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  • Wang, Hui, et al. (författare)
  • A pathway-based approach to find novel markers of local glucocorticoid treatment in intermittent allergic rhinitis
  • 2011
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - Wiley-Blackwell. - 0105-4538 .- 1398-9995. - 1398-9995 (Electronic) 0105-4538 (Linking) ; 66:1, s. 132-140
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>BACKGROUND: Glucocorticoids (GCs) may affect the expression of hundreds of genes in different cells and tissues from patients with intermittent allergic rhinitis (IAR). It is a formidable challenge to understand these complex changes by studying individual genes. In this study, we aimed to identify (i) pathways affected by local GC treatment and (ii) examine if those pathways could be used to find novel markers of local GC treatment in nasal fluids from patients with IAR. METHODS: Gene expression microarray- and iTRAQ-based proteomic analyses of nasal fluids, nasal fluid cells and nasal mucosa from patients with IAR were performed to find pathways enriched for differentially expressed genes and proteins. Proteins representing those pathways were analyzed with ELISA in an independent material of nasal fluids from 23 patients with IAR before and after treatment with a local GC. RESULTS: Transcriptomal and proteomic high-throughput analyses of nasal fluids, nasal fluid cells and nasal mucosal showed that local GC treatment affected a wide variety of pathways in IAR such as the glucocorticoid receptor pathway and the acute phase response pathway. Extracellular proteins encoded by genes in those pathways were analyzed in an independent material of nasal fluids from patients. Proteins that changed significantly in expression included known biomarkers such as eosinophil cationic protein but also proteins that had not been previously described in IAR, namely CCL2, M-CSF, CXCL6 and apoH. CONCLUSION: Pathway-based analyses of genomic and proteomic high-throughput data can be used as a complementary approach to identify novel potential markers of GC treatment in IAR.</p>
  • Ostblom, E, et al. (författare)
  • The impact of food hypersensitivity reported in 9-year-old children by their parents on health-related quality of life
  • 2008
  • Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - John Wiley & Sons. - 0105-4538 .- 1398-9995. ; 63:2, s. 211-218
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong>BACKGROUND:</strong> There are only a few studies on the impact of food hypersensitivity (FHS) in children on health-related quality of life (HRQL). The present study was designed to examine this impact in a population-based birth cohort (BAMSE).</p><p><strong>METHODS:</strong> A nested case-control study was performed within the cohort. The parents of 1378 nine-year-old children filled out a generic questionnaire with 13 subscales (Child Health Questionnaire Parental Form 28 - CHQ-PF28) supplemented with disease-specific questions concerning FHS. There were 212 children with report of FHS. Another 221 children with allergic diseases but not FHS were examined for comparison. Furthermore, the impact of pronounced symptoms of FHS and of increasing levels of food-specific IgE antibodies on HRQL was also analysed.</p><p><strong>RESULTS:</strong> The children with FHS exhibited significantly lower scores on the subscales physical functioning, role/social limitations - physical and general health in the generic instrument. Furthermore, children with food-related symptoms from the lower airways were scored lower on Self Esteem, Parental Impact - time and Family Cohesion. Sensitization per se did not alter these patterns, but high levels of food-specific IgE-antibodies affected mental health and general health negatively. A physician's diagnosis of food allergy did not affect any of the subscales negatively.</p><p><strong>CONCLUSIONS:</strong> Parents reported that FHS exerts a negative impact on the HRQL of 9-year-old children, in particular in children with symptoms from the lower airways or if the FHS is associated with high levels of food-specific IgE-antibodies. Healthcare-givers must put major effort into improving and maintaining the HRQL of these children.</p>
  • Maurer, M, et al. (författare)
  • New topics in bradykinin research.
  • 2011
  • Ingår i: Allergy. - Wiley-Blackwell. - 1398-9995. ; 66, s. 1397-1406
  • Tidskriftsartikel (refereegranskat)abstract
    • To cite this article: Maurer M, Bader M, Bas M, Bossi F, Cicardi M, Cugno M, Howarth P, Kaplan A, Kojda G, Leeb-Lundberg F, Lötvall J, Magerl M. New topics in bradykinin research. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02686.x ABSTRACT: Bradykinin has been implicated to contribute to allergic inflammation and the pathogenesis of allergic conditions. It binds to endothelial B(1) and B(2) receptors and exerts potent pharmacological and physiological effects, notably, decreased blood pressure, increased vascular permeability and the promotion of classical symptoms of inflammation such as vasodilation, hyperthermia, oedema and pain. Towards potential clinical benefit, bradykinin has also been shown to exert potent antithrombogenic, antiproliferative and antifibrogenic effects. The development of pharmacologically active substances, such as bradykinin receptor blockers, opens up new therapeutic options that require further research into bradykinin. This review presents current understanding surrounding the role of bradykinin in nonallergic angioedema and other conditions seen by allergists and emergency physicians, and its potential role as a therapeutic target.
  • Månsson, Anne, et al. (författare)
  • NOD-like receptors in the human upper airways: a potential role in nasal polyposis.
  • 2011
  • Ingår i: Allergy. - Wiley-Blackwell. - 1398-9995. ; 66, s. 621-628
  • Tidskriftsartikel (refereegranskat)abstract
    • To cite this article: Månsson A, Bogefors J, Cervin A, Uddman R, Cardell LO. NOD-like receptors in the human upper airways: a potential role in nasal polyposis. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02527.x. ABSTRACT: Background: Nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) are newly discovered cytosolic receptors belonging to the pattern-recognition receptor family. They detect various pathogen-associated molecular patterns, triggering an immune response. The knowledge about these receptors, and their role in health and disease, is limited. The aim of the present study was to characterize the expression of NOD1, NOD2, and NALP3 in the human upper airways. Methods: Surgical samples were obtained from patients with tonsillar disease (n = 151), hypertrophic adenoids (n = 9), and nasal polyposis (n = 24). Nasal biopsies were obtained from healthy volunteers (n = 10). The expression of NOD1, NOD2, and NALP3 was analyzed using real-time PCR and immunohistochemistry. Results: Expression of NOD1, NOD2, and NALP3 mRNA and protein were seen in all tissue specimens. The NLR mRNA was found to be higher in nasal polyps than in normal nasal mucosa, and local steroid treatment reduced the NLR expression in polyps. In contrast, tonsillar infection with Streptococcus pyogenes or Haemophilus influenzae did not affect the NLR expression. Conclusions: The present study demonstrates the presence of NLRs in several upper airway tissues and highlights a potential role of NLRs in chronic rhinosinusitis with polyps.
  • Bogefors, J, et al. (författare)
  • Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis?
  • 2010
  • Ingår i: Allergy. - Wiley-Blackwell. - 1398-9995. ; May 4, s. 1222-1226
  • Tidskriftsartikel (refereegranskat)abstract
    • To cite this article: Bogefors J, Rydberg C, Uddman R, Fransson M, Månsson A, Benson M, Adner M, Cardell LO. Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis? Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02315.x. Abstract Background: Recently, a new set of pattern-recognition receptors, the nucleotide-binding oligomerization domain (Nod)-like receptors (NLRs), have emerged. Their activation, either by allergens or microbes, triggers an inflammatory response. The knowledge about NLRs in human airways is limited. Aim of the study: To investigate presence of NLRs in the human nose of healthy individuals and patients with intermittent allergic rhinitis outside and during pollen season. Methods: The expression of Nod1, Nod2, and Nalp3 in nasal biopsies was determined with real-time RT-PCR and immunohistochemistry. Cultured primary human nasal epithelial cells (HNECs) were analyzed using real-time RT-PCR and flow cytometry to further verify the presence of NLRs in the epithelium. Results: Immunohistochemical analysis revealed presence of Nod1, Nod2, and Nalp3 in the nasal epithelium. This was corroborated in cultured HNECs. Patients suffering from symptomatic allergic rhinitis exhibited lower Nod1 and Nalp3 mRNA levels than both controls and patients during pollen season. Nod2 expression was found in all specimens tested, but no differences were seen between the three groups. Conclusion: Nod1, Nod2, and Nalp3 receptors were found to be present in the human nose. The expression of Nod1 and Nalp3 were down-regulated during pollen season among patients with allergic rhinitis. This opens up for new insights and novel therapeutic strategies in inflammatory airway disease.
  • Bossios, Apostolos, 1969-, et al. (författare)
  • IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome.
  • 2009
  • Ingår i: Allergy. - 1398-9995. ; :Nov 26
  • Tidskriftsartikel (refereegranskat)abstract
    • To cite this article: Bossios A, Sjöstrand M, Dahlborn A-K, Samitas K, Malmhäll C, Gaga M, Lötvall J. IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome. Allergy 2009. DOI: 10.1111/j.1398-9995.2009.02271.x.Abstract Background: Eosinophils develop from hematopoietic CD34(+) progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34(+) cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34(+) cells can be found in situ in ongoing eosinophilic disease. Methods: CD34(+) cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg-Strauss syndrome were analyzed by flow cytometry for CD34(+)/IL-5(+) cells, and immunohistochemical staining of CD34(+)/IL-5(+) cells in bronchial biopsies from an asthmatic patient was performed. Results: Both PB and BM CD34(+) cells can produce and release IL-5 when stimulated in vitro. In the Churg-Strauss patient, IL-5-producing CD34(+) cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34(+)/IL-5(+) cells were present in a patient with asthma. Conclusion: CD34(+) cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34(+) progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases.
  • Papadopoulos, N G, et al. (författare)
  • Viruses and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE* systematic review.
  • 2010
  • Ingår i: Allergy. - 1398-9995.
  • Forskningsöversikt (refereegranskat)abstract
    • To cite this article: Papadopoulos NG, Christodoulou I, Rohde G, Agache I, Almqvist C, Bruno A, Bonini S, Bont L, Bossios A, Bousquet J, Braido F, Brusselle G, Canonica GW, Carlsen KH, Chanez P, Fokkens WJ, Garcia-Garcia M, Gjomarkaj M, Haahtela T, Holgate ST, Johnston SL, Konstantinou G, Kowalski M, Lewandowska-Polak A, Lødrup-Carlsen K, Mäkelä M, Malkusova I, Mullol J, Nieto A, Eller E, Ozdemir C, Panzner P, Popov T, Psarras S, Roumpedaki E, Rukhadze M, Stipic-Markovic A, Todo Bom A, Toskala E, van Cauwenberge P, van Drunen C, Watelet JB, Xatzipsalti M, Xepapadaki P, Zuberbier T. Viruses and bacteria in acute asthma exacerbations - A GA(2) LEN-DARE systematic review. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02505.x. ABSTRACT: A major part of the burden of asthma is caused by acute exacerbations. Exacerbations have been strongly and consistently associated with respiratory infections. Respiratory viruses and bacteria are therefore possible treatment targets. To have a reasonable estimate of the burden of disease induced by such infectious agents on asthmatic patients, it is necessary to understand their nature and be able to identify them in clinical samples by employing accurate and sensitive methodologies. This systematic review summarizes current knowledge and developments in infection epidemiology of acute asthma in children and adults, describing the known impact for each individual agent and highlighting knowledge gaps. Among infectious agents, human rhinoviruses are the most prevalent in regard to asthma exacerbations. The newly identified type-C rhinoviruses may prove to be particularly relevant. Respiratory syncytial virus and metapneumovirus are important in infants, while influenza viruses seem to induce severe exacerbations mostly in adults. Other agents are relatively less or not clearly associated. Mycoplasma and Chlamydophila pneumoniae seem to be involved more with asthma persistence rather than with disease exacerbations. Recent data suggest that common bacteria may also be involved, but this should be confirmed. Although current information is considerable, improvements in detection methodologies, as well as the wide variation in respect to location, time and populations, underline the need for additional studies that should also take into account interacting factors.
  • Tomassen, P, et al. (författare)
  • Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis - a GA(2) LEN study.
  • 2011
  • Ingår i: Allergy. - 1398-9995. ; 66:4, s. 556-561
  • Tidskriftsartikel (refereegranskat)abstract
    • To cite this article: Tomassen P, Newson RB, Hoffmans R, Lötvall J, Cardell LO, Gunnbjörnsdóttir M, Thilsing T, Matricardi P, Krämer U, Makowska JS, Brozek G, Gjomarkaj M, Howarth P, Loureiro C, Toskala E, Fokkens W, Bachert C, Burney P, Jarvis D. Reliability of EP3OS symptom criteria and nasal endoscopy in the assessment of chronic rhinosinusitis - a GA(2) LEN study. Allergy 2010; DOI: 10.1111/j.1398-9995.2010.02503.x. ABSTRACT: Background:  The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA(2) LEN European survey. Methods:  On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chance-corrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. Results:  There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers (-3.0%, 95% CI: -5.0 to -1.0%, I(2)  = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. Conclusion:  Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS.
  • Schlehofer, B, et al. (författare)
  • Primary brain tumours and specific serum immunoglobulin E: a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort.
  • 2011
  • Ingår i: Allergy. - Wiley-Blackwell. - 1398-9995. ; 66, s. 1434-1441
  • Tidskriftsartikel (refereegranskat)abstract
    • To cite this article: Schlehofer B, Siegmund B, Linseisen J, Schüz J, Rohrmann S, Becker S, Michaud D, Melin B, Bas Bueno-de-Mesquita H, Peeters PHM, Vineis P, Tjonneland A, Olsen A, Overvad K, Romieu I, Boeing H, Aleksandrova K, Trichopoulou A, Bamia C, Lagiou P, Sacerdote C, Palli D, Panico S, Sieri S, Tumino R, Sanchez M-J, Rodriguez L, Dorronsoro M, Duell EJ, Chirlaque M-D, Barricarte A, Borgquist S, Manjer J, Gallo V, Allen NE, Key TJ, Riboli E, Kaaks R, Wahrendorf J. Primary brain tumours and specific serum immunoglobulin E: a case-control study nested in the European Prospective Investigation into Cancer and Nutrition cohort. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02670.x. ABSTRACT: Background: Case-control studies suggest that patients with allergic diseases have a lower risk of developing glioma but not meningioma or schwannoma. However, those data can be differentially biased. Prospective studies with objective measurements of immunologic biomarkers, like immunoglobulin E (IgE), in blood obtained before cancer diagnosis could help to clarify whether an aetiological association exists. Methods: The present case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) measured specific serum IgE as a biomarker for the most common inhalant allergens in 275 glioma, 175 meningioma and 49 schwannoma cases and 963 matched controls using the ImmunoCAP specific IgE test. Subjects with an IgE level ≥0.35 kUA/l (kilo antibody units per litre) were classified as sensitized by allergens. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by adjusted conditional logistic regression models for each tumour subtype. The effect of dose-response relationship was assessed in five increasing IgE level categories to estimate P-values for trend. Results: The risk of glioma was inversely related to allergic sensitization (OR = 0.73; 95% CI 0.51-1.06), especially pronounced in women (OR = 0.53; 95% CI 0.30-0.95). In dose-response analyses, for high-grade glioma, the lowest OR was observed in sera with the highest IgE levels (P for trend = 0.04). No association was seen for meningioma and schwannoma. Conclusion: The results, based on serum samples prospectively collected in a cohort study, provide some support for the hypothesis that individuals with allergic sensitization are at reduced risk of glioma and confirm results from previous case-control studies.
  • Stalder, J-F, et al. (författare)
  • Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe.
  • 2011
  • Ingår i: Allergy. - Wiley-Blackwell. - 1398-9995. ; 66, s. 1114-1121
  • Tidskriftsartikel (refereegranskat)abstract
    • To cite this article: Stalder J-F, Barbarot S, Wollenberg A, Holm EA, De Raeve L, Seidenari S, Oranje A, Deleuran M, Cambazard F, Svensson A, Simon D, Benfeldt E, Reunala T, Mazereeuv J, Boralevi F, Kunz B, Misery L, Mortz CG, Darsow U, Gelmetti C, Diepgen T, Ring J, Moehrenschlager M, Gieler U, Taïeb A, for the PO-SCORAD Investigators Group. Patient-Oriented SCORAD (PO-SCORAD): a new self-assessment scale in atopic dermatitis validated in Europe. Allergy 2011; DOI: 10.1111/j.1398-9995.2011.02577.x. ABSTRACT: Background: Patient-oriented medicine is an emerging concept, encouraged by the World Health Organization, to greater involvement of the patient in the management of chronic diseases. The Patient-Oriented SCORing Atopic Dermatitis (PO-SCORAD) index is a self-assessment score allowing the patient to comprehensively evaluate the actual course of atopic dermatitis (AD), using subjective and objective criteria derived mainly from the SCORAD, a validated AD severity clinical assessment tool. Objectives: To validate the PO-SCORAD index in a large European population of patients exhibiting all forms of AD severity by assessing its correlation with the SCORAD index. Patients/methods: Four hundred and seventy-one patients (185 adults, 286 children) consulting for AD in hospitals from 9 European countries were recruited. The investigators and the patients used the SCORAD and PO-SCORAD scales, respectively, to assess AD severity at inclusion (D0) and 28 ± 7 days later (D28). Results: Patient-Oriented SCORing Atopic Dermatitis and SCORAD scores were significantly correlated at D0 [r = 0.67 (95% CI: 0.62; 0.72), P < 0.0001]. Consistency was confirmed at D28, with a stronger linear correlation between both scales [r = 0.79 (95% CI: 0.75; 0.83), P < 0.0001]. Absolute changes from baseline in SCORAD and PO-SCORAD scores were also significantly correlated [r= 0.71 (95% CI: 0.64; 0.76), P < 0.0001]. Although no specific intervention was investigated, AD improved over the study, with a decrease of PO-SCORAD and SCORAD scores from D0 to D28 by -19.19% and -24.39%, respectively. The consistency of the correlations was similar in the adult and children groups. Conclusions: This study validated the use of PO-SCORAD to self-assess AD severity and demonstrated its good correlation with SCORAD.
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