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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
71

Role of endogenous and exogenous factors in chronic disease development and progression

Leone, Dominick Anthony 06 August 2024 (has links)
Genetic and molecular factors associated with chronic lung and kidney disease susceptibility, leading causes of domestic and global mortality, remain largely unexplained. Until recently, much of the research has focused on nucleotide differences in the human genome. However, the scope of gene studies has expanded beyond nucleotide variability, such as single nucleotide polymorphisms (SNPs). Current research utilizes multiple “omics” that consider not just inherited susceptibility factors, but also the macromolecules coded by the genome and gene-environment interactions. We conducted three studies to answer scientific questions, gain valuable insight into chronic lung and kidney disease processes, and provided meaningful guidance in prioritizing future research. This dissertation is particularly relevant to research in under-represented populations and when sample sizes are limited due to the nature of the disease or difficulty in obtaining biological specimens. We began with a common lung disease that affects millions annually, a potential risk factor for which little is known, and for which study is complicated because the diseased lung tissue is difficult to obtain for cases and more so for controls. In this study, we used easier-to-obtain nasal brushings and transcriptomics to measure counts of non-coding genetic elements. We then shifted to a kidney disease that has been best described in South America and South Asia, where genetic components of the disease might be very different from other more typical forms of kidney disease in North American and European populations. We used genetic variants explaining urinary metabolites to help prioritize future genetic research for the kidney disease, and we explored variants that explain blood concentration of urate to better understand metabolic processes in the at-risk population. In our first study, we examined the associations of Human Endogenous Retrovirus (HERV) transcription with lung function (FEV1/FVC) and Chronic Obstructive Pulmonary Disease (COPD) among current and former smokers. We sought evidence that greater transcription of HERVs was associated with lower lung function and higher risk of COPD. HERVs associated with FEV1/FVC were located within or near COPD genes, and HERV transcription was correlated with gene-regulation involved in FEV1 decline. RNA-seq data from two Detection of Early lung Cancer Among Military Personnel (DECAMP) cohorts were used to identify transcribed HERVs and estimate locus-specific HERV counts. A weight-of-evidence framework was then used to prioritize HERVs and was compared to a p-value based approach. We found 55 HERV loci with evidence that transcription was associated with higher or lower FEV1/FVC. Consistent with the prevailing theory that transcription and expression of HERVs is suppressed in adults, we observed HERV loci with lower mean counts and increased transcription was associated with worse lung function. However, we found some HERV loci with higher mean counts, and increased transcription was associated with better lung function. Most of the lung function-associated HERVs were intergenic and none were near COPD genes. Higher counts of HUERSP1 (15q21) were correlated with higher expression of down-regulated FEV1 decline genes (rho= 0.82; 95%CI: 0.77, 0.85; p= 1.1 x10-65). We also found, albeit with limited evidence, that overall higher transcriptional levels of some HERVs were associated with differential COPD risk. Contrary to our expectation, we observed lower odds of COPD among those with the highest transcription across all loci of HERLEQUIN (beta= 0.45; 95%CI: 0.21, 0.96), HERV-P71A (beta= 0.44; 95%CI: 0.21, 0.91) and HML2 (beta= 0.45; 95%CI: 0.22, 0.93) compared to those with the lowest transcriptional levels. Use of both weight-of-evidence and p-values to prioritize HERVs was better than exclusive use of either framework. We were unable to rule out the possibility that, for some HERVs, transcription might exhibit Goldilocks-like effects on pulmonary function and COPD risk. For the second study, we explored the role of genetic variants in metabolism as measured by urinary metabolite concentrations. Our sample population was Mesoamericans residing in Nicaragua who were at risk for chronic kidney disease of non-traditional origins (CKDnt). High serum urate, also indicative of altered metabolism, is more common than expected in this genetically distinct population. We suspected a potential genetic component that might explain both CKDnt risk and differences in urinary metabolites. However, our limited sample size for genome-wide association studies (GWAS) motivated the design of three approaches to test our hypotheses: (1) for our main hypothesis, we began by investigating associations between nucleotide variability of all variants and concentration of all urine metabolites, and we identified statistically significant associations after accounting for multiple testing; (2) we tested a more limited hypothesis that analyzed all variants but selected metabolites that differed in concentration from similar European workers; (3) for our most specific hypothesis we analyzed associations between a selection of variants that affect protein structure and all metabolites. We included 313 non-cases of CKDnt from our case-control genetics study and with available metabolite data in our analyses. Metabolites were identified, and their concentrations measured, using nuclear magnetic resonance. The effect of variants on metabolite concentration and CKDnt case odds ratios were estimated using generalized linear mixed model association tests. We accounted for population structure, using the top ten genetically determined principal components, and cryptic relatedness using a genetic relatedness matrix. We found that Mesoamericans in our study population carried genetic variants that predispose them to altered energy metabolism and renal transport of solutes, but the allele frequencies did not differ significantly between cases and non-cases of CKDnt. A non-synonymous AGXT2 variant (rs37370) significantly explained 3-Aminoisobutyric acid (beta= -0.68; 95%CI: -0.73, -0.47, p= 9.55 x10 -20) and Dihydrothymine (beta= -1.05; 95%CI: -1.23, -0.88; p= 1.83 x10 -31). Our other approaches identified variants in several other genes including TTC23L, ACADS, HAO2, TCIRG1, NDUFA10, and SLC26A10. While we failed to find a shared genetic link between metabolism and CKDnt, we observed genetic variability in biologically plausible genes such as AGXT2 and HAO2. We concluded that Mesoamericans at risk of CKDnt, due to heat and dehydration, may also carry gene variants that predispose them to higher body heat production. Our third study was a GWAS to further understand genetic factors related to serum uric acid (sUA) metabolism among Nicaraguans at risk of CKDnt. Prior longitudinal studies have found that sugarcane workers experience post-shift elevation in sUA, and abnormally high concentration (hyperuricemia) is a known risk factor for CKD. After onset of CKD, higher sUA is associated with a worse prognosis. Also, previous sUA GWAS have identified a set of genetic variants explaining urate concentration across ethnic populations and found SNPs where the effect on concentration depends on renal function. However, it was unclear if known sUA associated variants explain concentration among populations at risk of CKDnt. We also suspected that genetic variability, unique to Mesoamericans, might explain serum concentration more than known sUA associated SNPs. Therefore, we examined SNP variability and associations with sUA among Nicaraguans. We chose to separately analyze our cases and non-cases of CKDnt because sUA in these groups had different possible biological etiologies. Our aims were to: (1) determine if previously published variants, with established association to sUA among global populations, explained concentration among those diagnosed with CKDnt and those at-risk of the disease; (2) discover novel sUA SNPs among our sample of Mesoamericans; (3) boost our discovery of variants by exploiting kidney function as an effect modifier; (4) identify SNPs where association depends on renal function; and (5) identify SNPs explaining sUA among both CKDnt cases and non-cases. We drew two analytical samples from the Mesoamerican Nephropathy Case-Control Genetic Study: case-only (n= 609) and control-only (non-cases= 385). Renal function was measured as serum creatinine (sCr). In our case-only GWAS, we used two models: generalized linear mixed model (GLMM) that included top 10 principal components (PCs) and use of sUA-lowering medication (allopurinol), and also included an additional gene*sCr interaction term. Only among cases, we tested for joint effects of variant and the interaction with renal function. SNPs, which explained sUA in case-only GWAS or joint test, were examined for modification by renal function using the gene*sCr coefficient. Control-only GWAS was based on GLMM that only included top 10 PCs. In this pilot study, we observed a high prevalence of hyperuricemia (CKDnt cases= 78.8% and non-cases= 23.6%). Despite our limited power, we successfully replicated prior findings for the ABCG2 variant, rs74904971, which was among the top three SNPs explaining sUA in global populations. Among CKDnt cases, rs74904971 significantly explained sUA concentration (beta = 1.1; 95%CI: 0.8, 1.4; p= 9.2 x10 -12), but not among controls (beta = 0.41; 95%CI: 0.16, 0.66; p= 1.2 x10 -3). We found no evidence that renal function modified the genetic effects of rs74904971 (betaG*sCr = 0.44, pG*sCr = 0.17). Most other established urate-SNPs were not significant even at 0.05 significance-level. We found five novel SNPs associated with sUA in our control-only and case-only GWAS, but these variants all had low minor allele frequency (MAF < 5%). The best SNP from control-only GWAS, a GALNTL6 intron variant (rs17057585), was significantly associated with a 1.9 mg/dL increase in sUA (95%CI: 1.3, 2.6, p= 3.6 x10 -9). In our case-only GWAS, we found participants with more alternative alleles of rs61156970, located 89kbp downstream from MCTP2, had suggestively lower sUA (beta= -1.9; 95%CI: -2.6, -1.2; p= 1.8 x10 -7). The joint test allowed us to identify an additional 20 variants, of which 11 SNPs had MAF ≥ 10%, and we found 16 SNPs with significantly greater effects among cases with worse renal function compared to cases with better functioning kidneys. We used The Human Protein Atlas, an online database, to access the biological plausibility for the most significant SNPs from the joint test. We found limited support for the top intronic SNPs from the joint test: rs9499393 (within ERCC3) and rs89572695 (within TMEM9B) have MAF < 10% and are highly expressed genes that are non-specific to renal cells. The effect of indel rs11404676 (within MTHFD1L), which was significantly greater among CKDnt cases with worse renal function than cases with better function (betaG*sCr= 1.4, pG*sCr = 1.4 x10 -6), is more likely to be biologically relevant to purine biosynthesis and urate concentration. We have demonstrated that we can identify known sUA associated SNPs with large effects, and that other Mesoamerican-specific variants better explain serum urate than known ABCG2 SNPs. Renal function among non-cases should be addressed in future GWAS from this population and caution is advised when extrapolating multi-ethnic GWAS results to Mesoamericans.
72

Wirkungen der Bronchodilatation mit Salmeterol auf das autonome Nervensystem / Effects of bronchodilatation with salmeterol on the autonomic nervous system

Bornemann, Thore 15 June 2015 (has links)
No description available.
73

Relationship of Patient Self-Administered COPD Assessment Test (CAT) to Physician Standard Assessment of COPD in a Family Medicine Residency Training Program

Johnson, Leigh, Burchette, Jessica, Click, Ivy A., Williams, Sandra Alicia 08 May 2017 (has links)
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality in the United States. COPD is of particular concern in certain sectors of the country, including Central Appalachia where our clinic is located. Assessing patients with COPD presents many challenges as symptoms range from those considered "typical" such as shortness of breath and sputum production to those less often identified like anxiety and social isolation. We conducted a pilot study comparing physician standard assessment of COPD to patient self-assessment using the COPD Assessment Test (CAT). The CAT is an eight-item questionnaire that measures the impact COPD has on an individual patient’s well-being and daily life. Based on our small sample size, physicians tend to underestimate the impact of COPD on a patient’s daily life. This discrepancy did not differ significantly by year of residency. Potential clinical impact of these findings include the need for more formalized and frequent patient self-assessment of disease burden as well as increased COPD assessment training within the residency curriculum.
74

Relationship of Patient Self-Administered COPD Assessment Test (CAT) to a Physician Standard Assessment of COPD in a Family Medicine Residency Training Program

Sparks, J. A., Tugman, W. T., Johnson, Leigh, Click, Ivy A., Burchette, Jessica Epley 01 March 2017 (has links)
No description available.
75

Risk factors associated with lower defecation frequency in hospitalized older adults: a case control study

Gau, Jen-Tzer, Acharya, Utkarsh H., Khan, M. Salman, Kao, Tzu-Cheg January 2015 (has links)
BACKGROUND: Constipation is highly prevalent in older adults and may be associated with greater frequency of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We investigated the prevalence of lower defecation frequency (DF) and risk factors (including AECOPD) associated with lower DF among hospitalized elderly patients. METHODS: We conducted a retrospective case-control study in a community hospital of Southeast Ohio. Adults aged 65 years or older admitted during 2004 and 2006 were reviewed (N = 1288). Patients were excluded (N = 212) if their length of stay was less than 3 days, discharge diagnosis of Clostridium difficile-associated diarrhea, death or ventilator- dependent respiratory failure during hospitalization. Lower DF was defined as either an average DF of 0.33 or less per day or no defecation in the first three days of hospitalization; cases (N = 406) and controls (N = 670) were included for the final analysis. RESULTS: Approximately 38% had lower DF in this patient population. Fecal soiling/smearing of at least two episodes was documented in 7% of the patients. With the adjustment of confounders, AECOPD (adjusted odds ratio [AOR] =1.47, 95% confidence interval [CI] =1.01-2.13) and muscle relaxant use (AOR =2.94; 95% CI =1.29-6.69) were significantly associated with lower DF. Supplementation of potassium and antibiotic use prior to hospitalization was associated with lower risk of lower DF. CONCLUSIONS: Approximately 38% of hospitalized older adults had lower DF. AECOPD and use of muscle relaxant were significantly associated with lower DF; while supplementation of potassium and antibiotic use were protective for lower DF risk after adjusting for other variables.
76

The effectiveness of pursed lips breathing in the management of breathlessness in stable chronic obstructive pulmonary disease

Roberts, Suzanne Emily January 2011 (has links)
Introduction: This dissertation aims to explore, in a clinical setting, the effectiveness of pursed lips breathing (PLB), in the management of dyspnoea in stable COPD. Methodology: A mixed methodology that comprised a randomised controlled trial (RCT), a predominantly qualitative follow-up (FU) study and two measurement studies was used. The RCT intervention group was taught PLB at home over 8 weeks. Primary outcome measures were the Self Report Chronic Respiratory Disease Questionnaire (CRQ-SR) dyspnoea and mastery domains and Endurance Shuttle Walk Test (ESWT). The FU study investigated the long-term experience of PLB in a subset of RCT participants through telephone interview, focus group and observation of PLB technique at home visit. Prior to the RCT a study using limits of agreement (LoA) methodology was conducted to investigate reliability of hand-held spirometric measurement of inspiratory capacity (IC) with a view to using it as an outcome measure. Following the RCT a retrospective analysis of data collected from the ESWT was performed comparing a 1-walk protocol with the published 2-walk protocol. Results: Forty-one patients with COPD were recruited to the RCT (PLB n = 22, control n =19); mean age 68 years (SD 11), mean FEV1% predicted 47% (SD 15.80) and 13 were approached to participate in the FU; 11 of 13 agreed to telephone interview, 5 to attend the focus group and 6 to home visit. The median time since learning PLB was 17 months (6 - 23). The RCT found no statistically significant difference between groups in the primary outcome measures and in retrospect was insufficiently powered. Post hoc analysis found effect sizes for primary outcome measures were: CRQ-SR dyspnoea 0.05, CRQ-SR mastery 0.48 and ESWT 0.44. For secondary outcome measures the PLB group showed a significant (p = 0.02) improvement in oxygen saturation on ESWT. Long-term follow-up found 9 of 11 still used PLB, 8 reported definite benefit. Those using PLB used it for breathlessness with four themes identified: use of PLB with physical activity (8/11), to increase confidence and reduce panic (4/11), as an exercise (3/11), at night (3/11). Discontinuation of PLB (2/11) was due to no benefit. Hand-held spirometric measurement of IC found LoA for same-day IC measurement in healthy volunteers (n = 20) ± 0.630L (95%CI ± 0.255) and over 3 weeks (n = 11) ± 0.560L (95%CI ± 0.326). In COPD, same day LoA (n = 26) were ± 0.582L (95%CI ± 0.169) and over 6 weeks (n = 8) ± 0.486L (95%CI ± 0.302). Retrospective analysis of ESWT data identified that completion rates improved by 17% for the 1-walk protocol but that the ceiling-effect was 12.2% compared to 7.3% for the 2-walk protocol. LoA between protocols when measuring change over time (n = 31) was ±80% (95%CI 25.56); less than the difference described as "somewhat better" (113%) following pulmonary rehabilitation (PR) but greater than the m.c.i.d. of 68%. Conclusions: LoA for IC exceeded the clinically significant reported 0.3L; the protocol tested here was not sufficiently reliable for use as an outcome measure. Analysis of ESWT data showed the 1-walk protocol was adequate for identify change in clinical practice but, for research purposes the 2-walk protocol should be retained. From the RCT learning PLB resulted in reduced physiological stress with respect to oxygen desaturation when performing ESWT compared to the control group. Long-term follow-up showed that, in severe COPD perceived benefits persisted in 62% of patients.
77

Analysis of Pharmacotherapy by patients with diagnosis of COPD

Kartali Kaouni, Marilena January 2013 (has links)
Title: Analysis of Pharmacotherapy by patients with diagnosis of COPD Student: Marilena Kartali-Kaouni Tutor: Prof. RNDr. Jiri Vlcek, CSc Department of Social and Clinical Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Background: " Chronic Obstructive Pulmonary Disease (COPD) is characterized by airflow limitation that is not fully reversible. The airflow limitation is usually both progressive and associated with an abnormal inflammatory response of the lungs to noxious particles or gases". Tobacco smoking is the major risk factor in the development of COPD. COPD is a leading cause of morbidity and mortality worldwide. Aim: 1st from the current literature to understand the nature of COPD and obtain information about the aetiopathogenesis of the disease, diagnosis options and summarize the current view of strategies for achieving the goals of treatment. 2nd in a pilot study to analyze drug therapy in COPD patients visiting a pharmacy in Greece. Methods: 56 prescriptions with the diagnosis of COPD were collected during a period of 8 months from a Greek pharmacy. Information from the prescriptions with regard to COPD medications prescribed (active substances, trade names, strength, dosage scheme, pack size), patients characteristics (age and gender) and prescribing...
78

Detecção por espirometria de DPOC em usuários de um centro de convivência do idoso: alta prevalência de subdiagnóstico e redução da qualidade de vida / Detection of COPD by espirometry in users of a senior community center: high prevalence and underdiagnosis of reduced quality of life.

Santos, Simeão Rodrigo dos 02 September 2013 (has links)
Introdução: A doença pulmonar obstrutiva crônica (DPOC) é uma doença muito prevalente nos indivíduos acima de 40 anos. É uma doença com grande impacto social e econômico, podendo levar a um declínio na qualidade de vida de seus portadores. Objetivos: Avaliar as características da DPOC, a frequência do subdiagnóstico e a influência da doença sobre a qualidade de vida em um centro de convivência da comunidade. Casuística e Método: É um estudo observacional, transversal e analítico realizado na cidade de Uberaba MG. Todos os participantes responderam questionários sobre as características demográficas, socioeconômicas, de trabalho, da qualidade de vida e do estado de saúde. Foram realizadas também a avaliação antropométrica e a espirometria. Foi utilizado o teste t de Student não pareado e bicaudal para a comparação de médias de variáveis quantitativas entre dois grupos independentes: grupo DPOC e grupo sem DPOC (na 1ª parte da análise); e grupo DPOC com diagnóstico prévio e grupo com DPOC sem diagnóstico (na 2ª parte da análise). A comparação das proporções das variáveis qualitativas entre dois grupos independentes foi realizada com o Teste Qui Quadrado. Regressão logística e regressão logística múltipla foram utilizadas para identificar associações entre as variáveis qualitativas independentes e a variável qualitativa dependente (ter diagnóstico prévio de DPOC). Regressão linear simples e a múltipla foram utilizadas para identificar variáveis independentes que pudessem proporcionar mudanças significativas (explicativas) na variável resposta (escore total e escores dos domínios do questionário WHOQOL-bref). Resultados: 315 indivíduos com idade acima de 50 anos foram recrutados e 298 completaram o estudo, sendo 72 (24,2%) portadores de DPOC e, desses, 58 (80,6%) não relataram diagnóstico prévio da doença. Quando realizada a 1ª parte da análise (grupo com DPOC e sem DPOC) foi observado predomínio do gênero masculino (p 0,001), média de idade superior (p 0,001), menor aderência à atividade física nas dependências do centro de convivência (p 0,01) e maior prevalência de tabagismo (p 0,001) no grupo com DPOC. Quando comparados os domínios da qualidade de vida entre os grupos, 8 nossos resultados mostram comprometimento do domínio físico no grupo com DPOC (p 0,05). O domínio físico da qualidade de vida foi influenciado positivamente pelo gênero masculino (coef. = 1,319 e IC = 0,394; 2,243), e negativamente pela DPOC (coef. = -1,118 e IC = -2,002; -0,234) e pela inatividade por problemas de saúde (coef. = -1,983 e IC = -2,918; -0,868). Na 2ª parte da análise (grupo DPOC com diagnóstico prévio e grupo DPOC sem diagnóstico) foi observado que não houve associação entre as características socioeconômicas, antropométricas e fatores de risco com diagnóstico prévio da doença. Em relação aos sintomas, houve associação entre sibilos e diagnóstico prévio (p 0,05). Os valores espirométricos VEF1 e VEF1/CVF mostraram diferenças estatisticamente significantes (p<0,01) entre os grupos, sendo menores no grupo com diagnóstico prévio da doença. O estadiamento 2 da doença foi o mais encontrado em ambos os grupos e ocorreu associação entre os estadiamentos 3/4 (grave/muito grave) e diagnóstico prévio (p 0,05). Conclusões: A utilização da espirometria em usuários de centros de convivência pode ser uma estratégia simples e útil para aumentar o número de diagnósticos de DPOC. Como resultado, medidas efetivas para o tratamento e controle da doença poderiam ser implantadas diminuindo o impacto da doença avançada, melhorando a qualidade de vida do doente e de seus familiares. / Introduction: The chronic obstructive pulmonary disease (COPD) is a highly prevalent disease in individuals aged over 40 years. It is a disease with great social and economic impact that may lead to a decline in the quality of life of its patients. Objectives: To evaluate the characteristics of COPD, the frequency of underdiagnosis and the influence of the disease on the quality of life in a community center. Method: It is an observational, analytical and cross-sectional study conducted in the city of Uberaba-MG. All participants answered questionnaires on demographic, socioeconomic and labor characteristics, quality of life and health status. The anthropometric evaluation and the spirometry were also carried out. We used the unpaired two-tailed Student t-test to compare means of quantitative variables between two independent groups: COPD group and the group without COPD (in the first part of the analysis); COPD group previously diagnosed and group with COPD undiagnosed (in the second part of the analysis). To compare the proportions of the qualitative variables between two independent groups, we used the Chi-Square Test. Logistic regression and multiple logistic regression were used to identify associations between the independent qualitative variables and the dependent qualitative variable (having a previous diagnosis of COPD). Simple logistic regression and multiple analyses were carried out to identify independent variables that could provide significant changes (explanatory) in the response variable (total score and scores of the domains of the WHOQOL-BREF questionnaire). Results: 315 individuals aged 50 years or older were recruited and 298 completed the protocol, 72 (24.2%) patients with COPD and, of those, 58 (80.6%) had no previous diagnosis of the disease. When the first part of the analysis was performed, (COPD group and the group without COPD), we observed a predominance of males (p 0,001), higher mean age (p 0.001), lower adherence to physical activity in the premises of the community center (p 0.01) and a higher prevalence of tobacco smoking (p 0.001) in the group of patients with COPD. When comparing the domains of quality of life between groups, our results show a worse score of the 10 physical domain in the group of patients with COPD (p 0.05). The physical domain of quality of life was positively influenced by males (coef. = 1.319 and CI = 0.394; 2.243) and negatively by COPD (coef. = -1.118 and CI = -2.002; -0.234) and by inactivity by health problems (coef. = -1.983 and CI = -2.918; -0.868). In the second part of the analysis, (COPD group previously diagnosed and group with COPD undiagnosed), it was observed that there was no association between socioeconomic and anthropometric characteristics and risk factors with a previous diagnosis of the disease. Regarding symptoms, there was an association between wheezing and previous diagnosis (p 0.05). Spirometric values FEV1 and FEV1/FVC showed statistically significant differences (p 0.01) between groups, being lower in the group with a previous diagnosis of the disease. Stage 2 COPD was the most common severity level in both groups. We found association of stage 3/4 severe COPD with a previous diagnosis (p 0.05). Conclusions: The use of spirometry in users of community centers can be a simple and useful strategy to increase the number of diagnoses of COPD. As a result, effective measures for treatment and control of the disease could be implanted, reducing the impact of advanced disease, improving the quality of life of the patients and their relatives.
79

Detecção por espirometria de DPOC em usuários de um centro de convivência do idoso: alta prevalência de subdiagnóstico e redução da qualidade de vida / Detection of COPD by espirometry in users of a senior community center: high prevalence and underdiagnosis of reduced quality of life.

Simeão Rodrigo dos Santos 02 September 2013 (has links)
Introdução: A doença pulmonar obstrutiva crônica (DPOC) é uma doença muito prevalente nos indivíduos acima de 40 anos. É uma doença com grande impacto social e econômico, podendo levar a um declínio na qualidade de vida de seus portadores. Objetivos: Avaliar as características da DPOC, a frequência do subdiagnóstico e a influência da doença sobre a qualidade de vida em um centro de convivência da comunidade. Casuística e Método: É um estudo observacional, transversal e analítico realizado na cidade de Uberaba MG. Todos os participantes responderam questionários sobre as características demográficas, socioeconômicas, de trabalho, da qualidade de vida e do estado de saúde. Foram realizadas também a avaliação antropométrica e a espirometria. Foi utilizado o teste t de Student não pareado e bicaudal para a comparação de médias de variáveis quantitativas entre dois grupos independentes: grupo DPOC e grupo sem DPOC (na 1ª parte da análise); e grupo DPOC com diagnóstico prévio e grupo com DPOC sem diagnóstico (na 2ª parte da análise). A comparação das proporções das variáveis qualitativas entre dois grupos independentes foi realizada com o Teste Qui Quadrado. Regressão logística e regressão logística múltipla foram utilizadas para identificar associações entre as variáveis qualitativas independentes e a variável qualitativa dependente (ter diagnóstico prévio de DPOC). Regressão linear simples e a múltipla foram utilizadas para identificar variáveis independentes que pudessem proporcionar mudanças significativas (explicativas) na variável resposta (escore total e escores dos domínios do questionário WHOQOL-bref). Resultados: 315 indivíduos com idade acima de 50 anos foram recrutados e 298 completaram o estudo, sendo 72 (24,2%) portadores de DPOC e, desses, 58 (80,6%) não relataram diagnóstico prévio da doença. Quando realizada a 1ª parte da análise (grupo com DPOC e sem DPOC) foi observado predomínio do gênero masculino (p 0,001), média de idade superior (p 0,001), menor aderência à atividade física nas dependências do centro de convivência (p 0,01) e maior prevalência de tabagismo (p 0,001) no grupo com DPOC. Quando comparados os domínios da qualidade de vida entre os grupos, 8 nossos resultados mostram comprometimento do domínio físico no grupo com DPOC (p 0,05). O domínio físico da qualidade de vida foi influenciado positivamente pelo gênero masculino (coef. = 1,319 e IC = 0,394; 2,243), e negativamente pela DPOC (coef. = -1,118 e IC = -2,002; -0,234) e pela inatividade por problemas de saúde (coef. = -1,983 e IC = -2,918; -0,868). Na 2ª parte da análise (grupo DPOC com diagnóstico prévio e grupo DPOC sem diagnóstico) foi observado que não houve associação entre as características socioeconômicas, antropométricas e fatores de risco com diagnóstico prévio da doença. Em relação aos sintomas, houve associação entre sibilos e diagnóstico prévio (p 0,05). Os valores espirométricos VEF1 e VEF1/CVF mostraram diferenças estatisticamente significantes (p<0,01) entre os grupos, sendo menores no grupo com diagnóstico prévio da doença. O estadiamento 2 da doença foi o mais encontrado em ambos os grupos e ocorreu associação entre os estadiamentos 3/4 (grave/muito grave) e diagnóstico prévio (p 0,05). Conclusões: A utilização da espirometria em usuários de centros de convivência pode ser uma estratégia simples e útil para aumentar o número de diagnósticos de DPOC. Como resultado, medidas efetivas para o tratamento e controle da doença poderiam ser implantadas diminuindo o impacto da doença avançada, melhorando a qualidade de vida do doente e de seus familiares. / Introduction: The chronic obstructive pulmonary disease (COPD) is a highly prevalent disease in individuals aged over 40 years. It is a disease with great social and economic impact that may lead to a decline in the quality of life of its patients. Objectives: To evaluate the characteristics of COPD, the frequency of underdiagnosis and the influence of the disease on the quality of life in a community center. Method: It is an observational, analytical and cross-sectional study conducted in the city of Uberaba-MG. All participants answered questionnaires on demographic, socioeconomic and labor characteristics, quality of life and health status. The anthropometric evaluation and the spirometry were also carried out. We used the unpaired two-tailed Student t-test to compare means of quantitative variables between two independent groups: COPD group and the group without COPD (in the first part of the analysis); COPD group previously diagnosed and group with COPD undiagnosed (in the second part of the analysis). To compare the proportions of the qualitative variables between two independent groups, we used the Chi-Square Test. Logistic regression and multiple logistic regression were used to identify associations between the independent qualitative variables and the dependent qualitative variable (having a previous diagnosis of COPD). Simple logistic regression and multiple analyses were carried out to identify independent variables that could provide significant changes (explanatory) in the response variable (total score and scores of the domains of the WHOQOL-BREF questionnaire). Results: 315 individuals aged 50 years or older were recruited and 298 completed the protocol, 72 (24.2%) patients with COPD and, of those, 58 (80.6%) had no previous diagnosis of the disease. When the first part of the analysis was performed, (COPD group and the group without COPD), we observed a predominance of males (p 0,001), higher mean age (p 0.001), lower adherence to physical activity in the premises of the community center (p 0.01) and a higher prevalence of tobacco smoking (p 0.001) in the group of patients with COPD. When comparing the domains of quality of life between groups, our results show a worse score of the 10 physical domain in the group of patients with COPD (p 0.05). The physical domain of quality of life was positively influenced by males (coef. = 1.319 and CI = 0.394; 2.243) and negatively by COPD (coef. = -1.118 and CI = -2.002; -0.234) and by inactivity by health problems (coef. = -1.983 and CI = -2.918; -0.868). In the second part of the analysis, (COPD group previously diagnosed and group with COPD undiagnosed), it was observed that there was no association between socioeconomic and anthropometric characteristics and risk factors with a previous diagnosis of the disease. Regarding symptoms, there was an association between wheezing and previous diagnosis (p 0.05). Spirometric values FEV1 and FEV1/FVC showed statistically significant differences (p 0.01) between groups, being lower in the group with a previous diagnosis of the disease. Stage 2 COPD was the most common severity level in both groups. We found association of stage 3/4 severe COPD with a previous diagnosis (p 0.05). Conclusions: The use of spirometry in users of community centers can be a simple and useful strategy to increase the number of diagnoses of COPD. As a result, effective measures for treatment and control of the disease could be implanted, reducing the impact of advanced disease, improving the quality of life of the patients and their relatives.
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Rôle de P53 dans les macrophages alvéolaires en réponse à diverses agressions environnementales / Role of P53 in alveolar macrophages in response to different environmental factors

Chrusciel, Sandra 03 December 2014 (has links)
Il existe plusieurs types d’agressions environnementales : biologiques (virus, bactéries…), chimiques (gaz, fumées, métaux…), physiques (bruits, rayonnements…), et d’autres telles que le stress par exemple. L’appareil respiratoire, qui représente une interface majeure avec l’environnement, est particulièrement vulnérable vis-à-vis de ces agressions, qui ont souvent des conséquences pulmonaires, pouvant parfois conduire au décès. Le tabac notamment est la cause de près de 100 millions de décès au cours du XXème siècle d’après l’Organisation Mondiale de la Santé (OMS), et sera la cause d’environ un milliard de décès au prochain siècle. L’exposition à la fumée de cigarette engendre une inflammation chronique et est souvent corrélée au développement de cancers (1), mais induit aussi de nombreuses autres pathologies pulmonaires telles que la broncho-pneumopathie chronique obstructive (BPCO) / There are several types of environmental attacks: biological (viruses, bacteria …), chemical (gases, smokes, metals …), physical appearances (rumours, brilliances …), and others such as the stress for example. The respiratory system, which represents a major interface with the environment, is particularly vulnerable towards these attacks, which often have lung consequences, being able to sometimes lead to the death. The tobacco in particular is the cause of about 100 million deaths during the XXth century according to the World Health Organization (WHO), and will be the cause about a billion deaths in the next century. The exhibition in the smoke of cigarette engenders a chronic inflammation and is often correlated in the development of cancers (1), but also leads of numerous

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