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Sökning: WFRF:(Zetterström Olle 1940 )

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1.
  • Casas, Rosaura, 1954-, et al. (författare)
  • Downregulation of CXCR6 and CXCR3 in lymphocytes from birch-allergic patients
  • 2008
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 68:3, s. 351-361
  • Tidskriftsartikel (refereegranskat)abstract
    • Preferential expression of chemokine receptors on Th1 or Th2 T-helper cells has mostly been studied in cell lines generated in vitro or in animal models, however, results are less well characterized in humans. We determined T-cell responses through chemokine receptor expression on lymphocytes, and cytokine secretion in plasma from birch-allergic and healthy subjects. The expression of CCR2, CCR3, CCR4, CCR5, CCR7, CXCR3, CXCR4, CXCR6, IL-12 and IL-18R receptors was studied on CD4+ and CD8+ cells from birch-allergic (n = 14) and healthy (n = 14) subjects by flow cytometry. The concentration of IL-4, IL-5, IL-10, IL-12, IFN-γ and TNF-α cytokines was measured in plasma from the same individuals using a cytometric bead array human cytokines kit. The similar expression of CCR4 in T cells from atopic and healthy individuals argues against the use of the receptor as an in vivo marker of Th2 immune responses. Reduced percentages of CD4+ cells expressing IL-18R, CXCR6 and CXCR3 were found in the same group of samples. TNF-α, IFN-γ, IL-10, IL-5, IL-4 and IL-12 cytokines were elevated in samples from allergic individuals. Reduced expression of Th1-associated chemokine receptors together with higher levels of Th1, Th2 and anti-inflammatory cytokines in samples from allergic patients indicate that immune responses in peripheral blood in atopic diseases are complex and cannot be simplified to the Th1/Th2 paradigm. Not only the clinical picture of atopic diseases but also the clinical state at different time points of the disease might influence the results of studies including immunological markers associated with Th1- or Th2-type immune responses. © 2008 The Authors.
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2.
  • Casas, Rosaura, 1954-, et al. (författare)
  • Impaired maturation of monocyte-derived dendritic cells from birch allergic individuals in association with birch-specific immune responses
  • 2007
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:5, s. 591-598
  • Tidskriftsartikel (refereegranskat)abstract
    • Optimal activation of T lymphocytes requires a costimulatory signal provided by the interaction of molecules on the surface of T cells with their ligands expressed on dendritic cells (DC). We investigated whether DC differentiated from monocytes from healthy and birch allergic asthmatic individuals and further maturated by stimulation with cat and birch allergens and LPS differ in their phenotypic receptor expression. Similar expression of DC surface markers, including HLA-DR, CD80, CD86, CD83, CD1a and CD11c, was detected in monocyte-derived DC from allergic and healthy individuals. Cells from healthy donors stimulated either antigen showed a similar activation of the CD80 and double CD80/CD86 costimulatory molecules when compared with non-stimulated cells. In the case of cells from allergic individuals, birch allergen was unable to produce the same increased expression of CD80 alone or in combination with CD80/CD86, in comparison with cells stimulated with cat and LPS. Levels of IL-6, IL-8, IL-10, MCP-1/MCAF and MIP-1β were similar in the supernatant of non-stimulated DC from both groups of subjects. By contrast, the spontaneous secretion of IL-12p70 and TNF-α was higher in the supernatant of DC from healthy subjects when compared with that from allergic individuals. Stimulation with birch and LPS resulted in an increased secretion of IL-12p70 in samples from healthy when compared with that in allergic individuals. The results suggest an impaired specific maturation of DC from birch allergic individuals in association with birch-specific immune responses. Lower secretion of IL-12p70 from birch-stimulated DC from allergic individuals suggests that not only maturation, but also the specific Th1 function of these cells seems to be affected in those individuals.
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3.
  • Dahlén, Barbro, et al. (författare)
  • Specific problems : Asthma induced by aspirin and other non-steroidal anti-inflammatory drugs.
  • 2001. - 2
  • Ingår i: Manual of Asthma management. - London : Harcourt Publishers Limited. - 9780702025297 ; , s. 453-462
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • This unique manual provides comprehensive, practical, and easily accessible guidelines on the key points of asthma management in both adults and children. The updated 2nd edition incorporates the most recent national and international guidelines for the care of asthmatic patients, with vital information on how to address clinical issues while emphasizing essential basic science in diagnosing, managing, and treating asthma.
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  • Ferdousi, Hosne Ara, 1957-, et al. (författare)
  • Bronchial hyper-responsiveness predicts the development of mild clinical asthma within 2 yr in school children with hay-fever
  • 2005
  • Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 16:6, s. 478-486
  • Tidskriftsartikel (refereegranskat)abstract
    • In children with mild asthma, symptoms are not always apparent. Therefore, results of tests play an important role for the diagnosis. First, to investigate whether children with bronchial hyper-responsiveness (BHR) but no symptoms of asthma in 1992 had developed clinical asthma at follow up in 1994. The second aim was to find out the diagnostic properties of tests for asthma/allergic inflammation, using either doctor diagnosed asthma (DDA), self-assessed symptoms of asthma or iso-capnic hyperventilation of cold air (IHCA), as the standard, to diagnose asthma in a group of children with hay fever. Twenty-eight children with pollinosis, 12 of them with a history of asthma for the first time during the season 1992, were studied during the birch pollen season and in the autumn of 1994. During both periods, the bronchial hyper-reactivity was estimated by methacholine bronchial provocation tests (MBPT), bronchial variability by peak expiratory flow rate variability, subjective symptoms of asthma by visual analogue scale (VAS) and bronchial inflammation by serum and urine levels of inflammatory mediators. In 1994 IHCA was added during both seasons. Eight of 16 children with BHR but without clinical asthma in 1992 had developed asthma in 1994, 14 of 16 reacted to IHCA and 13 to MBPT. All 12 children with DDA in 1992 had still asthma in 1994 and 14 children with BHR in 1992 had persistent BHR in 1994. Of 23 children with BHR in 1992, 17 had DDA in 1994 and all maintained their BHR. Furthermore, 20 of them reacted to IHCA in 1994. In 1994, 24 of 28 hay-fever children had a positive IHCA tests and 24 had positive MBPT. In relation to VAS, the sensitivity of IHCA and MBPT to predict present asthma was high, but the specificity low, whereas the specificity of most other tests was high, but based on few individuals. In relation to DDA both the IHCA test (65–80%) and the MBPT test (79–85%) had a high sensitivity and it was three to six times more likely to find a positive test among asthmatics than in non-asthmatics. Children with hay fever without clinical asthma have a high risk of developing asthma within 2 yr. In relation to DDA, inhalation of cold air and the MBPT showed a high sensitivity.
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6.
  • Ferdousi, Hosne Ara, 1957-, et al. (författare)
  • Seasonal differences of peak expiratory flow rate variability and mediators of allergic inflammation in non-atopic adolescents
  • 2001
  • Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 12:5, s. 238-246
  • Tidskriftsartikel (refereegranskat)abstract
    • Variations in peak expiratory flow (PEF) and serum eosinophil mediators were studied in healthy adolescents. Twenty-five boys and 31 girls, 11–16 years of age (mean age 14.3 years), were selected and investigated during the birch pollen season of 1995; 45 were also investigated during the autumn of the same year. The PEF was measured twice daily and eosino-phil mediators in serum and in urine were measured by radioimmunoassay (RIA) once during the birch pollen season and once in autumn. The type values of the daily PEF variation, expressed in amplitude percentage mean, were 6.4 and 3.9%, mean values were 7.35 and 6.74%, and the 95th percentiles were 18 and 14%, during the birch pollen season and autumn, respectively. The 95th percentiles were 41 and 38 µg/l for serum eosinophil cationic protein (s-ECP), 74 and 62 µg/l for serum eosinophil protein X (s-EPX), 987 and 569 µg/l for serum myeloperoxidase (s-MPO), and 165 and 104 µg/mmol for urinary eosinophil protein X/urinary creatinine (u-EPX/u-creatinine), during the birch pollen season and autumn, respectively. The levels of the eosinophil mediators decreased significantly from May (n = 56) to November (n = 45), for s-ECP from a median value of 14 µg/l to 7 µg/l (p= 0.001), for s-EPX from a median value of 28 µg/l to 20 µg/l (p= 0.001), and for the neutrophil mediator, s-MPO, from a median value of 440 g/l to 292 g/l (p< 0.001). The PEF variability decreased significantly (p= 0.037), from spring (n = 55; median 8%, 95% confidence interval [CI] 7.8–10.19) to autumn (n = 44; median 6%, 95% CI 6.1–8.9). A significant correlation was found between the levels of s-ECP and s-EPX (rs = 0.7, p< 0.001), between s-ECP and s-MPO (rs = 0.6, p< 0.001), between s-EPX and s-MPO (rs = 0.4, p< 0.005), and between s-EPX and u-EPX/u-creatinine (rs = 0.6, p< 0.0001), in the birch pollen season (n = 56) and in the autumn (n = 45). There was a positive correlation found in PEF variability between the two seasons (n = 43; rs = 0.5, p= 0.0006). No other correlation was found between PEF variability and any other parameters. The difference in the levels of eosinophil mediators between seasons in non-atopic, healthy children is unexplained. Normal limits for mediators were higher and PEF variability was almost the same as has been reported in adults. When using normal values, seasonal influences should be considered.
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  • Haahtela, T, et al. (författare)
  • Formoterol as needed with or without budesonide in patients with intermittent asthma and raised NO levels in exhaled air : A SOMA study
  • 2006
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 28:4, s. 748-755
  • Tidskriftsartikel (refereegranskat)abstract
    • Patients with mild intermittent asthma sometimes show signs of inflammation, and guidelines suggesting bronchodilator therapy alone as needed may be questioned. The current study compared as-needed use of a rapid-acting β2-agonist with as-needed use of a β2-agonist and corticosterold combination as the only medication in asthma patients with intermittent symptoms. A total of 92 nonsmoking asthma patients (of 187 screened) using only an inhaled β2-agonist as needed (28 males, 64 females, mean age 37 yrs, mean forced expiratory volume in one second (FEV1) 101% predicted, mean reversibility 6.5% pred and fractional exhaled nitric oxide (FeNO) ≥20 parts per billion (ppb)) were randomised to treatment with formoterol (Oxis® Turbuhaler®) 4.5 μg as needed (n=47) or budesonide/formoterol (Symbicort® Turbuhaler®) 160/4.5 pg as needed (n=45) in a double-blind, parallel-group 24-week study. The primary variable of efficacy was change in FeNO. Baseline FeNO was 60 ppb and 59 ppb in the budesonide/formoterol and formoterol groups, respectively. Mean reductions in FeNO in the budesonide/formoterol and formoterol groups were 18.2 ppb and 2.8 ppb, respectively (95% confidence interval (CI) 7.5-23.5 ppb). The reduction in the budesonide/formoterol group occurred during the first 4 weeks of treatment and remained at this low level. Mean FEV1 increased by 1.8% pred normal value in the budesonide/formoterol group and decreased by 0.9% pred normal value in the formoterol group (95% Cl -4.7 - -0.7). In the budesonide/formoterol group, use of ≥4 inhalations-day-1 of study medication was seen on 21 treatment days compared with 74 in the formoterol group. In conclusion, as-needed use of an inhaled corticosteroid together with a rapid-acting bronchodilator may be more beneficial than a β2-agonist alone in patients with intermittent asthma and signs of airway inflammation. The long-term benefits are unknown. Copyright © ERS Journals Ltd 2006.
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10.
  • Mai, Xiaomei, 1969-, et al. (författare)
  • Urinary inflammatory mediators and inhalation of hypertonic saline in children
  • 2005
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 60:1, s. 60-64
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The inflammatory mechanisms of hypertonic saline-induced bronchoconstriction are not well understood. Methods: Seventeen asthmatics with (n = 11) and without bronchial hyperresponsiveness (BHR) (n = 6) and 18 randomly selected nonatopic nonasthmatic controls without BHR were evaluated by urine samples collected before and 1 h after hypertonic saline provocation test. Histamine, 11β-PGF2α, and LTE4 were analysed by enzyme immunoassay (EIA) and eosinophil protein X (EPX) by radioimmunoassay (RIA). Results: The levels of leukotriene E4 (LTE4) increased significantly after the challenge tests, both in the asthmatics (median: 354 pg/mg pre-challenge vs. 628 pg/mg post-challenge, P = 0.05) and in the controls (median: 294 pg/mg pre-challenge vs. 460 pg/mg post-challenge, P < 0.01). The levels of histamine also increased significantly in the latter (median: 299 μmol/mg pre-challenge vs. 569 μmol/mg post-challenge, P = 0.03). However, the levels of 11β-PGF2α and EPX did not change significantly after the challenge tests either in the asthmatics or in the controls. Conclusions: The inhalation of hypertonic saline increased urinary excretion of LTE4 both in the asthmatics and in the controls. The slight increase of leukotrienes was enough to induce airway obstruction in some of the asthmatics, because of the hyperresponsiveness in their airways.
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11.
  • Nyström Kronander, Ulla, 1957-, et al. (författare)
  • Prevalence and incidence of asthma related to waist circumference and BMI in a Swedish community sample
  • 2004
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 98:11, s. 1108-1116
  • Tidskriftsartikel (refereegranskat)abstract
    • Both asthma and obesity have become more common in affluent societies during the recent decades and several studies have shown a correlation between the presence of asthma and obesity. In order to further study this association we have investigated a population from a community in southern Sweden, where almost all inhabitants had their body indices measured as part of a study on diabetes at a primary care centre. An asthma unit working with a structured care programme for asthma was available. This organisation enabled us to study whether body mass index and waist circumference was associated with having or developing asthma. There was a significant association between both overweight, increased waist circumference and asthma, P
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13.
  • Roel, Eduardo, 1950-, et al. (författare)
  • Clinically diagnosed childhood asthma and follow-up of symptoms in a Swedish case control study
  • 2005
  • Ingår i: BMC Family Practice. - : Springer Science and Business Media LLC. - 1471-2296. ; 6
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Childhood asthma has risen dramatically not only in the western societies and now forms a major and still increasing public health problem. The aims of this study were to follow up at the age of ten the patterns of asthma symptoms and associations among children with a clinically diagnosed asthma in a sizeable urban-rural community and to in compare them with demographic controls using a standardised questionnaire. Methods: In a defined region in Sweden with a population of about 150 000 inhabitants, all children (n = 2 104) born in 1990 were recorded. At the age of seven all primary care and hospital records of the 1 752 children still living in the community were examined, and a group of children (n = 191) was defined with a well-documented and medically confirmed asthma diagnosis. At the age of ten, 86 % of these cases (n = 158) and controls (n = 171) completed an ISAAC questionnaire concerning asthma history, symptoms and related conditions. Results: Different types of asthma symptoms were highly and significantly over-represented in the cases. Reported asthma heredity was significantly higher among the cases. No significant difference in reported allergic rhinitis or eczema as a child was found between cases and controls. No significant difference concerning social factors or environmental exposure was found between case and controls. Among the control group 4.7 % of the parents reported that their child actually had asthma. These are likely to be new asthma cases between the age of seven and ten and give an estimated asthma prevalence rate at the age of ten of 15.1 % in the studied cohort. Conclusion: A combination of medical verified asthma diagnosis through medical records and the use of self-reported symptom through the ISAAC questionnaire seem to be valid and reliable measures to follow-up childhood asthma in the local community. The asthma prevalence at the age of ten in the studied birth cohort is considerably higher than previous reports for Sweden. Both the high prevalence figure and allowing the three-year lag phase for further settling of events in the community point at the complementary roles of both hospital and primary care in the comprehensive coverage and control of childhood asthma in the community. © 2005 Roel et al, licensee BioMed Central Ltd.
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  • Xu, Junyang, et al. (författare)
  • Apoptotic eosinophils in sputum from asthmatic patients correlate negatively with levels of IL-5 and eotaxin
  • 2007
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 101:7, s. 1447-1454
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Eosinophilic inflammation of the airways is a key characteristic of asthma. A defect in eosinophil apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. Objective: Our purpose was to examine whether the occurrence of apoptotic eosinophils in induced sputum from asthmatic patients correlate with interleukin (IL)-5 and eotaxin. Methods: Thirty stable and 30 exacerbated asthmatic patients were recruited. Twenty healthy subjects were enrolled as a control group. Induced sputum was obtained from asthmatic patients and from control subjects. The number of apoptotic eosinophils in sputum was assessed by flow cytometry. In sputum supernatant, eosinophil cationic protein (ECP) was measured by sensitive radioimmunoassay, and IL-5 and eotaxin by sandwich enzyme linked immunosorbant assay. Results: Levels of eosinophils, apoptotic eosinophils, IL-5, ECP and eotaxin from asthmatic patients were higher than those from healthy subjects. Thirty exacerbated asthmatics showed higher proportions of eosinophils (median 29.3%, range 13.4%-40.9%), more detectable levels of IL-5 (50.44, 32.99-67.01 pg/ml) and eotaxin (644.6, 197.4-937.7 pg/ml) in their sputum than the patients with stable asthma (P < 0.05). There were significant inverse correlations between the levels of sputum IL-5 and the proportion of sputum eosinophil apoptosis in patients with exacerbated and stable asthma (r = - 0.85 and -0.79, P < 0.01 and P < 0.05, respectively). Also inverse correlations were found between the levels of eotaxin and the proportion of sputum eosinophil apoptosis in exacerbated (r = - 0.85, P < 0.01), or stable asthma (r = - 0.69, P < 0.05). Additional positive corrlations between the levels of sputum IL-5 and eotaxin in either exacerbatated (r = 0.93, P < 0.01) or stable asthma (r = 0.82, P < 0.05) were observed. Conclusions: Apoptosis of eosinophils might be suppressed by proinflammatory cytokines and chemokines such as IL-5 and eotaxin leading to their accumulation in the lung. Stimulation of eosinophils in airway with IL-5 and eotaxin may play a crucial role in allergic inflammation. © 2007 Elsevier Ltd. All rights reserved.
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  • Zetterström, Olle, 1940-, et al. (författare)
  • Comparable morning versus evening administration of once-daily mometasone furoate dry powder inhaler
  • 2008
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 102:10, s. 1406-1411
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The control of daytime and nighttime symptoms is an important measure of effectiveness of asthma therapy, especially, when administered once-daily. Objective: To evaluate the efficacy of evening and morning administrations of mometasone furoate administered via a dry powder inhaler (MF-DPI) 400 μg once-daily (QD) to show equivalence. Methods: Open-label, randomized, parallel-group study in adult patients with mild to moderate asthma with a ≥3-month history of ICS use. Patients received MF-DPI 400 μg QD either in the morning (AM) or evening (PM) for 12 weeks. The primary measure was the change in asthma symptoms from baseline to week 12. Secondary outcomes included response to treatment, adherence, inhaler device evaluation, use of rescue medication, urinary cortisol levels, and differential white blood cell count. Results: A total of 1537 patients were randomized, the efficacy population comprised 543 and 479 patients in the MF-DPI QD morning and evening groups, respectively. Mean improvements from baseline in daytime symptom scores at week 12 with morning and evening administration of MF-DPI 400 μg were -0.11 ± 0.59 and -0.12 ± 0.68, respectively (95% CI, -0.095 to 0.061) and the corresponding improvements in nighttime symptom scores were -0.08 ± 0.59 and -0.07 ± 0.50, respectively (95% CI, -0.067 to 0.068). Use of rescue medication was the same in both groups (1 puff/day). MF-DPI QD was well tolerated regardless of time of administration. Conclusions: This open-label study did not identify differences between morning and evening dosing of MF-DPI 400 μg QD. A better effect of evening dosing compared to morning dosing found in previous double-blind placebo-controlled studies could not be confirmed. © 2008 Elsevier Ltd. All rights reserved.
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20.
  • Zetterström, Olle, 1940- (författare)
  • Compliance och astmabehandling.
  • 2000
  • Ingår i: Incitament. - 1103-503X. ; 7, s. 664-667
  • Tidskriftsartikel (populärvet., debatt m.m.)
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21.
  • Zetterström, Olle, 1940-, et al. (författare)
  • Improved asthma control with budesonide/formeterol in a single inhaler, compared with budesonide alone
  • 2001
  • Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 18:2, s. 262-268
  • Tidskriftsartikel (refereegranskat)abstract
    • Budesonide/formoterol in a single inhaler was compared with budesonide alone, and with concurrent administration of budesonide and formoterol from separate inhalers, in patients with asthma, not controlled with inhaled glucocorticosteroids alone. In this 12-week, double-blind, randomized, double-dummy study, 362 adult asthmatics (forced expiratory volume in one second 73.8% of predicted, inhaled glucocorticosteroid dose 960 ╡g╖day-1) received single inhaler budesonide/formoterol (Symbicort « Turbuhaler «) 160/4.5 ╡g, two inhalations b.i.d., or corresponding treatment with budesonide, or budesonide plus formoterol via separate inhalers. There was a greater increase in morning peak expiratory flow (PEF) with single-inhaler (35.7 L╖min-1) and separate-inhaler (32.0 L╖min-1) budesonide and formoterol, compared with budesonide alone (0.2 L╖min-1, p<0.001, both comparisons), the effect was apparent after 1 day (p<0.001 versus budesonide, both comparisons). Similarly, evening PEF, use of rescue medication, total asthma symptom scores and percentage of symptom-free days improved more with both single inhaler and separate inhaler therapy than with budesonide alone, as did asthma control days (~15% more, p<0.001 versus budesonide, both comparisons, with a marked increase in the first week). All treatments were well tolerated and the adverse event profile was similar in all three treatment groups. It is concluded that single inhaler therapy with budesonide and formoterol is a clinically effective and well-tolerated treatment for patients with asthma that is not fully controlled by inhaled glucocorticosteroids alone.
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  • Zetterström, Olle, 1940-, et al. (författare)
  • The whole story : treatment outcomes with Symbicort?
  • 2002
  • Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 96:Supplement A, s. 29-35
  • Tidskriftsartikel (refereegranskat)abstract
    • Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort(R) (budesonide and formoterol in a single inhaler), a treatment that provides better control of asthma compared with budesonide alone. While the prescribing costs of Symbicort(R) were found to be higher than for budesonide alone, these were partially offset by reduced costs due to fewer asthma exacerbations and a reduced need for other medications. Combined long-term therapy with budesonide and formoterol also improves patient quality of life compared with budesonide alone. Two other factors associated with asthma treatment success and cost-effectiveness are patient/physician education and good patient adherence to prescribed therapy. The introduction of a single inhaler that is easy to use in simple treatment regimens may improve patient adherence to prescribed medication, thus resulting in improved asthma control and fewer exacerbations. Treatment with Symbicort(R) is more cost-effective than treatment with budesonide alone.
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24.
  • Ädelroth, E, et al. (författare)
  • Recombinant humanized mAb-E25, an anti-IgE mAb, in birch pollen-induced seasonal allergic rhinitis
  • 2000
  • Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 106:2, s. 253-259
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Allergic rhinitis is a common condition often requiring treatment. Objective: We evaluated whether recombinant humanized (rhu)mAb-E25, a recombinant humanized construct of a murine antibody that binds to circulating IgE, could control symptoms and reduce intake of concomitant medication in seasonal allergic rhinitis (SAR) induced by birch pollen if given subcutaneously in a dose schedule predicted to reduce serum free IgE levels below 25 ng/mL. Methods: We randomly assigned 251 adult subjects with a history of SAR and a positive skin test response to birch pollen to receive 300 mg of rhumAb-E25 or placebo given 2 or 3 times during the season, depending on baseline IgE levels. The primary efficacy variable was the subject's average daily nasal symptom severity score (sneezing, itching, runny, and stuffy nose) from diary data collected over the double-blind treatment period. Secondary efficacy variables included the average number of rescue antihistamine tablets per day, the proportion of days with any SAR medication use, and rhinoconjunctivitis-specific quality of life (QOL). Results: Significant between-treatment differences in favor of rhumAb-E25 were observed in average daily nasal symptom severity scores, the average number of tablets of rescue antihistamines per day, the proportion of days with any SAR medication use, and all domains of QOL. Serum-free IgE levels were markedly lower in rhumAb-E25-treated subjects and were associated with clinical effectiveness. Recombinant humanized mAb-E25 was well tolerated. No anti-rhumAb-E25 antibodies were detected. Conclusion: Compared with placebo, rhumAb-E25 was safe and effective in controlling birch pollen-induced SAR symptoms, with less concomitant medication use and improved QOL. This study shows the therapeutic potential of anti-IgE antibody in SAR.
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