| 1. |
- Söderström, A, et al.
(author)
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A large Escherichia coli O157 outbreak in Sweden associated with locally produced lettuce.
- 2008
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In: Foodborne pathogens and disease. - : Mary Ann Liebert Inc. - 1556-7125 .- 1535-3141. ; 5:3, s. 339-49
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Journal article (peer-reviewed)abstract
- In 2005 a large outbreak of verotoxin-producing Escherichia coli (VTEC) occurred in Sweden. Cases were interviewed and cohort and case-control studies were conducted. Microbiological investigations were performed using polymerase chain reaction (PCR) to detect the Shiga-like toxin (Stx) genes followed by cultivation and pulsed-field gel electrophoresis. A total of 135 cases were recorded, including 11 cases of hemolytic uremic syndrome. The epidemiological investigations implicated lettuce as the most likely source of the outbreak, with an OR of 13.0 (CI 2.94-57.5) in the case-control study. The lettuce was irrigated by water from a small stream, and water samples were positive for Stx 2 by PCR. The identical VTEC O157 Stx 2 positive strain was isolated from the cases and in cattle at a farm upstream from the irrigation point. An active surveillance and reporting system was crucial and cooperation between all involved parties was essential for quickly identifying the cause of this outbreak. Handling of fresh greens from farm to table must be improved to minimize the risk of contamination.
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| 2. |
- Düringer, Caroline, et al.
(author)
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Agonist-specific patterns of beta(2)-adrenoceptor responses in human airway cells during prolonged exposure.
- 2009
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In: British Journal of Pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 158, s. 169-179
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Journal article (peer-reviewed)abstract
- Background and purpose: beta(2)-Adrenoceptor agonists (beta(2)-agonists) are important bronchodilators used in the treatment of asthma and chronic obstructive pulmonary disease. At the molecular level, beta(2)-adrenergic agonist stimulation induces desensitization of the beta(2)-adrenoceptor. In this study, we have examined the relationships between initial effect and subsequent reduction of responsiveness to restimulation for a panel of beta(2)-agonists in cellular and in vitro tissue models. Experimental approach: beta(2)-Adrenoceptor-induced responses and subsequent loss of receptor responsiveness were studied in primary human airway smooth muscle cells and bronchial epithelial cells by measuring cAMP production. Receptor responsiveness was compared at equi-effective concentrations, either after continuous incubation for 24 h or after a 1 h pulse exposure followed by a 23 h washout. Key findings were confirmed in guinea pig tracheal preparations in vitro. Key results: There were differences in the reduction of receptor responsiveness in human airway cells and in vitro guinea pig trachea by a panel of beta(2)-agonists. When restimulation occurred immediately after continuous incubation, loss of responsiveness correlated with initial effect for all agonists. After the 1 h pulse exposure, differences between agonists emerged, for example isoprenaline and formoterol induced the least reduction of responsiveness. High lipophilicity was, to some extent, predictive of loss of responsiveness, but other factors appeared to be involved in determining the relationships between effect and subsequent loss of responsiveness for individual agonists. Conclusions and implications: There were clear differences in the ability of different beta(2) agonists to induce loss of receptor responsiveness at equi-effective concentrations.
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| 3. |
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| 4. |
- Löfdahl, Claes-Göran, et al.
(author)
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The European Respiratory Society study on chronic obstructive pulmonary disease (EUROSCOP): recruitment methods and strategies
- 1998
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In: Respiratory Medicine. - 1532-3064. ; 92:3, s. 467-472
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Journal article (peer-reviewed)abstract
- The European Respiratory Society's study on chronic obstructive pulmonary disease (EUROSCOP) is a multicentre study performed initially in 12 countries to assess the effect of 3 years' treatment with inhaled corticosteroids on lung function decline in smokers with chronic obstructive pulmonary disease (COPD). It aimed at recruiting 50 subjects in 50 European centres. This study discusses the most successful, countrywise, recruitment strategies, an important issue since many multicentre European studies may follow in the future. The total number of recruited subjects was 2147 in 39 participating centres. In total, at least 25,000 screening spirometries were performed, and about 80,000 hospital records were checked. The most effective way of recruiting subjects was to screen subjects by spirometry after mass media campaigns (eight out of nine countries). Others used workplace screenings and different types of population survey, and only a few centres successfully recruited participants by hospital records. Inclusion criteria were slightly changed upon low initial accrual rate. Initial surveys in one country, where 2405 subjects were screened by spirometry, gave an important indication for the change of the inclusion criteria. Extension of the upper age limit from 60 to 65 yr considerably improved recruitment, as did a change of the upper limit of FEV1 from below 80% predicted normal to below 100% predicted normal, while maintaining the FEV1/VC ratio below 70%. A tremendous effort is needed to recruit individuals with preclinical COPD, but this is certainly feasible with adequate strategies adjusted to each country.
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| 5. |
- Nakagomi, S, et al.
(author)
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Substrate bias amplification of a SiC junction field effect transistor with a catalytic gate electrode
- 2004
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In: Materials Science Forum. - 0255-5476 .- 1662-9752. ; 457-460, s. 1507-1510
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Journal article (peer-reviewed)abstract
- The drain current-voltage (I-d-V-D) characteristics of a chemical gas sensor based on a catalytic metal insulator silicon carbide field effect transistor (SiC-FET) were measured in H-2 or O-2 ambient while applying negative substrate bias, V-sub, at temperatures up to 600degreesC. An increase in the negative V-sub gives rise to an increase of the drain voltage at a given drain current level, which can be used to adjust the device baseline. In addition, we found that the difference in drain voltage between H-2 and O-2 ambient at a given drain current level (the gas response to H-2) increases for an increased negative substrate bias. By modifying an equation for the drain current in a SIT (static induction transistor), the influence of substrate bias on the amplification factors, mu and eta, was estimated using the temperature dependence of the I-d-V-D characteristics. From this, the effect of substrate bias on the gas response to hydrogen was calculated. It was clarified that the increase in the gas response caused by the negative substrate bias is due to a substrate bias dependence of the amplification factor of the short channel device.
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| 6. |
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| 7. |
- Pauwels, R A, et al.
(author)
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Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. European Respiratory Society Study on Chronic Obstructive Pulmonary Disease
- 1999
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In: New England Journal of Medicine. - 0028-4793. ; 340:25, s. 1948-1953
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Journal article (peer-reviewed)abstract
- BACKGROUND: Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in patients with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 microg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years. RESULTS: Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the budesonide group, as compared with a decline of 81 ml per year in the placebo group (P<0.001). From nine months to the end of treatment, the FEV1 declined at similar rates in the two groups (P=0.39). Ten percent of the subjects in the budesonide group and 4 percent of those in the placebo group had skin bruising (P<0.001). Newly diagnosed hypertension, bone fractures, postcapsular cataracts, myopathy, and diabetes occurred in less than 5 percent of the subjects, and the diagnoses were equally distributed between the groups. CONCLUSIONS: In patients with mild COPD who continue smoking, the use of inhaled budesonide is associated with a small one-time improvement in lung function but does not appreciably affect the long-term progressive decline.
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| 8. |
- Zafari, Zafar, et al.
(author)
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Individualized prediction of lung-function decline in chronic obstructive pulmonary disease
- 2016
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In: CMAJ. - : CMA Joule Inc.. - 0820-3946. ; 188:14, s. 1004-1010
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Journal article (peer-reviewed)abstract
- Background: The rate of lung-function decline in chronic obstructive pulmonary disease (COPD) varies substantially among individuals. We sought to develop and validate an individualized prediction model for forced expiratory volume at 1 second (FEV1) in current smokers with mild-to-moderate COPD. Methods: Using data from a large long-term clinical trial (the Lung Health Study), we derived mixed-effects regression models to predict future FEV1 values over 11 years according to clinical traits. We modelled heterogeneity by allowing regression coefficients to vary across individuals. Two independent cohorts with COPD were used for validating the equations. Results: We used data from 5594 patients (mean age 48.4 yr, 63% men, mean baseline FEV1 2.75 L) to create the individualized prediction equations. There was significant between-individual variability in the rate of FEV1 decline, with the interval for the annual rate of decline that contained 95% of individuals being -124 to -15 mL/yr for smokers and -83 to 15 mL/yr for sustained quitters. Clinical variables in the final model explained 88% of variation around follow-up FEV1. The C statistic for predicting severity grades was 0.90. Prediction equations performed robustly in the 2 external data sets. Interpretation: A substantial part of individual variation in FEV1 decline can be explained by easily measured clinical variables. The model developed in this work can be used for prediction of future lung health in patients with mild-to-moderate COPD.
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| 9. |
- Ahlström, A., et al.
(author)
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No major differences in perinatal and maternal outcomes between uninterrupted embryo culture in time-lapse system and conventional embryo culture
- 2023
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In: Human Reproduction. - : Oxford University Press. - 0268-1161 .- 1460-2350. ; 38:12, s. 2400-2411
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Journal article (peer-reviewed)abstract
- STUDY QUESTION: Is embryo culture in a closed time-lapse system associated with any differences in perinatal and maternal outcomes in comparison to conventional culture and spontaneous conception?SUMMARY ANSWER: There were no significant differences between time-lapse and conventional embryo culture in preterm birth (PTB, <37 weeks), low birth weight (LBW, >2500 g) and hypertensive disorders of pregnancy for singleton deliveries, the primary outcomes of this study.WHAT IS KNOWN ALREADY: Evidence from prospective trials evaluating the safety of time-lapse incubation for clinical use show similar embryo development rates, implantation rates, and ongoing pregnancy and live birth rates when compared to conventional incubation. Few studies have investigated if uninterrupted culture can alter risks of adverse perinatal outcomes presently associated with IVF when compared to conventional culture and spontaneous conceptions.STUDY DESIGN, SIZE, DURATION: This study is a Swedish population-based retrospective registry study, including 7379 singleton deliveries after fresh embryo transfer between 2013 and 2018 from selected IVF clinics. Perinatal outcomes of singletons born from time-lapse-cultured embryos were compared to singletons from embryos cultured in conventional incubators and 71 300 singletons from spontaneous conceptions. Main perinatal outcomes included PTB and LBW. Main maternal outcomes included hypertensive disorders of pregnancy (pregnancy hypertension and preeclampsia).PARTICIPANTS/MATERIALS, SETTING, METHODS: From nine IVF clinics, 2683 singletons born after fresh embryo transfer in a time-lapse system were compared to 4696 singletons born after culture in a conventional incubator and 71 300 singletons born after spontaneous conception matched for year of birth, parity, and maternal age. Patient and treatment characteristics from IVF deliveries were cross-linked with the Swedish Medical Birth Register, Register of Birth Defects, National Patient Register and Statistics Sweden. Children born after sperm and oocyte donation cycles and after Preimplantation Genetic testing cycles were excluded. Odds ratio (OR) and adjusted OR were calculated, adjusting for relevant confounders.MAIN RESULTS AND THE ROLE OF CHANCE: In the adjusted analyses, no significant differences were found for risk of PTB (adjusted OR 1.11, 95% CI 0.87-1.41) and LBW (adjusted OR 0.86, 95% CI 0.66-1.14) or hypertensive disorders of pregnancy; preeclampsia and hypertension (adjusted OR 0.99, 95% CI 0.67-1.45 and adjusted OR 0.98, 95% CI 0.62-1.53, respectively) between time-lapse and conventional incubation systems. A significantly increased risk of PTB (adjusted OR 1.31, 95% CI 1.08-1.60) and LBW (adjusted OR 1.36, 95% CI 1.08-1.72) was found for singletons born after time-lapse incubation compared to singletons born after spontaneous conceptions. In addition, a lower risk for pregnancy hypertension (adjusted OR 0.72 95% CI 0.53-0.99) but no significant difference for preeclampsia (adjusted OR 0.87, 95% CI 0.68-1.12) was found compared to spontaneous conceptions. Subgroup analyses showed that some risks were related to the day of embryo transfer, with more adverse outcomes after blastocyst transfer in comparison to cleavage stage transfer.LIMITATIONS, REASONS FOR CAUTION: This study is retrospective in design and different clinical strategies may have been used to select specific patient groups for time-lapse versus conventional incubation. The number of patients is limited and larger datasets are required to obtain more precise estimates and adjust for possible effect of additional embryo culture variables.WIDER IMPLICATIONS OF THE FINDINGS: Embryo culture in time-lapse systems is not associated with major differences in perinatal and maternal outcomes, compared to conventional embryo culture, suggesting that this technology is an acceptable alternative for embryo incubation.
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| 10. |
- Andersson, F, et al.
(author)
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Adding formoterol to budesonide in moderate asthma--health economic results from the FACET study
- 2001
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In: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 95:6, s. 505-512
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Journal article (peer-reviewed)abstract
- The FACET (Formoterol and Corticosteroid Establishing Therapy) study established that there is a clear clinical benefit in adding formoterol to budesonide therapy in patients who have persistent symptoms of asthma despite treatment with low to moderate doses of an inhaled corticosteroid. We combined the clinical results from the FACET study with an expert survey on average resource use in connection with mild and severe asthma exacerbations in the U.K., Sweden and Spain. The primary objective of this study was to assess the health economics of adding the inhaled long-acting beta2-agonist formoterol to the inhaled corticosteroid budesonide in the treatment of asthma. The extra costs of adding the inhaled beta2-agonist formoterol to the corticosteroid budesonide in asthmatic patients in Sweden were offset by savings from reduced use of resources for exacerbations. For Spain the picture was mixed. Adding formoterol to low dose budesonide generated savings, whereas for moderate doses of budesonide about 75% of the extra formoterol costs could be recouped. In the U.K., other savings offset about half of the extra cost of formoterol. All cost-effectiveness ratios are within accepted cost-effectiveness ranges reported from previous studies. If productivity losses were included, there were net savings in all three countries, ranging from Euro 267-1183 per patient per year. In conclusion, adding the inhaled, long-acting beta2-agonist formoterol to low-moderate doses of the inhaled corticosteroid budesonide generated significant gains in all outcome measures with partial or complete offset of costs. Adding formoterol to budesonide can thus be considered to be cost-effective.
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| 11. |
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| 12. |
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| 13. |
- Fattahi, Fatemeh, et al.
(author)
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Atopy is a risk factor for respiratory symptoms in COPD patients: results from the EUROSCOP study
- 2013
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In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 14
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Journal article (peer-reviewed)abstract
- Background: The pathogenesis of COPD is complex and remains poorly understood. The European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP) investigated long-term effects of budesonide; 18% of the COPD participants were atopic. So far effects of atopy on the long-term course of COPD have not been elucidated. Methods: Factors related to the presence of atopy (positive phadiatop) in 1277 mild-to-moderate COPD patients participating in EUROSCOP were analysed using regression analysis. Incidence and remission of respiratory symptoms during 3-year follow-up were analysed using generalised estimating equations models, and association of atopy with lung function decline using linear mixed effects models. Results: Independent predisposing factors associated with the presence of atopy were: male gender (OR: 2.21; 95% CI: 1.47-3.34), overweight/obese (OR: 1.41; 95% CI: 1.04-1.92) and lower age (OR: 0.98; 95% CI: 0.96-0.99). Atopy was associated with a higher prevalence of cough (OR: 1.71; 95% CI: 1.26-2.34) and phlegm (OR: 1.50; 95% CI: 1.10-2.03), but not with lung function levels or FEV1 decline. Atopic COPD patients not treated with budesonide had an increased incidence of cough over time (OR: 1.79, 95% CI: 1.03-3.08, p = 0.038), while those treated with budesonide had increased remission of cough (OR: 1.93, 95% CI: 1.11-3.37, p = 0.02) compared to non-atopic COPD patients. Conclusions: Atopic COPD patients are more likely male, have overweight/obesity and are younger as compared with non-atopic COPD patients. Atopy in COPD is associated with an increased incidence and prevalence of respiratory symptoms. If atopic COPD patients are treated with budesonide, they more often show remission of symptoms compared to non-atopic COPD patients who are treated with budesonide. We recommend including atopy in the diagnostic work-up and management of COPD.
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| 14. |
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| 15. |
- Juniper, E F, et al.
(author)
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Asthma quality of life during 1 year of treatment with budesonide with or without formoterol
- 1999
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In: European Respiratory Journal. - 1399-3003. ; 14:5, s. 1038-1043
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Journal article (peer-reviewed)abstract
- The Formoterol and Corticosteroids Establishing Therapy (FACET) study has provided the first opportunity to examine the long-term effects of inhaled steroids and long-acting beta2-agonists on asthma-specific quality of life. The objectives of the present study were to: evaluate the effects of long-term (1 yr) formoterol and increasing doses of budesonide on asthma quality of life; 2) to determine whether initial improvements in quality of life are sustained when improvements in clinical indices persist; and 3) to evaluate the long-term relationship between changes in clinical indices and changes in quality of life. Of the 852 asthmatic adults enrolled, 470 from five countries participated in this quality of life evaluation. After a 4-week run-in on 1,600 microg budesonide, patients were randomized to either 200 microg (Bud200) or 800 microg budesonide (Bud800) in combination with either 24 microg formoterol (F) or placebo daily for 1 yr. The Asthma Quality of Life Questionnaire (AQLQ) was completed and conventional clinical indices measured at enrolment and randomization and on seven occasions during the following 12 months. During the run-in, there was an improvement in AQLQ score (changes (delta) in overall score approximately 0.50; p<0.0001). After randomization, there was a further improvement in the Bud800+F group (delta=0.21; p=0.028). One month post-randomization, improvements in all groups stabilized and were sustained throughout the 12 months in a pattern very similar to that observed for the conventional clinical indices. The correlation of individual patient changes in clinical indices and changes in AQLQ score during the 12-month randomized period were weak to moderate (maximum r=0.51). Improvements in quality of life, which were greatest in the 800 microg budesonide plus 24 microg formoterol group, were sustained throughout the 12 months in a similar manner to the clinical indices. Long-term changes in conventional clinical indices cannot be used to predict the effect of treatment on individual patient experience.
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| 16. |
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| 17. |
- Kraen, M., et al.
(author)
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Fibroblast growth factor 23 is an independent marker of COPD and is associated with impairment of pulmonary function and diffusing capacity
- 2021
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In: Respiratory Medicine. - : Elsevier BV. - 0954-6111. ; 182
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Journal article (peer-reviewed)abstract
- Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone that in recent years has been reported to have significant effects on numerous tissues. Chronic obstructive pulmonary disease (COPD) is associated with hypophosphatemia but the evidence for elevated plasma levels of FGF23 in COPD subjects is ambiguous. Recently, FGF23 has even been shown to be involved in the inflammatory pathways activated in COPD, so FGF23 could be a novel biomarker for COPD and impairment of pulmonary function. The purpose was thus to explore the association of FGF23 with COPD and measures of pulmonary function. This was a cross sectional study of 450 subjects who underwent spirometry, body plethysmography, determination of diffusing capacity (DL,CO) and biomarker analysis of FGF23, interleukin (IL)-1 receptor antagonist, IL-6 and IL-8. Forty-four participants were excluded due to missing data or renal impairment (eGFR <45 mL/min/m2). Spirometry identified 123 subjects with COPD. FGF23 levels were elevated in COPD subjects compared to non COPD subjects, and this remained significant after adjustment for age, sex and smoking habits (OR = 1.6, p = 0.02). Linear regression showed significant relationships between FGF23 and FEV1 (β = −0.15, p = 0.003), RV/TLC (β = 0.09, p = 0.05) and DL, CO (β = −0.24, p < 0.001). In conclusion we found that plasma levels of FGF23 are elevated in COPD subjects even when adjusting for traditional risk factors. Furthermore, FGF23 is associated with impairment in lung function as measured by FEV1 and DL,CO. Further studies are needed to establish whether FGF23 could serve as a novel biomarker of COPD and emphysema development.
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| 18. |
- Kraen, M., et al.
(author)
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Matrix Metalloproteinases in COPD and atherosclerosis with emphasis on the effects of smoking
- 2019
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:2
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Journal article (peer-reviewed)abstract
- Background Matrix metalloproteinases (MMP´s) are known biomarkers of atherosclerosis. MMP´s are also involved in the pathophysiological processes underlying chronic obstructive pulmonary disease (COPD). Cigarette smoking plays an important role in both disease states and is also known to affect the concentration and activity of MMP´s systemically. Unfortunately, the epidemiological data concerning the value of MMP´s as biomarkers of COPD and atherosclerosis with special regards to smoking habits are limited. Methods 450 middle-aged subjects with records of smoking habits and tobacco consumption were examined with comprehensive spirometry, carotid ultrasound examination and biomarker analysis of MMP-1, -3, -7, -10 and -12. Due to missing data 33 subjects were excluded. Results The remaining 417 participants were divided into 4 different groups. Group I (n = 157, no plaque and no COPD), group II (n = 136, plaque but no COPD), group III (n = 43, COPD but no plaque) and group IV (n = 81, plaque and COPD). Serum levels of MMP-1,-7,-10-12 were significantly influenced by smoking, and MMP-1, -3, -7 and-12 were elevated in subjects with COPD and carotid plaque. This remained statistically significant for MMP-1 and-12 after adjusting for traditional risk factors. Conclusion COPD and concomitant plaque in the carotid artery were associated with elevated levels of MMP-1 and -MMP-12 even when adjusting for risk factors. Further studies are needed to elucidate if these two MMP´s could be useful as biomarkers in a clinical setting. Smoking was associated with increased serum levels of MMP´s (except for MMP-3) and should be taken into account when interpreting serum MMP results.
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| 19. |
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| 20. |
- Larsson, Kjell, et al.
(author)
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Så blir KOL-vården bättre
- 2011
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 108:35, s. 1604-1605
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Journal article (peer-reviewed)
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| 21. |
- Löfdahl, Claes-Göran, et al.
(author)
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Possible protection by inhaled budesonide against ischaemic cardiac events in mild COPD.
- 2007
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 29:6, s. 1115-1119
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Journal article (peer-reviewed)abstract
- Epidemiological studies have indicated that chronic obstructive pulmonary disease (COPD) may be associated with an increased incidence of ischaemic cardiac events. The current authors performed a post hoc analysis of the European Respiratory Society's study on Chronic Obstructive Pulmonary Disease (EUROSCOP); a 3-yr, placebo-controlled study of an inhaled corticosteroid budesonide 800 pg-day-1 in smokers (mean age 52 yrs) with mild COPD. The current study evaluates whether long-term budesonide treatment attenuates the incidence of ischaernic cardiac events, including angina pectorls, myocardial infarction, coronary artery disorder and myocardial ischaemia. Among the 1,175 patients evaluated for safety, 49 (4.2%) patients experienced 60 ischaernic cardiac events. Patients treated with budesonide had a significantly lower incidence of ischaernic cardiac events (18 out of 593; 3.0%) than those receiving placebo (31 out of 582; 5.3%). The results of the present study support the hypothesis that treatment with inhaled budesonide reduces ischaernic cardiac events in patients with mild chronic obstructive pulmonary disease.
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| 22. |
- Löfdahl, Claes-Göran, et al.
(author)
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Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients
- 1999
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In: BMJ. - 0959-8138. ; 319:7202, s. 87-90
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To determine the ability of montelukast, a leukotriene receptor antagonist, to allow tapering of inhaled corticosteroids in clinically stable asthmatic patients. DESIGN: Double blind, randomised, placebo controlled, parallel group study. After a single blind placebo run in period, during which (at most) two inhaled corticosteroids dose decreases occurred, qualifying, clinically stable patients were allocated randomly to receive montelukast (10 mg tablet) or matching placebo once daily at bedtime for up to 12 weeks. SETTING: 23 academic asthma centres in United States, Canada, and Europe. PARTICIPANTS: 226 clinically stable patients with chronic asthma receiving high doses of inhaled corticosteroids (113 randomised to montelukast and 113 to placebo). INTERVENTIONS: Every 2 weeks, the inhaled corticosteroids dose was tapered, maintained, or increased (rescue) based on a standardised clinical score. MAIN OUTCOME MEASURES: Last tolerated dose of inhaled corticosteroids. RESULTS: Compared with placebo, montelukast allowed significant (P=0. 046) reduction in the inhaled corticosteroid dose (montelukast 47% v placebo 30%; least square mean difference 17.6%, 95% confidence interval 0.3 to 34.8). Fewer patients on montelukast (18 (16%) v 34 (30%) placebo, P=0.01) required discontinuation because of failed rescue. CONCLUSIONS: Montelukast reduces the need for inhaled corticosteroids among patients requiring moderate to high doses of corticosteroid to maintain asthma control.
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| 23. |
- Miravitlles, Marc, et al.
(author)
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The Relationship Between 24-Hour Symptoms and COPD Exacerbations and Healthcare Resource Use : Results from an Observational Study (ASSESS)
- 2016
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In: COPD: Journal of Chronic Obstructive Pulmonary Disease. - : Informa UK Limited. - 1541-2555 .- 1541-2563. ; 13:5, s. 561-568
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Journal article (peer-reviewed)abstract
- This observational study assessed the relationship between nighttime, early-morning and daytime chronic obstructive pulmonary disease (COPD) symptoms and exacerbations and healthcare resource use. COPD symptoms were assessed at baseline in patients with stable COPD using a standardised questionnaire during routine clinical visits. Information was recorded on exacerbations and healthcare resource use during the year before baseline and during a 6-month follow-up period. The main objective of the analysis was to determine the predictive nature of current symptoms for future exacerbations and healthcare resource use. 727 patients were eligible (65.8% male, mean age: 67.2 years, % predicted forced expiratory volume in 1 second: 52.8%); 698 patients (96.0%) provided information after 6 months. Symptoms in any part of the day were associated with a prior history of exacerbations (all p <0.05) and nighttime and early-morning symptoms were associated with the frequency of primary care visits in the year before baseline (both p <0.01). During follow-up, patients with baseline symptoms during any part of the 24-hour day had more exacerbations than patients with no symptoms in each period (all p <0.05); there was also an association between 24-hour symptoms and the frequency of primary care visits (all p ≤ 0.01). Although there was a significant association between early-morning and daytime symptoms and exacerbations during follow-up (both p <0.01), significance was not maintained when adjusted for potential confounders. Prior exacerbations were most strongly associated with future risk of exacerbation. The results suggest 24-hour COPD symptoms do not independently predict future exacerbation risk.
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| 24. |
- Mitchell, G., et al.
(author)
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Measurement of the turbulence intensities in a flat plate boundary layer
- 2003
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In: Proc. of Turbulence, Heat and Mass Transfer, 4th Int. Symp., Antalya, Turkey. ; , s. 261-268
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Conference paper (other academic/artistic)abstract
- Detailed information on the flow in the vicinity of the wall is of particular interest for various types of flow and heat transfer predictions and of basic importance for turbulence modelling. The time-averaged value can be determined accurately by a number of methods, however time resolved part is rather more difficult to measure. In this work, the results of measurements of the wall shear stress fluctuations in a turbulent boundary layer are presented. Described experiments are performed for the case of zero-pressure gradient flow on a flat plate at Reynolds number, Reθ, ranging from about 1000 to 6000. A main feature of this work is that the miniature wall mounted hot wires fabricated with very high accuracy were implemented in the measurements.
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| 25. |
- Montnemery, Peter, et al.
(author)
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Prevalence of obstructive lung diseases and respiratory symptoms in southern Sweden
- 1998
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In: Respiratory Medicine. - 1532-3064. ; 92:12, s. 1337-1345
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Journal article (peer-reviewed)abstract
- The prevalence of obstructive lung diseases is increasing in Scandinavia and worldwide. The reasons for this are not known. The prevalence varies between countries but also between different areas within the same country. In northern Europe a north-south gradient and also an east-west gradient have been proposed. To our knowledge this is the first comprehensive epidemiological study concerning obstructive lung diseases and respiratory symptoms in the southern part of Sweden. The prevalence of bronchial asthma, chronic bronchitis/emphysema, respiratory symptoms, smoking habits and medication in a random sample of 12,071 adults aged 20-59 years was assessed in a postal survey with a slightly modified questionnaire previously used in central and northern Sweden (the OLIN Studies). The questionnaire was based on the British Medical Research Council (BMRC) questionnaire. We also compared the prevalence figures of asthma found in the postal survey with those reported in the medical records in a part of the study area. After two reminders, the response rate was 70.1% (n = 8469); 33.8% of the responders were smokers. Among younger (20-39 year age group) individuals, smoking was most common in women, whereas in those aged 40-59 years, smoking was more common in men. In all, 469 subjects (5.5%) stated that they had asthma, 41.6% of whom reported a family history of asthma compared to 15.9% of the study sample not reporting asthma. Of all subjects reporting asthma, 60.1% (n = 282) answered that they used asthma drugs. Inhaled steroids were used by 20.7%. Chronic bronchitis and/or emphysema was reported by 4.6% (n = 392), 28.6% of whom reported a family history of chronic bronchitis or emphysema compared to 6.8% of the study sample not reporting chronic bronchitis. The most common respiratory symptom in the study population was 'phlegm when coughing' reported by 15.1% (n = 1279). Our data show a prevalence of self-reported asthma of 5.5% compared with 7% reported by Lunback et al. in northern Sweden, which indicates a north-south gradient.
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| 26. |
- Nana, A, et al.
(author)
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High-dose inhaled budesonide may substitute for oral therapy after an acute asthma attack
- 1998
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In: Journal of Asthma. - 0277-0903. ; 35:8, s. 647-655
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Journal article (peer-reviewed)abstract
- Patients attending the emergency room with acute asthma, participating in a study comparing salbutamol (albuterol in the United States) via a dry powder inhaler (Turbuhaler) with pressurized metered-dose inhaler (pMDI), were included in this 1-week follow-up study with the aim of assessing whether inhaled budesonide via Turbuhaler may be an alternative to prednisolone tablets after an acute asthma attack. Eighty-one patients with a mean age of 38 years and forced expiratory volume in 1 sec (FEV1) of 64% predicted normal value after treatment with salbutamol were randomized in this double-blind, double-dummy, parallel-group study. The doses given were budesonide 1600 microg b.i.d. or prednisolone in daily doses from 40 mg (day 1) decreased to 5 mg (day 7). FEV1 was recorded before and after the 7-day treatments and peak expiratory flow (PEF) morning and evening, clinical symptoms (visual analogue scale 0-100), and doses of rescue medication (terbutaline Turbuhaler 0.25 mg/dose) were recorded daily. The mean increase in FEV1 from baseline to day 7 was 17.3% in the budesonide Turbuhaler group and 17.6% in the prednisolone group. Mean values of morning PEF increased from day 1 to day 7 by 67 L/min in the budesonide Turbuhaler group and by 57 L/min in the prednisolone group (not significant). There were no statistically significant differences between the groups in clinical symptoms and in the number of doses of rescue medication. Because of disease deterioration, five patients in the Turbuhaler group and three in the prednisolone group needed additional symptomatic as well as corticosteroid treatment. Inhaled budesonide in high doses may be a substitute for oral therapy as follow-up treatment after an acute asthma attack.
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| 27. |
- Pauwels, Romain A, et al.
(author)
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Effect of inhaled formoterol and budesonide on exacerbations of asthma. Formoterol and Corticosteroids Establishing Therapy (FACET) International Study Group
- 1997
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In: New England Journal of Medicine. - 0028-4793. ; 337:20, s. 1405-1411
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Journal article (peer-reviewed)abstract
- BACKGROUND: The role of long-acting, inhaled beta2-agonists in treating asthma is uncertain. In a double-blind study, we evaluated the effects of adding inhaled formoterol to both lower and higher doses of the inhaled glucocorticoid budesonide. METHODS: After a four-week run-in period of treatment with budesonide (800 microg twice daily), 852 patients being treated with glucocorticoids were randomly assigned to one of four treatments given twice daily by means of a dry-powder inhaler (Turbuhaler): 100 microg of budesonide plus placebo, 100 microg of budesonide plus 12 microg of formoterol, 400 microg of budesonide plus placebo, or 400 microg of budesonide plus 12 microg of formoterol. Terbutaline was permitted as needed. Treatment continued for one year; we compared the frequency of exacerbations of asthma, symptoms, and lung function in the four groups. A severe exacerbation was defined by the need for oral glucocorticoids or a decrease in the peak flow to more than 30 percent below the base-line value on two consecutive days. RESULTS: The rates of severe and mild exacerbations were reduced by 26 percent and 40 percent, respectively, when formoterol was added to the lower dose of budesonide. The higher dose of budesonide alone reduced the rates of severe and mild exacerbations by 49 percent and 37 percent, respectively. Patients treated with formoterol and the higher dose of budesonide had the greatest reductions -- 63 percent and 62 percent, respectively. Symptoms of asthma and lung function improved with both formoterol and the higher dose of budesonide, but the improvements with formoterol were greater. CONCLUSIONS: In patients who have persistent symptoms of asthma despite treatment with inhaled glucocorticoids, the addition of formoterol to budesonide therapy or the use of a higher dose of budesonide may be beneficial. The addition of formoterol to budesonide therapy improves symptoms and lung function without lessening the control of asthma.
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| 28. |
- Pietrow, A. G. M., et al.
(author)
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A comparative study of two X2.2 and X9.3 solar flares observed with HARPS-N : Reconciling Sun-as-a-star spectroscopy and high-spatial resolution solar observations in the context of the solar-stellar connection
- 2024
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In: Astronomy and Astrophysics. - 0004-6361 .- 1432-0746. ; 682
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Journal article (peer-reviewed)abstract
- Context. Stellar flares cannot be spatially resolved, which complicates ascertaining the physical processes behind particular spectral signatures. Due to their proximity to Earth, solar flares can serve as a stepping stone for understanding their stellar counterparts, especially when using a Sun-as-a-star instrument and in combination with spatially resolved observations.Aims. We aim to understand the disk-integrated spectral behaviors of a confined X2.2 flare and its eruptive X9.3 successor, which had energies of 2.2 × 1031 erg and 9.3 × 1031 erg, respectively, as measured by Sun-as-a-star observations with the High Accuracy Radial velocity Planet Searcher for the Northern hemisphere (HARPS-N).Methods. The behavior of multiple photospheric (Na D1 & D2, Mg I at 5173 Å, Fe I at 6173 Å, and Mn I at 4031 Å) and chromospheric (Ca II H & K, Hα, Hβ, and He ID3) spectral lines were investigated by means of activity indices and contrast profiles. A number of different photospheric lines were also investigated by means of equivalent widths, and radial velocity measures, which were then related to physical processes directly observed in high-resolution observations made with the Swedish 1-m Solar Telescope (SST) and the Atmospheric Imaging Assembly (AIA) on board of the Solar Dynamics Observatory (SDO).Results. Our findings suggest a relationship between the evolving shapes of contrast profile time and the flare locations, which assists in constraining flare locations in disk-integrated observations. In addition, an upward bias was found in flare statistics based on activity indices derived from the Ca II H & K lines. In this case, much smaller flares cause a similar increase in the activity index as that produced by larger flares. Hα-based activity indices do not show this bias and are therefore less susceptible to activity jitter. Sodium line profiles show a strongly asymmetric response during flare activity, which is best captured with a newly defined asymmetrical sodium activity index. A strong flare response was detected in Mn I line profiles, which is unexpected and calls for further exploration. Intensity increases in Hα, Hβ, and certain spectral windows of AIA before the flare onset suggest their potential use as short-term flare predictors.
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| 29. |
- Plymoth, Amelie, et al.
(author)
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Rapid proteome analysis of bronchoalveolar lavage samples of lifelong smokers and never-smokers by micro-scale liquid chromatography and mass spectrometry
- 2006
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In: Clin Chem.. - : Oxford University Press (OUP). ; 52:4, s. 671-679
-
Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to determine whether relative qualitative and quantitative differences in protein expression could be related to smoke exposure or smoke-induced airway inflammation. We therefore explored and characterized the protein components found in bronchoalveolar lavage (BAL) fluid sampled from either lifelong smokers or never-smokers. METHODS: BAL fluid samples obtained by bronchoscopy from 60-year-old healthy never-smokers (n = 18) and asymptomatic smokers (n = 30) were analyzed in either pooled or individual form. Initial global proteomic analysis used shotgun digestion approaches on unfractionated BAL fluid samples (after minimal sample preparation) and separation of peptides by gradient (90-min) liquid chromatography (LC) coupled with on-line linear ion trap quadropole mass spectrometry (LTQ MS) for identification and analysis. RESULTS: LTQ MS identified 481 high- to low-abundance proteins. Relative differences in patterns of BAL fluid proteins in smokers compared with never-smokers were observed in pooled and individual samples as well as by 2-dimensional gel analysis. Gene ontology categorization of all annotated proteins showed a wide spectrum of molecular functions and biological processes. CONCLUSIONS: The described method provides comprehensive qualitative proteomic analysis of BAL fluid protein expression from never-smokers and from smokers at risk of developing chronic obstructive pulmonary disease. Many of the proteins identified had not been detected in previous studies of BAL fluid; thus, the use of LC-tandem MS with LTQ may provide new information regarding potentially important patterns of protein expression associated with lifelong smoking.
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| 30. |
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| 31. |
- Tattersfield, Anne E, et al.
(author)
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Comparison of formoterol and terbutaline for as-needed treatment of asthma: a randomised trial
- 2001
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In: The Lancet. - 1474-547X. ; 357:9252, s. 257-261
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Journal article (peer-reviewed)abstract
- BACKGROUND: Asthma guidelines recommend that long-acting inhaled beta-agonists should be used as maintenance therapy for patients with asthma inadequately controlled on an inhaled corticosteroid. We studied the safety and efficacy of the long-acting beta-agonist formoterol compared with terbutaline, each taken as needed, in patients with moderate to severe asthma. METHODS: Patients were taking an inhaled corticosteroid (mean dose 870 microg daily) and had a forced expiratory volume in 1 s (FEV1) of at least 50% predicted (mean 74%). Those requiring an inhaled beta-agonist three to eight times a day during the study run-in period (362 of 621 who started) were randomly assigned formoterol 4.5 microg or terbutaline 0.5 mg as needed by Turbuhaler in daily doses up to 54 microg and 6 mg, respectively, for 12 weeks in a double-blind, parallel-group study. Analyses were by intention to treat. FINDINGS: The 362 randomised patients (157 men, 205 women) had a mean age of 47 years. Patients taking formoterol had a longer time to their first severe asthma exacerbation (relative-risk ratio 0.55 [95% CI 0.34-0.89]), took fewer inhalations of study drug, and had larger increases in FEV1 (5%) and morning and evening peak expiratory flow (mean difference in increase 11 L/min and 8 L/min) than those taking terbutaline. No safety issues were identified. INTERPRETATION: When taken as needed, formoterol 4.5 microg provided better asthma control than terbutaline 0.5 mg in patients requiring moderate doses of relief medication despite inhaled corticosteroid treatment. Safety studies should be extended to a wider population of patients with asthma.
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| 32. |
- Tattersfield, A E, et al.
(author)
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Exacerbations of asthma: a descriptive study of 425 severe exacerbations. The FACET International Study Group
- 1999
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In: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 160:2, s. 594-599
-
Journal article (peer-reviewed)abstract
- The identification, prevention, and prompt treatment of exacerbations are major objectives of asthma management. We looked at change in PEF, symptoms, and use of rescue beta-agonists during the 425 severe exacerbations that occurred during a 12-mo parallel group study (FACET) in which low and high doses of budesonide with and without formoterol were compared in patients with asthma. Oral corticosteroids were prescribed for severe exacerbations, the main study end point, defined as the need for a course of oral corticosteroids (n = 311) or a reduction in morning PEF of > 30% on two consecutive days. PEF, symptoms, and bronchodilator use over the 14 d before and after the exacerbation were obtained from diary cards. Exacerbations were characterized by a gradual fall in PEF over several days, followed by more rapid changes over 2 to 3 d; an increase in symptoms and rescue beta-agonist use occurred in parallel, and both the severity and time course of the changes were similar in all treatment groups. Exacerbations identified by the need for oral corticosteroids were associated with more symptoms and smaller changes in PEF than those identified on the basis of PEF criteria. Female sex was the main patient characteristic associated with an increased risk of having a severe exacerbation. Exacerbations may be characterized predominantly by change in symptoms or change in PEF, but the pattern was not affected by the dose of inhaled corticosteroid or by whether the patient was taking formoterol.
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| 33. |
- Watson, L, et al.
(author)
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Predictors of COPD symptoms: does the sex of the patient matter?
- 2006
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 28:2, s. 311-318
-
Journal article (peer-reviewed)abstract
- Although chronic obstructive pulmonary disease (COPD) patients frequently report symptoms, it is not known which factors determine the course of symptoms over time and if these differ according to the sex of the patient. The current study investigated predictors for presence, development and remission of COPD symptoms in 816 males and 312 females completing 3-yr-follow-up in the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP). The following were included in generalised estimating equations logistic regression analyses: explanatory variables of treatment; pack-yrs smoking; age, forced expiratory volume in one second % predicted (FEV1 % pred); annual increase in FEV1 and number of cigarettes smoked; body mass index; and phadiatop. Interaction terms of sex multiplied by explanatory variables were tested. Over 3 yrs, similar proportions of males and females reported symptoms. In males only, higher FEV1 % pred was associated with reduction in new symptoms of wheeze and dyspnoea, and symptom prevalence was reduced with annual FEV1 improvement and phlegm prevalence reduced with budesonide treatment (odds ratio 0.66; 95% confidence interval 0.52-0.83). Additionally an increase in the number of cigarettes smoked between visits increased the risk of developing phlegm (1.40 (1.14-1.70)) and wheeze (1.24 (1.03-1.51)) in males but not females. The current study shows longitudinally that symptom reporting is similar by sex. The clinical course of chronic obstructive pulmonary disease can differ by sex, as males show greater response to cigarette exposure and treatment.
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| 34. |
- Watson, L, et al.
(author)
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Predictors of lung function and its decline in mild to moderate COPD in association with gender: Results from the Euroscop study
- 2006
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In: Respiratory Medicine. - : Elsevier BV. - 1532-3064 .- 0954-6111. ; 100:4, s. 746-753
-
Journal article (peer-reviewed)abstract
- Background: There is increasing appreciation of gender differences in COPD but scant data whether risk factors for tow lung function differ in men and women. We analysed data from 3 years follow-up in 178 women and 464 men with COPD, participants in the Euroscop Study who were smokers unexposed to inhaled corticosteroids. Methods: Explanatory variables of gender, age, starting age and pack-years smoking, respiratory symptoms, FEV1%FVC and FEV1%IVC (clinically important measures of airway obstruction), body mass index (BMI), and change in smoking were included in multiple linear regression models with baseline and change in postbronchodilator FEV1 as dependent variables. Results: Reduced baseline FEV1 was associated with respiratory symptoms in men only. Annual decline in FEV1 was not associated with respiratory symptoms in either men or women, and was 55 ml less in obese men (BMI >= 30 kg/m(2)) than men having normal BMI, an effect not seen in women. It was 32ml faster in women with FEV1%FVC < median than women with less airway obstruction, a larger difference than in men (8ml per year). It was 17.7ml/year faster when increasing the daily number of cigarettes by 10 in men only, but not significantly greater than in women. Conclusion: Respiratory symptoms were associated with reduced baseline FEV, in men with COPD. In men, obesity was associated with reduced decline and increasing the number of cigarettes smoked with increased decline in lung function. In women more severe airway obstruction was associated with accelerated decline.
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| 35. |
- Wingbrant, Helena, et al.
(author)
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MISiCFET chemical sensors for applications in exhaust gases and flue gases
- 2002
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In: Materials Science Forum. - 0255-5476 .- 1662-9752. ; 433-4, s. 953-956
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Journal article (peer-reviewed)abstract
- A chemical gas sensor based on a silicon carbide field effect transistor with a catalytic gate metal has been under development for a number of years. The choice of silicon carbide as the semiconductor material allows the sensor to operate at high temperatures, for more than 6 months in flue gases at 300degreesC and for at least three days at 700degreesC. The chemical inertness of silicon carbide and a buried gate design makes it a suitable sensor technology for applications in corrosive environments such as exhaust gases and flue gases from boilers. The selectivity of the sensor devices is established through the choice of type and structure of the gate metal as well as the operation temperature. In this way NH3 sensors with low cross sensitivity to NOx have been demonstrated as potential sensors for control of selective catalytic reduction (SCR) of NOx by urea injection into diesel exhausts. Here we show that sensors with a porous platinum or iridium gate show different temperature ranges for NH3 detection. The hardness of the silicon carbide makes it for example more resistant to water splash at cold start of a petrol engine than existing technologies, and a sensor which can control the air to fuel ratio, before the exhaust gases are heated, has been demonstrated. Silicon carbide sensors are also tested in flue gases from boilers. Efficient regulation of the combustion in a boiler will decrease fuel consumption and reduce emissions.
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| 36. |
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