| 1. |
- Carlson, Marie, et al.
(författare)
-
Degranulation of eosinophils from pollen-atopic patients with asthma is increased during pollen season
- 1992
-
Ingår i: Journal of Allergy and Clinical Immunology. - 0091-6749 .- 1097-6825. ; 89:1 Pt 1, s. 131-139
-
Tidskriftsartikel (refereegranskat)abstract
- The secretion of granule proteins from eosinophils and neutrophils was studied in isolated cells, obtained from 11 pollen-atopic patients with asthma, twice during and twice outside pollen season. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase (MPO) were measured by means of specific radioimmunoassay (RIA). Eosinophils from the pollen-atopic patients obtained during pollen season released significantly more (p less than 0.02) ECP and EPX than cells from the same patients obtained before pollen season. The released amount of ECP and EPX was correlated (r = 0.54; p less than 0.003) to the total pollen count. The release of MPO from neutrophils was only raised (p less than 0.01) at the end of the pollen season. Serum concentrations of ECP and EPX and blood eosinophil counts were significantly raised (p less than 0.002, p less than 0.001, and p less than 0.009, respectively) before pollen season and increased further at the end of the pollen season. There were no changes in lung function during pollen season and consequently no discernible relationships to eosinophil and neutrophil degranulation. We conclude that eosinophils and, to some extent, neutrophils from birch pollen-atopic subjects have an increased propensity to secrete their granule proteins during a pollen season. We suggest that these cells have been primed as a consequence of allergen exposure.
|
|
| 2. |
- Carlson, Marie, et al.
(författare)
-
Secretion of granule proteins from eosinophils and neutrophils is increased in asthma
- 1991
-
Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 87:1 Pt 1, s. 27-33
-
Tidskriftsartikel (refereegranskat)abstract
- The activity of eosinophil and neutrophil granulocytes with respect to secretion of granule proteins was studied in 30 patients with asthma and with varying severity of their disease. Granulocytes were stimulated with serum-opsonized Sephadex particles, and the released amount of eosinophil cationic protein (ECP), eosinophil protein X (EPX), and myeloperoxidase was measured by means of specific radioimmunoassays. Eosinophils from patients with asthma released significantly more (p less than 0.001) ECP and EPX after 20 minutes of incubation than cells from control subjects without asthma. The release of myeloperoxidase from neutrophils was also somewhat higher (p less than 0.03). The serum concentrations of ECP and EPX were also significantly increased (p less than 0.001) in the group with asthma. No significant relationships were found between clinical variables and the secretory activity of either eosinophils or neutrophils. We conclude that eosinophils and, to some extent, neutrophils from subjects with asthma have an increased propensity to release their granule proteins, which we suggest is a consequence of priming of these cells.
|
|
| 3. |
- Dahlén, Inger, et al.
(författare)
-
Changes in inflammatory markers following treatment of acute exacerbationsof obstructive pulmonary disease
- 2001
-
Ingår i: Respiratory Medicine. - : Elsevier BV. - 0954-6111 .- 1532-3064. ; 95:11, s. 891-897
-
Tidskriftsartikel (refereegranskat)abstract
- The aim ofthe study was to investigate changes in inflammatory markers following emergency treatment of obstructive pulmonary disease. The study comprised 43 patients. After acute treatment, they were given either 30 mg of prednisolone p.o. or 1600 microg of inhaled budeson de daily for 1 week. Over the following 3 weeks, all the patients were given 1600 microg of inhaled budesonide daily. Blood samples for measurements of eosinophil cationic protein (S-ECP), eosinophil peroxidase (S-EPO), total eos nophil count (B-Eos), myeloperoxidase (S-MPO) and human neutrophil lipocaline (HNL) were taken and spirometry was performed before emergency treatment and after 1 and 4 weeks. There was no difference in the improvement in forced expiratory volume in 1 sec (FEV1) between patients given prednisolone or budesonide. Patients with an improvement in FEV1 of >20% of baseline after 1 and 4 weeks displayed a larger decrease in eosinophil markers. The correlation between deltaFEV1 and deltaS-ECP was r= -0.37, P < 0.05, deltaS-EPO -0.40, P < 0.01 and deltaB-Eos -0.44, P < 0.01, after 4 weeks. This correlation was highly significant in patients who had smoked < or = 5 pack-years, while the correlation was not significant in patients with a longer smoking history and chronic airflow limitation (best FEV <80% of predicted). We conclude that the change in eosinophil markers is correlated to the improvement in lung function in non-smokers or short-term smokers following the emergency treatment of obstructive pulmonary disease. This study indicates that following eosinophil markers is more useful in patients with asthma than patients with COPD.
|
|
| 4. |
- Dahlén, Inger, et al.
(författare)
-
Inflammatory markers in acute exacerbations of obstructive pulmonary disease : predictive value in relation to smoking history
- 1999
-
Ingår i: Respiratory Medicine. - 0954-6111 .- 1532-3064. ; 93:10, s. 744-751
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the relationship between the effect of emergency treatment and inflammatory markers in patients with acute exacerbations of obstructive pulmonary disease, especially with respect to smoking history. We investigated 50 unselected patients with acute bronchial obstruction. Blood, urine and sputum samples were taken and analysed for eosinophil and neutrophil markers. The patients were observed for at least 2 h and recordings of forced expiratory volume in 1 s (FEV1) were taken. They were re-examined after 1 and 4 weeks. The absolute levels of inflammatory markers did not differ significantly between non- or short-term smokers (< or = 5 pack-years) and long-term smokers (> 5 pack-years) with the exception of myeloperoxidase in serum (S-MPO), which was higher in long-term smokers. The patients with higher levels of eosinophil markers before emergency treatment experienced a greater improvement in lung function. In non- or short-term smokers this relationship was found in blood and urine, whereas in long-term smokers it was seen in sputum. No correlation was found between neutrophil markers and changes in lung function. We conclude that patients with obstructive pulmonary disease with acute exacerbations and high levels of eosinophil markers respond well to treatment.
|
|
| 5. |
- Emtner, Margareta, et al.
(författare)
-
A 3-year follow-up of asthmatic patients participating in a 10-week rehabilitation program with emphasis on physical training
- 1998
-
Ingår i: Archives of Physical Medicine and Rehabilitation. - 0003-9993 .- 1532-821X. ; 79:5, s. 539-544
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine if asthmatic patients who had participated in a 10-week rehabilitation program with emphasis on physical training (1) continued with physical training, (2) maintained their improved cardiovascular condition and lung function, and (3) retained their good asthma control through the following 3 years. Design: A descriptive 3-year follow-up study. Patients and Setting: A convenience sample of 58 patients who had previously undergone a 10-week outpatient rehabilitation program were followed up 6 months and 1, 1.5, 2, and 3 years after the start of the program at a lung clinic in a university hospital. Main Outcome Measures: A training log was kept by each patient to record frequency, intensity, and mode of training. Physical condition was evaluated with a submaximal 6-minute ergometry test and a 12-minute walking test, respiratory function with static and dynamic spirometry, and bronchial hyperreactivity with a metacholine provocation test. Asthma symptoms and asthma control were measured with a study-specific questionnaire. Results: Thirty-nine subjects (68%) exercised regularly during all 3 years. The cardiovascular condition and lung function values remained almost unchanged in all 58 patients. There was a significant decrease in number of emergency room visits the year after the 10-week rehabilitation program compared to the year before. It remained stable throughout the following 2 years. There was also a decrease in asthma symptoms in all patients, but the decrease was significant only in a subgroup of 26 patients, who exercised one or two times a week. Conclusions: It is possible for asthmatic subjects to exercise at a moderate intensity level on a long-term basis without deleterious effects. Moreover, the high compliance rate might indicate that inactive asthmatic patients who are taught how to exercise choose to continue to be physically active.
|
|
| 6. |
- Jönsson, Ulla-Britt, et al.
(författare)
-
A (G -> C) transversion in the 3 ' UTR of the human ECP (eosinophil cationic protein) gene correlates to the cellular content of ECP
- 2006
-
Ingår i: Journal of Leukocyte Biology. - : Oxford University Press (OUP). - 0741-5400 .- 1938-3673. ; 79:4, s. 846-851
-
Tidskriftsartikel (refereegranskat)abstract
- Eosinophil cationic protein (ECP) is a cytotoxic protein produced by and secreted from human eosinophil granulocytes. ECP may be involved in the injury of epithelial cells in allergic diseases such as asthma. The objectives were to determine the prevalence of the ECP gene polymorphism 562(G > C) in apparently healthy subjects and subjects with allergy and relate the prevalence to clinical disease and to serum and cellular levels of ECP. The 562(G > C) ECP gene polymorphism was determined by gene sequencing of the ECP gene from DNA prepared from 163 apparently healthy subjects and 151 subjects with allergic and nonallergie asthma or other diseases. ECP was measured by a sensitive radioimmunoassay. A polymorphism was detected at position 562, which mapped to the 3' untranslated region (UTR) of the gene encoding the ECP (RNase 3). Sixty-nine percent of the population had the 562GG genotype and 4%, the 562CC genotype. The cellular content of ECP in peripheral blood cosinophid granulocytes was significantly lower in cells from subjects with the 562GC (4.6 +/- 1.5 mu g/10(6) eosinophils) and 562CC (3.2 +/- 0.7 mu g/10(6) eosinophils) genotypes as compared with those with the 562GG genotype (6. 0 +/- 1.9 mu g/10(6) eosinophils; P < 0.001). A close link was found to the 434(G > C) ECP gene polymorphism. Associations between the 562(G > C) polymorphism or haplotypes of the two polymorphisms to allergy were not found. The 562(G > C) polymorphism in the 3'-end of the UTR of the ECP gene may determine the ECP content in human eosinophils, but unlike the 434(G > C) polymorphism, the 562(G > C) polymorphism is not related to allergy.
|
|
| 7. |
- Jönsson, Ulla-Britt, et al.
(författare)
-
The production of the eosinophil proteins ECP and EPX/EDN are regulated in a reciprocal manner
- 2014
-
Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - : Wiley. - 0903-4641 .- 1600-0463. ; 122:4, s. 283-291
-
Tidskriftsartikel (refereegranskat)abstract
- Previous studies showed that the biological activity and the eosinophil content of eosinophil cationic protein (ECP, RNase 3) are determined by single-nucleotide polymorphisms (SNPs) in the ECP (RNase3) gene. In this study, we report the prevalence of a common SNP in the eosinophil protein x/eosinophil-derived neurotoxin (EPX/EDN, RNase2) and the association with the cellular contents of EPX/EDN and ECP. The genes were sequenced and the EPX/EDN405(G>C) rs2013109 SNPs were also determined by TaqMan 5nuclease allelic discrimination assay. ECP and EPX/EDN in purified eosinophils or in whole blood extracts were analysed by sensitive immunoassays. The study included 379 non-allergic and allergic subjects. The genotype prevalence of the EPX/EDN405(G>C) polymorphism was GG 59%, GC 36% and CC 6%. The cellular contents of ECP and EPX/EDN were related in a reciprocal fashion with the sums of the protein contents being constant. The contents were associated with the ECP562(G>C) rs2233860 and EPX/EDN405(G>C) gene polymorphisms. The cellular content of eosinophil peroxidase (EPO) was not associated with the ECP and EPX/EDN genotypes. The prevalence of the EPX/EDN405(G>C) genotypes and the contents of the proteins were similar in non-allergic and allergic subjects. The production and storage of the two ancestral proteins, ECP and EPX/EDN likely share common regulatory mechanisms, which result in opposing productions of the two proteins.
|
|
| 8. |
- Kämpe, Mary, 1956-
(författare)
-
Eosinophil Inflammation in Allergic Disease : Clinical and experimental studies in allergic asthma and allergic rhinitis
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Allergic diseases are chronic inflammatory conditions, characterised by eosinophil inflammation systemically and in target organs, where cytotoxic granule proteins are responsible for tissue injury. Allergic rhinitis is known to be a risk factor for the development of asthma, yet not all with rhinitis develop asthma. The overall aim was to investigate the involvement of eosinophils in allergic rhinitis and allergic asthma in vivo and in experimental settings, with a focus on differences between rhinitis and asthma. Birch pollen allergy was used as a model and patients were studied during pollen season and after nasal and bronchial allergen challenge. During pollen season and at baseline, allergic rhinitis and allergic asthma had the same degree of systemic eosinophil inflammation. Despite this, impairment in lung function during season and increased bronchial responsiveness at baseline were more common in the asthmatics. Systemic inflammation was more pronounced after seasonal exposure than after experimental challenge. Allergic rhinitis and allergic asthma had the same degree of eosinophil airway inflammation after bronchial challenge, but only the asthmatics had increased bronchial responsiveness measured as PD20 for birch allergen. Allergen primed eosinophils were investigated in vitro for C3b-induced degranulation after seasonal and experimental challenge. The released amount of eosinophil granule proteins was within the same range for all three allergen challenge models with just minor differences in propensity for degranulation between rhinitics and asthmatics. Signalling through PI3K for degranulation was studied with the specific inhibitor Wortmannin. PI3K signalling for eosinophil degranulation was clearly involved in allergic rhinitis and allergic asthma irrespective of the model for allergen exposure. Asthmatics demonstrated less inhibition of degranulation through PI3K during pollen season, indicating that other pathways contribute to eosinophil degranulation in allergic asthmatics. Conclusion: Allergic rhinitis and allergic asthma present with the same degree of systemic and local eosinophil inflammation. The eosinophils are primed for degranulation equally and follow the same pathway through PI3K for degranulation. Our data indicates that eosinophil inflammation per se is not sufficient for the development of asthma.
|
|
| 9. |
- Kämpe, Mary, 1956-, et al.
(författare)
-
Experimental and seasonal exposure to birch pollen in allergic rhinitis and allergic asthma with regard to the inflammatory response
- 2010
-
Ingår i: The Clinical Respiratory Journal. - : Blackwell Publishing Ltd. - 1752-6981. ; 4:1, s. 37-44
-
Tidskriftsartikel (refereegranskat)abstract
- Background and Aims: Seasonal allergy is an interesting model to study the pathophysiological mechanisms involved in allergic inflammation. However, experimental allergen exposure is easier to perform and standardise. The primary aim of this study was to compare the inflammatory responses to high-dose bronchial challenge and natural exposure during birch pollen season. The second aim was to compare the responses of patients with allergic rhinitis and allergic asthma, respectively to both types of allergen exposure. Methods: Fifteen birch pollen-allergic patients (seven with asthma and eight with rhinitis) and five healthy individuals were studied during pollen season and after challenge with birch allergen. Symptoms, medication and peak expiratory flow rate (PEFR) were recorded, and blood samples, spirometry and induced sputum were analysed during season and after challenge. Results: Patients with allergic asthma demonstrated a greater bronchial responsiveness to bronchial provocation with birch allergen than patients with rhinitis (P = 0.04) whereas no difference was found regarding nasal challenge. No significant association was found between the level of responsiveness and the inflammatory response after seasonal exposure. Seasonal exposure was related to a more marked systemic inflammatory blood–eosinophil increase than bronchial challenge [(median) (0.25 vs 0.11 × 109/L, P = 0.03)] and after nasal challenge, respectively [(median) (0.25 vs 0.04 × 109/L, P = 0.003)]. A significant correlation in eosinophil cationic protein in induced sputum was found between the experimental and seasonal exposure (rho = 0.62, P = 0.02). Conclusions: Bronchial allergen challenge with inhalation of birch pollen gives a similar inflammatory response in the airway but less systemic inflammation than seasonal exposure in birch pollen allergic patients with asthma and rhinitis.
|
|
| 10. |
- Kämpe, Mary, et al.
(författare)
-
PI3-Kinase Regulates Eosinophil and Neutrophil Degranulation in Patients with Allergic Rhinitis and Allergic Asthma Irrespective of Allergen Challenge Model
- 2012
-
Ingår i: Inflammation. - : Springer Science and Business Media LLC. - 0360-3997 .- 1573-2576. ; 35:1, s. 230-239
-
Tidskriftsartikel (refereegranskat)abstract
- The PI3K pathway plays a major role in many vital cell processes. Our primary aim was to investigate signalling through PI3K for in vitro degranulation from allergen-primed eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen challenge. Nine patients with allergic rhinitis, eight with allergic asthma and four controls were studied during birch pollen season and after nasal and bronchial allergen challenge. Primed blood eosinophils and neutrophils were stimulated for in vitro degranulation with C3b-coated Sephadex particles, after prior incubation with Wortmannin, a PI3K inhibitor. The released amounts of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) were measured by radioimmunoassay. Wortmannin (10(-6) to 10(-9) M) inhibited ECP, EPO and MPO release in a dose-dependent manner in allergic rhinitis and allergic asthma in all three allergen challenge models. Inhibition of ECP release tended to be lower in the asthmatics in all allergen challenge models, statistically significant compared to the controls during season for 10(-8) M Wortmannin (p = 0.01). A clear propensity towards less inhibition in the rhinitic patients was seen after nasal and bronchial challenge compared to seasonal exposure, significant for ECP (10(-8) M Wortmannin; p = 0.034 and 0.002, respectively). Signalling through PI3K is clearly involved in ECP, EPO and MPO release in allergic rhinitis and allergic asthma irrespective of allergen challenge model. Allergic asthma demonstrated less inhibition of ECP release via PI3K during pollen season, indicating that other pathways play a greater role in eosinophil degranulation in allergic asthma than allergic rhinitis.
|
|
| 11. |
- Kämpe, Mary, 1956-, et al.
(författare)
-
Systemic and local eosinophil inflammation during the birch pollen season in allergic patients with predominant rhinitis or asthma
- 2007
-
Ingår i: Clinical and Molecular Allergy. - : BioMed Central. - 1476-7961. ; 5, s. 4-
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe aim of the study was to investigate inflammation during the birch pollen season in patients with rhinitis or asthma.MethodsSubjects with birch pollen asthma (n = 7) or rhinitis (n = 9) and controls (n = 5) were studied before and during pollen seasons. Eosinophils (Eos), eosinophil cationic protein (ECP) and human neutrophil lipocalin were analysed.ResultsAllergic asthmatics had a larger decline in FEV1 after inhaling hypertonic saline than patients with rhinitis (median) (-7.0 vs.-0.4%, p = 0.02). The asthmatics had a lower sesonal PEFR than the rhinitis group. The seasonal increase in B-Eos was higher among patients with asthma (+0.17 × 109/L) and rhinitis (+0.27 × 109/L) than among controls (+0.01 × 109/L, p = 0.01). Allergic asthmatics and patients with rhinitis had a larger increase in sputum ECP (+2180 and +310 μg/L) than the controls (-146 μg/L, p = 0.02). No significant differences in inflammatory parameters were found between the two groups of allergic patients.ConclusionPatients with allergic asthma and rhinitis have the same degree of eosinophil inflammation. Despite this, only the asthmatic group experienced an impairment in lung function during the pollen season.
|
|
| 12. |
- Mary, Kämpe, et al.
(författare)
-
Patients with allergic rhinitis and allergic asthma share the same pattern of eosinophil and neutrophil degranulation after allergen challenge
- 2011
-
Ingår i: Clinical and Molecular Allergy. - : Springer Science and Business Media LLC. - 1476-7961. ; 9:1, s. 3-
-
Tidskriftsartikel (refereegranskat)abstract
- Background:Patients with allergic rhinitis and allergic asthma demonstrate comparable local and systemic eosinophil inflammation, and yet they present with different clinical pictures. Less is even known about the contribution of neutrophil inflammation in allergic diseases. The aim of the study was to examine the propensity and selectivity of granule release from primed systemic eosinophils and neutrophils in allergic rhinitis and allergic asthma after seasonal and experimental allergen exposure. We hypothesize that the dissimilar clinical manifestations are due to diverse eosinophil and neutrophil degranulation. Methods: Nine birch pollen allergic patients with rhinitis, eight with asthma and four controls were studied during pollen season and after nasal and bronchial allergen challenge. Eosinophils and neutrophils were incubated in vitro with assay buffer and opsonized Sephadex particles for spontaneous and C3b-induced granule protein release. The released amount of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO) and myeloperoxidase (MPO) was measured by specific radioimmunoassay.Results:C3b-induced degranulation resulted in increased release of ECP and MPO from primed blood eosinophils and neutrophils in both allergic rhinitis and allergic asthma during pollen season and after both nasal and bronchial challenge (p-values 0.008 to 0.043). After bronchial challenge, the ECP release was significantly higher in the rhinitic group compared to the asthmatic group [19.8 vs. 13.2 %, (p=0.010)]. The propensity for EPO release was weak in all challenge models but followed the same pattern in both allergic groups.Conclusion: Systemically allergen primed eosinophils and neutrophils have similar patterns of degranulation after allergen exposure in allergic rhinitis and allergic asthma. The released amount of ECP, EPO and MPO was similar in all allergen challenge models in both allergic groups. Our results indicate that other mechanisms than the magnitude of eosinophil and neutrophil inflammation or the degranulation pattern of the inflammatory cells determines whether or not an allergic patient develops asthma.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Rydell, Niclas, et al.
(författare)
-
Use of an oral diphtheria vaccine in human
- 2006
-
Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 24:33-34, s. 5928-5930
-
Tidskriftsartikel (refereegranskat)abstract
- Starch microparticles have been shown to be effective as a particulate adjuvant carrier in oral vaccination. In mice, formulations with bacterial antigens have elicited both systemic and mucosal immune responses providing protection upon challenge with live bacteria. A vaccine formulation with formaldehyde-treated diphtheria toxin cross-reacting material, CRM197, optimised in mice, was tested in healthy volunteers in a booster design. Specific antibodies as well as toxin-neutralising antibodies in a Vero cell analysis indicated that the vaccine was not effective in man. It is obvious that the longer transit time in the human GI tract and possible unfavourable distribution of Peyer's patches and M-cells necessary for the uptake of the starch particles require a more stable formulation. It is proposed that enteric coating of the particles or particles in a gastro-resistant capsule could be a more efficacious vaccine formulation.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Stålenheim, Gunnemar, et al.
(författare)
-
The size of the disease relevant IgE antibody fraction in relation to 'total-IgE' predicts the efficacy of anti-IgE (Xolair (R)) treatment
- 2009
-
Ingår i: Allergy. - : Wiley. - 1398-9995 .- 0105-4538. ; 64:10, s. 1472-1477
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Some patients with allergic asthma treated with anti-IgE (Xolair (R)) do not become symptom free. Better criteria for response assessment than allergy skin tests or IgE determination are needed. The impact of the size of the disease relevant allergen-specific IgE antibody fraction, i.e. the percentage of IgE antibody of total IgE, was evaluated in cat allergic patients treated with the recommended doses of Xolair (R). Results were measured as changes in basophil allergen threshold sensitivity (CD-sens). Methods: In a double-blind placebo controlled trial 20 patients with a high (> 3.8%) and 18 with a low (< 1%) percentage of IgE antibodies to cat were given Xolair (R) for 16 weeks and the change in CD-sens was compared to 11 and 10 patients, respectively, in each group receiving placebo. Results: The CD-sens dropped significantly in both the high (P < 0.001) and low (P < 0.001) group on Xolair (R) but did not change significantly after placebo. For Xolair (R)-treated patients, at the end of the trial there was a highly significant (P < 0.001) difference in CD-sens between the high group, where no patients, and the low group, where 13/18 patients, had become negative. Conclusions: The currently recommended doses of Xolair (R) very efficiently eliminate IgE antibodies if the IgE antibody fraction is < 1% of total IgE but has not enough effect on allergen sensitivity if the fraction is > 3-4%. Further studies will show if increased doses of Xolair (R) would help also these patients, who seem to represent about 1/3 of the patient population.
|
|
