| 1. |
- Andersson, Mikael, 1979-
(author)
-
Assessing Physical Activity and Physical Capacity in Subjects with Chronic Obstructive Pulmonary Disease
- 2014
-
Doctoral thesis (other academic/artistic)abstract
- The overall aim of this thesis was to assess measurement properties of methods suitable for screening or monitoring of physical capacity and physical activity in subjects with chronic obstructive pulmonary disease (COPD), and to explore factors associated with physical activity levels.Methods: Four observational studies were conducted. Participants in studies I-III (sample sizes) (n=49, n=15, n=73) were recruited from specialist clinics, and in study IV from a population-based cohort (COPD n=470 and Non-COPD n=659). Psychometric properties of methods assessing physical capacity (study I) and physical activity (study II) were investigated in laboratory settings. Daily physical activity and clinical characteristics were assessed with objective methods (study III) and with subjective methods (study IV).Results: Physical capacity as measured by walking speed during a 30-metre walk test displayed high test-retest correlations (ICC>0.87) and small measurement error. The accuracy for step count and body positions differed between activity monitors and direct observations. In study III 92% of subjects had an activity level below what is recommended in guidelines. Forty five percent of subjects’ activity could be accounted for by clinical characteristics with lung function (22.5%), walking speed (10.1%), quadriceps strength (7.0%) and fat-free mass index (3.0%) being significant predictors. In study IV, low physical activity was significantly more prevalent in COPD subjects from GOLD grade ≥II than among Non-COPD subjects (22.4 vs. 14.6%, p = 0.016). The strongest factors associated with low activity in COPD subjects were a history of heart disease, OR (CI 95%) 2.11 (1.10-4.08) and fatigue, OR 2.33 (1.31-4.13) while obesity was the only significant factor in Non-COPD subjects, OR 2.26 (1.17-4.35).Conclusion: The 30 meter walk test and activity monitors are useful when assessing physical capacity and physical activity, respectively in patients with COPD. Impaired physical activity in severe COPD is related to low lung function, low walking speed, low muscle strength and altered body composition, whereas comorbidities and fatigue are linked to insufficient physical activity in patients with moderately severe COPD.
|
|
| 2. |
- Andersson, Mikael, 1964-
(author)
-
Characterisation of Chromatography Media Aimed for Purification of Biomolecules
- 2014
-
Doctoral thesis (other academic/artistic)abstract
- Chromatography media (resins) are very important for and widely used by the biopharma industry in large scale production of biopharmaceuticals, e.g. monoclonal antibodies. Today there are several hundred biopharmaceuticals released globally on the healthcare market. This thesis discusses various strategies and methods for the characterisation of chemical and functional stability of chromatography media. In addition, various analytical techniques used in these areas were evaluated and applied. Further, more specific physical and chemical characterisation methods were evaluated and applied to explore different properties of various chromatography media.In Papers I-III, established methodologies for performing chemical and functional stability studies were used. Mainly agarose-based chromatography media were investigated. For fast screening of the chemical stability, the total organic carbon analysis technique was evaluated and applied. This technique that measures the carbon leakage from the chromatography media at different conditions, proved to be very suitable and robust. For detection and/or identification of leakage compounds responsible for or for part of the measured carbon leakage, different methods such as (high performance) liquid chromatography and gas chromatography mass spectrometry were used.In Papers IV-VII, different properties (i.e. functional performance, ligand content and surface chemistry) were evaluated for different agarose-based chromatography media. Standard chromatographic methods (ion exchange chromatography) and spectroscopic methods (e.g. Fourier transform infrared spectroscopy and time-of-flight secondary ion mass spectrometry) were evaluated and applied. Chemometric methods were used for efficient evaluation of data.Information of chemical, functional and leakage data of chromatography media are valuable and important for the biopharmaceutical companies to be able to fulfil the regulatory requirements of biopharmaceuticals. In addition, information of various chemical, functional and physical properties of chromatography media is likewise important during development and set up of new biopharmaceutical processes.
|
|
| 3. |
- Appelberg, Jonas, 1964-
(author)
-
Ventilation and Lung Volume During Sleep and in Obstructive Sleep Apnea
- 2003
-
Doctoral thesis (other academic/artistic)abstract
- Obstructive sleep apnea (OSA) appears to affect up to 5% of the population. The extent to what pulmonary function awake and during sleep relates to obstructive breathing and hypoxemia during sleep in these patients is unclear. The aim of this study was to investigate respiratory function in patients with varying degree of snoring and OSA and to analyse regional lung aeration during sleep.In all, 35 healthy subjects and 90 patients with snoring and OSA were studied. The ventilatory response to CO2 (VRCO2) was measured. Lung function tests were performed. A technique based on computed tomography was developed to study lung aeration during sleep.Patients with OSA displayed a higher VRCO2 in comparison to healthy subjects and snorers (p<0.01). Increased closing volume and reduced expiratory reserve volume (ERV) were found in patients with OSA (p<0.001). In a multiple regression analysis, ERV was an independent predictor of nocturnal apnea (R2=0.13; p=0.001) and desaturation frequency (R2=0.11; p<0.01). In both healthy subjects and OSA patients, lung aeration was reduced during sleep by 0.10 ml gas/g tissue in the dorsal lung region (p<0.05 and p<0.01). OSA patients had a significantly lower gas/tissue ratio in comparison to healthy subjects both awake (-23%; p<0.04) and during sleep (-25%; p<0.04). In a univariate analysis, functional residual capacity (FRC) correlated with the change in lung aeration from wakefulness to sleep (r=-0.78; p<0.001). In patients with OSA, ERV (r=-0.69; p<0.05) and sleep time (r=0.69; p<0.05) correlated with the fall in lung aeration. In conclusion, patients with OSA display an increased ventilatory response to CO2, reduced ERV and increased closing volume. ERV predicts nocturnal apnea and desaturation frequency to a similar extent as obesity. Lung aeration is reduced in the dorsal region during sleep and patients with OSA display a lower amount of gas in comparison to healthy subjects. Decrease in lung volumes, promoting airway closure, and loss of muscle tone contributed to the altered lung function during sleep.
|
|
| 4. |
- Cai, Guihong, 1981-
(author)
-
Fungal DNA, Mould, Dampness and Allergens in Schools and Day Care Centers and Respiratory Health
- 2013
-
Doctoral thesis (other academic/artistic)abstract
- Day care centers and schools are important environments for children, but few epidemiological studies exist from these environments. Mould, dampness, fungal DNA and allergens levels in these environments and respiratory health effects in school children were investigated in this thesis. In the day care centers studies, Allergen Avoidance Day care Centers (AADCs) and Ordinary Day care Centers were included. One third of the Swedish day care centers had a history of dampness or mould growth. Total fungal DNA levels were positively associated with risk construction buildings, reported dampness/moulds, rotating heat exchangers, linoleum floors and allergens (cat, dog, horse allergen) levels. The two school studies included secondary schools in Johor Bahru, Malaysia and elementary schools from five European countries (Italy, Denmark, Sweden, Norway, and France) (HESE-study). In Malaysia, 13 % of the pupils reported doctor-diagnosed asthma but only 4 % had asthma medication. The prevalence of wheeze in the last 12 months was 10 % in Malaysia and 13 % in the HESE-study. Cough and rhinitis were common among children in the HESE-study. There were associations between fungal DNA and reported dampness or mould growth. Fungal DNA levels and viable mould (VM) concentration in the classrooms were associated with respiratory symptoms (wheeze, rhinitis, cough, daytime breathlessness) in school children. In the HESE-study, associations were found between total fungal DNA, Aspergillus/Penicillium DNA and respiratory symptoms among children. Moreover, Aspergillus versicolor DNA and Streptomyces DNA were associated with respiratory symptoms in Malaysia and the HESE-study, as well as reduced lung function [forced vitality capacity (FVC) and forced expiratory volume in 1 second (FEV1)] among children in the HESE-study. In conclusion, fungal DNA and pet allergens were common in day care centers and schools and respiratory symptoms in school children were common. The associations between VM concentration and fungal DNA levels in the schools and respiratory health effects in school children indicated a need for improvement of these environments. Moreover, risk constructions should be avoided and buildings should be maintained to avoid dampness and microbial growth. Health relevance of microbial exposure and biodiversity needs to be further studied using molecular methods.
|
|
| 5. |
- Donoso, Felipe, 1984-
(author)
-
Function and morbidity of the esophagus and respiratory system in the growing child with esophageal atresia
- 2020
-
Doctoral thesis (other academic/artistic)abstract
- Background: Esophageal atresia (EA) is a congenital malformation that consists of various degrees of discontinuity of the esophagus and affects about 1:3000 live births. EA is usually corrected at birth with survival rates over 90%, which has shifted the focus towards improvement of associated morbidity and health-related quality of life.The aims of this thesis were to investigate how morbidity in the esophagus and respiratory system in children with EA relates with diagnostic and function tests included in the follow-up programme after EA repair and evaluate the efficacy of the recommended proton pump inhibitor (PPI) prophylaxis.Methods: The study population consists of 169 children treated for EA in the Department of Pediatric Surgery at University Children’s Hospital, Uppsala between 1994 and 2018. The patients participated in the multidisciplinary follow-up programme that was established in 2011 for patients with EA. The thesis is based on four observational studies that investigated the outcome of the patients and generalisability of the results; risk factors for anastomotic strictures and the efficacy of PPI-treatment regimen in reducing its incidence; pulmonary function and risk factors for pulmonary function impairment; and association between ambulatory 24h pH test, endoscopic findings of esophagitis and hiatal hernia, symptoms of gastroesophageal reflux (GER), and histopathological esophagitis. The studies were approved by the Regional Committee for Medical Research Ethics.Results: The demographics and outcome of our study population are comparable with centres of higher caseload, showing low mortality rate but significant morbidity, especially considering anastomotic strictures and patients with long gap EA. Long gap EA, higher birth weight, and anastomotic tension were independent risk factors of anastomotic stricture formation. Prophylactic PPI-treatment did not reduce anastomotic strictures compared with symptomatic PPI-treatment. Respiratory morbidity and obstruction of the airways were common in children and adolescents after EA repair. The risk for pulmonary function impairment increased with lower birth weight and older age at follow-up. Neither ambulatory 24h pH-metry, clinical symptoms of GER nor endoscopic esophagitis were reliable tools to identify histopathological esophagitis in children and adolescents after EA repair and cannot replace esophageal biopsies.Conclusion: The poor correlation between clinical symptoms and morbidity of the esophagus and respiratory system justifies the need of clinical follow-up programmes in patients with EA. A general recommendation to stop prophylactic PPI-treatment after EA repair cannot be supported, however, sufficient evidence is available to support randomised controlled studies.
|
|
| 6. |
- Edell-Gustafsson, Ulla, 1947-
(author)
-
Sleep, psychological symptoms and quality of life in patients undergoing coronary artery bypass grafting
- 1999
-
Doctoral thesis (other academic/artistic)abstract
- In this thesis sleep, psychological symptoms and quality of life (Qol) in patients undergoing coronary artery bypass grafting (CABG) at the University Hospital in Linköping were evaluated. Interviews and 24-hour polysomnography were performed prior to surgery, immediately after surgery and again at one month, with a six-month-follow-up mailed questionnaire. Habitual sleep was evaluated using the Uppsala Sleep Inventory questionnaire and a diary the recorded mornings. The Spielberger State of Anxiety Scale and the Zung's Self-rating Depression Scale were used to measure anxiety and depression, respectively. Physical functional capacity was assessed according to the New York Heart Association's (NYHA) classes and Qol, with the Nottingham Health Profile instrument (NHP).A retrospective evaluation of nurse's documentation about sleep was also performed. In addition, the quality and quantity of sleep were assessed before surgery and in the immediate postoperative period in a pilot study, with a one-month follow-up interview. The results indicated disturbed sleep, and changes in behaviour and mental state after surgery due to fragmented sleep, pain and anxiety.Forty-four patients were examined prior to surgery. The results showed that almost two-fifths experienced too little sleep habitually and 50 % had a combination of at least two sleep problems. Poorer health, higher level of anxiety and increased difficulties maintaining sleep (DMS) were consistent with significantly longer sleep latency, increased fragmented sleep, and reduced stages 3 and 4 and RIM sleep measured by polysomnography. The level of Qol on the NBP was significantly associated with objectively measured sleep.In the immediate period following CABG there is a changed distribution of sleep, with a reduction of nocturnal sleep duration and an increase in daytime sleep, which had almost returned to preoperative values one month after surgery. Qol was significantly improved six months after surgery compared to before surgery.It was noted that patients with a more anxiety prone reactivity during six months following CABG had significantly more sleep disturbances, reduced energy and functional physical capacity, and lower quality of life, compared to those without such reactivity. Significantly more sleep disturbances, reduced energy and lower quality of life were more prominent among those with sadness/depression or cognitive/behavioural fatigue as reactions to sleep loss. A higher degree of cognitive/behavioural fatigue and dysphoria reactions were associated with a higher NYHA class.In conclusion, patients with coronary artery disease have poor quantity and quality of sleep. Increased psychological symptoms in patients with CAD prior to surgery were associated with greater symptoms six months after surgery. Physical functional capacity and quality of life were significantly improved six months after surgery.
|
|
| 7. |
- Ellingsen, Jens, 1979-
(author)
-
Chronic obstructive pulmonary disease: exacerbations and mortality : Prognostic value of biomarkers and comorbidities
- 2024
-
Doctoral thesis (other academic/artistic)abstract
- Background: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. COPD is associated with systemic inflammation, and comorbidities are common. A characteristic feature is acute exacerbations (AECOPDs), i.e., episodes of worsening symptoms. AECOPDs are associated with increased mortality.Aim: To find prognostic risk factors for COPD mortality and AECOPDs, focusing on comorbidities and inflammatory biomarkers.Methods: In Paper I, associations between comorbidities, pharmacological treatment, and mortality were analysed in a real-world cohort of almost 18,000 primary care COPD patients. Data from medical records and national registers were analysed in Cox proportional hazards regressions.Papers II–IV were based on the Tools Identifying Exacerbations (TIE) cohort study of 572 COPD patients recruited from primary and secondary care in three Swedish regions. Participants were invited to three yearly visits, including phlebotomy, spirometry, and health questionnaires.In Paper II, the ability of blood neutrophil-to-lymphocyte ratio (NLR) and eosinophils (B-Eos) to predict AECOPDs was analysed with mixed-effects logistic regressions.In Paper III, the ability of C-reactive protein (CRP), fibrinogen, blood leukocytes (B-Leu), and four blood cell indices to predict AECOPDs was analysed with ordinal logistic regressions.In Paper IV, an algorithm for clinical phenotyping previously developed to predict mortality was studied. The algorithm’s ability to predict AECOPDs and mortality was analysed with Cox proportional hazards regressions; additionally, the identified phenotypes were analysed concerning differences in blood-based inflammatory biomarkers.Results: Several comorbidities, including heart diseases, were associated with increased mortality risk. Some pharmacological treatments were associated with increased or decreased mortality risk (Paper I). NLR, B-Eos, CRP, fibrinogen, and B-Leu (Papers II–III) predicted AECOPDs after adjustment for confounders, whereas other blood cell indices were of limited value (Paper III). The clinical phenotyping algorithm predicted AECOPDs and mortality, and the phenotypes had different patterns of inflammatory biomarkers (Paper IV).Conclusions: Comorbidities, particularly heart diseases, are substantial risk factors for mortality in COPD and should be an integral part of management of COPD patients. NLR, B-Eos, CRP, fibrinogen, and B-Leu are independent predictors of AECOPDs and should be further investigated as parts of, e.g., risk prediction tools. A previously developed algorithm for clinical phenotyping predicts mortality and AECOPDs.
|
|
| 8. |
- Farkhooy, Amir, 1970-
(author)
-
Lung function in relation to exercise capacity in health and disease
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- Background: Exercise capacity (EC) is widely recognized as a strong and independent predictor of mortality and disease progression in various diseases, including cardiovascular and pulmonary diseases. Furthermore, it is generally accepted that exercise capacity in healthy individuals and in patients suffering from cardiovascular diseases is mainly limited by the maximum cardiac output.Objectives: This thesis investigated the impact of different lung function indices on EC in healthy individuals, patients with cardiovascular disease (e.g., pulmonary hypertension (PH)) and patients with pulmonary disease (e.g., chronic obstructive pulmonary disease (COPD)).Methods: The present thesis is based on cross-sectional and longitudinal analyses of patients suffering from COPD, attending pulmonary rehabilitation at Uppsala University Hospital (studies I and II), and healthy men enrolled in the “Oslo ischemia study” (study IV). Study III is a cross-sectional study of patients suffering from PH attending the San Giovanni Battista University Hospital in Turin. EC was assessed using a bicycle ergometer in studies I and IV, with 12-minute walk tests (12MWT) in study II and with 6-minute walk tests (6MWT) in study III. Extensive pulmonary function tests, including diffusing capacity of the lung (DLCO), were performed in studies I-III and dynamic spirometry was used to assess lung function in study IV.Results: DLCO is more closely linked to decreased levels of EC than airway obstruction in COPD patients. Furthermore, the decline in 12MWT over a 5-year period was mainly explained by deterioration in DLCO in COPD patients. Spirometric parameters indicating airway obstruction significantly related to EC and exercise-induced desaturation in PH patients. A significant, but weak association between lung function parameters and EC was found in healthy subjects and this association is strengthened with increasing age.Conclusion: DLCO is the strongest predictor of low EC and EC decline in COPD. In PH, airway obstruction is strongly related to reduced 6MWT. Therefore, extensive analysis of lung function, including measurements of diffusing capacity, along with standard assessment of airway obstruction, gives a more comprehensive assessment of the functional exercise capacity in patients suffering from pulmonary hypertension or COPD. Lung function is also significantly linked to EC even in healthy subjects, lacking evident cardiopulmonary diseases.
|
|
| 9. |
- Frisk, Margot L. A., 1945-
(author)
-
Asthma and respiratory symptoms related to the housing environment
- 2007
-
Doctoral thesis (other academic/artistic)abstract
- The overall aim of this dissertation was to study the housing environment with a focus on indoor climate factors which may maintain or worsen respiratory symptoms among persons with asthma.Quasi-experimental and cross-sectional designs and a case-control approach were used. In Study I data was collected from a consecutive series of patients with asthma (n=21) and in the three other studies from a randomly selected sample, representative of the general population (n=6732). This sample was classified into subgroups (Study II): persons with asthma (n=261), healthy persons (n=5266) and persons with symptoms (n=1205). In Study III persons with asthma (n=49) were compared to persons without asthma (n=48), and the same group, persons with asthma (n=49) was also included in Study IV. Data were gathered using subjective information from diaries and questionnaires as well as objective measurements of medical and environmental factors.Lung function was improved and there was a tendency for the indoor climate to improve after the removal of textile wall-to-wall carpets or the increase of air exchange rate. No statistically significant differences were found in the housing environment when persons with and without asthma were compared. However in some individual homes, environmental factors at levels that could increase symptoms were identified. In single-family houses higher levels of humidity, insufficient ventilation and the occurrence of house dust mites indicated a less favorable indoor climate compared to multi-family houses. Respiratory symptoms attributed to specific environmental exposures increased in both healthy and unhealthy persons when they reported occurrence of indoor climate risk indicators. No statistically significant associations were found between separate risk indicators, identified by a ‘Housing Environmental-index’, or the frequency of indicators and clinical tests. The lack of significant associations may show that the chosen cut-off levels in the index were too high in reference to persons with asthma and further research is needed to establish relevant cut-off levels.In some of the investigated houses there was a need for secondary preventive interventions to improve the indoor climate in order to decrease the exposure of allergens and airway irritants. In this dissertation one aspect of the complex relationship between the person and the environment, i.e. accessibility, has been studied. Further research is needed to address the aspect of usability, i.e. the person’s own evaluation of the degree to which they can be in and use the environment.
|
|
| 10. |
- Fu, Xi, 1984-
(author)
-
Self-rated health and respiratory symptoms among civil aviation pilots : Occupational and non-occupational risk factors
- 2017
-
Doctoral thesis (other academic/artistic)abstract
- There is concern about the indoor environment in aircraft but few stud-ies exist on self-rated health (SRH) and respiratory symptoms among pilots. Occupational and non-occupational risk factors for SRH, respira-tory symptoms and other symptoms among commercial pilots were investigated in this thesis. One cohort study and one prevalence study were performed among pilots in one Scandinavian airline company. Fungal DNA, furry pet allergens and volatile organic compounds of microbial origin (MVOC) were measured on board. Cat (fel d1), dog (Can f1) and horse (Ecu cx) allergens were found in all dust samples and allergen levels were 27-75 times higher in aircraft with textile seats as compared to leather surfaces. The sum of MVOCs in the cabin air was 3.7 times higher than in homes in Uppsala and 2-methyl-1-butanol and 3-methyl-1-butanol concentrations were 15-17 times higher. Asper-gillus/Penicillium DNA and Aspergillus versicolor DNA were more common in aircraft with textile seats. One fifth reported SRH as poor or fair, 62% had fatigue, 46% overweight/obesity and 71% insomnia. Poor or fair SRH was associated with overweight/obesity, lack of exercise, insomnia, low sense of coherence (SOC) and high work demand. Re-covery from work was worse among those with insomnia and low social support at work. Fatigue was more common among young or female pilots and related to insomnia and high work demand. Pilots flying MD80 or Saab 2000 aircraft had less fatigue. Pilots exposed to environmental tobacco (ETS) on board had more eye symptoms and fatigue which were reduced after the ban of smoking (in 1997). Pilots with increased work demand developed more rhinitis, dermal symptoms and fartigue and those with decreased work control developed more eye symptoms. The incidence of doctors’ diagnosed asthma and atopy were 2.4 and 16.6 per 1000 person years, respectively. Pilots changing type of flight got more airway infections. Those reporting decreased work control had a higher incidence of atopy. Risk factors in the home environment included ETS, dampness or mould, window pane condensation in winter and living in houses built after 1975. In conclusion, SRH and respiratory health among pilots are associated with specific occupational and non-occupational risk factors.
|
|
