a velocidade máxima, o que foi totalmente devido as mudanças de volume do abdômen. O sincronismo entre PCR e AB também melhorou em 1 e 3 meses após o CRVP (p <0,001, p <0,05, respectivamente). Em conclusão, em pacientes com DPOC grave LVRS modifica a ação da musculatura abdominal expiratória e melhora a sincronização entre a caixa torácica pulmonar e o abdome. Estas melhorias são associadas e, possivelmente, explicam o aumento da capacidade de exercício e da diminuição da dispnéia. / Better-synchronized chest wall displacement has been identified as one of the factors for the reduction of dyspnea and increase in exercise capacity after Lung Volume Reduction Surgery (LVRS). To elucidate the effects of LVRS on chest wall volume variations at rest and during exercise six patients (FEV1 26.5±5.5 % and RV 224.6±30.2 %) were studied before LVRS, 1 and 3 months after the surgery. Pulmonary function test and 6-min walking test, volume changes of the pulmonary rib cage (RCp), abdominal rib cage and abdomen (AB) were recorded by Opto-Electronic-Plethysmography (OEP) at rest and during an incremental test on a treadmill. After LVRS, all spirometric and lung volume values, dyspnea scores and 6-minute walking distance significantly improved. Before surgery, end-expiratory volume of the chest wall tended to decrease at the onset of exercise and to increase thereafter. Conversely, after surgery, the increase of end-expiratory volume was significant from 1 mph to the maximum speed and it was totally due to the abdomen. The synchronism between RCp and AB also improved at 1 and 3 month after LVRS (p<0.001,p<0.05, respectively). In conclusion, in severe COPD patients LVRS determines a different action of the abdominal expiratory muscles and a better synchronization between the pulmonary rib cage and abdominal displacement. These improvements are associated to and possibly explain the increased exercise capacity and decreased dyspnea.

INTRODUÇÃO: A desvantagem mecânica induzida pela hiperinsuflação leva os pacientes com doença pulmonar obstrutiva crônica (DPOC) a usar a musculatura acessória da respiração. Os efeitos do alongamento destes músculos em pacientes com DPOC não são bem conhecidos. OBJETIVOS: a) Comparar a ativação dos músculos acessórios da respiração em pacientes com DPOC e controles e estudar a relação entre a ativação muscular e a capacidade inspiratória (CI); b) avaliar os efeitos de uma técnica de facilitação neuromuscular proprioceptiva (FNP) sobre os músculos acessórios da respiração em pacientes com DPOC. MÉTODOS: Foram estudados 30 homens com DPOC e 30 controles com espirometria normal. Todos os indivíduos realizaram espirometria, medida das pressões inspiratória e expiratória máxima (PImáx, PEmáx) e avaliação da ativação muscular através da eletromiografia de superfície (EMGs). Os pacientes com DPOC foram randomizados para FNP dos músculos acessórios da respiração ou contração isotônica do bíceps (tratamento simulado, TS). Capacidade vital forçada (CVF), CI, PImáx, PEmáx, oximetria de pulso (SpO2) e mobilidade torácica foram medidos antes e após a intervenção. RESULTADOS: Os valores basais dos pacientes com DPOC foram: CVF 2,69 ± 0,6 L, VEF1 1,07 ± 0,23 L (34,9 ± 8,2%), CI 2,25 ± 0,5 L, PImáx -71,8 ± 19,8 cmH2O e PEmáx 106,1 ± 29,9 cmH2O. No grupo controle os valores funcionais basais foram normais. Pacientes com DPOC apresentaram maior ativação dos músculos escalenos e intercostal direito no repouso e do músculo escaleno e intercostal esquerdo durante a manobra da CI (p<0,05). Foi observada correlação moderada entre CI e atividade muscular do esternocleidomastoideo direito (r=-0,41;p=0,026) e do escaleno esquerdo (r=- 0,40;p=0,031) em pacientes com DPOC. Nenhuma associação foi verificada no grupo controle. A CI variou (OCI) 0,083 ± 0,04 L após FNP e -0,029 ± 0,015 L após TS (p=0,03). A PEmáx aumentou de 102,4 ± 20,6 cmH2O para 112,4 ± 24,5 cmH2O (p=0,02) após FNP e não variou significativamente após TS. Observou-se um aumento significativo da SpO2 com a FNP (p=0,02). Não houve alteração da CV, da PImáx e da mobilidade torácica após a FNP. Não houve alteração no sinal EMG após FNP ou TS. CONCLUSÕES: Nossos resultados sugerem que pacientes com DPOC apresentam maior ativação dos músculos acessórios da respiração no repouso e durante a realização da CI em comparação com controles e que esta ativação está inversamente associada com a CI. Nosso estudo também demonstrou que uma sessão de FNP dos músculos acessórios da respiração em pacientes com DPOC aumentou a CI, a PEmáx e a SpO2, sem alteração no sinal EMG. Estudos adicionais são necessários para avaliar os efeitos da técnica de FNP em longo prazo em pacientes com DPOC. / BACKGROUND: The mechanical disadvantage induced by hyperinflation forces chronic obstructive pulmonary disease (COPD) patients to use their accessory respiratory muscles. In COPD patients the effects of applying stretching techniques to these muscles are not well understood. AIM: The aims of our study were: a) to compare the activation of accessory respiratory muscles in patients with COPD and control subjects and study the relationship between muscle activation and inspiratory capacity (IC); b) to analyze the effects of a proprioceptive neuromuscular facilitation (PNF) stretching technique applied to the accessory respiratory muscles on patients with COPD. METHODS: We studied 30 male COPD and 30 control subjects. All subjects underwent spirometry, measurement of maximal inspiratory and expiratory pressures (MIP, MEP) and assessment of muscle activation by surface electromyography (sEMG). COPD patients were randomized for PNF of accessory respiratory muscles or isometric contraction of the biceps (sham treatment; ST). Mean forced vital capacity (FVC), IC, MIP, MEP, pulse oximetry (SpO2) and thoracic expansion were measured before and after intervention. RESULTS: Baseline values of COPD patients were: FVC 2.69 ± 0.6 l, FEV1 1.07 ± 0.23 l (34.9 ± 8.2%), IC 2.25 ± 0.5l, PImax -71.8 ± 19.8 cmH2O and PEmax 106.1 ± 29.9 cmH2O. Control subjects had all baseline values normal. Patients with COPD showed higher activation of both scalene and right intercostal muscles at rest and of left intercostal and left scalene muscle during the IC maneuver (p <0.05). Moderate correlation was observed between CI and the right sternocleidomastoid muscle activity (r = -0.41, p = 0.026) and left scalene (r = -0.40, p = 0.031) in patients with COPD. No association was observed in the control group. CI varied (OCI) 0.083 ± 0.04 l after PNF and -0.029 ± 0.015 l after ST (p = 0.03). The MEP increased from 102.4 ± 20.6 to 112.4 ± 24.5 cmH2O (p = 0.02) after PNF and did not change significantly after TS. There was a significant increase in the SpO2 with PNF (p=0.02). There was no change in FVC, MIP or thoracic mobility after PNF. There was no change in EMG after PNF or TS. CONCLUSIONS: Our results showed that patients with COPD have greater activation of accessory respiratory muscles at rest and during CI compared with controls, and that this activation is inversely associated with CI. Our study also demonstrated that a session of PNF applied to the accessory respiratory muscles in patients with COPD increased CI, MEP and SpO2, with no change in the sEMG signal. Additional studies are needed to evaluate the long-term effects of PNF applied to the acessory respiratory muscles on patients with COPD.

Objetivos: analisar os efeitos, após um período de 24 meses, de um Programa de Reabilitação Pulmonar sobre os níveis de ansiedade, depressão, qualidade de vida e desempenho no teste de caminhada em 30 pacientes com DPOC (idade: 60,8±10 anos; 70% do sexo masculino). Pacientes e Métodos: os participantes do estudo realizaram um Programa de Reabilitação Pulmonar com 12 semanas de duração, incluindo 24 sessões de exercício físico, 24 sessões de fisioterapia, 12 sessões de psicoterapia e 3 sessões educacionais. Todos os pacientes foram avaliados na linha de base (pré-teste) e ao término (pós-teste) do PRP através de quatro instrumentos: Inventário de Ansiedade de Beck, Inventário de Depressão de Beck , Questionário Respiratório de Saint George e Teste da Caminhada de 6 minutos. Vinte e quatro meses após a conclusão do PRP os pacientes foram reavaliados com os mesmos instrumentos de medida (teste atual). Resultados: Os pacientes demonstraram na comparação entre pré e pósteste, redução significativa dos níveis de ansiedade (pré: 10,7±6,3; pós: 5,5±4,4; p=0,0005), depressão (pré:11,7±6,8; pós:6±5,8; p=0,001) e melhora no índice de qualidade de vida (pré: 51±15,9; pós: 34,7±15,1; p=0,0001). No teste de caminhada houve um aumento significativo (pré: 428,6±75; pós: 474,9±86,3; p=0,03). Na comparação do pós-teste com o teste atual, os índices não demonstraram diferença estatística em nenhum dos critérios avaliados. Ansiedade (pós: 5,5±4,4; atual: 7,3±4,8; p=0,127), depressão (pós: 6±5,8; atual:7,8±5,7; p= 0,228), qualidade de vida ( pós: 34,7±15,1; atual: 40±13,3; p=0,157) e teste de caminhada (pós: 474,9±86,3; atual: 451±74,2; p=0,254) Conclusões: os benefícios obtidos pelos pacientes com a reabilitação pulmonar sobre os índices de ansiedade, depressão, qualidade de vida e teste de caminhada, persistiram ao longo dos 24 meses. / Study Objectives: to verify the long-term outcome of a pulmonary rehabilitation program on the levels of anxiety, depression and quality of life, as well, the six-minute walking test performance of 30 COPD patients (mean±SD, 60.8±10 years; 70% male). Design: the participants under went a 12-week treatment program: 24 session of physical exercises, 24 sessions of physiotherapy, 12 psychological sessions and three educational sessions. All patients were evaluated at baseline (pretest), at completion of the rehabilitation program (post-test), and two years later (current test) through four instruments: Beck Anxiety Inventory, Beck Depression Inventory, The St. George’s Respiratory Questionnaire and the Six- Minute Walk Test. Results: the comparison between pre and post-test demonstrated significant statistical improvements, including reduced anxiety (pre: 10.7±6.3; post: 5.5±4.4; p=0.0005) and depression (pre: 11.7±6.8; post: 6±5.8; p=0.001), increase endurance (pre: 428.6±75; post: 474.9±86.3; p=0.03), and better quality of life (pre: 51±15.9; post: 34.7±15.1; p=0.0001). There were no statistic differences when the results of the post-test were analyzed against the data of the current test. Anxiety (post: 5.5±4.4; current: 7.3±4.8; p=0.127), depression (post: 6±5.8; current: 7.8±5.7; p=0.228), endurance (post: 474.9±86.3; current: 451±74.2; p= 0.254) and quality of life (post: 34.7±15.1; current: 40±13.3; p=0.157). Conclusions: COPD patients are able to maintain the psychological and physical improvements acquired during a pulmonary rehabilitation program for two years.