| 1. |
- Almqvist, Catarina, et al.
(författare)
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The impact of birth mode of delivery on childhood asthma and allergic diseases : a sibling study
- 2012
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Ingår i: Clinical and experimental allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Caesarean section (CS) has been reported to increase the risk of asthma in offspring. This may be due to that infants delivered by CS are unexposed to vaginal flora, according to the ‘hygiene hypothesis’. Objective: Our aim was to investigate if CS increases risk of childhood asthma, and if the risk increase remains after adjustment for familial confounding using sibling design. Methods: A register-based cohort study with 87 500 Swedish sibling pairs was undertaken. Asthma outcome variables were collected from national health registers as diagnosis or asthma medication (ICD-10 J45-J46; ATC code R03) during the 10th or 13th year of life (year of follow-up). Mode of delivery and confounders were retrieved from the Medical Birth Register. The data were analysed both as a cohort and with sibling control analysis which adjusts for unmeasured familial confounding. Results: In the cohort analyses, there was an increased risk of asthma medication and asthma diagnosis during year of follow-up in children born with CS (adjusted ORs, 95% CI 1.13, 1.04–1.24 and 1.10, 1.03–1.18 respectively). When separating between emergency and elective CS the effect on asthma medication remained for emergency CS, but not for elective CS, while both groups had significant effects on asthma diagnosis compared with vaginal delivery. In sibling control analyses, the effect of elective CS on asthma disappeared, while similar but non-significant ORs of medication were obtained for emergency CS. Conclusions and Clinical Relevance: An increased risk of asthma medication in the group born by emergency CS, but not elective, suggests that there is no causal effect due to vaginal microflora. A more probable explanation should be sought in the indications for emergency CS.
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| 2. |
- Tedner, Sandra G, et al.
(författare)
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Fetal growth and risk of childhood asthma and allergic disease
- 2012
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Ingår i: Clinical & Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Early genetic and environmental factors have been discussed as potential causes for the high prevalence of asthma and allergic disease in the western world, and knowledge on fetal growth and its consequence on future health and disease development is emerging. Objective: This review article is an attempt to summarize research on fetal growth and risk of asthma and allergic disease. Current knowledge and novel findings will be reviewed and open research questions identified, to give basic scientists, immunologists and clinicians an overview of an emerging research field. Methods: PubMed-search on pre-defined terms and cross-references. Results: Several studies have shown a correlation between low birth weight and/or gesta- tional age and asthma and high birth weight and/or gestational age and atopy. The exact mechanism is not yet clear but both environmental and genetic factors seem to contribute to fetal growth. Some of these factors are confounders that can be adjusted for, and twin studies have been very helpful in this context. Suggested mechanisms behind fetal growth are often linked to the feto-maternal circulation, including the development of placenta and umbilical cord. However, the causal link between fetal growth restriction and subse- quent asthma and allergic disease remains unexplained. New research regarding the catch-up growth following growth restriction has posited an alternative theory that dis- eases later on in life result from rapid catch-up growth rather than intrauterine growth restriction per se. Several studies have found a correlation between a rapid weight gain after birth and development of asthma or wheezing in childhood. Conclusion and clinical relevance: Asthma and allergic disease are multifactorial. Several mechanisms seem to influence their development. Additional studies are needed before we fully understand the causal links between fetal growth and development of asthma and allergic diseases.
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| 3. |
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| 4. |
- Flanigan, Catherine, et al.
(författare)
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Prenatal maternal psychosocial stress and offspring’s asthma and allergic disease : a systematic review and meta-analysis
- 2018
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Ingår i: Clinical & Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prenatal maternal stress may influence offspring's atopic risk through sustained cortisol secretion resulting from activation of the hypothalamic-pituitary-axis (HPA), leading to Th2-biased cell differentiation in the fetus. We undertook a systematic review and meta-analysis investigating the relationship between prenatal maternal psychosocial stress and risk of asthma and allergy in the offspring. METHODS: We searched 11 electronic databases from 1960 to 2016, search the grey literature, and contacted experts in the field. Type of stress indicator included mood disorders, anxiety, exposure to violence, bereavement and socio-economic problems occurring during pregnancy, both objectively or subjectively measured. We included all possible asthma and IgE-mediated allergy outcomes. We conducted random-effects meta-analyses to synthesize the data. RESULTS: We identified 9,779 papers of which 30 studies (enrolling >6 million participants) satisfied inclusion criteria. The quality of 25 studies was moderate, four were strong, and one was weak. Maternal exposure to any type of stressors was associated with an increased risk of offspring atopic eczema/dermatitis (OR 1.34, 95%CI 1.22-1.47), allergic rhinitis (OR 1.30, 95%CI 1.04-1.62), wheeze (OR 1.34, 95%CI 1.16-1.54) and asthma (OR 1.15, 95%CI 1.04-1.27). Exposure to anxiety and depression had strongest effect compared to other stressors. Exposure during the third trimester had the greatest impact compared to first and second trimesters. The increased risk was stronger for early-onset and persistent than for late-onset wheeze. Bereavement of a child (HR 1.28, 95%CI 1.10-1.48) or a spouse (HR 1.40, 95%CI 1.03-1.90) increased the risk of offspring asthma. CONCLUSIONS: Exposure to prenatal maternal psychosocial stress was associated with increased risk, albeit modestly, of asthma and allergy in the offspring. The pronounced risk during the third trimester may represent cumulative stress exposure throughout pregnancy rather than trimester-specific effect. Our findings may represent a causal effect or a result of inherent biases in studies, particularly residual confounding.
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| 5. |
- Tedner, Sandra G, et al.
(författare)
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Depression or anxiety in adult twins is associated with asthma diagnosis but not with offspring asthma
- 2017
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Ingår i: Clinical & Experimental Allergy. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 1365-2222 .- 0954-7894.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Asthma is common in both children and adults in the Western world, just like anxiety and depression. While some research has revealed that these diseases might share important environmental and pathophysiological aspects, the exact mechanisms still remain unclear. Objective: To study the correlation firstly between depression or anxiety and asthma diagnosis in adult twins, and secondly the association between parental depression or anxiety and offspring asthma in children of twins. Methods: In total, 24,685 adult twins aged 20-47 years were interviewed or completed a web-based questionnaire and their children were identified through the Multi-Generation Register. Asthma diagnosis was obtained from the Patient Register and the Prescribed Drug Register. Assessment of depression and anxiety was obtained from questionnaires using Center for Epidemiologic Studies Depression Scale (CES-D), Major Depression and Generalized Anxiety Disorder (GAD) from DSM-IV. The association between depression or anxiety and asthma was analyzed with logistic regression adjusting for confounders in twins and offspring. To address genetic and familial environmental confounding we performed a co-twin analysis using disease-discordant twin pairs. Results: We found an association between asthma and CES-D, major depression and GAD, e.g. adjusted OR for major depression and register-based asthma 1.56(1.36-1.79). Most of the point estimates remained in the co-twin control analysis, indicating that the association was likely not due to genetic or familial environmental factors. There was no association between parental depression and/or anxiety and asthma diagnosis in the offspring which implies lack of genetic confounding. Conclusions: We found an association between own asthma diagnosis and anxiety or depression, but not with offspring asthma. Our results indicate that the associations were not due to confounding from genes or environment shared by the twins.
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| 6. |
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| 7. |
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| 8. |
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| 9. |
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| 10. |
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| 11. |
- Benson, Mikael, 1954, et al.
(författare)
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DNA microarrays to study gene expression in allergic airways.
- 2002
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Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 0954-7894 .- 1365-2222. ; 32:2, s. 301-8
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Tidskriftsartikel (refereegranskat)abstract
- Allergic rhinitis results from interactions between a large number of cells and mediators in different compartments of the body. DNA microarrays allow simultaneous measurement of expression of thousands of genes in the same tissue sample.
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| 12. |
- Benson, Mikael, 1954, et al.
(författare)
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Gene profiling reveals decreased expression of uteroglobin and other anti-inflammatory genes in nasal fluid cells from patients with intermittent allergic rhinitis
- 2005
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Ingår i: Clin Exp Allergy. - : Wiley. ; 35:4, s. 473-478
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Intermittent allergic rhinitis (IAR) results from interactions between a large number of pro- and anti-inflammatory mediators. Little is known about anti-inflammatory mediators in IAR. DNA microarrays allow simultaneous analysis of the whole transcriptome in a sample. OBJECTIVE: To identify anti-inflammatory transcripts in nasal fluid cells from patients with IAR during season and from healthy controls. METHODS: Nasal lavage fluids were obtained from 15 patients with symptomatic birch/and or grass pollen-induced IAR and 28 healthy controls. RNA was extracted from the nasal fluid cells and pooled into one patient- and one control pool. These were analysed with DNA microarrays containing more than 44,927 genes and variants. RESULTS: Seventeen thousand three hundred and fifty three genes were expressed in the controls and 17 928 in the patients. One thousand five hundred and seventy nine of the genes had higher expression in patients than in controls, and 1570 had lower expression in patients. Out of 189 up-regulated inflammatory genes, 187 were pro-inflammatory and two were anti-inflammatory. These genes regulated key steps of inflammation, ranging from influx of leukocytes to immunoglobulin production. By comparison, out of 49 down-regulated inflammatory genes, 36 were pro-inflammatory and 13 were anti-inflammatory. The anti-inflammatory gene that decreased most in expression in the patients was uteroglobin (also known as Clara Cell protein 16, CC16). The nasal fluid concentrations of uteroglobin protein were significantly lower in patients than in controls, 5.43+/-1.53 and 12.93+/-2.53 ng/mL, respectively (P<0.05). CONCLUSION: IAR is associated with decreased expression of uteroglobin and other anti-inflammatory genes.
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| 13. |
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| 14. |
- Bousquet, J, et al.
(författare)
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Increased risk of asthma attacks and emergency visits among asthma patients with allergic rhinitis: a subgroup analysis of the improving asthma control trial
- 2005
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 35:6, s. 723-727
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Tidskriftsartikel (refereegranskat)abstract
- Background Inadequately controlled allergic rhinitis (AR) in asthmatic patients can contribute towards increased asthma exacerbations and poorer symptom control, which may increase medical resource use. We assessed asthma-related medical resource use and attacks in asthmatic patients who did and did not have concomitant AR and were adding montelukast or salmeterol to baseline treatment with inhaled. fluticasone. Methods A post hoc resource use analysis of a 52-week, double-blind multicentre clinical trial (IMPACT: IMProving Asthma Control Trial) including 1490 adults with chronic asthma, aged 15 72 years, with FEV1 50-90% of predicted and >= 12% increase in FEV1 after salbutamol administration, treated with either montelukast 10mg daily or salmeterol 50 mu g twice daily in addition to. fluticasone 200 mg, was undertaken. Asthma- related medical resource use included medical visits ( defined as either an unscheduled visit [to a general practitioner, a specialist or a nonmedical provider] or a specialist visit), emergency room visits and hospitalizations during follow-up. Asthma attacks were defined as the worsening of asthma requiring unscheduled visit, emergency visit, hospitalization or oral/intravenous/intramuscular corticosteroids. Results A self-reported history of concomitant AR was identified in 60% of the patients (n=893). Univariate analysis suggests that significantly more patients with concomitant AR experienced emergency room visits (3.6% vs. 1.7%, P=0.029) and asthma attacks (21.3% vs. 17.1%, P=0.046). Multivariate analysis adjusting for treatment group, age and baseline asthma severity confirmed these results since the presence of concomitant AR in patients with asthma increases the likelihood of emergency room visit ( odds ratio ( OR) 52.35, 95% confidence interval (CI) = 1.12 - 4.80) and asthma attack (OR = 1.35, 95% CI = 1.03 - 1.77). Patients with asthma alone compared with patients with both conditions did not differ in terms of unscheduled or specialist visits and hospitalizations. Conclusions Presence of self-reported concomitant AR in patients with asthma resulted in a higher rate of asthma attacks and more emergency room visits compared with asthma patients without concomitant AR.
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| 15. |
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| 16. |
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| 17. |
- Erjefält, Jonas, et al.
(författare)
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Allergen challenge-induced extravasation of plasma in mouse airways
- 1998
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 28:8, s. 1013-1020
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Mouse models are extensively used to study genetic and immunological mechanisms of potential importance to inflammatory airway diseases, e.g. asthma. However, the airway pathophysiology in allergic mice has received less attention. For example, plasma extravasation and the ensuing tissue-deposition of plasma proteins, which is a hallmark of inflammation, has not been examined in allergic mice. OBJECTIVE: This study aims to examine the vascular permeability and the distribution of plasma proteins in mouse airways following exposure to allergen and serotonin. METHODS: Extravasated plasma was quantified by a dual isotop technique using intravascular (131I-albumin) and extrasvascular (125I-albumin) plasma tracers. Histological visualization of fibrinogen and colloidal gold revealed the tissue distribution of extravasated plasma. RESULTS: Allergen aerosol exposure (3% OVA, 15min) of sensitized animals resulted in a marked plasma extravasation response in the trachea (P < 0.01) and the bronchi but not in the lung parenchyma. A similar extravasation response was induced by serotonin (P<0.001). Extravasating vessels (assessed by Monastral blue dye) were identified as intercartilaginous venules. Extravasated plasma abounded in the subepithelial tissue but was absent in the epithelium and airway lumen. The allergen-induced response was dose-dependently inhibited by iv administration of formoterol (P < 0.001), a vascular antipermeability agent. CONCLUSION: The present study demonstrates that serotonin and allergen challenge of sensitized mice increase airway venular permeability to cause transient extravasation and lamina propria distribution of plasma in the large airways. We suggest that the extravasation response is a useful measure of the intensity and the distribution of active inflammation
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| 18. |
- Erjefält, Jonas, et al.
(författare)
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Association between inflammation and epithelial damage-restitution processes in allergic airways in vivo
- 1997
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 27:11, s. 1344-1355
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Associations between allergen challenge-induced sites of epithelial damage and the distribution of leucocytes and extravasated plasma remain unexplored. OBJECTIVE: To study neutrophils, eosinophils, and fibrinogen at allergen challenge-induced patchy epithelial damage-restitution sites in guinea-pig trachea. METHODS: After local challenge tracheal tissue (cryo sections and whole-mounts) and lumen (selective tracheal lavage) were examined at 1, 5, and 24 h. Eosinophils, neutrophils and fibrinogen were identified by histochemistry. RESULTS: Neutrophils increased markedly in tracheal lavage fluids and in tissue and were strongly associated with the challenge-induced epithelial craters of damage-restitution. At 1 and 24 h eosinophils were increased in the tracheal lumen whereas the surrounding tissue displayed a reversed pattern. Gels rich in fibrinogen, neutrophils, and eosinophils were present in epithelial crater areas, protruding into the lumen. Clusters of free eosinophil granules, Cfegs, released through lysis of eosinophils, and neutrophils with long cytoplasmatic protrusions abounded in these crater areas. CONCLUSION: The present findings provide important new insights into allergic airways where sites of epithelial damage-restitution processes emerge as the major loci for eosinophil, neutrophil, and plasma protein activities, the latter likely causing leukocyte adhesion and activation in vivo. The distribution of eosinophils in this study suggests roles of these cells both in airway mucosa and in regional lymph nodes. Based on the present study we also propose that lysis of eosinophils and Cfegs generation are a major paradigm for activation of these cells in vivo.
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| 19. |
- Erjefält, Jonas, et al.
(författare)
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Epithelial pathways for luminal entry of bulk plasma
- 1995
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 25:2, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- Inflammatory challenges of the airway mucosa cause luminal entry of bulk plasma. Extravasation of plasma is well described but the routes for epithelial passage of plasma are largely unknown. Using colloidal gold (5 nm) as tracer we have now examined the fate of extravasated plasma in the airways. The tracer was given intravenously to anaesthetized, ovalbumin-sensitized guinea-pigs 2min prior to airway mucosal challenge with 12pmol ovalbumin (the dose was selected from a separate dose-response study). Tissue specimens were collected 30s, 3 and 6 min after end of challenge (separate time course experiments suggested that the peak rate of entry of plasma occurred at about 5 min). The colloidal gold particles were visualized by autometallographic silver intensification. The gold produced no circulatory disturbance and had a uniform vascular distribution with negligible adherence to vascular endothelium. After challenge gold was first widely distributed in the lamina propria. At 3 and 6 min the tracer was also in the epithelium and airway lumen. It appeared that plasma was moved distinctly between and all around each epithelial cell. Bright field-, scanning-, and transmission electron-microscopy indicated that the luminal entry of plasma did not affect the integrity of the epithelial lining. This study demonstrates that the plasma exudate moves across an intact epithelial layer through ubiquitous paracellular pathways. Even at a pronounced acute plasma exudation response exceedingly small amounts of plasma may pass around a single cell explaining the non-injurious nature of mucosal exudation of bulk plasma in health and disease.
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| 20. |
- Erjefält, Jonas, et al.
(författare)
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Prompt epithelial damage and restitution processes in allergen challenged guinea-pig trachea in vivo
- 1997
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 27:12, s. 1458-1470
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Little is known about the induction and the morphology of epithelial damage, and of the ensuing epithelial restitution processes in allergic airways. OBJECTIVE: To examine epithelial damage and restitution in allergen challenged guinea-pig trachea. METHODS: Whole-mount techniques, transmission and scanning electron microscopy, cryosectioning, and histochemical staining were used. Cell proliferation was monitored by BrdU-immunohistochemistry. RESULTS: Allergen challenge produced patchy, crater-like, and leucocyte-rich epithelial damage sites. At 1, 5, and 24 h damage was associated with poorly differentiated epithelial restitution cells. Already at 1 h the epithelial craters had a floor of flattened restitution cells and the damaged areas comprised < 1% of the mucosal surface area (whole-mount preparations). In contrast, cryo sections displayed large areas (approximately 20%, 1 h) of denudation. Epithelial, and subepithelial (fibroblasts, smooth muscle) proliferation was increased 5 and 24 h after challenge (P < 0.01). CONCLUSION: Within 1 h allergen challenge has induced patchy damage sites where epithelial restitution is already advanced; although easily produced by cryosectioning frank denudation was not evident in whole-mount preparations. The present findings may explain the well maintained, functional tightness of allergic airways displaying epithelial damage, shedding, and even denudation. The present data also suggest the possibility that epithelial damage-restitution may be causative to allergic airway remodelling.
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| 21. |
- Farahi, N, et al.
(författare)
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Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearance.
- 2011
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 41:5, s. 673-687
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Tidskriftsartikel (refereegranskat)abstract
- Background Eosinophils are pro-inflammatory cells implicated in the pathogenesis of asthma and atopy. Apoptosis has been proposed as a potential mechanism underlying the resolution of eosinophilic inflammation and studies have indicated the ability of interventions that induce human eosinophil apoptosis to promote the resolution of eosinophilic inflammation. Recently, the cyclin-dependent kinase (CDK) inhibitor R-roscovitine was shown to enhance neutrophil apoptosis and promote the resolution of neutrophilic inflammation. Objective The purpose of this study was to examine the expression of CDKs in human blood eosinophils, the effects of R-roscovitine on eosinophil survival in vitro and whether R-roscovitine could influence eosinophilic lung inflammation in vivo. Methods Eosinophils were isolated from human peripheral blood and the effects of R-roscovitine on apoptosis, degranulation and phagocytic uptake examined in vitro. The effects of R-roscovitine on eosinophilic lung inflammation in vivo were also assessed using an ovalbumin mouse model. Results Our data demonstrate that human eosinophils express five known targets for R-roscovitine: CDK1, -2, -5, -7 and -9. R-roscovitine induced eosinophil apoptosis in a time- and concentration-dependent manner but also accelerated transition to secondary necrosis as assessed by microscopy, flow cytometry and caspase activation. In addition, we show that R-roscovitine can override the anti-apoptotic signals of GM-CSF and IL-5. We report that the pro-apoptotic effect of R-roscovitine is associated with suppression of Mcl-1L expression and that this compound enhanced phagocytic clearance of eosinophils by macrophages. Finally, we show that R-roscovitine induces apoptosis in murine peripheral blood and spleen-derived eosinophils; despite this, R-roscovitine did not modulate the tissue and lumen eosinophilia characteristic of the ovalbumin mouse model of airway eosinophilia. Conclusion and Clinical Relevance These data demonstrate that R-roscovitine is capable of inducing rapid apoptosis and secondary necrosis in eosinophils but does not affect the onset or improve the resolution of eosinophilic airway inflammation in vivo.
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| 22. |
- Greiff, Lennart, et al.
(författare)
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Mucosal output of eotaxin in allergic rhinitis and its attenuation by topical glucocorticosteroid treatment
- 2001
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 31:8, s. 1321-1327
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Eotaxin is a chemokine that attracts and activates eosinophils. The present study examines the occurrence of eotaxin in nasal mucosal surface liquids in patients with seasonal allergic rhinitis without allergen exposure and during repeat allergen challenge with and without topical glucocorticosteroid treatment. The number of subepithelial eosinophils and mucosal outputs of bulk plasma (alpha2-macroglobulin) and eosinophil cationic protein (ECP) are also examined. METHODS: Twelve patients underwent daily allergen challenges for 6 days. Separately, 14 patients, who were receiving budesonide and placebo in a parallel group design, also underwent allergen challenge for 6 days. Nasal biopsies were obtained before and 24 h after the allergen challenge series, and lavages were carried out before and 15 min after selected allergen challenges. RESULTS: At baseline nasal lavage fluid levels of eotaxin correlated to levels of alpha2-macroglobulin and ECP. After the first allergen challenge there was a correlation between nasal lavage fluid levels of eotaxin and ECP. Repeat allergen exposure increased the mucosal output of eotaxin (P <0.05) and ECP (P <0.01) as well as eosinophil numbers (P <0.01), but no correlation was found between increased eosinophil numbers and eotaxin. Budesonide reduced eotaxin levels during repeat allergen challenge (P <0.05). CONCLUSIONS: Repeat allergen exposure in allergic rhinitis is associated with increased mucosal output of eotaxin. Topical budesonide attenuates this effect, suggesting the possibility that inhibitory effects on mucosal eotaxin may contribute to anti-eosinophilic actions of topical glucocorticosteroids.
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| 23. |
- Holgate, S. T., et al.
(författare)
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Efficacy and safety of a recombinant anti-immunoglobulin E antibody (omalizumab) in severe allergic asthma
- 2004
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 34:4, s. 632-638
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with severe asthma are often inadequately controlled on existing anti-asthma therapy, constituting an unmet clinical need. Objective This randomized, double-blind, placebo-controlled trial evaluated the ability of omalizumab, a humanized monoclonal anti-IgE antibody, to improve disease control sufficiently to enable inhaled corticosteroid reduction in patients with severe allergic asthma. Methods After a run-in period when an optimized fluticasone dose (greater than or equal to1000 mug/day) was received for 4 weeks, patients were randomized to receive subcutaneous omalizumab [minimum 0.016 mg/kg/IgE (IU/mL) per 4 weeks; n=126] or matching placebo (n=120) at intervals of 2 or 4 weeks. The study comprised a 16-week add-on phase of treatment followed by a 16-week fluticasone-reduction phase. Short-/long-acting beta(2)-agonists were allowed as needed. Results Median reductions in fluticasone dose were significantly greater with omalizumab than placebo: 60% vs. 50% (P=0.003). Some 73.8% and 50.8% of patients, respectively, achieved a greater than or equal to50% dose reduction (P=0.001). Fluticasone dose reduction to less than or equal to500 mug/day occurred in 60.3% of omalizumab recipients vs. 45.8% of placebo-treated patients (P=0.026). Through both phases, omalizumab reduced rescue medication requirements, improved asthma symptoms and asthma-related quality of life compared to placebo. Conclusion Omalizumab treatment improves asthma control in severely allergic asthmatics, reducing inhaled corticosteroid requirements without worsening of symptom control or increase in rescue medication use.
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| 24. |
- Håkansson, S, et al.
(författare)
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Caesarean section increases the risk of hospital care in childhood for asthma and gastroenteritis.
- 2003
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 33:6, s. 757-764
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate if caesarean section (CS) increases the risk for childhood asthma and gastroenteritis with reference made to children born with vaginal delivery (VD). MethodsRetrospective study of data from linked Swedish medical service registers - Medical Birth Registry (MBR) and Hospital Discharge Registry (HDR). Data were obtained from women without any background/perinatal morbidity noted, and from children without any neonatal complications. Children that had reached at least 1 year of age and were found in the HDR were considered as cases, whereas children not found in the HDR or hospitalized for other causes than asthma or gastroenteritis were defined as controls. Odds ratios (OR) stratified for year of birth, maternal age, parity and smoking in early pregnancy were calculated. Investigations were made comparing the risk for in hospital treatment for asthma or gastroenteritis in CS children and in VD siblings of CS children. The overall inpatient morbidity in CS and VD children were also investigated. ResultsThe OR for asthma in CS children was 1.31 [95% confidence interval (CI) 1.23-1.40]. The same OR, 1.31, was found for gastroenteritis (95% CI 1.24-1.38). The OR for CS children having experienced both asthma and gastroenteritis was further increased (1.74, 95% CI 1.36-2.23). The risk for asthma in VD siblings of CS children was not significantly increased, whereas VD siblings experienced a slightly increased risk for gastroenteritis. CS children had an increased overall in hospital morbidity when compared to VD children. ConclusionThere is a significant increase of the risk for developing symptoms of asthma and/or gastroenteritis that motivates admission for hospital care in CS children older than 1 year. It is speculated that a disturbed intestinal colonization pattern in CS children may be a common pathogenic factor.
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| 25. |
- Johansson, Björn, et al.
(författare)
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Alpha-1-antitrypsin is present in the specific granules of human eosinophilic granulocytes
- 2001
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 31:3, s. 379-386
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Tidskriftsartikel (refereegranskat)abstract
- Eosinophils may be found at sites of inflammation, for example in asthma, allergy and helminthic infestation, but their role in human inflammatory disease is unclear. In the present study, we investigated the presence of alpha-1-antitrypsin (AAT), a serine proteinase inhibitor, in human eosinophils. When lysates of highly purified eosinophils were subjected to Western blotting, with a chemiluminescent substrate, immunoreactive bands were seen. An ELISA was developed to measure the AAT content, which was found to be about 100 ng/5 x 106 eosinophils, about 50 ng/5 x 106 neutrophils, and about 25 ng/5 x 106 monocytes. Immunoelectron microscopy showed localization of AAT to the specific granules of eosinophils. During prolonged incubation of eosinophils, no significant increase in the total amount of AAT could be detected by ELISA. However, there was an increased level of AAT in the medium, in parallel with a decrease in the intracellular AAT content, suggesting release of preformed AAT. Apparent complex formation between iodinated elastase and AAT in eosinophil lysates provided evidence that the AAT is functionally active. On the basis of these findings it is suggested that by releasing AAT, eosinophils may, in a microenvironment, play a role in counteracting the tissue damage caused by serine proteinases released by neutrophils in inflammatory conditions.
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| 26. |
- John, R J, et al.
(författare)
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Functional effects of the inhibition of the cysteine protease activity of the major house dust mite allergen Der p 1 by a novel peptide-based inhibitor
- 2000
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 30:6, s. 784-793
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The house dust mite (HDM) Dermatophagoides pteronyssinus is an important source of allergens, which can cause allergic conditions. The cysteine protease activity of Der p 1 may enhance the potency of this major mite allergen through cleavage of CD23 and CD25 from the surface of immune cells, IgE independent mast cell activation, increases in epithelial cell permeability and inactivation of an endogenous serine protease inhibitor. Inhibition of the enzymatic activity of Der p 1 may therefore be of therapeutic benefit. OBJECTIVE: To examine the activity of PTL11028, a newly developed Der p 1 inhibitor, in a range of assays that directly or indirectly measure Der p 1 protease activity and to compare its activity to endogenous cysteine protease inhibitors. METHODS: The proteolytic activities of purified Der p 1 or HDM extract and inhibitory properties of PTL11028 were examined through cleavage of an artificial peptidyl substrate, cleavage of CD23 from human B cells and permeability studies on primary human bronchial epithelial cells. RESULTS: PTL11028 is a highly potent and specific Der p 1 inhibitor, being effective against both purified protease and Der p 1 within HDM extract. PTL11028 can completely inhibit Der p 1-mediated CD23 cleavage from human B cells and also reduces HDM-induced human bronchial epithelial cell permeability by 50%. Der p 1 is potently inhibited by cystatin A and to a lesser extent by cystatins C and E/M. CONCLUSION: PTL11028 is a highly potent and selective irreversible inhibitor of the cysteine protease activity of Der p 1, an activity that may be modulated in vivo by some human cystatins. PTL11028 prevents the Der p 1-mediated cleavage of CD23 from human B cells and significantly reduces HDM-induced permeabilization of the epithelial barrier. PTL11028 is an important tool to examine the biological effects of Der p 1 in a range of in vitro and in vivo model systems.
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| 27. |
- Jones, MG, et al.
(författare)
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Association of HLA-DQ5 and HLA-DR1 with sensitization to organic acidanhydrides
- 2004
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 34:5, s. 812-816
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Tidskriftsartikel (refereegranskat)abstract
- Background Organic acid anhydrides are low molecular weight industrial chemicals, able to cause rhinoconjunctivitis and asthma associated with specific IgE against hapten-carrier protein conjugate. Only a proportion of exposed workers develop IgE-associated allergy to acid anhydrides. Objective We determined whether genetic susceptibility, in particular, HLA Class II alleles may be a risk factor. Methods We undertook HLA typing in 52 cases who had confirmed specific IgE and in 73 referents matched on site, age and duration of acid anhydride exposure identified in cross-sectional studies of workers exposed to hexahydrophthalic (HHPA), methylhexahydrophthalic (MHHPA) and methyltetrahydrophthalic (MTHPA) anhydrides. Results The linked alleles DQ5 (odds ratio [OR]=4.3; 95% confidence interval [95% CI]=1.7, 11) and DR1 (OR 3.0; 95% CI 1.2, 11) were more prevalent in cases than in referents. Within DQ5, DQB1*0501 was particularly frequent (OR 3.0; 95% CI 1.2, 7.4). Conclusion DQB1*05 gene confers susceptibility to develop specific IgE antibodies against HHPA, MHHPA and a non-significant trend with MTHPA. DQB1*0501 is protective for other low molecular chemical sensitizers (isocyanates and plicatic acid) which may indicate varying affinities for the corresponding specific class II molecules.
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| 28. |
- Kinhult, Johan, et al.
(författare)
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Increased expression of surface activation markers on neutrophils following migration into the nasal lumen
- 2003
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Ingår i: Clinical and Experimental Allergy. - : Wiley-Blackwell. - 0954-7894 .- 1365-2222. ; 33:8, s. 1141-1146
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The sequence of events following the recruitment of a free-flowing neutrophil in the peripheral circulation, via adhesion, migration and release of mediators, to a neutrophil on the surface of the nasal epithelium is a co-ordinated process. Little is known about the state of neutrophil activation following this course of events.OBJECTIVES: To investigate the expression of surface activation markers on neutrophils, reflecting activation during their recruitment to the nose, and to see whether the inflammatory process during allergic rhinitis influences this process.METHOD: Nine healthy controls and 12 patients with grass pollen-induced intermittent allergic rhinitis were investigated during the peak of the pollen season. The expression of CD11b, CD66b and CD63 on the neutrophil cell surface, as a reflection of activation, was analysed using flow cytometry. Neutrophils were derived from peripheral blood and nasal lavage fluid. In addition, eosinophil cationic protein (ECP) and myeloperoxidase (MPO) as well as L-, P- and E-selectins in the nasal lavage fluid were analysed using RIA and ELISA, respectively.RESULTS: A marked increase in the expression of all three CD markers on the neutrophil cell surface was noticed following migration from the bloodstream to the surface of the nasal mucosa. At the peak of the grass pollen season, the MPO levels increased, reflecting an increase in the total number of nasal fluid neutrophils. In parallel, the expression of CD11b was further augmented. The expression of the CDb11b was reduced on neutrophils remaining in the circulation. In addition, the level of L-selectin was reduced on neutrophils derived from the blood during allergic inflammation.CONCLUSION: Neutrophils might become activated during their transfer from the blood to the surface of the nasal mucosa, but these changes may also be due to depletion of activated neutrophils in the blood via activated endothelial/epithelial adhesion and chemoattractant measures. The increased expression of surface activation markers during allergic rhinitis suggests roles for neutrophils in the inflammatory process.
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| 29. |
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| 30. |
- Levin, Mattias, et al.
(författare)
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Diversity of IgE-encoding transcripts in sinus mucosa of subjects diagnosed with non-allergic fungal eosinophilic sinusitis
- 2011
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 41:6, s. 811-820
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in UndeterminedBackground The role of allergy in the aetiopathogenesis of chronic rhinosinusitis (CRS) remains controversial. For example, in some cases with sinus fungal infections allergy can be demonstrated by standard tests. In other cases, such signs can be absent despite elevated levels of IgE-positive cells in sinus tissue and the presence of IgE and eosinophils in the sinus mucous. Objective To define the nature of molecular diversity in antibodies of the IgE isotype at the site of local inflammation in subjects diagnosed with non-allergic fungal eosinophilic sinusitis (NAFES). Methods The local occurrence and sequence characteristics of IgE-encoding transcripts in NAFES patients were investigated and compared with sequences found in subjects diagnosed with CRS featuring systemic allergy. These sequences have also been compared with other reported IgE-encoding transcriptomes. Results IGHV genes derived from major subgroups 1, 3, 4 and 5 and a diverse set of IGHD and IGHJ genes were shown to create the IgE repertoire in patients diagnosed with NAFES and CRS. The average lengths of the third hypervariable loop in these populations were 15.8 and 14.6 residues. The sequences showed evidence of extensive somatic hypermutation (mutation frequency: NAFES, 6.4±3.2%; CRS, 7.0±4.4%) with substitutions targeted to complementarity-determining regions. These sequence collections thus show extensive similarities to those found in other polyclonal Ig repertoires including those encoding IgE. Conclusion and Clinical Relevance We conclude that sinus IgE-encoding transcripts in subjects diagnosed with NAFES show evidence of conventional IgE responses and we suggest that allergens with characteristics of classical antigens should be investigated for a role in the local response occurring in NAFES. This investigation illustrates that assessment of local immunity might be an important diagnostic tool in conditions like NAFES with no systemic signs of allergy to identify or rule out an allergic component of the patient's disease.
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| 31. |
- Lindstedt, Malin, et al.
(författare)
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Individuals with occupational allergy to detergent enzymes display a differential transcriptional regulation and cellular immune response
- 2005
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 35:2, s. 199-206
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Tidskriftsartikel (refereegranskat)abstract
- Background: In spite of significant safety measures, allergy to industrial enzymes remains a major concern. The increasing prevalence of occupational allergy emphasizes the need to investigate the functional properties of enzyme-exposed dendritic cells (DCs), as DCs possess a potent ability to activate allergen-specific T cells. Objective: This study aims at elucidating the molecular mechanisms underlying allergic immune responses to lipase, an industrial enzyme. For this purpose, we studied the effect of both hypoallergenic and wild-type lipase on the transcriptional regulation in DCs and their stimulatory effect on memory CD4+ T cells. Methods: Five individuals with documented lipase allergy were tested for specific serum IgE. DCs from these individuals, stimulated with lipases, were assayed for their ability to affect proliferation and polarization of memory T cells. The effect of lipases on transcriptional activity in DCs was evaluated using global expression analysis. Results: Lipase-specific IgE levels varied considerably between donors, with donor 4 exhibiting highest levels, and a potent specific CD4+ T cell recall response was demonstrated only for donor 4. No difference was detected in cytokine profile when T cells from donor 4 were co-cultured with DCs pulsed with either hypoallergenic or wild-type lipase, as demonstrated by high IL-4 and IL-13, and low IFN-? production. However, the lipases induced different genetic signatures in DCs from donor 4, as compared with the non-responders. Conclusions: DCs from individuals with clinically diagnosed allergy to lipase displayed a differential response to stimulation with hypoallergenic and wild-type lipase in vitro. Only allergen-pulsed DCs from donor 4 were able to induce CD4+ T cell proliferation. The lipase-specific T cells displayed a T-helper type 2 phenotype, which was not altered by hypoallergenic lipase-pulsed DCs. Furthermore, DCs derived from donor 4 and stimulated with either of the lipases displayed different transcriptional profiles, as compared with the other donors. These signatures represent genes of potential importance for an immunoregulatory role of DC in an ongoing allergic response. © 2005 Blackwell Publishing Ltd.
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| 32. |
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| 33. |
- Oxelius, Vivi-Anne, et al.
(författare)
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Immunoglobulin constant heavy G chain genes as risk factors in childhood allergies.
- 2006
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 36:12, s. 1616-1624
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Tidskriftsartikel (refereegranskat)abstract
- Background Several candidate genes have been found to be associated with the inflammatory response of IgE-mediated allergy, so also the immunoglobulin constant heavy G chain (IGHG) genes. The IGHG genes are situated close to the IGHE gene on chromosome 14q32, 5'μ, δ, γ3, γ1, α1, γ2, γ4, e, α2, 3'. They are inherited in a Mendelian fashion and expressed randomly in allelic exclusion. The alternative and functionally different γ3, γ1 and γ2 gene variants are found in four IGHG haplotypes, coding four B cell variants. Objective The aim of this study was to assess the frequency of different IGHG genes in relation to phenotypes associated with allergy, in a case–control study. Methods We identified the constant heavy-chain genes of IgG in 198 allergic and non-allergic children participating in the Phase II of the International Study of Asthma and Allergy in Children. The IGHG genes were assessed by the alternative serum IgG subclass allotypes expressing the alternative alleles of γ3, γ1 and γ2 genes, using ELISA and double immunodiffusion. Results The IGHG*bfn haplotype (=B1 cells) and IGHG2*n allele dominated (51% vs. 24%, P=0.002) and the IGHG*bf-n haplotype (=B2 cells) was infrequent (16% vs. 52%, P<0.001) in allergic children with a family history of allergy, clinical manifest allergy and positive skin prick test (SPT). The frequency of IGHG genes was similar in children with maternal and paternal heredity and in children with wheezing, eczema or rhinitis, as well as in children with different positive SPT. The IGHG*bfn haplotype with the IGHG2*n allele was strongly associated with heredity for allergy. The IGHG*bf-n haplotype was inversely related to allergy. Conclusions IgG allotypes, immunochemical and functional variants of IgG molecules from IGHG genes are associated with atopy. The IGHG*bfn haplotype (=B1 cells) with the IGHG2*n allele dominates, associated with an increased risk for atopy. In contrast, the IGHG*bf-n haplotype (=B2 cells) with the IGHG2*-n allele is associated with low risk.
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| 34. |
- Persson, Carl, et al.
(författare)
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Airway permeability
- 1995
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222. ; 25:9, s. 807-814
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Forskningsöversikt (refereegranskat)
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| 35. |
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| 36. |
- Persson, Carl, et al.
(författare)
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Roles of plasma exudation in asthma and COPD
- 2009
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 39:11, s. 1626-1629
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Cite this as: C. Persson and L. Uller, Clinical & Experimental Allergy, 2009 (39) 1626-1629.
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| 37. |
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| 38. |
- Tufvesson, Ellen, et al.
(författare)
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Cysteinyl-leukotriene levels in sputum differentiate asthma from rhinitis patients with or without bronchial hyperresponsiveness.
- 2007
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 37:7, s. 1067-1073
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Tidskriftsartikel (refereegranskat)abstract
- Background We have previously reported that asthma differs from rhinitis with or without bronchial hyperresponsiveness in the perception and degree of lower airway inflammation. Objective The aim of the present study was to investigate whether sputum levels of inflammatory markers could further distinguish these patient groups. Methods Patients with seasonal allergic rhinitis with or without asthma or bronchial hyperresponsiveness to methacholine were investigated. Induced sputum was performed during as well as off season, and analysed for cysteinyl-leukotrienes, hyaluronan, eosinophilic cationic protein (ECP) and other inflammatory markers. Resutls Asthmatic patients differentiated from those with rhinitis with or without bronchial hyperresponsiveness in levels of cysteinyl-leukotrienes [geometric mean: 3.3 (lower 95%-upper 95% confidence interval (CI) of geometric mean: 1.9-5.1) vs. 1.4 (0.9-2.2) and 0.7 (0.3-1.6) pg/mu g total protein] and hyaluronan [0.30 (0.22-0.43) vs. 0.15 (0.10-0.20) and 0.20 (0.12-0.35) ng/mu g total protein] in sputum. The levels of cysteinyl-leukotrienes decreased in sputum from the asthmatic patients, while the levels of hyaluronan remained elevated off-season. Furthermore, elevated levels of ECP were noticed among both the asthmatic and rhinitis patients with hyperresponsiveness compared with controls [0.022 (0.014-0.033) and 0.015 (0.011-0.021) compared with 0.010 (0.007-0.014) ng/mu g total protein]. The level of ECP remained elevated off season. Conclusions Cysteinyl-leukotrienes are possibly more related to mast cell-mediated inflammation and remodelling, also indicated by increased levels of hyaluronan during and off season. This inflammation may be partly different from the eosinophil-driven inflammation.
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| 39. |
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| 40. |
- Virtala, R, et al.
(författare)
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Airway inflammation evaluated in a human nasal lipopolysaccharide challenge model by investigating the effect of a CXCR2 inhibitor.
- 2012
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 42:4, s. 590-596
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The existence of a link between inflammation in upper and lower airways is well established. It may therefore be assumed that the nose could be used to study inflammatory events in the lower airways. OBJECTIVE: This study aimed to evaluate a lipopolysaccharide (LPS) nasal challenge model by investigating the effect of the CXCR2 inhibitor AZD8309 on neutrophilic inflammation. METHODS: A total of 18 healthy volunteers were randomized in a placebo-controlled, double-blind, cross-over study. AZD8309 or placebo was dosed for 3 days. Subjects were challenged nasally with LPS (50 μg/nostril), and nasal lavage was performed 6 and 24 h later. Leucocytes, neutrophils and inflammatory mediators were assessed in the lavage fluid. The outcome was compared with data from analogous experiments performed in a model of inhaled LPS followed by induced sputum. This trial was registered in the Current Controlled Trials register (ISRCTN trial number: ISRCTN46666382). RESULTS: The leucocytes in nasal lavage consisted to 99% of neutrophils on average. Treatment with AZD8309 reduced the leucocyte count to 48% of placebo 6 h after the LPS challenge. There was also a reduction in LTB4 levels to 45% of placebo after 6 h and in the neutrophil elastase activity after 24 h. No major adverse events were seen with either AZD8309 or placebo. The nasal LPS model induced only minimal local irritation and no signs of systemic inflammation. CONCLUSIONS AND CLINICAL RELEVANCE: LPS-induced neutrophil recruitment was reduced by inhibition of CXCR2. This outcome mimicked the response previously seen in a lower airway LPS model. Hence, the nasal model offers a convenient and well-tolerated alternative for pharmacological evaluation of anti-inflammatory drugs affecting neutrophilic migration and activity.
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| 41. |
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| 42. |
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| 43. |
- Annus, T, et al.
(författare)
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Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren
- 2001
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 31:12, s. 1846-1853
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Tidskriftsartikel (refereegranskat)abstract
- Background: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. Objective: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. Methods: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Link÷ping (n = 911) and ╓stersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Results: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in ╓stersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Link÷ping and 58% in ╓stersund) bronchial hyper-responsiveness (BHR) (48% in Link÷ping and ╓stersund) and anti-asthmatic treatment (63% in Link÷ping and 81% in ╓stersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (╓stersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. Conclusions: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.
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| 44. |
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| 45. |
- Gehring, U, et al.
(författare)
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Asthma and allergic symptoms in relation to house dust endotoxin : Phase Two of the International Study on Asthma and Allergies in Childhood (ISAAC II)
- 2008
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 38:12, s. 1911-1920
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several studies have consistently reported inverse associations between exposure to endotoxin in house dust and atopy. With regard to the association between house dust endotoxin and asthma, the results are inconsistent. Objectives: To study the association between house dust endotoxin levels and respiratory symptoms and atopy in populations from largely different countries. Methods: Data were collected within the International Study on Asthma and Allergies in Childhood Phase Two, a multi-centre cross-sectional study of 840 children aged 9-12 years from six centres in the five countries of Albania, Italy, New Zealand, Sweden and the United Kingdom. Living room floor dust was collected and analysed for endotoxin. Health end-points and demographics were assessed by standardized questionnaires. Atopy was assessed by measurements of allergen-specific IgE against a panel of inhalant allergens. Associations between house dust endotoxin and health outcomes were analysed by logistic regression. Odds ratios (ORs) were presented for an overall interquartile range increase in exposure. Results: Many associations between house dust endotoxin in living room floor dust and health outcomes varied between countries. Combined across countries, endotoxin levels were inversely associated with asthma ever [adjusted OR (95% confidence interval (CI)) 0.53 (0.29-0.96) for endotoxin levels per m(2) of living room floor] and current wheeze [adjusted OR (95% CI) 0.77 (0.64-0.93) for endotoxin levels per gram of living room floor dust]. There were inverse associations between endotoxin concentrations and atopy, which were statistically significant in unadjusted analyses, but not after adjustment for gender, parental allergies, cat and house dust mite allergens. No associations were found with dust quantity and between endotoxin exposure and hayfever. Conclusion: These findings suggest an inverse association between endotoxin levels in living room floor dust and asthma in children.
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| 46. |
- Lidén, Maria, et al.
(författare)
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Cow's milk protein sensitivity assessed by the mucosal patch technique is related to irritable bowel syndrome in patients with primary Sjögren's syndrome
- 2008
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 38:6, s. 929-935
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Patients with primary Sjögren's syndrome (pSS) are reported to have a variety of gastrointestinal symptoms partly attributed to an overrepresentation of celiac disease. We have observed that irritable bowel syndrome (IBS)-like symptoms are frequent complaints in this patient group. Allergic manifestations to various drugs are also common in pSS. A role of food allergy in IBS has been proposed. OBJECTIVE: This study is aimed at evaluating the mucosal response to rectal challenge with cow's milk protein (CM) in patients with pSS and relates possible CM reactivity to their intestinal symptoms. Methods: A rectal challenge with CM was performed in 21 patients with pSS and 18 healthy controls. Fifteen hours after challenge the mucosal production of nitric oxide (NO) and the release of myeloperoxidase (MPO) as signs of mucosal inflammatory reaction were measured using the mucosal patch technique. RESULTS: Eight out of 21 patients with pSS had a definite increase of mucosal NO synthesis and the luminal release of MPO after rectal CM challenge. This sign of milk sensitivity was not linked to IgG/IgA antibodies to milk proteins. The symptoms for IBS according to Rome III criteria were fulfilled in 13 patients. All patients who were CM sensitive suffered from IBS. In a small open study, patients reactive to CM reported an improvement of intestinal symptoms on a CM-free diet. CONCLUSION: A rectal mucosal inflammatory response after CM challenge is seen in 38% of patients with pSS as a sign of CM sensitivity. IBS-like symptoms were common in pSS, linked to CM sensitivity.
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| 47. |
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| 48. |
- Sjögren, Ylva Margareta, 1981-, et al.
(författare)
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Altered early infant gut microbiota in children developing allergy up to 5 years of age.
- 2009
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Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222 .- 0954-7894. ; 39:4, s. 518-526
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Early colonization with bifidobacteria and lactobacilli is postulated to protect children from allergy, while Clostridium (C.) difficile colonization might be associated with allergic disease. Previous studies of infant gut microbiota in relation to subsequent allergy development have mostly employed culture-dependent techniques, studied genera of bacteria and the follow-up period was limited to 2 years. OBJECTIVE: To relate gut microbiota in early infancy, notably bifidobacteria and lactobacilli at species level, to allergy development during the first 5 years of life and study if environmental factors influence the early infant gut microbiota. METHODS: Fecal samples were collected at 1 week, 1 month and 2 months after birth from 47 Swedish infants, followed prospectively to 5 years of age. Bacterial DNA was analysed with real-time PCR and related to allergy development, family size as well as endotoxin and Fel d 1 levels in house dust samples. Primers binding to C. difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis were used. Children regarded as allergic manifested allergic symptoms and were skin prick test positive during their first 5 years while non-allergic children were neither. RESULTS: Children who developed allergy were significantly less often colonized with lactobacilli group I (Lactobacillus (L.) rhamnosus, L. casei, L. paracasei), Bifidobacterium adolescentis and C. difficile during their first 2 months. Infants colonized with several Bifidobacterium species had been exposed to higher amounts of endotoxin and grew up in larger families than infants harbouring few species. CONCLUSION: A more diverse gut microbiota early in life might prevent allergy development and may be related to the previously suggested inverse relationship between allergy, family size and endotoxin exposure.
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| 49. |
- Bråbäck, Lennart, et al.
(författare)
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Migration and asthma medication in international adoptees and immigrant families in Sweden
- 2011
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 66, s. 571-572
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Tidskriftsartikel (refereegranskat)abstract
- Background Studies of asthma in migrant populations illustrate the effects of environmental changes. Objective In this register study we investigated the importance of exposure to a western lifestyle in different phases of development in Swedish residents with an origin in regions in the world where asthma usually is less prevalent. Methods The study population comprised 24 252 international adoptees, 47 986 foreign-born and 40 971 Swedish-born with foreign-born parents and 1 770 092 Swedish-born residents with Swedish-born parents (age 6-25 years). Purchased prescribed inhaled corticosteroids (ICS) during 2006 were used as an indicator of asthma. Results International adoptees and children born in Sweden by foreign-born parents had three-to fourfold higher rates of asthma medication compared with foreign-born children. The odds ratios (ORs) of asthma medication declined persistently with age at immigration. For adoptees the ORs compared with infant adoptees were 0.78 [95% confidence interval (CI) 0.71-0.85] for those adopted at 1-2 years, 0.51 (0.42-0.61) at 3-4 years and 0.35 (0.27-0.44) after 5 or more years of age. Corresponding ORs for foreign-born children with foreign-born parents immigrating at 0-4 years, at 5-9 years, at 10-14 years and at 15 years or more were 0.73 (0.63-0.86), 0.56 (CI 0.46-0.68) and 0.35 (CI 0.28-0.43), respectively. The ORs were only marginally affected by adjustment for region of birth and socio-economic indicators. Conclusions and Clinical Relevance Age at immigration is a more important determinant of purchased ICS than population of origin. This indicates the importance of environmental factors for asthma in schoolchildren and young adults.
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| 50. |
- Aberg, N, et al.
(författare)
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Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991.
- 1995
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Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 0954-7894. ; 25:9, s. 815-9
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Tidskriftsartikel (refereegranskat)abstract
- A previous study has shown a twofold increase in prevalence of asthma and allergic rhinitis (AR) in Swedish recruits during the 1970s. The increase was higher in more northerly colder regions.To follow up the previously found trend to increasing prevalences with time as well as the climatic variations within the country.The prevalences of asthma, allergic rhinitis and eczema were assessed using two questionnaire studies, 12 years apart (1979 and 1991) with identical questions about the diseases. The study comprised representative samples of children from the Göteborg area on the south-western coast (in 1979: 7-year-olds, n = 4255, in 1991: 7-year-olds, n = 1649) and in Kiruna, a mining town in the northernmost inland mountains (in 1979: 7-year-olds, n = 427, in 1991: 7-9-year-olds, n = 832). In 1991 there was also a personal interview and a skin-prick test (SPT) on subsamples.The prevalence of all these diseases present over the last year had roughly doubled over the 12-year period. On both occasions, most symptoms were more prevalent in the northern area. In 1991, the prevalence of one or more symptoms in Göteborg was 23.8% and 32.5% and in Kiruna 29.9% and 44.8% in the questionnaire and the interview, respectively.Asthma, AR and eczema increase continuously in prevalence in Sweden and the climatic distribution of the prevalences suggests possible major risk factors to be found in a closed indoor climate.
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