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  • 1. Brannan, J D
    et al.
    Gulliksson, Magdalena
    Anderson, S D
    Chew, N
    Seale, J P
    Kumlin, Maria
    Sophiahemmet University.
    Inhibition of mast cell PGD2 release protects against mannitol-induced airway narrowing2006In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, no 5, p. 944-50Article in journal (Refereed)
    Abstract [en]

    Mannitol inhalation increases urinary excretion of 9alpha,11beta-prostaglandin F2 (a metabolite of prostaglandin D2 and marker of mast cell activation) and leukotriene E4. The present study tested the hypothesis that beta2-adrenoreceptor agonists and disodium cromoglycate (SCG) protect against mannitol-induced bronchoconstriction by inhibition of mast cell mediator release. Fourteen asthmatic subjects inhaled mannitol (mean dose 252+/-213 mg) in order to induce a fall in forced expiratory volume in one second (FEV1) of > or = 25%. The same dose was given 15 min after inhalation of formoterol fumarate (24 microg), SCG (40 mg) or placebo. Pre- and post-challenge urine samples were analysed by enzyme immunoassay for 9alpha,11beta-prostaglandin F2 and leukotriene E4. The maximum fall in FEV1 of 32+/-10% on placebo was reduced by 95% following formoterol and 63% following SCG. Following placebo, there was an increase in median urinary 9alpha,11beta-prostaglandin F2 concentration from 61 to 92 ng.mmol creatinine(-1), but no significant increase in 9alpha,11beta-prostaglandin F2 concentration in the presence of either formoterol (69 versus 67 ng.mmol creatinine(-1)) or SCG (66 versus 60 ng.mmol creatinine(-1)). The increase in urinary leukotriene E4 following placebo (from 19 to 31 ng.mmol creatinine(-1)) was unaffected by the drugs. These results support the hypothesis that the drug effect on airway response to mannitol is due to inhibition of mast cell prostaglandin D2 release.

  • 2. Dahlén, Sven-Eric
    et al.
    Kumlin, Maria
    Sophiahemmet University.
    Monitoring mast cell activation by prostaglandin D2 in vivo2004In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 59, no 6, p. 453-5Article in journal (Other academic)
  • 3. Gaber, Flora
    et al.
    Acevedo, F
    Delin, I
    Sundblad, Britt-Marie
    Palmberg, Lena
    Larsson, Kjell
    Kumlin, Maria
    Sophiahemmet University.
    Dahlén, Sven-Eric
    Saliva is one likely source of leukotriene B4 in exhaled breath condensate2006In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 28, no 6, p. 1229-35Article in journal (Refereed)
    Abstract [en]

    Leukotriene (LT)B4 in exhaled breath condensate (EBC) has been reported to be elevated in airway inflammation. The origin of leukotrienes in EBC is, however, not established. The aims of this study are to measure LTB4 levels in EBC collected in two challenges characterised by a strong neutrophilic airway inflammation and to compare LTB4 levels in EBC with levels in sputum and saliva. LTB4 and alpha-amylase were measured in EBC from 34 healthy subjects exposed in a pig confinement building or to a lipopolysaccharide provocation. These markers were also measured in induced sputum in 11 of the subjects. For comparison, LTB4 and alpha-amylase were measured in saliva from healthy subjects. Only four out of 102 EBC samples had detectable LTB4 (28-100 pg x mL(-1)). alpha-amylase activity was detected in the LTB4-positive samples. In contrast, LTB4 was detected in all examined sputum supernatants in the same study (median 1,190 pg x mL(-1)). The median LTB4 level in saliva was 469 pg x mL(-1). High levels of leukotriene B4 in saliva and the presence of leukotriene B4 in exhaled breath condensate only when alpha-amylase was detected, indicate that leukotriene B4 found in exhaled breath condensate is the result of saliva contamination. As leukotriene B4 was consistently present in sputum supernatants, exhaled breath condensate may be inappropriate for monitoring airway leukotriene B4.

  • 4. Gaber, Flora
    et al.
    Daham, K
    Higashi, A
    Higashi, N
    Gülich, A
    Delin, Ingrid
    James, A
    Skedinger, M
    Gyllfors, Per
    Nord, M
    Dahlén, Sven-Erik
    Kumlin, Maria
    Sophiahemmet University.
    Dahlén, B
    Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma2008In: Thorax, ISSN 1468-3296, Vol. 63, no 12, p. 1076-82Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E(4) (LTE(4)) is increased in aspirin-intolerant asthma. A study was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B(4) (LTB(4)) in saliva, sputum and ex vivo stimulated blood in subjects with aspirin-intolerant and aspirin-tolerant asthma. The effects of aspirin- and allergen-induced bronchoconstriction on leukotriene levels in saliva and ex vivo stimulated blood were also compared with the effects of the provocations on urinary mediators. METHODS: Induced sputum, saliva, urine and blood were obtained at baseline from 21 subjects with asthma. At a separate visit, 11 subjects showed a positive response to lysine-aspirin inhalation and 10 were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of CysLTs and LTB(4) and the prostaglandin D(2) metabolite 9alpha,11beta-prostaglandin F(2) were performed and the fraction of exhaled nitric oxide was measured. RESULTS: Subjects with aspirin-intolerant asthma had higher exhaled nitric oxide levels and higher baseline levels of CysLTs in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in LTB(4) levels between the groups. Levels of urinary LTE(4) and 9alpha,11beta-prostaglandin F(2) increased after aspirin provocation whereas leukotriene levels in saliva and ex vivo stimulated blood did not increase. CONCLUSION: These findings support a global and specific increase in CysLT production in aspirin-intolerant asthma. Measurement of CysLTs in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.

  • 5. Gaber, Flora
    et al.
    James, Anna
    Delin, Ingrid
    Wetterholm, Anders
    Sampson, Anthony P
    Dahlén, Barbro
    Dahlén, Sven-Erik
    Kumlin, Maria
    Sophiahemmet University.
    Assessment of in vivo 5-lipoxygenase activity by analysis of leukotriene B4 in saliva: effects of treatment with zileuton2007In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 119, no 5, p. 1267-8Article in journal (Other academic)
  • 6.
    Gellerstedt, Linda
    et al.
    Sophiahemmet University.
    Medin, Jörgen
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Rydell Karlsson, Monica
    Sophiahemmet University.
    Nurses' experiences of hospitalised patients' sleep in Sweden: a qualitative study2015In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 24, no 23/24, p. 3664-3673Article in journal (Refereed)
    Abstract [en]

    AIMS AND OBJECTIVES:

    The aim was to describe nurses' experiences of patients' sleep at an emergency hospital and their perceptions of sleep-promoting interventions.

    BACKGROUND:

    Promotion of patients' sleep during hospital care is an important intervention for the nursing profession. To promote sleep and to initiate sleep-promoting interventions, nurses need basic knowledge about sleep and its physiology. Therefore, it is of importance to explore and expand knowledge about how nurses experience patients' sleep and how they perceive working with it while providing care.

    DESIGN:

    A qualitative descriptive design was used.

    METHODS:

    Data were collected from four focus groups and seven individual interviews. A total of twenty-two registered nurses participated. Data were analysed using a qualitative content analysis.

    RESULTS:

    Nurses expressed a desire and an ambition to work in ways that promote patients' sleep during hospitalisation. Nurses reported that health care services and emergency hospitals were not organised according to patients' perspective and needs. Furthermore, they did not have opportunities to work effectively to promote sleep according to the patients' wishes. Several nurses stated that they did not have sufficient knowledge about sleep and that they did the best they could under prevailing circumstances. Nurses emphasised the importance of sleep for patients and that it was an area that should be given far greater priority.

    CONCLUSIONS:

    The results indicate that nurses currently have insufficient knowledge about sleep and sleep-promoting interventions. These aspects of nursing is based on personal experience and common sense rather than being evidence based. Furthermore, sleep as a nursing topic needs to be developed and given more focus in order for nurses to be able to deliver high quality care at emergency hospitals.

    RELEVANCE TO CLINICAL PRACTICE:

    Nurses require more knowledge and education to gain deeper understanding of sleep and to deliver evidence-based, high quality care.

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  • 7.
    Gellerstedt, Linda
    et al.
    Sophiahemmet University.
    Medin, Jörgen
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Rydell Karlsson, Monica
    Nursing care and management of patients' sleep during hospitalisation: a cross-sectional study2019In: Journal of Clinical Nursing, ISSN 0962-1067, E-ISSN 1365-2702, Vol. 28, no 19-20, p. 3400-3407Article in journal (Refereed)
    Abstract [en]

    AIM: To explore and describe how patients' sleep is addressed at acute-care hospitals in Sweden with regard to nursing care, management, and the development of knowledge in this area.

    BACKGROUND: Sleep is a basic human need and thus important for health and health maintenance. Patients describe sleeping in hospital as a stressor, and research shows that nurses tend to underestimate patients' perceived problems with sleep during hospitalization. How do nursing staff at acute hospitals address patients' sleep and the development of knowledge in this area?.

    DESIGN/METHOD: A cross-sectional descriptive study was conducted based on data collected through a web survey. Head nurses, registered nurses, nursing care developers, and local training supervisors at 36 randomized acute-care hospitals in Sweden were invited to participate. This study was executed and reported in accordance with SQUIRE 2.0.

    RESULTS: The results of the survey (53 responses from 19 wards at 15 acute-care hospitals) showed that no policy documents exist and no current training addresses sleep during hospital stay. All participants agreed that sleep should be considered a nursing topic and that it is important for hospitalized patients.

    CONCLUSION: Patients' sleep during hospitalization is undermanaged at acute-care hospitals. Nurses, health care managers, and organizations face challenges if they are to achieve better outcomes.

    RELEVANCE TO CLINICAL PRACTICE: This study shows that nurses do consider patients' sleep important and addressing sleep as part of nursing care. Future studies in the area should focus on what kinds of support and education are needed in the clinical context. This article is protected by copyright. All rights reserved.

  • 8.
    Gellerstedt, Linda
    et al.
    Sophiahemmet University.
    Medin, Jörgen
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Rydell Karlsson, Monica
    Sophiahemmet University.
    Patients' experiences of sleep in hospital: a qualitative interview study2014Conference paper (Other academic)
  • 9.
    Gellerstedt, Linda
    et al.
    Sophiahemmet University.
    Medin, Jörgen
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Rydell Karlsson, Monica
    Sleep as a topic in nursing education programs? A mixed method study of syllabuses and nursing students' perceptions2019In: Nurse Education Today, ISSN 0260-6917, E-ISSN 1532-2793, Vol. 79, p. 168-174, article id S0260-6917(18)30846-3Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Sleep is a basic human need and is considered important for maintaining health. It is even more important during illness due to its impact for example on our immune system. Nurses have an important role in identifying sleep deprivation. They are also in a unique position to promote and address sleep among patients. However, it is essential that they are provided with the appropriate knowledge during training.

    AIM: To explore and describe nursing students' perceptions of preparedness to adress and support patients' sleep during hospitalization and to apply sleep-promoting interventions in a clinical context. Furthermore, the aim was to investigate if, and how, the topic of sleep is explicitly incorporated in nursing education programs.

    DESIGN: A descriptive study based on a mixed method approach.

    METHODS: Quantitative and qualitative data were collected from program and course syllabuses and intended learning outcomes from three universities. Twenty-one nursing students from the same universities were interviewed during their final year of education.

    RESULTS: The results of both quantitative and qualitative data consistently show that education regarding sleep and patients' sleep is limited and, in some respects, absent in the Bachelor of Science Nursing programs investigated.

    CONCLUSION: This study indicates that education about sleep and patients' sleep in the nursing programs studied is insufficient and limited. This gap in knowledge may lead to prospective registered nurses using their own experiences instead of evidence-based knowledge when assessing, supporting and applying sleep-promoting interventions.

  • 10.
    Gellerstedt, Linda
    et al.
    Sophiahemmet University.
    Rydell Karlsson, Monica
    Medin, Jörgen
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Patients' sleep in hospital: Outcomes of self-assessed vs objectively measured sleep as a nursing toolManuscript (preprint) (Other academic)
  • 11. Gulliksson, Magdalena
    et al.
    Brunnström, Åsa
    Johannesson, Malin
    Backman, Linda
    Nilsson, Gunnar
    Harvima, Ilkka
    Dahlén, Barbro
    Kumlin, Maria
    Sophiahemmet University.
    Claesson, Hans-Erik
    Expression of 15-lipoxygenase type-1 in human mast cells2007In: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1771, no 9, p. 1156-65Article in journal (Refereed)
    Abstract [en]

    Mast cells play a key role in the pathophysiology of asthma. These cells exert their effector functions by releasing a variety of proinflammatory and immunoregulatory compounds. Mast cells infiltrate the bronchial epithelium and smooth muscle to a higher degree in patients with asthma compared to control subjects. 15-Lipoxygenase type-1 (15-LO-1) is a prooxidant enzyme which is expressed in asthmatic lungs leading to formation of pro- and anti-inflammatory mediators. Here we report that interleukin-4 (IL-4) induced the expression of 15-LO-1 in human cord blood derived mast cells (CBMC) as demonstrated by RT-PCR, western blot and immunocytochemistry. The major metabolite of arachidonic acid formed via the 15-LO pathway in IL-4 treated CBMC was identified as 15-ketoeicosatetraenoic acid (15-KETE, also named 15-oxo-ETE) with smaller amounts of 15-hydroxyeicosatetraenoic acid (15-HETE) as identified by HPLC and mass spectrometry (MS/MS). Furthermore, immunohistochemical stainings demonstrated the expression of 15-LO-1 in mast cells in lung and skin in vivo. Osmotic activation of CBMC with mannitol resulted in activation of the 15-LO-1 pathway. In conclusion, the expression of 15-LO-1 and release of 15-LO-1 derived products by mast cells may contribute to the role of these cells in asthma and other inflammatory diseases.

  • 12. Gulliksson, Magdalena
    et al.
    Palmberg, Lena
    Nilsson, G
    Ahlstedt, S
    Kumlin, Maria
    Sophiahemmet University.
    Release of prostaglandin D2 and leukotriene C4 in response to hyperosmolar stimulation of mast cells2006In: Allergy. European Journal of Allergy and Clinical Immunology, ISSN 0105-4538, E-ISSN 1398-9995, Vol. 61, no 12, p. 1473-9Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Mannitol-induced bronchoconstriction in subjects with exercise-induced asthma is associated with increased urinary excretion of 9alpha, 11beta-PGF(2), a metabolite of prostaglandin D(2) (PGD(2)) serving as a mast cell marker. It has however been questioned whether or not human mast cells release PGD(2) and leukotriene C(4) (LTC(4)) after osmotic challenge with mannitol in vitro. METHODS: Cord blood-derived human mast cells were stimulated osmotically, immunologically or with a combination of both. Supernatants were analysed for PGD(2), LTC(4) and histamine contents with enzyme immunoassays. RESULTS: Significant release of de novo synthesized eicosanoids, predominantly PGD(2) [12 (8.8, 14) pmol/10(6)cells; median (25th, 75th percentile) but also LTC(4) (0.1 (0.08, 0.15) pmol/10(6) cells] were found in mast cells in vitro in response to 0.7 M mannitol stimulation. A massive release of histamine [70 (5.3)% of total; mean (SEM)] was also found. There were no correlations between the levels of released mediators after mannitol stimulation. In contrast, there was a correlation between release of PGD(2) and LTC(4), following immunological stimulation. CONCLUSION: The findings support that hyperosmolar challenge activates mast cells, but different than antigen stimulation.

  • 13. Gyllfors, Per
    et al.
    Kumlin, Maria
    Sophiahemmet University.
    Dahlén, Sven-Eric
    Gaber, Flora
    Ehrs, P-O
    Dahlén, B
    Relation between bronchial responsiveness to inhaled leukotriene D4 and markers of leukotriene biosynthesis2005In: Thorax, ISSN 0040-6376, E-ISSN 1468-3296, Vol. 60, no 11, p. 902-8Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: While clinical trials with antileukotrienes have shown overall beneficial effects in asthma, the factors that determine leukotriene dependent asthma are still unclear. A study was undertaken to determine whether or not leukotriene responsiveness in the airways correlates with endogenous leukotriene biosynthesis. METHODS: Bronchial responsiveness to leukotriene (LT) D4 was assessed as PD20FEV1 in 20 subjects with mild asthma and 10 healthy controls, and compared with bronchial responsiveness to methacholine and two global measures of leukotriene production-urinary LTE4 and ex vivo production of LTB4 in whole blood. RESULTS: In patients with asthma the bronchoconstrictor activity of LTD4 was about 1300 times greater than methacholine (geometric mean PD20 0.69 nmol v 887 nmol). Those who were most responsive to LTD4 were relatively less responsive to methacholine (p<0.01). There was, however, no correlation between bronchial responsiveness to LTD4 and urinary LTE4 or blood ex vivo LTB4 levels in asthmatic subjects or healthy controls. Subjects with asthma treated with inhaled corticosteroids produced higher levels of LTB4 (p<0.05). CONCLUSIONS: General measures of leukotriene production cannot predict bronchial responsiveness to LTD4. The unique bronchoconstrictive potency of LTD4 on human airways may relate to the locally regulated expression of the cysteinyl LT1 receptor.

  • 14. Gyllfors, Pär
    et al.
    Dahlén, Sven-Erik
    Kumlin, Maria
    Sophiahemmet University.
    Larsson, Kjell
    Dahlén, Barbro
    Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate2006In: Journal of Allergy and Clinical Immunology, ISSN 0091-6749, E-ISSN 1097-6825, Vol. 118, no 1, p. 78-83Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Inhaled corticosteroids are highly effective in asthma, reducing inflammatory markers and bronchial hyperresponsiveness. Cysteinyl-leukotrienes are major mediators of airway obstruction and display proinflammatory effects. Although the synthesis of leukotrienes is not affected by corticosteroid treatment, the influence of corticosteroids on the leukotriene pathway remains unresolved. OBJECTIVE: We investigated whether or not bronchial responsiveness to leukotriene (LT) D(4) is reduced by fluticasone propionate in subjects with asthma. METHODS: In 13 subjects with mild asthma, inhalation challenges with methacholine and LTD(4) were performed on consecutive days before and after 2 weeks of treatment with inhaled fluticasone 500 mug, twice daily, in a double-blind, randomized, placebo-controlled study with crossover design and 3 weeks of washout between periods. Exhaled nitric oxide was measured as a marker of corticosteroid responsiveness, and baseline urinary LTE(4) concentrations as an index of cysteinyl-leukotriene biosynthesis. RESULTS: Fluticasone produced a significant decrease in methacholine responsiveness, corresponding to 2.6-fold shift in the PD(20) FEV(1), and a significant reduction in the levels of exhaled nitric oxide. By contrast, bronchial responsiveness to LTD(4) in the same subjects was unaffected by fluticasone, as were urinary LTE(4) concentrations. CONCLUSION: These new data indicate that neither the biosynthesis nor the actions of leukotrienes appear to be sensitive to inhaled corticosteroids. CLINICAL IMPLICATIONS: The study provides mechanistic support for the additive therapeutic efficacy of antileukotrienes and inhaled corticosteroids in asthma.

  • 15. Higashi, Ai
    et al.
    Kumlin, Maria
    Sophiahemmet University.
    Higashi, Noritaka
    Daham, Kameran
    Gaber, Flora
    Lindeberg, Agneta
    James, Anna
    Skedinger, Maria
    Delin, Ingrid
    Gyllfors, Pär
    Dahlén, Sven-Erik
    Dahlén, Barbro
    Challenge of isolated sputum cells supports in vivo origin of intolerance reaction to aspirin/non-steroidal anti-inflammatory drugs in asthma2012In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 158, no 3, p. 299-306Article in journal (Refereed)
    Abstract [en]

    Background: There is no in vitro test to diagnose aspirin-intolerant asthma (AIA). The aim of this study was to test if challenge with aspirin of sputum cells from subjects with AIA triggers the release of cysteinyl leukotrienes (CysLTs), known to be mediators of bronchoconstriction in AIA. Methods: Sputum induction was performed at baseline and at another visit 2 h after a lysine-aspirin bronchoprovocation in 10 subjects with AIA and 9 subjects with aspirin-tolerant asthma (ATA). The isolated sputum cells were incubated for ex vivo challenge. Results: Release of CysLTs by sputum cells from patients with AIA was not induced by lysine-aspirin ex vivo, neither when cells were collected at baseline nor in sputum cells recovered after lysine-aspirin-induced bronchoconstriction, whereas release of CysLTs from sputum cells was triggered by an ionophore on both occasions. However, the CysLT levels elicited by the ionophore were higher in the AIA group both at baseline (AIA vs. ATA: 3.3 vs. 1.6 ng/million cells; p < 0.05) and after the lysine-aspirin bronchoprovocation (3.9 vs. 1.7 ng/million cells; p < 0.05). This difference in the amount of CysLTs released between the groups appeared to be related to the number of eosinophils. Conclusions: Intolerance to aspirin could not be triggered in sputum cells isolated from subjects with AIA. Together with the previous inability to demonstrate intolerance to non-steroidal anti-inflammatory drugs in isolated blood cells, these results support the requirement of tissue-resident cells in the adverse reaction. However, ex vivo stimulation of sputum cells may be developed into a new test of capacity for LT release in inflammatory cells recovered from airways.

  • 16. Ihre, E
    et al.
    Gyllfors, Per
    Gustafsson, L E
    Kumlin, Maria
    Sophiahemmet University.
    Dahlén, B
    Early rise in exhaled nitric oxide and mast cell activation in repeated low-dose allergen challenge2006In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 27, no 6, p. 1152-9Article in journal (Refereed)
    Abstract [en]

    Repeated low-dose allergen inhalation challenge mimics natural allergen exposure, providing a model for early mechanisms in the triggering of asthma. The current authors performed a controlled study to evaluate the time course of changes in exhaled nitric oxide fraction (F(e,NO)) and urinary biomarkers of airway inflammation. Eight subjects with mild allergic asthma completed two 7-day repeated low-dose challenge periods, with diluent and allergen, respectively. Subjects were symptom free at inclusion and were investigated when not exposed to specific allergen. Pulmonary function and symptoms were followed, and F(e,NO) and urinary mediators were correlated to changes in airway responsiveness to histamine and adenosine. Despite no change in pulmonary function (forced expiratory volume in one second mean+/-sem fall 0.3+/-0.7 versus 0.6+/-1.0%, for diluent and allergen, respectively) and no asthma symptoms, repeated allergen exposure, in contrast to diluent, caused significant increases in histamine responsiveness (2.3 doubling doses), an early and gradual increase in F(e,NO) (up to a doubling from baseline) and a small increase in the mast cell marker 9alpha11beta-prostaglandin F(2) after adenosine challenge. In conclusion, serial measurements of exhaled nitric oxide fraction have the potential to provide a very sensitive strategy for early detection of emerging airway inflammation and subsequent changes in airway hyperresponsiveness to histamine.

  • 17. James, Anna
    et al.
    Daham, Kameran
    Backman, Linda
    Brunnström, Åsa
    Tingvall, Tove
    Kumlin, Maria
    Sophiahemmet University.
    Edenius, Charlotte
    Dahlén, Sven-Erik
    Dahlén, Barbro
    Claesson, Hans-Erik
    The influence of aspirin on release of eoxin C4, leukotriene C4 and 15-HETE, in eosinophilic granulocytes isolated from patients with asthma2013In: International Archives of Allergy and Immunology, ISSN 1018-2438, E-ISSN 1423-0097, Vol. 162, no 2, p. 135-42Article in journal (Refereed)
    Abstract [en]

    Background: The effect of aspirin on the release of key arachidonic acid metabolites in activated eosinophils from subjects with aspirin-intolerant asthma (AIA) has not been investigated previously, despite the characteristic eosinophilia in AIA. Methods: Peripheral blood eosinophils were isolated from four groups of subjects: healthy volunteers (HV; n = 8), mild asthma (MA; n = 8), severe asthma (SA; n = 9) and AIA (n = 7). In the absence or presence of lysine-aspirin, eosinophils were stimulated with arachidonic acid or calcium ionophore to trigger the 15-lipoxygenase-1 (15-LO) and 5-lipoxygenase (5-LO) pathways, respectively. 15(S)-hydroxy-eicosatetraenoic acid (15-HETE) and eoxin C4 (EXC4) were measured as 15-LO products and leukotriene (LT)C4 as a product of the 5-LO pathway. Results: Activated eosinophils from patients with SA and AIA produced approximately five times more 15-HETE than eosinophils from HV or MA patients. In the presence of lysine-aspirin, eosinophils from AIA, MA and SA patients generated higher levels of 15-HETE than in the absence of lysine-aspirin. Furthermore, in the presence of lysine-aspirin, formation of EXC4 was also significantly increased in eosinophils from AIA patients, and LTC4 synthesis was increased both in AIA and SA patients. Conclusions: Taken together, this study shows an increased release of the recently discovered lipid mediator EXC4, as well as the main indicator of 15-LO activity, 15-HETE, in activated eosinophils from severe and aspirin-intolerant asthmatics, and also elevated EXC4 and LTC4 formation in eosinophils from AIA patients after cellular activation in the presence of lysine-aspirin. The findings support a pathophysiological role of the 15-LO pathway in SA and AIA.

  • 18.
    Jangard, Mattias
    et al.
    Sophiahemmet University.
    Svedberg, Marie
    Sophiahemmet University.
    Gladh, Hanna
    Araya Holmqvist, Susana
    Ryott, Michael
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Nasal irrigation with hot saline provides better postoperative outcome after fess compared to the traditional use of nasal packing2018Conference paper (Other academic)
  • 19.
    Kullenberg, Helena
    et al.
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Nyström, Thomas
    Svedberg, Marie
    Sophiahemmet University.
    Diabetes and symptoms in dementia: A register-based study2021Conference paper (Other academic)
  • 20.
    Kullenberg, Helena
    et al.
    Sophiahemmet University.
    Nyström, Thomas
    Kumlin, Maria
    Sophiahemmet University.
    Svedberg, Marie
    Sophiahemmet University.
    Correlation between insulin-degrading enzyme versus total tau and selected cytokines in patients with Alzheimer´s disease compared to non-demented controls.2023In: Neuroendocrinology Letters, ISSN 2354-4716, Vol. 44, no 4, p. 199-205Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: It has been increasingly recognized that the pathological progress of Alzheimer´s disease (AD) is connected to metabolic function and inflammation. Insulin-degrading enzyme (IDE) is essential for glucose metabolism and the degradation of amyloid-β. We aimed to explore the associations between IDE, total tau, and cytokines levels in plasma from subjects with AD and non-demented controls.

    METHODS AND MATERIAL: Plasma samples (18 patients diagnosed with AD and 6 non-demented controls) from the Netherlands Brain Bank were used to analyze IDE levels and total tau with an enzyme-linked immunosorbent assay. Cytokines were analyzed with Luminex custom plex assays for interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor-alpha (TNF-α). Results were analyzed using the Mann-Whitney U and Spearman´s rank correlation tests.

    RESULTS: Total tau in plasma was significantly increased in AD subjects compared to non-demented control subjects (p = 0.044). Total tau was positively correlated with IDE levels in plasma in all subjects (r = 0.494, p = 0.017). Significant correlations could be demonstrated between plasma levels of IDE and IL-6 (r = 0.546, p = 0.019), IL-8 (r = 0.664, p = 0.003), IL-10 (r = 0.833, p < 0.001), and TNF-α (r = 0.633, p = 0.005) in subjects with AD, but not in non-demented controls.

    CONCLUSION: Results from this study suggest that plasma IDE levels may be associated with inflammation and neurodegeneration and could potentially be a target for future diagnostic and treatment strategies.

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  • 21.
    Kullenberg, Helena
    et al.
    Sophiahemmet University.
    Rossen, Jenny
    Sophiahemmet University.
    Johansson, Unn-Britt
    Sophiahemmet University.
    Hagströmer, Maria
    Sophiahemmet University.
    Nyström, Thomas
    Kumlin, Maria
    Sophiahemmet University.
    Svedberg, Marie
    Sophiahemmet University.
    Correlations between insulin-degrading enzyme and metabolic markers in patients diagnosed with type 2 diabetes, Alzheimer's disease, and healthy controls: A comparative study2024In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 84, no 2, p. 450-458Article in journal (Refereed)
    Abstract [en]

    PURPOSE: This study aimed to explore correlations between insulin-degrading enzyme (IDE) and markers of metabolic function in a group of patients diagnosed with type 2 diabetes mellitus (T2DM) or Alzheimer's disease (AD) and metabolically healthy volunteers.

    METHOD: We included 120 individuals (47 with T2DM, 9 with AD, and 64 healthy controls). Serum levels of IDE were measured with commercial kits for ELISA. Differences in IDE levels between groups were analyzed with non-parametric ANCOVA, and correlations were analyzed with Spearman's rank correlations. We also investigated the influence of age, sex, and the use of insulin on the correlation using a non-parametric version of partial correlation.

    RESULTS: Patients diagnosed with T2DM had higher IDE levels than patients diagnosed with AD and healthy controls after adjustment for age and sex. IDE was increasingly associated with body mass index (BMI), fasting blood glucose, C-peptide, hemoglobin A1c (HbA1c), insulin resistance, and triglycerides. In stratified analyses, we found a decreasing partial correlation between IDE and HbA1c in patients diagnosed with AD and a decreasing partial correlation between IDE and C-peptide in healthy controls. In patients diagnosed with T2DM, we found no partial correlations.

    CONCLUSION: These results indicate that IDE is essential in metabolic function and might reflect metabolic status, although it is not yet a biomarker that can be utilized in clinical practice. Further research on IDE in human blood may provide crucial insights into the full function of the enzyme.

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  • 22.
    Kullenberg, Helena
    et al.
    Sophiahemmet University.
    Rossen, Jenny
    Sophiahemmet University.
    Johansson, Unn-Britt
    Sophiahemmet University.
    Hagströmer, Maria
    Sophiahemmet University.
    Nyström, Thomas
    Kumlin, Maria
    Sophiahemmet University.
    Svedberg, Marie
    Sophiahemmet University.
    Increased levels of insulin-degrading enzyme in patients with type 2 diabetes mellitus2022In: Endocrine, ISSN 1355-008X, E-ISSN 1559-0100, Vol. 77, no 3, p. 561-565Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Decreasing levels of serum insulin-degrading enzyme (IDE) have been associated with an increased risk for Alzheimer´s disease (AD) in patients with type 2 diabetes mellitus (T2DM). Research on serum IDE levels in patients with T2DM is sparse and the aim of this study was to explore serum levels of IDE in patients with T2DM.

    METHOD: Blood serum samples were obtained from a biobank. Samples from subjects with T2DM and without metabolic disease were divided into subgroups; lifestyle treatment (n = 10), oral antidiabetic treatment (n = 17), insulin treatment (n = 20) and metabolically healthy controls (n = 18). Serum levels of IDE were analysed using specific ELISA assays.

    RESULTS: Serum levels of IDE were elevated in subjects with T2DM compared to metabolically healthy individuals (p = 0.033). No significant differences were detected between treatment subgroups.

    CONCLUSION: The present study indicates that patients with T2DM have increased serum IDE levels, compared to metabolically healthy individuals. However, for IDE to be clinically useful as a biomarker, its full function and possible use needs to be further elucidated in larger studies showing reproducible outcomes.

  • 23.
    Kullenberg, Helena
    et al.
    Sophiahemmet University.
    Wibom, Moa
    Kumlin, Maria
    Sophiahemmet University.
    Nyström, Thomas
    Svedberg, Marie
    Sophiahemmet University.
    Associations between the use of metformin and behavioral and psychological symptoms in patients with Alzheimer's disease, and type 2 diabetes mellitus: A register-based study2023In: Current Alzheimer Research, ISSN 1567-2050, E-ISSN 1875-5828, Vol. 20, no 2, p. 109-119Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Metformin, the first-line anti-diabetic drug treatment in patients with type 2 diabetes mellitus (T2DM), is suggested to be anti-inflammatory, antioxidative, and improve cognitive function, making it a promising contribution to treating Alzheimer´s disease (AD). However, the effect of metformin on behavioral and psychological symptoms of dementia (BPSD) in patients with AD has not been explored.

    OBJECTIVE: To investigate the associations between metformin and BPSD in patients with AD and T2DM and explore possible interaction with other antidiabetic drugs.

    METHODS: This cross-sectional study was based on data from the Swedish BPSD register. A total of 3745 patients with AD and antidiabetic drug treatment were included. Associations and interactions between antidiabetic drugs and BPSD were investigated by binary logistic regression.

    RESULTS: The use of metformin was associated with lower odds for symptoms of depression (OR 0.77, CI (95%) 0.61-0.96, p = 0.022) and anxiety (OR 0.74, CI (95%) 0.58-0.94, p = 0.015) after adjustment for age, gender, specific diagnosis, and drugs. We could not demonstrate this association with another antidiabetic drug. Interaction effects were limited to an increasing association in eating and appetite disorders using metformin and other antidiabetic drugs (i.e., drugs other than insulin, sulfonylurea, or dipeptidyl peptidase-4 inhibitors).

    CONCLUSION: The result of this study suggests that metformin could be beneficial for patients diagnosed with AD, other than for blood glucose control. Although, more knowledge is needed before assigning metformin a role in treating BPSD.

  • 24.
    Kullenberg, Helena
    et al.
    Sophiahemmet University.
    Wibom, Moa
    Nyström, Thomas
    Kumlin, Maria
    Sophiahemmet University.
    Svedberg, Marie
    Sophiahemmet University.
    Behavioral and psychological symptoms in patients with cognitive disease and diabetes: A register based study2022Conference paper (Other academic)
  • 25. Larsson, Britt-Marie
    et al.
    Kumlin, Maria
    Sophiahemmet University.
    Sundblad, Britt-Marie
    Larsson, Kjell
    Dahlén, Sven-Erik
    Palmberg, Lena
    Effects of 5-lipoxygenase inhibitor zileuton on airway responses to inhaled swine house dust in healthy subjects2006In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 100, no 2, p. 226-37Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Inhalation of swine house dust induces acute airway inflammation and increased bronchial responsiveness in healthy subjects. OBJECTIVE: The aim of the study was to investigate whether 5-lipoxygenase products such as leukotrienes may have a role in this reaction. METHODS: Twenty-three healthy subjects were randomised into two groups receiving treatment with either zileuton (600 mg) or placebo four times a day. After 5 days of treatment, all subjects were exposed for 3h in a swine barn. Bronchial responsiveness, exhaled nitric oxide (NO), and mediators in nasal lavage (NAL), blood and urine were measured before and after the exposure. RESULTS: The exposure induced an increased bronchial responsiveness to methacholine in both groups with 2-3 doubling concentration steps, no significant difference between treatments. Leukotriene E(4) in urine increased significantly following exposure in the placebo group from 37.3 (29.1-45.6) (mean (95% confidence interval)) ng/mmol creatinine to 47.7 (36.3-59.0) ng/mmol creatinine (P<0.05), but not in the zileuton group. The post-exposure increase of LTB(4) levels in NAL fluid was totally abolished in the zileuton group (P<0.05 vs. the placebo). The levels of exhaled NO increased significantly (P<0.01), two-fold in both groups. The PGD(2) metabolite 9alpha, 11beta-PGF(2) increased in placebo-treated subjects (P<0.01; P<0.05 vs. zileuton), strengthening mast cell participation. Neutrophil counts and levels of IL-6 in peripheral blood increased in both groups, with a significantly larger increase in zileuton treated subjects (P<0.05 and P<0.001, respectively compared to placebo). CONCLUSIONS: Pre-treatment with clinically recommended doses of the 5-lipoxygenase inhibitor zileuton did not affect the increase of bronchial reactivity induced by swine dust exposure. The intervention totally abolished the LTB(4) release in NAL fluid, but only partially inhibited the formation of leukotrienes as monitored by urinary levels. The enhanced increase of neutrophils and IL-6 in peripheral blood in the zileuton group, suggests that inhibition of 5-lipoxygenase may have pro-inflammatory effects.

  • 26. Larsson, Susanna C
    et al.
    Kumlin, Maria
    Sophiahemmet University.
    Ingelman-Sundberg, Magnus
    Wolk, Alicja
    Dietary long-chain n-3 fatty acids for the prevention of cancer: a review of potential mechanisms2004In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 79, no 6, p. 935-45Article in journal (Refereed)
    Abstract [en]

    Increasing evidence from animal and in vitro studies indicates that n-3 fatty acids, especially the long-chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, present in fatty fish and fish oils inhibit carcinogenesis. The epidemiologic data on the association between fish consumption, as a surrogate marker for n-3 fatty acid intake, and cancer risk are, however, somewhat less consistent. This review highlights current knowledge of the potential mechanisms of the anticarcinogenic actions of n-3 fatty acids. Moreover, a possible explanation of why some epidemiologic studies failed to find an association between n-3 fatty acid intake and cancer risk is provided. Several molecular mechanisms whereby n-3 fatty acids may modify the carcinogenic process have been proposed. These include suppression of arachidonic acid-derived eicosanoid biosynthesis; influences on transcription factor activity, gene expression, and signal transduction pathways; alteration of estrogen metabolism; increased or decreased production of free radicals and reactive oxygen species; and mechanisms involving insulin sensitivity and membrane fluidity. Further studies are needed to evaluate and verify these mechanisms in humans to gain more understanding of the effects of n-3 fatty acid intake on cancer risk.

  • 27. Nordström, Axel
    et al.
    Jangard, M
    Ryott, M
    Svedberg, Marie
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Assessment of health-related quality of life and olfactory loss inrelation to nasal polyp recurrence after endoscopic sinus surgeryin patients with chronic rhinosinusitis: A real life-studyManuscript (preprint) (Other academic)
  • 28.
    Nordström, Axel
    et al.
    Sophiahemmet University.
    Jangard, M
    Ryott, M
    Tang, X
    Svedberg, Marie
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Mucosal LTE4, PGD2 and 15(S)-HETE as potential prognosticmarkers for polyp recurrence in chronic rhinosinusitisIn: Article in journal (Other academic)
  • 29.
    Nordström, Axel
    et al.
    Sophiahemmet University.
    Jangard, Mattias
    Ryott, Michael
    Tang, Xiao
    Svedberg, Marie
    Sophiahemmet University.
    Kumlin, Maria
    Sophiahemmet University.
    Mucosal LTE4, PGD2 and 15(S)-HETE as potential prognostic markers for polyp recurrence in chronic rhinosinusitis2024In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 174, article id 106886Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Altered biosynthesis of eicosanoids is linked to type 2 inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP), but their role in recalcitrant NPs is unclear.

    OBJECTIVES: We sought to identify endotypes that are linked to recalcitrant CRSwNP, based on eicosanoids, their biosynthetic enzymes, and receptors as well as cytokines and the presence of eosinophils and mast cells in recurrent NPs.

    METHODS: Mucosal tissue collected at the time of sinus surgery from 54 patients with CRSwNP and 12 non-CRS controls were analysed for leukotriene (LT) E4, prostaglandin (PG) D2, 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) and 17 cytokines with ELISAs and Bio-Plex immunoassays. Patient subgroups were identified by cluster analysis and the probability of NP recurrence were tested with logistic regression analyses. Gene expressions were analysed with qPCR. Tryptase and eosinophil-derived neurotoxin (EDN) were measured with ELISAs as indications of the presence of mast cells and eosinophils, respectively.

    RESULTS: Clustering of patients showed that an inflammatory signature characterised by elevated LTE4, PGD2, 15(S)-HETE and IL-13 was associated with NP recurrence. Previous NP surgery as well as aspirin-exacerbated respiratory disease were significantly more common among these patients. Expression of cyclooxygenase 1 was the only gene associated with NP recurrence. Levels of EDN, but not tryptase, were significantly higher in patients with recurrent NPs.

    CONCLUSION: Distinguishing endotypes that include LTE4, PGD2, 15HETE and conventional biomarkers of type 2 inflammation could help predict recurrent nasal polyposis and thus identify cases of recalcitrant CRSwNP.

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  • 30.
    Nordström, Axel
    et al.
    Sophiahemmet University.
    Jangard, Mattias
    Svedberg, Marie
    Sophiahemmet University.
    Kullenberg, Helena
    Sophiahemmet University.
    Ryott, Michael
    Kumlin, Maria
    Sophiahemmet University.
    Hot saline irrigation in comparison to nasal packing after sinus surgery2021Conference paper (Other academic)
  • 31.
    Nordström, Axel
    et al.
    Sophiahemmet University.
    Jangard, Mattias
    Svedberg, Marie
    Sophiahemmet University.
    Kullenberg, Helena
    Sophiahemmet University.
    Ryott, Michael
    Kumlin, Maria
    Sophiahemmet University.
    Hot saline irrigation in comparison to nasal packing after sinus surgery2021In: Laryngoscope Investigative Otolaryngology (LIO), E-ISSN 2378-8038, Vol. 6, no 6, p. 1267-1274Article in journal (Refereed)
    Abstract [en]

    Objectives: Previous studies have shown that hot saline solution (HSS) nasal irrigation is effective against nasal bleeding and is used to treat nasal hemorrhage. In a pilot study, we evaluated hot saline nasal irrigation in comparison to a routinely used nasal packing in terms of self-reported complications and mucosal healing after functional endoscopic sinus surgery.

    Methods: Patients undergoing surgery for bilateral chronic rhinosinusitis received polyvinyl acetate (PVA) nasal packing in the left nostril, and the right nostril was rinsed with 47°C sterile saline immediately after surgery. Patients' experiences of pain, bleeding, and other types of uncomfortable experiences were measured using a visual analog scale for each nostril before, during, and immediately after nasal packing removal. Two weeks post-surgery, the assessments were repeated including an endoscopic evaluation of the mucosa by the surgeon.

    Results: Twenty-seven patients completed the study. Prior to removal of the packing, the patients experienced significantly more pain and other uncomfortable experiences in the nostril treated with nasal packing, as compared to the nostril solely rinsed with hot saline. After removal, patients reported significantly more uncomfortable experiences from the packing treated nostril. Two weeks post-surgery, no difference in mucosal healing was observed between the two nostrils.

    Conclusions: The results from this study indicate that irrigation with HSS could be an alternative postoperative treatment to conventional PVA nasal packing. Hot saline irrigation may contribute to patients experiencing improved control of postoperative bleeding, pain, and less suffering of other causes as well as health-economic benefits, without affecting the mucosal healing up to 2 weeks post-surgery.

    Level of Evidence: 1b.

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  • 32.
    Nordström, Axel
    et al.
    Sophiahemmet University.
    Jangard, Mattias
    Svedberg, Marie
    Sophiahemmet University.
    Ryott, Michael
    Kumlin, Maria
    Sophiahemmet University.
    Altered eicosanoid profile in association with nasal polyp severity in patients with chronic rhinosinusitis2022Conference paper (Other academic)
  • 33.
    Nordström, Axel
    et al.
    Sophiahemmet University.
    Jangard, Mattias
    Svedberg, Marie
    Sophiahemmet University.
    Ryott, Michael
    Kumlin, Maria
    Sophiahemmet University.
    Distinct eicosanoid patterns in severe recalcitrant nasal polyposis2023In: International Forum of Allergy & Rhinology, ISSN 2042-6984, Vol. 13, no 11, p. 2043-2054Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Although altered eicosanoid levels are related to disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP), identifying patients prone to recurrent NPs is still difficult. We investigated levels of nasally secreted eicosanoids before and after NP surgery in patients with or without NP recurrence and explored potential endotypes based on pre-surgical eicosanoid levels.

    METHODS: Levels of leukotriene (LT) E4 , LTB4 , prostaglandin (PG) D2 , PGE2 and 15(S) hydroxyeicosatetraenoic acid (15(S)-HETE) were measured in nasal secretions with specific immunoassays at pre-surgery (n = 38) and six- and 12-months post-surgery (n = 35) where NP recurrence was identified endoscopically. Pre- and post-surgical levels were compared between patients with and without NP recurrence. Eicosanoid patterns among patients were explored with cluster analysis and evaluated with clinical parameters.

    RESULTS: Patients with recurrent NPs had pronounced pre-surgical levels of nasal 15(S)-HETE, PGD2 and LTE4 . From pre-surgery to 12-months after, NP recurrence was associated with significant decrease of 15(S)-HETE and PGD2 relative to non-recurrence whereas levels of LTE4 decreased at six-months but increased again at 12-months. Clustering revealed three potential endotypes. Cluster 1 and 3 featured high and low eicosanoid levels, respectively. Cluster 2 had higher levels of LTE4 and PGD2 , lower levels of PGE2 and LTB4 , and more cases of recurrent NPs and previous NP surgeries.

    CONCLUSION: Elevated nasal LTE4 , 12-month post-surgery, in NP recurrent subjects suggests that postoperative LTE4 measurements may indicate rapid NP regrowth. A distinct nasal eicosanoid profile may be used for the identification of the most severe recalcitrant patients in need of targeted immunomodulatory therapies. This article is protected by copyright. All rights reserved.

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  • 34.
    Nordström, Axel
    et al.
    Sophiahemmet University.
    Jangard, Mattias
    Svedberg, Marie
    Sophiahemmet University.
    Ryott, Michael
    Kumlin, Maria
    Sophiahemmet University.
    Exploring nasally secreted eicosanoids as prognostic markers for nasal polyp recurrence in chronic rhinosinusitis2022Conference paper (Other academic)
  • 35.
    Nordström, Axel
    et al.
    Sophiahemmet University.
    Jangard, Mattias
    Svedberg, Marie
    Sophiahemmet University.
    Ryott, Michael
    Kumlin, Maria
    Sophiahemmet University.
    Levels of eicosanoids in nasal secretions and urine associated with nasal polyp severity in chronic rhinosinusitis2022Conference paper (Other academic)
  • 36.
    Nordström, Axel
    et al.
    Sophiahemmet University.
    Jangard, Mattias
    Svedberg, Marie
    Sophiahemmet University.
    Ryott, Michael
    Kumlin, Maria
    Sophiahemmet University.
    Levels of eicosanoids in nasal secretions associated with nasal polyp severity in chronic rhinosinusitis2022In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 184, article id 102474Article in journal (Refereed)
    Abstract [en]

    Severe nasal polyposis and mucosal inflammation, in patients with chronic rhinosinusitis (CRS) may include a dysregulated eicosanoid profile, but a clinical role for eicosanoids in CRS with nasal polyps (NP; CRSwNP) remains to be elucidated. This study focused on assessing levels and clinical implications of inflammatory mediators in nasal secretions and urine from patients with different NP severity or Aspirin Exacerbated Respiratory Disease (AERD). Levels of leukotrienes E4 and B4, prostaglandins D2 and E2 as well as 15(S)-hydroxyeicosatetraenoic acid were measured with enzyme immunoassays and cytokines with magnetic bead immunoassays. Patients with CRSwNP were subdivided based on NP score; CRSwNP-low (NP score ≤ 4, n = 11) or CRSwNP-high (NP score ≥ 5, n = 32) and compared to CRS without polyps (CRSsNP, n = 12), CRSwNP-AERD (n = 11) and individuals without CRS (n = 25). Smell test score, fractional exhaled nitric oxide (FeNO), blood eosinophils and Sinonasal outcome test-22 were assessed as clinical markers. Leukotriene E4, prostaglandin D2 and 15(S)-hydroxyeicosatetraenoic acid in nasal secretions correlated with NP score. Nasal leukotriene E4 also correlated with FeNO and smell test score, with highest levels found in CRSwNP-AERD. Levels of prostaglandin D2 in nasal secretion as well as urinary levels of the prostaglandin D2 metabolite 11β-prostaglandin F differed between CRSNP-high and CRSwNP-low. Urinary 11β-prostaglandin F was associated with asthma comorbidity whereas a similar association with prostaglandin D2 in nasal secretions was not observed. In conclusion, subdividing patients based on NP severity in combination with analysis of eicosanoids in non-invasively collected nasal secretions, may have clinical implications when assessing CRS disease severity.

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  • 37. Roos, Cecilia
    et al.
    Stenke, Leif
    Ohm, Lotta
    Widell, Susanne
    Kumlin, Maria
    Sophiahemmet University.
    Lindgren, Jan Åke
    Sophiahemmet University.
    Tornhamre, Susanne
    Clinical imatinib mesylate treatment induces early normalisation of aberrant neutrophil leukotriene C4 synthase expression and activity in chronic myeloid leukaemia2008In: British journal of haematology, ISSN 1365-2141, Vol. 142, no 6, p. 992-5Article in journal (Refereed)
  • 38. Selg, Ewa
    et al.
    Låstbom, Lena
    Ryrfeldt, Åke
    Kumlin, Maria
    Sophiahemmet University.
    Dahlén, Sven-Erik
    Effects of selective and non-selective COX inhibitors on antigen-induced release of prostanoid mediators and bronchoconstriction in the isolated perfused and ventilated guinea pig lung2008In: Prostaglandins, Leukotrienes and Essential Fatty Acids, ISSN 0952-3278, E-ISSN 1532-2823, Vol. 78, no 2, p. 89-97Article in journal (Refereed)
    Abstract [en]

    The contribution of cycloxygenase (COX)-1 and COX-2 in antigen-induced release of mediators and ensuing bronchoconstriction was investigated in the isolated perfused guinea pig lung (IPL). Antigen challenge with ovalbumin (OVA) of lungs from actively sensitised animals induced release of thromboxane (TX)A(2), prostaglandin (PG)D(2), PGF(2)(alpha), PGI(2) and PGE(2), measured in the lung effluent as immunoreactive TXB(2), PGD(2)-MOX, PGF(2)(alpha), 6-keto PGF(1)(alpha) and PGE(2), respectively. This release was abolished by the non-selective COX inhibitor flurbiprofen (10 microM). In contrast, neither the selective COX-1 inhibitor FR122047 nor the selective COX-2 inhibitor celecoxib (10 microM each) significantly inhibited the OVA-induced bronchoconstriction or release of COX products, except for PGD(2). Another non-selective COX inhibitor, diclofenac (10 microM) also significantly inhibited antigen-induced bronchoconstriction. The data suggest that both COX isoenzymes, COX-1 and COX-2 contribute to the immediate antigen-induced generation of prostanoids in IPL and that the COX-1 and COX-2 activities are not associated with different profiles of prostanoid end products.

  • 39. Sundblad, Britt-Marie
    et al.
    Sahlander, Karin
    Ek, Alexandra
    Kumlin, Maria
    Sophiahemmet University.
    Olsson, Marianne
    Larsson, Kjell
    Palmberg, Lena
    Effect of respirators equipped with particle or particle-and-gas filters during exposure in a pig confinement building2006In: Scandinavian Journal of Work, Environment and Health, ISSN 0355-3140, E-ISSN 1795-990X, Vol. 32, no 2, p. 145-53Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: This study compared the protective effect of two respiratory protection devices during exposure in a pig confinement building. METHODS: Thirty-six healthy persons were exposed for 3 hours in the building, 12 without any protection, 12 with a particle-filter mask, and 12 with a mask filtering both particles and gases. Symptoms, body temperature, nasal lavage fluid, exhaled nitric oxide, and bronchial responsiveness to methacholine were assessed before and after the exposure. Pre- and postexposure urine and blood samples were collected. RESULTS: After the exposure, the participants with respirators reported fewer symptoms than those without. Wearing a mask also reduced the inflammatory response assessed with nasal lavage (cell concentration, interleukins 6 and 8) and peripheral blood (cell number). Lung function was significantly impaired only in the unprotected group; postexposure vital capacity and forced expiratory volume in 1 second showed a decrease of 3-4% from the preexposure levels (P=0.006 and P=0.002, respectively). Bronchial responsiveness (P<0.01) and body temperature (P<0.001) increased similarly in the three groups. Bronchial responsiveness to methacholine increased 2.7, 2.4, and 2.1 doubling concentration steps for those unprotected, those using a particle-filter mask, and those using a mask with particle and gas filters, respectively. The prostaglandin D2 metabolite, 9a, 11b-PGF2 increased significantly (P=0.003) only in those unprotected. CONCLUSIONS: Wearing a respirator in a pig confinement building reduces the inflammatory reaction but does not influence the increase in bronchial responsiveness, with no difference between the use of a particle-filter mask or a mask with a particle-gas filter combination.

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