Thesis (MScPhysio)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Background: Pulmonary tuberculosis (PTB) remains a major concern worldwide. Although PTB is curable, both the disease and its treatment may have considerable medical, social and psychological consequences which may result in a decreased quality of life and functioning. Characterization of the functional capabilities of PTB patients post-treatment and the impact of PTB on their quality of life may identify a need for more holistic management of PTB treatment that extends beyond microbiological cure. Methods: Firstly, an in-depth scoping review was conducted using the following key words: Pulmonary tuberculosis (MESH term) and Health related quality of life (HRQoL), Pulmonary tuberculosis (MESH term) and Spirometry and Pulmonary tuberculosis (MESH term) and Six minute walk test or 6MWT to review the current literature reporting on the HRQoL, lung function measurements and exercise capacity of a PTB population (Chapter 2). Secondly, a cross-sectional, quantitative, descriptive study was conducted. The study setting included five primary health care facilities (PHCF) in the Breede Valley sub-district of the Cape Winelands East District, Western Cape, South Africa. Adult patients diagnosed with PTB, 18 years and older and who were successfully managed through the Cape Winelands District Health Care system were considered for the study if they had least two negative sputum sample results and had completed at least five months of anti-tuberculosis treatment. Post treatment bronchodilator lung function tests, health related quality of life using the BOLD core questionnaire and six minute walk test distance (6MWD) was measured. Findings: The comprehensive broad search of the literature yielded a total of 2446 articles. A total of 2422 articles were excluded since the title; abstract or full text article did not conform to the review question or were eliminated as duplicates across databases. Twenty-seven articles divided amongst the three subsections i.e. PTB and HRQoL (n=13), PTB and Spirometry (n=9) and PTB and exercise capacity (n=6), were included in the review. In the cross-sectional study, 328 names were obtained from the TB registers of the five included PHCF of which 45 patients were included in the study (56% male; mean age, 39.88±10.20 years). The majority of patients (n= 206; 63%) were not contactable, and could not be recruited. Approximately half the total sample, (n=23; 52%) presented with normal lung function while n=11 (25%) presented with a restrictive pattern, n=9 (21%) presented with an obstructive pattern and only n=1 (2%) presented with a mixed pattern (defined as FEV1<80% predicted, FVC<80% predicted and FEV1/FVC<0.7). The mean six minute walk distance (6MWD) was 294.5m±122.7m. Respondents scored poorly on all sub-domains of the SF-12v2 except vitality. Role emotional and role physical scored lowest with mean scores of 28.1 and 35.27 respectively, while vitality scored the highest with 52.78. Stellenbosch University https://scholar.sun.ac.za 4 | P a g e Conclusion The findings of this thesis suggest that even after microbiological cure, PTB patients may suffer from a decreased quality of life, impaired lung function and a decreased exercise capacity. Specific challenges to data collection in a rural region were identified; which included patient recruitment, field testing of exercise capacity (6MWD), and the generalizabilty of standardized questionnaires in rural regions. The findings of this pilot study serves to inform the planning of a larger observational study, in the rural Cape Winelands of the Western Cape, South Africa. / AFRIKAANSE OPSOMMING: Agtergrond Pulmonêre tuberkulose (PTB) wek wêreldwyd steeds groot kommer. Hoewel dit geneeslik is, kan die siekte sowel as die behandeling daarvan beduidende mediese, maatskaplike en sielkundige gevolge hê, wat lewensgehalte en funksionering kan knou. Die tipering van PTB-pasiënte se funksionele vermoëns ná behandeling sowel as die impak van PTB op hul lewensgehalte kan dalk dui op ’n behoefte aan die meer holistiese bestuur van PTB-behandeling, wat méér as blote mikrobiologiese genesing insluit. Metodes Eerstens is ’n diepgaande bestekstudie aan die hand van die volgende trefwoorde onderneem: pulmonêre tuberkulose (MeSH-term) en gesondheidsverwante lewensgehalte (HRQoL), pulmonêre tuberkulose (MeSH-term) en spirometrie, en pulmonêre tuberkulose (MeSH-term) en die ses minute lange stapafstandtoets (6MWT). Na aanleiding daarvan is die huidige literatuur oor die HRQoL, longfunksiemetings en oefenvermoë van ’n PTB-populasie bestudeer (hoofstuk 2). Tweedens is ’n kwantitatiewe, beskrywende deursneestudie onderneem. Die studie-omgewing het bestaan uit vyf fasiliteite vir primêre gesondheidsorg in die Breedevallei-subdistrik van die streek Kaapse Wynland-Oos, Wes-Kaap, Suid-Afrika. Volwasse pasiënte van 18 jaar en ouer wat met PTB gediagnoseer is en suksesvol deur die distriksgesondheidsorgstelsel van die Kaapse Wynland-streek bestuur word, is vir die studie oorweeg indien minstens twee van die pasiënt se sputummonsters TB-negatiewe resultate opgelewer het en die persoon reeds minstens vyf maande vir tuberkulose behandel is. Studiemetings het ingesluit brongodilator-longfunksietoetse ná behandeling, gesondheidsverwante beoordelings van lewensgehalte met behulp van die BOLD-vraelys, en die aflegging van ’n ses minute lange stapafstandtoets (6MWT). Bevindinge Die omvattende breë soektog van die literatuur het 'n totaal van 2446 artikels opgelewer. 'n Totaal van 2422 artikels is uitgesluit, aangesien die titel; abstrakte of volledige teks artikel het nie voldoen aan die navorsings vraag, of is uitgeskakel as duplikate oor databasisse. Sewe en twintig artikels verdeel tussen die drie onderafdelings, naamlik PTB en HRQoL (n = 13), PTB en Spirometrie (n = 9) en PTB en oefening kapasiteit (n = 6), is ingesluit in die oorsig. In die deursneestudie is 328 name uit die TB-registers van die vyf ondersoekpersele bekom. Altesaam 45 pasiënte (56% mans; gemiddelde ouderdom 39.88±10.20 jaar) is by die studie ingesluit. Die oorgrote meerderheid pasiënte (n = 206; 63%) kon nie bereik word nie, en dus ook nie gewerf word nie. Ongeveer die helfte van die algehele steekproef (n = 23; 52%) se longfunksie was normaal; n = 11 (25%) het ’n restriktiewe patroon getoon; n = 9 (21%) ’n obstruktiewe patroon, en slegs n = 1 (2%) ’n gemengde patroon (wat omskryf word as ’n FEV1-voorspellingswaarde van <80%, ’n FVC-voorspellingswaarde van <80%, en FEV1/FVC van <0.7). Die gemiddelde afstand wat in die ses minute lange staptoets afgelê is (6MWD), was 294,5 m±122,7 m. Respondente behaal swak Stellenbosch University https://scholar.sun.ac.za 6 | P a g e op al die sub-domein van die SF-12v2 behalwe vitaliteit. Rol emosionele en rol fisiese behaal laagste met die gemiddelde tellings van 28.1 en 35,27 onderskeidelik, terwyl vitaliteit behaal die hoogste met 52,78. Gevolgtrekking Die bevindinge van hierdie tesis gee te kenne dat PTB-pasiënte selfs ná mikrobiologiese genesing dalk swakker lewensgehalte, verswakte longfunksie en ’n afname in oefenvermoë ondervind. Bepaalde uitdagings vir data-insameling in ’n landelike omgewing is uitgewys, onder meer pasiëntewerwing, veldtoetsing van oefenvermoë (6MWD) en die veralgemeenbaarheid van gestandaardiseerde vraelyste in landelike gebiede. Die bevindinge van hierdie proefstudie kan gebruik word om die beplanning van ’n groter waarnemingstudie in die landelike Kaapse Wynland-streek in die Wes-Kaap, Suid-Afrika, te rig.

abstract: Heart failure is a major worldwide health concern and is the leading cause of hospitalization among elderly Americans. Approximately 50% of those diagnosed with heart failure have heart failure with preserved ejection fraction (HFPEF). HFPEF presents a therapeutic dilemma because pharmacological strategies that are effective for the treatment of heart failure and reduced ejection fraction have failed to show benefit in HFPEF. Long term moderate intensity exercise programs have been shown to improve diastolic function in patients HFPEF. High intensity interval training (HIIT) has been shown to improve diastolic function in patients with heart failure and reduced ejection fraction. However, the effects of high intensity interval training in patients with HFPEF are unknown. Fourteen patients with HFPEF were randomized to either: (1) a novel program of high-intensity aerobic interval training (n = 8), or (2) a commonly prescribed program of moderate-intensity (MOD) aerobic exercise training (n = 6). Before and after four weeks of exercise training, patients underwent a treadmill graded exercise test for the determination of peak oxygen uptake (VO2peak), a brachial artery reactivity test for assessment of endothelium-dependent flow-mediated dilation (BAFMD), aortic pulse wave velocity assessment as an index of vascular stiffness and two-dimensional echocardiography for assessment of left ventricular diastolic and systolic function. I hypothesized that (1) high-intensity aerobic interval training would result in superior improvements in FMD, aortic pulse wave velocity, VO2peak, diastolic function and, (2) changes in these parameters would be correlated with changes in VO2peak. The principal findings of the study were that a one month long high intensity interval training program resulted in significant improvements in diastolic function as measured by two-dimensional echocardiography [pre diastolic dysfunction (DD) grade - 2.13 + 0.4 vs. post DD grade - 1.25 + 0.7, p = 0.03]. The left atrial volume index was reduced in the HIIT group compared to MOD ( - 4.4 + 6.2 ml/m2 vs. 5.8 + 10.7 ml/m2, p = 0.02). Early mitral flow (E) improved in the HIIT group (pre - 0.93 + 0.2 m/s vs. post - 0.78 + 0.3 m/s, p = 0.03). A significant inverse correlation was observed between change in BAFMD and change in diastolic dysfunction grade (r = - 0.585, p = 0.028) when all the data were pooled. HIIT appears to be a time-efficient and safe strategy for improving diastolic function in patients with heart failure and preserved ejection fraction. These data may have implications for cardiovascular risk reduction in this population. / Dissertation/Thesis / Ph.D. Exercise and Wellness 2012

A carcinomatose peritoneal (CP), secundária ao avanço neoplásico maligno na cavidade abdominal, causa grande morbidade e tem como recomendação terapêutica atual um tratamento multimodal, que consiste na combinação de cirurgia citorredutora (CCR) agressiva e quimioterapia hipertérmica intraperitoneal (HIPEC). O objetivo do presente estudo é caracterizar a função respiratória desse grupo de pacientes, potencialmente candidatos à abordagem de tratamento multimodal e a relação da função respiratória com a capacidade de exercício e qualidade de vida relacionada à saúde (QVRS). Nesse estudo transversal, 25 pacientes com CP candidatos à abordagem de tratamento multimodal, foram avaliados em um centro terciário de saúde, entre maio de 2013 e abril de 2014. Foram avaliados o performance status (PS), espirometria, pressões respiratórias máximas, capacidade de exercício pelo teste de caminhada de seis minutos (TC6m) e um questionário de QVRS (QQVRS) específico para portadores de câncer. Os valores médios da avaliação de força muscular respiratória e da espirometria estavam dentro dos limites de normalidade. Todavia, foram encontrados valores reduzidos na pressão inspiratória máxima (PImax), na pressão expiratória máxima (PEmax) e na distância percorrida no TC6m em 6/25 (24%), 4/25 (16%), e 9/20 (45%), respectivamente. A PImax se associou com o PS, enquanto que a PEmax se associou com a capacidade de exercício, escala funcional do QQVRS e PS. Em conclusão, uma significativa proporção de pacientes apresentava fraqueza muscular respiratória e redução da capacidade de exercício. A força muscular respiratória mostrou associação significativa com PS, enquanto que a PEmax se relacionou com a capacidade de exercício e escala funcional do questionário de QVRS. / Peritoneal carcinomatosis (PC), secondary to advanced abdominal malignancies, causes great morbidity and is currently treated using multimodal approaches combining aggressive cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (HIPEC). The aim of the present study is to characterize the respiratory functional status of patients with PC potentially candidates to multimodal treatment approaches and the relationship of respiratory function with exercise capacity and health related quality of life (HRQL). In a cross-sectional study, 25 patients with PC referred for CRS plus HIPEC treatment approach at a tertiary care center between May 2013 and April 2014 were evaluated. Performance status, spirometry, maximal respiratory pressure measures,6-minute walk test (6MWT) and cancer specific HRQL questionnaire were assessed. Mean values of spirometry and respiratory muscle strength were above normal limits. However, reduced maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and 6MWT distance was found in 6/25 (24%), 4/25 (16%), and 9/20 (45%), respectively. MIP was associated with performance status while MEP was associated with exercise capacity, functional scale of HRQL questionnaire and performance status. A significant proportion of patients presented respiratory muscle weakness and impaired exercise capacity. MEP and MIP were related with performance status while MEP was additionally associated with exercise capacity and functional scale of HRQL.

Submitted by LIANA SOUSA COELHO null (lianascoelho@gmail.com) on 2016-03-04T12:42:34Z No. of bitstreams: 1 Liana S Coelho Tese doutorado.pdf: 4949880 bytes, checksum: 8a00b19396b78d2b3710b90868709838 (MD5) / Approved for entry into archive by Ana Paula Grisoto (grisotoana@reitoria.unesp.br) on 2016-03-04T17:42:42Z (GMT) No. of bitstreams: 1 coelho_ls_dr_bot.pdf: 4949880 bytes, checksum: 8a00b19396b78d2b3710b90868709838 (MD5) / Made available in DSpace on 2016-03-04T17:42:42Z (GMT). No. of bitstreams: 1 coelho_ls_dr_bot.pdf: 4949880 bytes, checksum: 8a00b19396b78d2b3710b90868709838 (MD5) Previous issue date: 2016-02-26 / A associação entre Doença Pulmonar Obstrutiva Crônica (DPOC) e Doença Arterial Coronariana (DAC) é importante causa de morbidade e mortalidade em pacientes com DPOC. Dados da literatura mostram que essa associação ocorre independente de fatores de risco comuns – tabagismo, idade e gênero e que o processo inflamatório pode ser o elo entre essas doenças. Além disso, a presença de comorbidades pode alterar de forma significativa a gravidade da DPOC e/ou DAC. O presente estudo tem como objetivos avaliar a prevalência da associação entre DPOC e DAC em pacientes com diagnóstico primário de uma das doenças e avaliar as características gerais dos pacientes com DPOC, DAC e ambas as doenças. Além disso, avaliar intensidade da dispneia, tolerância ao exercício, qualidade de vida, estado inflamatório e achados ecocardiográficos em cada grupo de pacientes. Foram avaliados 95 pacientes, de ambos os gêneros e idade ≥ 40 anos. Destes, 43 foram diagnosticados com DPOC, 47 com DAC e 5 com ambas as doenças. Todos foram submetidos a avaliação clínica, eletrocardiograma, ecocardiograma, radiograma de tórax, avaliação da composição corporal, teste de caminhada de 6 minutos (DP6), exames laboratoriais, espirometria e responderam aos questionários de qualidade de vida. A prevalência de DAC em DPOC foi de 10,4%, enquanto que no grupo de pacientes com DAC a prevalência de DPOC foi de 9,6% e, quando avaliados DAC tabagistas, foi de 17,2%. O grupo DPOC apresentou maior percepção de dispneia (p<0,001), menor DP6 (p=0,037), pior qualidade de vida, avaliada pelo SF-36 (p<0,001) e aumento da proteína C-reativa (PCR) (p=0,020) em comparação com grupo DAC. Regressão linear não identificou correlação entre o estado inflamatório avaliada por PCR e IL-6 à presença de DAC (p=0,992 e p=0,978, respectivamente). Em nosso estudo, a prevalência de DAC em DPOC assemelhou-se aos menores valores encontrados na literatura. Pacientes com ambas as doenças apresentaram maior intensidade de dispneia, pior qualidade de vida e maior estado inflamatório que os outros grupos. Não encontramos relação entre o estado inflamatório e a prevalência de DAC em DPOC; esta associação parece dever-se à alta prevalência dos fatores de risco clássicos para DAC nos pacientes com DPOC. / The association between Chronic Obstructive Pulmonary Disease (COPD) and coronary artery disease (CAD) is an important cause of morbidity and mortality in patients with COPD. Published data show that this association is independent of common risk factors - smoking, age and gender, and that the inflammatory process may be a link between these diseases. Furthermore, the comorbidities can significantly alter the severity of COPD and/or CAD. This study aims to evaluate the prevalence of the association between COPD and CAD in patients with a primary diagnosis of a disease and assessing the general characteristics of patients with COPD, CAD and both diseases. Also, to assess the severity of dyspnea, exercise tolerance, health status, inflammatory status, echocardiographic findings in each group of patients. We evaluated 95 patients of both genders and age ≥ 40 years-old. Of these, 43 were diagnosed with COPD, 47 with CAD and 5 with both diseases. All patients underwent clinical evaluation, electrocardiogram, echocardiogram, chest X-ray, assessment of body composition, 6-minute walk test, laboratory tests, spirometry and answered all health status’ questionnaires. The prevalence of CAD in COPD was 10.4% while in patients with CAD, the prevalence of COPD was 9.6%, and in DAC with smoking history, the prevalence was 17.2%. The COPD group had a higher perception of dyspnea (p<0.001), lower 6-minute walking distance (6MWD) (p=0.037), worse health status assessed by the SF-36 (p<0.001) and increased C-reactive protein (CRP) (p=0.020) compared to CAD group. Linear regression did not identify correlation between inflammatory status, assessed neither by CRP nor by IL-6, and the presence of CAD (p 0.992 and p 0.978, respectively). In our study, the prevalence of CAD in COPD resembles the lower values found in the literature. Patients with both diseases presented more intense dyspnea, lower exercise tolerance, worse health status and higher inflammatory status than other groups. There was no relationship between inflammatory status and the prevalence of CAD in COPD; this association is probably due to the high prevalence of classic risk factors for CAD in patients with COPD.

Orientador: Irma de Godoy / Resumo: A associação entre Doença Pulmonar Obstrutiva Crônica (DPOC) e Doença Arterial Coronariana (DAC) é importante causa de morbidade e mortalidade em pacientes com DPOC. Dados da literatura mostram que essa associação ocorre independente de fatores de risco comuns – tabagismo, idade e gênero e que o processo inflamatório pode ser o elo entre essas doenças. Além disso, a presença de comorbidades pode alterar de forma significativa a gravidade da DPOC e/ou DAC. O presente estudo tem como objetivos avaliar a prevalência da associação entre DPOC e DAC em pacientes com diagnóstico primário de uma das doenças e avaliar as características gerais dos pacientes com DPOC, DAC e ambas as doenças. Além disso, avaliar intensidade da dispneia, tolerância ao exercício, qualidade de vida, estado inflamatório e achados ecocardiográficos em cada grupo de pacientes. Foram avaliados 95 pacientes, de ambos os gêneros e idade ≥ 40 anos. Destes, 43 foram diagnosticados com DPOC, 47 com DAC e 5 com ambas as doenças. Todos foram submetidos a avaliação clínica, eletrocardiograma, ecocardiograma, radiograma de tórax, avaliação da composição corporal, teste de caminhada de 6 minutos (DP6), exames laboratoriais, espirometria e responderam aos questionários de qualidade de vida. A prevalência de DAC em DPOC foi de 10,4%, enquanto que no grupo de pacientes com DAC a prevalência de DPOC foi de 9,6% e, quando avaliados DAC tabagistas, foi de 17,2%. O grupo DPOC apresentou maior percepção de dispneia (p<0,001), m... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The association between Chronic Obstructive Pulmonary Disease (COPD) and coronary artery disease (CAD) is an important cause of morbidity and mortality in patients with COPD. Published data show that this association is independent of common risk factors - smoking, age and gender, and that the inflammatory process may be a link between these diseases. Furthermore, the comorbidities can significantly alter the severity of COPD and/or CAD. This study aims to evaluate the prevalence of the association between COPD and CAD in patients with a primary diagnosis of a disease and assessing the general characteristics of patients with COPD, CAD and both diseases. Also, to assess the severity of dyspnea, exercise tolerance, health status, inflammatory status, echocardiographic findings in each group of patients. We evaluated 95 patients of both genders and age ≥ 40 years-old. Of these, 43 were diagnosed with COPD, 47 with CAD and 5 with both diseases. All patients underwent clinical evaluation, electrocardiogram, echocardiogram, chest X-ray, assessment of body composition, 6-minute walk test, laboratory tests, spirometry and answered all health status’ questionnaires. The prevalence of CAD in COPD was 10.4% while in patients with CAD, the prevalence of COPD was 9.6%, and in DAC with smoking history, the prevalence was 17.2%. The COPD group had a higher perception of dyspnea (p<0.001), lower 6-minute walking distance (6MWD) (p=0.037), worse health status assessed by the SF-36 (p<0.001) ... (Complete abstract click electronic access below) / Doutor

A carcinomatose peritoneal (CP), secundária ao avanço neoplásico maligno na cavidade abdominal, causa grande morbidade e tem como recomendação terapêutica atual um tratamento multimodal, que consiste na combinação de cirurgia citorredutora (CCR) agressiva e quimioterapia hipertérmica intraperitoneal (HIPEC). O objetivo do presente estudo é caracterizar a função respiratória desse grupo de pacientes, potencialmente candidatos à abordagem de tratamento multimodal e a relação da função respiratória com a capacidade de exercício e qualidade de vida relacionada à saúde (QVRS). Nesse estudo transversal, 25 pacientes com CP candidatos à abordagem de tratamento multimodal, foram avaliados em um centro terciário de saúde, entre maio de 2013 e abril de 2014. Foram avaliados o performance status (PS), espirometria, pressões respiratórias máximas, capacidade de exercício pelo teste de caminhada de seis minutos (TC6m) e um questionário de QVRS (QQVRS) específico para portadores de câncer. Os valores médios da avaliação de força muscular respiratória e da espirometria estavam dentro dos limites de normalidade. Todavia, foram encontrados valores reduzidos na pressão inspiratória máxima (PImax), na pressão expiratória máxima (PEmax) e na distância percorrida no TC6m em 6/25 (24%), 4/25 (16%), e 9/20 (45%), respectivamente. A PImax se associou com o PS, enquanto que a PEmax se associou com a capacidade de exercício, escala funcional do QQVRS e PS. Em conclusão, uma significativa proporção de pacientes apresentava fraqueza muscular respiratória e redução da capacidade de exercício. A força muscular respiratória mostrou associação significativa com PS, enquanto que a PEmax se relacionou com a capacidade de exercício e escala funcional do questionário de QVRS. / Peritoneal carcinomatosis (PC), secondary to advanced abdominal malignancies, causes great morbidity and is currently treated using multimodal approaches combining aggressive cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (HIPEC). The aim of the present study is to characterize the respiratory functional status of patients with PC potentially candidates to multimodal treatment approaches and the relationship of respiratory function with exercise capacity and health related quality of life (HRQL). In a cross-sectional study, 25 patients with PC referred for CRS plus HIPEC treatment approach at a tertiary care center between May 2013 and April 2014 were evaluated. Performance status, spirometry, maximal respiratory pressure measures,6-minute walk test (6MWT) and cancer specific HRQL questionnaire were assessed. Mean values of spirometry and respiratory muscle strength were above normal limits. However, reduced maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and 6MWT distance was found in 6/25 (24%), 4/25 (16%), and 9/20 (45%), respectively. MIP was associated with performance status while MEP was associated with exercise capacity, functional scale of HRQL questionnaire and performance status. A significant proportion of patients presented respiratory muscle weakness and impaired exercise capacity. MEP and MIP were related with performance status while MEP was additionally associated with exercise capacity and functional scale of HRQL.

A carcinomatose peritoneal (CP), secundária ao avanço neoplásico maligno na cavidade abdominal, causa grande morbidade e tem como recomendação terapêutica atual um tratamento multimodal, que consiste na combinação de cirurgia citorredutora (CCR) agressiva e quimioterapia hipertérmica intraperitoneal (HIPEC). O objetivo do presente estudo é caracterizar a função respiratória desse grupo de pacientes, potencialmente candidatos à abordagem de tratamento multimodal e a relação da função respiratória com a capacidade de exercício e qualidade de vida relacionada à saúde (QVRS). Nesse estudo transversal, 25 pacientes com CP candidatos à abordagem de tratamento multimodal, foram avaliados em um centro terciário de saúde, entre maio de 2013 e abril de 2014. Foram avaliados o performance status (PS), espirometria, pressões respiratórias máximas, capacidade de exercício pelo teste de caminhada de seis minutos (TC6m) e um questionário de QVRS (QQVRS) específico para portadores de câncer. Os valores médios da avaliação de força muscular respiratória e da espirometria estavam dentro dos limites de normalidade. Todavia, foram encontrados valores reduzidos na pressão inspiratória máxima (PImax), na pressão expiratória máxima (PEmax) e na distância percorrida no TC6m em 6/25 (24%), 4/25 (16%), e 9/20 (45%), respectivamente. A PImax se associou com o PS, enquanto que a PEmax se associou com a capacidade de exercício, escala funcional do QQVRS e PS. Em conclusão, uma significativa proporção de pacientes apresentava fraqueza muscular respiratória e redução da capacidade de exercício. A força muscular respiratória mostrou associação significativa com PS, enquanto que a PEmax se relacionou com a capacidade de exercício e escala funcional do questionário de QVRS. / Peritoneal carcinomatosis (PC), secondary to advanced abdominal malignancies, causes great morbidity and is currently treated using multimodal approaches combining aggressive cytoreductive surgery (CRS) and intraperitoneal hyperthermic chemotherapy (HIPEC). The aim of the present study is to characterize the respiratory functional status of patients with PC potentially candidates to multimodal treatment approaches and the relationship of respiratory function with exercise capacity and health related quality of life (HRQL). In a cross-sectional study, 25 patients with PC referred for CRS plus HIPEC treatment approach at a tertiary care center between May 2013 and April 2014 were evaluated. Performance status, spirometry, maximal respiratory pressure measures,6-minute walk test (6MWT) and cancer specific HRQL questionnaire were assessed. Mean values of spirometry and respiratory muscle strength were above normal limits. However, reduced maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and 6MWT distance was found in 6/25 (24%), 4/25 (16%), and 9/20 (45%), respectively. MIP was associated with performance status while MEP was associated with exercise capacity, functional scale of HRQL questionnaire and performance status. A significant proportion of patients presented respiratory muscle weakness and impaired exercise capacity. MEP and MIP were related with performance status while MEP was additionally associated with exercise capacity and functional scale of HRQL.

Submitted by PPG Pediatria e Sa?de da Crian?a (pediatria-pg@pucrs.br) on 2018-04-27T17:58:37Z No. of bitstreams: 1 Tese de doutorado corrigida Fernanda.pdf: 4883244 bytes, checksum: b51a91fe19e35875a088cb500cc4add5 (MD5) / Approved for entry into archive by Caroline Xavier (caroline.xavier@pucrs.br) on 2018-05-14T11:21:02Z (GMT) No. of bitstreams: 1 Tese de doutorado corrigida Fernanda.pdf: 4883244 bytes, checksum: b51a91fe19e35875a088cb500cc4add5 (MD5) / Made available in DSpace on 2018-05-14T11:25:06Z (GMT). No. of bitstreams: 1 Tese de doutorado corrigida Fernanda.pdf: 4883244 bytes, checksum: b51a91fe19e35875a088cb500cc4add5 (MD5) Previous issue date: 2018-03-09 / Conselho Nacional de Pesquisa e Desenvolvimento Cient?fico e Tecnol?gico - CNPq / Introduction: Cystic fibrosis (CF) is a genetic, multisystemic disease characterized by progressive loss of lung function and airway obstruction. Thus, airflow limitation and dynamic hyperinflation may limit exercise capacity of these patients. In addition, exercise capacity has correlated with survival in children and adults with CF. Objective: To evaluate the effect of respiratory physiotherapy on exercise capacity and the role of maximal oxygen consumption as a predictor of mortality in CF patients. Methods: This thesis is divided into two articles. Article 1 was a prospective randomised, cross-over pilot study performed on children diagnosed with CF, aged >9 years and >128 cm tall. Two visits were performed with one month of interval, one with respiratory physiotherapy using positive expiratory pressure and autogenic drainage, before spirometry, plethysmography and the cardiopulmonary exercise test (CPET), and another without respiratory physiotherapy. The CPET was performed on a cycle ergometer using the Godfrey protocol. All tests followed international recommendations. Article 2 consisted of systematic review and meta-analysis, in which an online search was performed in PubMed, Embase, LILACS and SciELO databases. Were included cohort studies that assessed mortality rates after maximal oxygen uptake (VO2peak) measurements during CPET. The quality analysis of the selected articles was performed using the Newcastle-Ottawa scale. The main outcome evaluated was the mortality of CF patients. Whenever possible, and if appropriate, a random effect meta-analysis was performed. Results: Study 1 included 12 patients with CF with mean age of 12.83?1.85 years, body mass index in Z score was 0.08?0.82 and 75% of them presented at least one allele ?F508. No significant differences were found in maximal oxygen consumption with respiratory physiotherapy. However, there was a significant decrease in minute ventilation (VE) and ventilatory equivalents for oxygen consumption (VEVO2) and for carbon dioxide production (VEVCO2) at lactate threshold when respiratory physiotherapy was performed prior to CPET. The mean VE (L.min-1) was 26.67? 5.49 vs 28.92?6.30 (p=0.05), VEVO2 (L.min-1) was 24.5?1.75 vs 26.05?2.50 (p=0.03) and VEVCO2 (L.min-1) was 26.58?2.41 vs 27.98?2.11 (p=0.03). In study 2, six cohort studies were included, totaling 551 participants. Five studies were classified with high methodological quality. Two different analyzes were carried out to evaluate the influence of VO2peak on mortality. The significant standardized total difference between the VO2peak averages in the survival or non-survival groups was -0.606 (95%CI= -0.993 ? -0.219; p=0.002). In addition, patients with lower VO2peak were associated with a significantly higher mortality risk (RR: 4.896; 95%CI= 1.086 ? 22.072; p=0.039). Conclusion: The results suggest that the performance of respiratory physiotherapy prior to exercise may lead to improved ventilatory dynamics during exercise in CF patients. In addition, the systematic review with meta-analysis has shown that low levels of maximal oxygen uptake are associated with an increase of 4.8 in the risk of mortality, indicating that VO2peak could also be an important follow-up variable. / Introdu??o: A fibrose c?stica (FC) ? uma doen?a gen?tica, multissist?mica, caracterizada pela perda progressiva da fun??o pulmonar e obstru??o das vias a?reas. Assim, a limita??o ao fluxo a?reo e a hiperinsufla??o din?mica podem limitar da capacidade de exerc?cio desses pacientes. Al?m disso, a capacidade de exerc?cio t?m se correlacionado com a sobrevida de crian?as e adultos com FC. Objetivo: Avaliar o efeito da fisioterapia respirat?ria sobre a capacidade de exerc?cio e o papel do consumo m?ximo de oxig?nio como preditor de mortalidade em pacientes com FC. M?todos: Est? tese est? dividida em dois artigos. O artigo 1 foi um estudo piloto, prospectivo, randomizado e cross-over realizado em crian?as com diagn?stico de FC, com idade >9 anos e >128 cm de altura. Foram realizadas duas visitas com um m?s de intervalo, sendo uma com a realiza??o da fisioterapia respirat?ria utilizando press?o expirat?ria positiva e drenagem autog?nica, antes da espirometria, pletismografia e do teste de exerc?cio cardiopulmonar (TECP), e outra sem a realiza??o da fisioterapia respirat?ria. O TECP foi realizado no ciclo erg?metro com a utiliza??o do protocolo de Godfrey. Todos os testes seguiram as recomenda??es internacionais. O artigo 2 consistiu em uma revis?o sistem?tica e meta-an?lise, no qual foi realizada uma pesquisa on-line nas bases de dados PubMed, Embase, LILACS e SciELO. Foram inclu?dos estudos de coorte que avaliaram as taxas de mortalidade ap?s medi??es do consumo m?ximo de oxig?nio (VO2pico) durante um TECP. A an?lise de qualidade dos artigos selecionados foi realizada com a escala Newcastle-Ottawa. O principal desfecho avaliado foi a mortalidade de pacientes com FC. Sempre que poss?vel, e se apropriado, foi realizada uma meta-an?lise de efeito aleat?rio. Resultados: No estudo 1 foram inclu?dos 12 pacientes com FC com m?dia de idade de 12,83?1,85 anos, o ?ndice de massa corporal em escore Z foi 0,08?0,82 e 75% deles apresentavam um alelo ?F508. N?o foram encontradas diferen?as significativas no consumo m?ximo de oxig?nio com a realiza??o da fisioterapia respirat?ria. No entanto, houve uma diminui??o significativa na ventila??o minuto (VE) e nos equivalentes ventilat?rios para o consumo de oxig?nio (VEVO2) e para a produ??o de g?s carb?nico (VEVCO2) no limiar anaer?bico quando realizaram fisioterapia respirat?ria antes do TECP. A m?dia da VE (L.min-1) foi 26,67?5,49 vs 28,92?6,30 (p=0,05), VEVO2 (L.min-1) foi 24,5?1,75 vs 26,05?2,50 (p=0,03) e VEVCO2 (L.min-1) foi 26,58?2,41 vs 27,98?2,11 (p=0,03). No estudo 2 foram inclu?dos seis estudos de coorte, totalizando 551 participantes. Cinco estudos foram classificados com alta qualidade metodol?gica. Foram realizadas duas an?lises diferentes para avaliar a influ?ncia do VO2pico sobre a mortalidade. A diferen?a total padronizada significativa entre as m?dias do VO2pico nos grupos sobrevivente ou n?o-sobrevivente foi -0,606 (IC95%= -0,993 ? -0,219; p=0,002). Al?m disso, os pacientes com menor VO2pico foram associados a um risco de mortalidade significativamente maior (RR: 4,896; IC95%= 1,086 ? 22,072; p=0,039). Conclus?o: Os resultados obtidos sugerem que a realiza??o de fisioterapia respirat?ria antes do exerc?cio pode levar a uma melhora da din?mica ventilat?ria durante o exerc?cio em pacientes com FC. Al?m disso, a revis?o sistem?tica com meta-an?lise demonstrou que baixos n?veis de absor??o m?xima de oxig?nio est?o associados a um aumento de 4,8 vezes no risco de mortalidade na FC, indicando que o VO2pico tamb?m pode ser uma importante vari?vel de acompanhamento.

La décompensation cardiaque se manifeste par une symptomatologie de dyspnée et de fatigue, et par une diminution de l’aptitude aérobie. La décompensation cardiaque peut être globale ou gauche (DCG), ou droite comme dans le cas de l’hypertension artérielle pulmonaire (HTAP). Les mesures fonctionnelles de repos (fonction ventriculaire gauche ou pression artérielle pulmonaire moyenne) sont peu corrélées à l’aptitude aérobie, qui est cependant un élément important de la mise au point et du suivi clinique des patients atteints de DCG ou d’HTAP. L’aptitude aérobie est évaluée par une ergospirométrie. Réalisée sur cycloergomètre ou sur tapis roulant elle mesure l’évolution des variables ventilatoires (ventilation, consommation en oxygène et production de CO2), la fréquence cardiaque et la tension artérielle lors d’un effort à intensité croissante jusqu’à l’effort maximal. Elle apporte une analyse fine du comportement à l’exercice des patients, de la cause de la limitation à l’effort et permet la détermination précise de la consommation d’oxygène maximale (VO2max). Plus simple que l’ergospirométrie, le test de marche de 6 minutes (TDM6) mesure la distance maximale parcourue en marchant 6 minutes. Il évalue la réponse intégrée des systèmes cardiovasculaire, respiratoire et musculaire à l’effort, mais, contrairement à l’ergospirométrie, il ne permet pas d’identifier les facteurs déterminants l’aptitude aérobie. Le TDM6 est corrélé de façon significative, mais non étroite, à la VO2 max et à la classe fonctionnelle telle qu’évaluée par l’échelle à 4 points de la New York Heart Association. Les travaux réunis dans le présent travail ont eu pour but de contribuer à l’étude de la pathophysiologie de l’aptitude aérobie et à la compréhension des tests utilisés pour l’évaluer dans l’HTAP et de la DCG. Dans une première étude, nous avons comparé le profil ergospirométrique et le périmètre de marche de 6 minutes chez les patients DCG ou HTAP. Les résultats montrent que la VO2 max et le TDM sont diminués dans les mêmes proportions chez des patients à handicap fonctionnel (NYHA) comparable, avec toutefois une propension plus marquée à l’hyperventilation dans l’HTAP. Dans une seconde étude, nous avons mesuré la réponse métabolique au TDM6 au moyen d’un ergospiromètre portable chez des patients HTAP. Les résultats montrent que le TDM6 est réalisé à une VO2 correspondant à la VO2max mesurée à l’ergospirométrie sur cycloergomètre, avec cependant une ventilation, un quotient respiratoire et une fréquence cardiaque inférieures. Durant le TDM6, les patients stabilisent leur effort à un quotient respiratoire légèrement inférieur à 1. Ces résultats s’expliquent soit par la cinétique de la VO2 durant l’ergospirométrie à protocole standardisé comportant un incrément de charge trop rapide par minute, soit par une différence des masses musculaires mises en œuvre durant la marche ou l’effort sur bicyclette. Ces résultats suggèrent que le TDM6 pourrait être un test plus adéquat que l’ergospirométrie pour évaluer l’aptitude aérobie dans l’HTAP. Dans un troisième travail, plus modeste, nous avons réalisé la réplique du précédent, dans la DCG. Nous y avons observé les mêmes résultats. Dans un dernier travail nous avons évalué la valeur pronostique de l’ergospirométrie et du TDM6 dans l’HTAP. Nous avons analysé les ergospirométries et TDM6 de 65 patients atteints d’HTAP et discerné un sous groupe de patients atteints d’HTAP idiopathique ou associée à la prise d’anorexigène. Le TDM6 et le produit « distance x poids » étaient pronostiques de mortalité dans le groupe entier de patients et dans le sous groupe de patients atteints d’HTAP idiopathique ou associée à la prise d’anorexigène. La pente VE/VCO2 n’était facteur pronostique de mortalité que dans le groupe de patients atteints d’HTAP idiopathique ou associée à la prise d’anorexigène. La VO2pic n’était prédictive de mortalité dans aucun des groupes de patients. En conclusion, nos travaux ont montré que la DCG et l’HTAP menaient à une diminution similaire de la capacité à l’exercice. Ils ont également contribué à montrer l’intérêt du TDM6 (avec mesures ergospirométriques) dans l’évaluation de cette amputation de l’aptitude à l’effort. Le TDM6 paraît plus adéquat pour la mesure de l’aptitude purement aérobie (quotient respiratoire < 1). Ceci permet probablement de comprendre la supériorité du TDM6 par rapport à l’ergospirométrie en tant que facteur pronostique et en sensibilité aux effets d’interventions thérapeutiques.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. Besides abnormities within the respiratory system COPD is also associated with effects outside the lungs, so called systemic effects. One systemic effect that has been highlighted is skeletal muscle dysfunction which has also been associated with reduced exercise capacity. Apart from changes in muscle morphology, low levels of physical activity have also been suggested as a plausible mediator of reduced exercise capacity in COPD. The aim of this thesis was to study muscle morphology and physical activity patterns in patients with different degrees of COPD and to examine the associations between muscle morphology, physical activity and exercise capacity in these patients. Skeletal muscle morphology was found to shift towards a more glycolytic muscle profile in COPD patients and changes in muscle morphology were found to be correlated to disease severity and to exercise capacity. Muscle capillarization was also found to be lower in COPD compared with healthy subjects and to be correlated to disease severity and exercise capacity. When studying signalling pathways involved in muscle capillarization, an overexpression of VHL was found in patients with mild and moderate COPD compared with healthy subjects. Furthermore, COPD patients were found to be less physically active compared with healthy subjects and the level of physical activity was associated with exercise capacity.In conclusion, changes in skeletal muscle morphology and low levels of physical activity are present in COPD patients and may partly explain the lower exercise capacity observed in these patients. The more glycolytic muscle profile in COPD is suggested to be mediated by hypoxia and low levels of physical activity in this patient group. Furthermore, increased levels of VHL may lead to impaired transduction of the hypoxic signalling pathway, which may contribute to the decreased muscle capillarization observed in COPD.