The thesis deals with the possibility to influence the values of the lung function in patiens with chronic obstructive pulmonary disease (COPD) after exercise carried out according to the Methodology of sensorimotor training. The thesis contains a summary of theoretical knowledge about the pathophysiologic expresion of COPD, including their consequences not only for the respiratory system, but musculoskeletal system as well. Furthermore the thesis includes the information about the Methodology of sensorimotor training, that was used to influence the posture correction in our research. Methods: The spirometric examination of flow-volume curves monitor the changes prior to and after the exercise according to sensorimotor training in patiens with COPD (mean age 60, 733 ± 11,817). Results: The using of sensorimotor training can provide correction of the position of the whole body, of the chest, and change a chest mobility and in total to set up conditions for more economical muscle activation. This enable the changes in the values of the lung functions in the patiens with COPD, that we measured. Not all changes showed statistically significant change. Conclusion: Using sensorimotor training have an objective effect on the values of the lung function in patiens with COPD.

Made available in DSpace on 2014-06-11T19:22:14Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-02-28Bitstream added on 2014-06-13T18:48:42Z : No. of bitstreams: 1 lima_jf_me_botfm.pdf: 34272424 bytes, checksum: caf2cdee25b036ee6d09df776a9aee39 (MD5) / Universidade Estadual Paulista (UNESP) / A simpatectomia torácica videoassistida (STVA) é uma cirurgia eficaz na correção da hiperidrose primária, porém as repercusões sobre a função cardiopulmonar são pouco discutidas até o momento pela literatura. Analisar o comportamento funcional respiratório no pós-operatório de simpatectomia videotoracoscópica, bem como avaliar se as alterações mecânicas interferem diretamente nos resultados de testes de exercícios cardiopulmonar, como o teste de caminhada e de escada. Testes de função pulmonar, teste de caminhada de 6 minutos e o teste de escada foram realizados em 51 pacientes submetidos a STVA, nos momentos do préoperatório, primeiro dia, sétimo dia e trigésimo dia pós-operatórios. Todas as variáveis analisadas apresentaram diferença bastante significante no PO1, com melhora no PO7, mas ainda significativamente diferentes do PRÉ. No PO30 todas elas mostraram retorno aos valores PRÉ, mas apesar dos testes de exercício não mostrarem nesse momento diferença significante com o PRÉ, a frequência de pulso tanto em repouso, quanto após os testes, mostraram-se significativamente reduzidas. Os pacientes submetidos a STVA apresentam alterações da função pulmonar e dos testes de exercício cardiopulmonar no pós-operatório, em todos os parâmetros avaliados, porém há um retorno rápido às condições pré-operatórias, com manutenção de valores de fp inferiores ao PRÉ / Video assisted thoracic sympathectomy (VATS) is an effective surgery for treating primary hyperhidrosis, but the effects on cardiopulmonary function are not discussed in the literature so far. To assess the respiratory function in thoracoscopic sympathectomy postoperative, and to evaluate whether the mechanical changes directly influence the results of cardiopulmonary exercise testing, as the walk test and stair-climbing test. Pulmonary function tests, 6 minute walking test and stair climbing test were performed in 51 patients undergoing VATS, in moments of pre-operative, first day, seventh day and thirtieth days postoperatively. All variables showed very significant difference in PO1, with improvement in PO7, but still significantly different from PRE. In PO30 all of them returned to PRE values, but despite the exercise tests show no significant difference at that with the PRE, the heart rate both at rest and after the tests were significantly reduced. Patients undergoing VATS show changes in lung function and cardiopulmonary exercise testing in the postoperative period in all parameters evaluated, but there is a fast return to preoperative conditions, with the maintenance of heart rate lower than PRE

Multiple breath washout (MBW) of inert gas for assessment of airway disease in children is an emerging technique. In many studies Lung Clearance Index (LCI), derived from multiple breath washout of SF6, is more able to detect early or mild lung disease than standard lung function measurements. It is also able to detect very early lung disease in progressive conditions such as Cystic Fibrosis (CF). Where infants born with this condition were thought to have minimal lung disease activity, LCI is higher in these children than healthy controls. Lack of available commercial devices has hampered expansion of this technique to centres other than specialist research teams. Innocor (Innovision, Dk), a photoacoustic mass spectrometer capable of performing multiple breath washout, was adapted within this research group for use in adults. This thesis describes the setup, adaptation and validation of Innocor for use in children. In 4 studies, healthy controls, children with asthma and children with CF were recruited to perform MBW. In one study, 29 healthy controls and 31 children with asthma were recruited. Healthy controls performed 1 set of washouts, establishing a normative range. Children with asthma performed measurements before and after bronchodilator. Results showed increased LCI in children with asthma even though they were clinically stable as defined by symptoms. LCI stayed high even following bronchodilator suggesting evidence of residual airway disease in well controlled asthmatics despite adequate symptom control. To investigate short term variability of MBW measurements, two other studies recruited 18 children with CF in each. They performed measurements before and after standard physiotherapy manoeuvres and during sitting and lying posture. LCI did not change significantly after airway clearance physiotherapy, compared with children who did no intervention. Variability was high in both groups however suggesting CF lung disease is a complex interaction of changing ventilation in adjacent lung units. Lying posture induced greater changes in lung function in children with CF than controls. LCI appears to be more sensitive to this change than standard lung function measurements (spirometry). In another study 32 children with CF were recruited to perform serial lung function measurements over 18 months. These were data collected as part of the UK Cystic Fibrosis Gene Therapy Consortium (CFGTC) clinical studies in preparation for planned gene therapy trials. LCI appears comparable to FEV1 and may be able to detect another aspect of airway disease. All initial studies were performed in older children (>5yrs). The basic Innocor device is unsuitable for testing of younger patients with low breath volume and high respiratory rate. In-house adaptations following detailed lung model experimentation led to a faster analyser response, potentially capable of MBW in younger children. The second part of this thesis concerns lab experiments and an in-vivo comparison with the current gold-standard MBW device, a respiratory mass spectrometer. 16 healthy volunteers and 9 children with CF were recruited. Ages ranged from 0.4 yrs to 49 yrs. Innocor values for lung volume estimation compared favourably with the mass spectrometer. No evidence of bias caused by Innocor error was seen, however intra-test variability was rather high, reducing the precision of the results. These studies indicate Innocor is a robust, simple to use device with potential as a commercial lung function system. Modifications were made to make it suitable for use in all ages. Further development will need to focus on the patient interface and software, which is the domain of the manufacturers. The experiments contained in this thesis are therefore of interest to the wider respiratory research community as well as manufacturers of MBW devices.

Cystic fibrosis (CF) is the most common life-restricting, genetically inherited disease among Caucasians affecting approximately 30,000 people in the United States. Lung disease is the major cause of morbidity and mortality in CF. A number of oral, inhaled, and intravenous therapies are available to combat CF lung disease. Of these, this research project focused on inhaled dornase alfa, oral azithromycin, inhaled tobramycin, and inhaled aztreonam. Data to address three research aims were requested and obtained from the Cystic Fibrosis Foundation Patient Registry (CFFPR). The first aim examined the use of inhaled dornase alfa in younger children with CF. With no clinical efficacy data of dornase alfa in children ≤ 6 years of age, the study utilized subsequent forced expiratory volume in 1 second (FEV₁) measured between 6 - 7 years of age, to assess the effectiveness of long-term dornase alfa use ≤ 6 years of age. Propensity score methods were used to reduce the likelihood of treatment indication bias. The results suggested that receiving treatment with dornase alfa before 6 years of age did not improve FEV₁ between 6 - 7 years. Unmeasured covariates leading to treatment indication bias were likely one of the key explanations for these results. Additionally, lack of a more sensitive outcome than FEV₁ to assess lung function in young patients with early lung damage was thought to be another reason for the failure to reject the null hypothesis. The second aim assessed the long-term clinical effectiveness of chronic azithromycin use on the rate of FEV₁ decline in CF patients between 6 - 20 years of age. This study was novel in that the rate of FEV₁ decline, rather than change in FEV₁ from baseline, was the primary outcome, which was characterized using propensity score matching followed by a linear mixed model analysis. The results of the analysis suggested that the rate of FEV₁ decline was slower in patients who did not receive chronic treatment with azithromycin. Treatment indication bias was thought to play an important role in the direction of the association between treatment and outcome. Associations between FEV₁ % predicted and many of the other study variables included in the analysis were consistent with previous studies. The final aim compared the clinical effectiveness of a combination of inhaled tobramycin and aztreonam with inhaled tobramycin alone on the rate of FEV₁ decline in CF patients between 6 - 20 years of age. This aim was novel in that the effect of this combination treatment on rate of decline in FEV₁ has never been assessed. A linear mixed model analysis was used after matching patients in the two treatment groups on their propensity scores. Once again, the results were contrary to the alternative hypothesis with the combination group having a steeper rate of FEV₁ decline than the group that was treated with tobramycin alone. An important reason for this result was thought to be unresolved treatment indication bias that could not be eliminated even with the use of the propensity score methods used to test the associated hypothesis. The use of validated methods of analysis, i.e., propensity scores, to counter treatment indication bias using the largest available observational dataset for CF, was one of the key strengths of this study. Moreover, this study highlighted important weaknesses in the CFFPR with regards to lack of data on patient and physician-level variables - an area of active interest for the Cystic Fibrosis Foundation.

ABSTRACT Occupational exposure to wood dust and biohazards associated with wood dust (endotoxins, (1->3)-b-D-glucans, Gram (-)ve bacteria and fungi), their correlation to respiratory function, and symptoms among woodworkers have been investigated in the present study. Wood dust, endotoxins, and allergenic fungi are the main hazards found in woodworking environments. Relatively very few studies have been done on wood dust exposure. The present study was designed to comprehensively investigate the health effects of wood dust exposure, and in particular provide new information regarding: Exposure to (1->3)-b-D-glucans in an occupational environment; Levels of exposure to wood dust and biohazards associated with wood dust in different woodworking environments; Correlations among personal exposures, especially correlations between (1->3)-b-D-glucans and fungi exposures, and endotoxins and Gram (-)ve bacteria exposures; Effects of personal exposure to biohazards on lung function; Effects of personal exposure to biohazards on work-related symptoms; and Determinants of inhalable exposures (provide which factors in the environment influence the personal inhalable exposures). Workers at four different woodworking processes; two logging sites, four sawmills, one major woodchipping operation and five joineries situated in the state of New South Wales in Australia were studied for personal exposure to inhalable dust (n=182) and respirable dust (n=81), fungi (n=120), Gram (-)ve bacteria (n=120), inhalable endotoxin (n=160), respirable endotoxin (n=79), inhalable (1->3)-b-D-glucan (n=105), and respirable (1->3)-b-D-glucan (n=62). The workers (n=168) were also tested for lung function. A questionnaire study (n=195) was carried out to determine the prevalence of work-related symptoms. The geometric mean inhalable exposure at logging sites was 0.56 mg/m3 (n=7), sawmills 1.59 mg/m3 (n=93), the woodchipping mill 1.86 mg/m3 (n=9) and joineries 3.68 mg/m3 (n=66). Overall, sixty two percent of the exposures exceeded the current standards. Among joineries, 95% of the hardwood exposures and 35% of the softwood exposures were above the relevant standards. Compared with green mills, the percentage of samples, which exceeded the hardwood standard was high for dry mills (70% in dry mills, 50% in green mills). The respirable dust exposures were high at the joineries compared with the other worksites. Exposure levels to fungi at logging sites and sawmills were in the range 103-104 cfu/m3, woodchipping 103-105 cfu/m3 and joineries 102-104 cfu/m3. The predominant fungi found at sawmills were Penicillium spp. High exposure levels of Aureobasidium pullulans were also found at two sawmills. At the woodchipping mill the predominant species were Aspergillus fumigatus, Penicillium spp., and Paecilomyces spp. The sawmills, which employed kiln drying processes, had lower exposure levels of fungi compared with the green mills. Those workplaces which had efficient dust control systems showed less exposure to fungi and bacteria. Although mean endotoxin levels were lower than the suggested threshold value of 20 ng/m3, some personal exposures at sawmills and joineries exceeded the threshold limit value. The mean inhalable (1->3)-b-D-glucan level at the woodchipping mill was 2.32 ng/m3, at sawmills 1.37 ng/m3, at logging sites 2.02 ng/m3, and at joineries 0.43 ng/m3. For the respirable size fraction, mean endotoxin and mean (1->3)-b-D-glucan concentrations were much lower, being similar to observed dust concentrations. Significant correlations were found between mean inhalable endotoxin and Gram (-)ve bacteria levels (p<0.0001), and mean airborne inhalable (1->3)-b-D-glucan and fungi levels (p=0.0003). The correlations between mean respirable endotoxin levels vs Gram (-)ve bacteria exposure levels (p=0.005), and respirable (1->3)-b-D-glucan exposure levels vs total fungi levels (p=0.005) were also significant. Significant correlations were found between lung function and personal exposures. Multivariate analyses showed that the effect of all the personal exposures on cross-shift decrements in lung function was more prominent among sawmill and chip mill workers compared with joinery workers. Woodworkers had markedly high prevalence of cough, phlegm, chronic bronchitis, frequent headaches, throat and eye irritations, and nasal symptoms compared with controls. Among the woodworkers, smokers had a high prevalence of chronic bronchitis (20%) compared with non-smokers (10%). Some workers also reported a variety of allergy problems due to exposure to various types of wood dust. Both joinery workers and sawmill and chip mill workers revealed significant correlations between work-related symptoms and personal exposures. Chronic bronchitis was significantly correlated with personal exposure to wood dust, endotoxin, (1->3)-b-D-glucan, fungi, and Gram (-)ve bacteria among joinery workers. Whereas among sawmill workers chronic bronchitis was significantly correlated with personal exposure to endotoxin, (1->3)-b-D-glucan, and fungi. Woodworkers showed significant positive correlations between percentage cross-shift change (decrease) in lung function and respiratory symptoms. Significant inverse correlations were also found among percentage predicted lung function and respiratory symptoms. The elevated inhalable dust exposures observed in this study can be explained by a combination of factors, including: lack of awareness of potential health effects of wood dust exposure among both management and workers, aging equipment, inadequate and ineffective dust extraction systems or usually none especially for hand held tools, poor maintenance of the ventilation system in some, non-segregation of dusty processes, dry sweeping, and the use of compressed air jets. The determinant-of-exposure analysis confirmed the field observations. The significant determinants of personal inhalable dust exposures (n=163) were found to be: local exhaust ventilation, job title, use of hand-held tools, cleaning method used, use of compressed air, and green or dry wood processed. Type of wood processed was not found to be statistically significant. A majority of workers (~90%) did not wear appropriate respirators approved for wood dust, while the workers who did wear them, used them on average less than 50% of the time. Workers should be protected by controlling dust at its source. When exposure to wood dust cannot be avoided, engineering controls should be supplemented with the use of appropriate personal protective equipment.

Adiposity has been linked to impaired respiratory function in adults but whether the distribution of adipose tissue has a differential effect on pulmonary function is still uncertain. Moreover, in children, the relationship between adiposity and lung dysfunction is not clearly understood. A two-stage multivariate analysis was conducted using data from 5604 Canadians aged 6 to 79 years who participated in the Canadian Health Measures Survey (CHMS). The associations of various anthropometric and skinfold measures with lung function were examined separately in adults and children. After adjustment of covariates, waist circumference and subscapular skinfold thickness showed the strongest inverse associations with FVC and FEV1 in men. In women, BMI and sum of five skinfolds had the largest impact on pulmonary function. FVC and FEV1 in boys were most affected by waist-to-hip ratio and triceps skinfold. In girls, adiposity was not linked to the lung function testing variables. Adiposity measures have differing effects on respiratory function depending on age and sex group.

Several epidemiological studies have revealed an association between particulate matter (PM) pollution and various health effects. Importantly, there is evidence to suggest that individuals with pre-existing respiratory disease, such as asthma, are more sensitive to elevated ground levels of particulate matter as compared to healthy subjects. Among the various sources of PM pollution, diesel powered vehicles have been identified as important contributors. The aim of this thesis was to investigate the airway effects of experimental chamber exposure to diesel exhaust (DE) in healthy and asthmatic subjects, focusing on airway responsiveness, airway inflammation and lung function. To achieve a comprehensive picture of the airway responses to DE, a number of different methods were used, including lung function measurements, methacholine inhalation tests, induced sputum and bronchoscopy. Each subject acted as his/her own control by being exposed both to filtered air and DE in a crossover design. Short term exposure to DE, at a particle concentration (PMi0) of 300 ug/m3, was associated with a clinically significant increase in bronchial hyperresponsiveness in asthmatic subjects. In accordance with the epidemiological data suggesting a 1-4 day lag effect for most health outcomes to PM pollution, the increase was detected one day after DE exposure, indicating a long lasting response to DE in asthmatic airways. Diesel exhaust induced a range of airway inflammatory changes as reflected in induced sputum, bronchoalveolar lavage and bronchial mucosal biopsies. In healthy subjects, DE exposure was associated with an increase in neutrophils and IL-6 in sputum, elevated levels of IL-8 and IL-6 in bronchial wash (BW), enhanced expression of IL-8 and GRO-a in the bronchial epithelium and with increases in P-selectin and VCAM-1 in the airway mucosa. In contrast, asthmatics responded with an increase in IL-6 in sputum and an enhanced expression of IL-10 in the bronchial epithelium following exposure DE. Thus, clear differences were identified between healthy and asthmatic subjects in the inflammatory response to DE. Airway epithelial cells constitute the first line of cellular defence towards inhaled air pollutants and increasing evidence suggests that these cells contribute markedly to the initiation of airway inflammatory responses. The bronchial epithelium was identified to have an important regulatory role in response to diesel exhaust, including the capacity to produce chemoattractant and immunoregulatory proteins associated with development of airway inflammation and bronchial hyperresponsiveness. Lung function measurements revealed that short-term exposure to DE induces an immediate bronchoconstrictive response in both healthy and asthmatic individuals, with significant increases in airway resistance (Raw) following DE exposure. This thesis also investigated the effects of a lower concentration of DE (PMio 100 ug/m3) than previously studied. It was shown that exposure to DE at a concentration corresponding to a PM level that may be encountered in busy traffic situations, was still associated with potentially adverse airway responses in healthy and asthmatic subjects. In summary, the results presented here indicate that short term exposure to diesel exhaust, at high ambient concentrations, has the potential to induce a range of biological events in the airways of healthy and asthmatic subjects. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 2002, härtill 4 uppsatser.</p> / digitalisering@umu

Smooth muscle is a primary determinant of physiology as its ability to contract affords dynamic control of diameter of the hollow organs it encircles including the airways. Mature airway smooth muscle (ASM) cells are phenotypically plastic, enabling them to subserve contractile, proliferative, migratory and secretory roles that relates to its function in health and disease. ASM cells can control airway diameter both acutely, via reversible contraction, and chronically, by driving fixed changes in structure and function properties of the airway wall. However, the scope of research on ASM biology and function has broadened greatly in the past two decades, embracing the now recognized dynamic and multifunctional behavior, but there is always a need to investigate the role of new proteins regulating ASM phenotype in vitro and lung function in vivo. The multimeric dystrophin-glycoprotein complex (DGC) links the extracellular matrix (ECM) and actin cytoskeleton while caveolae form membrane arrays on ASM cells. Using ASM cells and tissues from human and canine and intact mouse for lung physiology, we investigated the role of DGC in phenotype maturation. We also investigated the mechanism for the organization of DGC with caveolae and further tested whether this is functionally important in mobilizing intracellular calcium in ASM cells, contraction of ASM tissue and finally its role in airway physiology. Our data demonstrate that the expression of DGC is an integral feature and a key determinant for phenotype maturation of human ASM cells. Our new data reveals an interaction between caveolin-1 and DGC and indicate that this association, in concert with anchoring to the actin cytoskeleton, underpins the spatial organization of caveolae on the membrane and has a functional role in receptor-mediated calcium release in ASM in vitro, ASM contraction ex vivo and lung function in vivo. Collectively our study indicates that the organization of caveolae and DGC, and its link from ECM to the actin cytoskeleton with in caveolae are a determinant of phenotype and functional properties of ASM, which underpins its role in physiology and pathophysiology of chronic airway diseases such as asthma.

Adiposity has been linked to impaired respiratory function in adults but whether the distribution of adipose tissue has a differential effect on pulmonary function is still uncertain. Moreover, in children, the relationship between adiposity and lung dysfunction is not clearly understood. A two-stage multivariate analysis was conducted using data from 5604 Canadians aged 6 to 79 years who participated in the Canadian Health Measures Survey (CHMS). The associations of various anthropometric and skinfold measures with lung function were examined separately in adults and children. After adjustment of covariates, waist circumference and subscapular skinfold thickness showed the strongest inverse associations with FVC and FEV1 in men. In women, BMI and sum of five skinfolds had the largest impact on pulmonary function. FVC and FEV1 in boys were most affected by waist-to-hip ratio and triceps skinfold. In girls, adiposity was not linked to the lung function testing variables. Adiposity measures have differing effects on respiratory function depending on age and sex group.

Smooth muscle is a primary determinant of physiology as its ability to contract affords dynamic control of diameter of the hollow organs it encircles including the airways. Mature airway smooth muscle (ASM) cells are phenotypically plastic, enabling them to subserve contractile, proliferative, migratory and secretory roles that relates to its function in health and disease. ASM cells can control airway diameter both acutely, via reversible contraction, and chronically, by driving fixed changes in structure and function properties of the airway wall. However, the scope of research on ASM biology and function has broadened greatly in the past two decades, embracing the now recognized dynamic and multifunctional behavior, but there is always a need to investigate the role of new proteins regulating ASM phenotype in vitro and lung function in vivo. The multimeric dystrophin-glycoprotein complex (DGC) links the extracellular matrix (ECM) and actin cytoskeleton while caveolae form membrane arrays on ASM cells. Using ASM cells and tissues from human and canine and intact mouse for lung physiology, we investigated the role of DGC in phenotype maturation. We also investigated the mechanism for the organization of DGC with caveolae and further tested whether this is functionally important in mobilizing intracellular calcium in ASM cells, contraction of ASM tissue and finally its role in airway physiology. Our data demonstrate that the expression of DGC is an integral feature and a key determinant for phenotype maturation of human ASM cells. Our new data reveals an interaction between caveolin-1 and DGC and indicate that this association, in concert with anchoring to the actin cytoskeleton, underpins the spatial organization of caveolae on the membrane and has a functional role in receptor-mediated calcium release in ASM in vitro, ASM contraction ex vivo and lung function in vivo. Collectively our study indicates that the organization of caveolae and DGC, and its link from ECM to the actin cytoskeleton with in caveolae are a determinant of phenotype and functional properties of ASM, which underpins its role in physiology and pathophysiology of chronic airway diseases such as asthma.