Submitted by Alison Vanceto (alison-vanceto@hotmail.com) on 2017-06-07T12:32:04Z No. of bitstreams: 1 DissEZK.pdf: 2194814 bytes, checksum: f579334d7cc673d9063f83b128e26017 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-06-13T13:24:43Z (GMT) No. of bitstreams: 1 DissEZK.pdf: 2194814 bytes, checksum: f579334d7cc673d9063f83b128e26017 (MD5) / Approved for entry into archive by Ronildo Prado (ronisp@ufscar.br) on 2017-06-13T13:24:49Z (GMT) No. of bitstreams: 1 DissEZK.pdf: 2194814 bytes, checksum: f579334d7cc673d9063f83b128e26017 (MD5) / Made available in DSpace on 2017-06-13T13:29:54Z (GMT). No. of bitstreams: 1 DissEZK.pdf: 2194814 bytes, checksum: f579334d7cc673d9063f83b128e26017 (MD5) Previous issue date: 2017-02-24 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Chronic obstructive pulmonary disease (COPD) is a major cause of disability, hospital admissions, and the demand for care in health systems. Periods of exacerbations are frequent and are associated with increased risk for cardiovascular disease and reduced overall health status. The involvement of cardiac autonomic modulation (CAM) has been evidenced in this population in stable periods; however, knowledge about CAM in exacerbated hospitalized COPD, as well as on the influence of functional aspects in this function is still scarce. In this context, of exacerbation of COPD and the possibility of advancing the knowledge about the cardiac autonomic nervous system and the functional capacity in this clinical condition motivated the development of this dissertation, which will consist of the presentation of a study titled " Increased parasympathetic cardiac modulation in patients with acute exacerbation of chronic obstructive pulmonary disease: how should we interpret it?". The aim of this study was to evaluate MAC responses in patients with COPD during exacerbation of the disease compared to patients in stable condition and to verify the possible association of these responses with functional capacity. Patients with COPD were included in the study and divided into two groups according to the clinical condition: stable and exacerbated. The exacerbated patients were evaluated in the first 24-48 hours after initiation of pharmacological therapy for exacerbation. The HR signal and the RR intervals were recorded for 10 minutes in seated position for later analysis of MAC using heart rate variability (HRV) indices. Clinical and functional data were obtained by evaluating handgrip strength, dyspnea and general health status. Our results showed higher values of the representative indices of the parasympathetic modulation for the exacerbated patients compared to the stable patients: RMSSD (17.8 ± 5.6 vs 11.7 ± 9.5 ms); HF (111.3 ± 74.9 vs. 45.6 ± 80.7 ms2); SD1 (12.7 ± 3.9 vs. 8.3 ± 6.7 ms). Significant and negative associations between HF and handgrip strength (r = -0.58) and LF with dyspnea were found (r = -0.53) (P <0.05). These findings can be attributed, among other factors, to the influence of vagal activity on the respiratory system, which results in narrowing of the airways and consequent worse clinical status. Reinforcing these findings it was possible to verify that the parasympathetic modulation is inversely associated to the functional capacity in the exacerbation of the disease. These results add knowledge that may be useful to the clinical practice of the professional involved in the care of this patient. / A doença pulmonar obstrutiva crônica (DPOC) representa causa importante de invalidez, internações hospitalares e da demanda de cuidados dos sistemas de saúde. Os períodos de exacerbações são frequentes e associam-se ao risco aumentado para doenças cardiovasculares e redução do estado geral de saúde. O comprometimento da modulação autonômica cardíaca (MAC) tem sido evidenciado nesta população em períodos estáveis, no entanto, o conhecimento sobre a MAC em pacientes com DPOC exacerbados hospitalizados, bem como sobre a influência de aspectos funcionais nesta função ainda é escasso. Neste contexto, a temática da exacerbação da DPOC e possibilidade de avanço no conhecimento sobre o sistema nervoso autonômico cardíaco e a capacidade funcional nesta condição clínica motivou o desenvolvimento desta dissertação que constará da apresentação de um estudo intitulado de “Predomínio da modulação cardíaca parassimpática em pacientes com doença pulmonar obstrutiva crônica exacerbada: como devemos interpretar?”. Este teve como objetivo avaliar as respostas da MAC em pacientes com DPOC durante a exacerbação da doença comparada à pacientes em condição estável e verificar a possível associação destas respostas com a capacidade funcional. Pacientes com DPOC foram inseridos no estudo e divididos em dois grupos de acordo com a condição clínica: estáveis e exacerbados. Os pacientes exacerbados foram avaliados nas primeiras 24-48 horas após início da terapia farmacológica para exacerbação. O sinal de FC e dos intervalos RR foram registrados durante 10 minutos em repouso sentado para posterior análise da MAC por meio da utilização de índices da variabilidade da frequência cardíaca (VFC). Os dados clínicos e funcionais também foram obtidos, por meio da avaliação da força de preensão palmar, dispneia e estado geral de saúde. Nossos resultados apontaram maiores valores dos índices representativos da modulação parassimpática para os pacientes exacerbados comparados aos pacientes estáveis: RMSSD (17,8±5,6 vs 11,7±9,5 ms); AF (111,3±74,9 vs 45,6±80,7 ms2); SD1 (12,7±3,9 vs 8,3±6,7 ms). Também foram encontradas associações significativas e negativas entre AF e força de preensão palmar (r = -0,58) e BF com a dispneia (r = -0,53). (P <0,05). Estes achados podem ser atribuídos, entre outros fatores, à influência da atividade vagal no sistema respiratório, que se traduz em estreitamento das vias aéreas e consequente pior estado clínico. Reforçando estes achados foi possível verificar que a modulação parassimpática está inversamente associada à capacidade funcional na exacerbação da doença. Estes resultados adicionam conhecimento que pode ser útil à prática clínica do profissional envolvido no cuidado deste paciente.

Abstract The purpose of this work was to determine on the basis of the national hospital discharge register and cause-of-death statistics the extent of the hospital treatment required for chronic obstructive pulmonary disease (COPD) in Finland over the period 1972–2001, i.e. the use made of hospital services, factors affecting the length of stay in hospital and the correlation of length of stay with the prognosis. Different intervals within this period were taken for study according to the themes of the individual papers. The results suggest that the length of stay in hospital varies both geographically and seasonally in Finland, the shortest times being recorded in Northern Finland in summer. The main explanations for this would appear to lie in regional differences in health care resources and treatment practises and in climatic variations. The mean length of stay in hospital in the total material in 1987–1998 was nine days. The longest periods applied to cases with concurrent pneumonia or a cerebrovascular disorder. The duration of treatment for the exacerbation stage of COPD decreased by two days between 1993 and 2001, with the longest periods of treatment observed in the case of elderly women. One week of treatment with current modalities may be regarded as optimal, as this was associated with the longest interval before the next exacerbation, just over six months. About 3% of all emergency admissions ended in death, most commonly on a Friday in winter or spring. Patients admitted at a weekend died within the first 24 hours more frequently than did those admitted on a weekday. The mean duration of treatment and frequency of hospitalization increased towards the terminal stage. About one fourth of the patients had died within a year of the first admission for COPD and about a half within five years. Hospital treatment for COPD intensified in Finland during the 1990s as the numbers of hospital beds decreased. Treatment times became shorter and deaths in hospital during exacerbation became less frequent. It will be necessary from now onwards, however, to anticipate the ageing of the population and to develop treatment modalities to replace hospitalization, in order to reduce the costs accruing from this disease. Early diagnosis and outpatient rehabilitation should be developed, and special attention should be paid to appropriate treatment at the terminal stage. / Tiivistelmä Tutkimuksen tarkoituksena oli selvittää valtakunnallisen hoitoilmoitusrekisterin ja kuolemansyytilaston avulla keuhkoahtaumataudista (KAT) aiheutunutta sairaalahoitoa Suomessa 1972–2001: sairaalapalvelujen käyttöä, hoitojakson pituuteen vaikuttavia tekijöitä sekä hoitoajan yhteyttä ennusteeseen. Lähdeaineistosta valittiin erilaisia ajanjaksoja tutkimusasetelman mukaan. Tulokset viittaavat siihen, että hoitoajan pituus vaihtelee Suomessa maantieteellisesti ja vuodenaikojen mukaan: lyhyin hoitoaika on Pohjois-Suomessa kesällä. Ilmiötä selittänevät pääosin terveydenhuollon resurssien ja hoitokäytäntöjen alueelliset erot sekä ilmasto-olosuhteiden vaihtelu. Vuosina 1987–1998 keskimääräinen hoitoaika koko aineistossa oli yhdeksän vuorokautta. Jos potilaalla oli samanaikaisina sairauksina keuhkokuume tai aivoverenkiertohäiriö, nämä johtivat pisimpiin hoitoaikoihin. KAT:n pahenemisvaiheen hoitoaika lyheni kaksi vuorokautta vuodesta 1993 vuoteen 2001. Iäkkäitten naisten hoitoajat olivat pisimmät. Viikon pituinen hoitoaika nykyisillä hoitomuodoilla oli optimaalinen, sillä tällöin aika seuraavan pahenemisvaiheen hoitojakson alkuun oli pisin: vähän yli puoli vuotta. Kaikista päivystyshoitojaksoista potilaan kuolemaan päättyi kolmisen prosenttia. Yleisimmin tällainen hoitojakso päättyi potilaan kuolemaan perjantaisin ja todennäköisimmin talvella tai keväällä. Viikonloppuna sairaalaan tulleista potilaista kuoli ensimmäisen vuorokauden aikana enemmän kuin arkipäivinä tulleista. Keskimääräinen hoitoaika oli pisin ja sairaalahoito runsainta sairauden loppuvaiheessa kuoleman lähestyessä. Ensimmäisen KAT:n aiheuttaman hoitojakson jälkeen noin neljännes potilaista oli kuollut vuoden sisällä ja viiden vuoden kuluessa noin puolet. Keuhkoahtaumataudin sairaalahoito on tehostunut Suomessa 1990-luvulla sairaansijojen vähentyessä. Hoitoajat ovat lyhentyneet ja pahenemisvaiheiden sairaalakuolleisuus on vähäistä. Väestön ikääntyminen on kuitenkin ennakoitava ja sairaalaa korvaavia hoitomuotoja kehitettävä taudista aiheutuneiden kustannusten hillitsemiseksi. Varhaisdiagnostiikkaa ja avokuntoutusta on kehitettävä ja erityinen huomio kiinnitettävä sairauden loppuvaiheen asianmukaiseen hoitoon.

Alemtuzumab exerts its clinical efficacy by its specific pattern of depletion and repopulation of different immune cell subsets. Recently, single cases of multiple sclerosis patients who developed severe exacerbation after the first alemtuzumab application, accompanied by re-appearance of peripheral B cells, were reported. Here we present a case with underlying B cell-driven multiple sclerosis that impressively improves after alemtuzumab, although peripheral B cell repopulation took place. Our detailed clinical, histopathological, imaging and immunological data suggest that alemtuzumab can act as an effective rescue treatment in highly active B cell-driven and antibody/complement-mediated multiple sclerosis type II patients.