| 1. |
- James, Anna, et al.
(författare)
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The influence of aspirin on release of eoxin C4, leukotriene C4 and 15-HETE, in eosinophilic granulocytes isolated from patients with asthma
- 2013
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 162:2, s. 135-42
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Alahmadi, Fahad, et al.
(författare)
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Measures of adherence in patients with severe asthma prescribed systemic steroids in the U-BIOPRED cohort
- 2018
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Ingår i: European Respiratory Journal. - : European Respiratory Society. - 0903-1936 .- 1399-3003. ; 52
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Rates of sub-optimal adherence to medications in asthma range up to 70%; the impact in severe asthma is likely to be particularly high. We measured self-reported adherence in participants in the U-BIOPRED cohort prescribed daily prednisolone using the Medication Adherence Response Scale (MARS), and compared to measured urinary prednisolone and metabolites in order to determine: 1. the prevalence of suboptimal adherence by each method; 2. the ability of MARS to predict urinary steroid detection.Methods: Participants completed the MARS, and/or provided urine samples (analysed for prednisolone and metabolites by LCMS). The performance characteristics of the MARS predicting undetected urinary steroid were calculated in the subgroup having both tests.Results: 181 participants currently taking regular oral corticosteroids were included, 59% female, mean (SD) age 54(12)yrs, FEV1 64.7(20.4)% predicted. Sub-optimal adherence (MARS score < 4.5) was reported in 62 participants, and 76 did not have detectable urinary prednisolone or metabolites. Good adherence by both methods was detected in only 52 participants (34%, see table). There was no difference in daily prednisolone dose between detectable and undetectable metabolites groups (p=0.848).Conclusion: Low levels of adherence to treatment in severe asthma is a common problem, when measured either directly or self-reported. There was very poor agreement (48% concordance) between these two methods, and we suggest that, for now both approaches should be used.
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| 3. |
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| 4. |
- Dahlén, Barbro, et al.
(författare)
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Specific problems : Asthma induced by aspirin and other non-steroidal anti-inflammatory drugs.
- 2001. - 2
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Ingår i: Manual of Asthma management. - London : Harcourt Publishers Limited. - 9780702025297 ; , s. 453-462
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This unique manual provides comprehensive, practical, and easily accessible guidelines on the key points of asthma management in both adults and children. The updated 2nd edition incorporates the most recent national and international guidelines for the care of asthmatic patients, with vital information on how to address clinical issues while emphasizing essential basic science in diagnosing, managing, and treating asthma.
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| 5. |
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| 6. |
- Diamant, Zuzana, et al.
(författare)
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Toward clinically applicable biomarkers for asthma : An EAACI position paper
- 2019
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Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 74:10, s. 1835-1851
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Tidskriftsartikel (refereegranskat)abstract
- Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best-defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non-type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point-of-care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.
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| 7. |
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| 8. |
- Gaber, Flora, et al.
(författare)
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Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma
- 2008
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Ingår i: Thorax. - : BMJ. - 1468-3296 .- 0040-6376. ; 63:12, s. 1076-82
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Gülen, Theo, et al.
(författare)
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Distinct plasma biomarkers confirm the diagnosis of mastocytosis and identify increased risk of anaphylaxis
- 2021
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 148:3, s. 889-894
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mastocytosis encompasses a heterogeneous group of disorders characterized by accumulation of clonal mast cells (MCs) in the skin and/or internal organs. Patients typically present with a broad variety of recurrent mediator-related clinical symptoms, including severe anaphylaxis. However, not all patients with mastocytosis experience anaphylactic reactions.Objective: We sought to identify disease-specific biomarkers in plasma that could be used to predict patients with mastocytosis with increased risk of anaphylaxis.Methods: Nineteen patients (>_18 years) and 2 control groups (11 subjects with allergic asthma and 13 healthy volunteers without history of atopy) were recruited. In total, 248 plasma proteins were analyzed by Proximity Extension Assay using Olink Proseek Multiplex panels.Results: We identified 4 novel proteins, in addition to tryptase, E-selectin, adrenomedullin, T-cell immunoglobulin, and mucin domain 1, and CUB domain-containing protein 1/CD138 to be significantly increased in patients with mastocytosis compared with both patients with asthma and healthy controls. Furthermore, we investigated whether we could discriminate between patients with mastocytosis with or without anaphylaxis. In addition to tryptase, we identified 3 novel proteins, that is, allergin-1, pregnancy-associated plasma protein-A, and galectin-3, with significantly different levels in patients with mastocytosis with anaphylaxis compared with those without anaphylaxis.Conclusions: Newly identified proteomic biomarkers may be used to predict patients with mastocytosis with increased risk of anaphylaxis.
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| 10. |
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| 11. |
- Gyllfors, Pär, et al.
(författare)
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Bronchial responsiveness to leukotriene D4 is resistant to inhaled fluticasone propionate
- 2006
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 118:1, s. 78-83
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 12. |
- Higashi, Ai, et al.
(författare)
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Challenge of isolated sputum cells supports in vivo origin of intolerance reaction to aspirin/non-steroidal anti-inflammatory drugs in asthma
- 2012
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 158:3, s. 299-306
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 13. |
- Hou, Ruihua, et al.
(författare)
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The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts
- 2023
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Ingår i: Brain, behavior, and immunity. - : Academic Press. - 0889-1591 .- 1090-2139. ; 111, s. 249-258
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Tidskriftsartikel (refereegranskat)abstract
- Background: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. Methods: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate. Results: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05). Conclusions: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition.
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| 14. |
- Jansson, Sven-Arne, et al.
(författare)
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Health-related quality of life, assessed with a disease-specific questionnaire, in Swedish adults suffering from well-diagnosed food allergy to staple foods
- 2013
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 3:21
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundOur aim was to investigate the factors that affect health related quality of life (HRQL) in adult Swedish food allergic patients objectively diagnosed with allergy to at least one of the staple foods cow’s milk, hen’s egg or wheat. The number of foods involved, the type and severity of symptoms, as well as concomitant allergic disorders were assessed.MethodsThe disease-specific food allergy quality of life questionnaire (FAQLQ-AF), developed within EuroPrevall, was utilized. The questionnaire had four domains: Allergen Avoidance and Dietary Restrictions (AADR), Emotional Impact (EI), Risk of Accidental Exposure (RAE) and Food Allergy related Health (FAH). Comparisons were made with the outcome of the generic questionnaire EuroQol Health Questionnaire, 5 Dimensions (EQ-5D). The patients were recruited at an outpatient allergy clinic, based on a convincing history of food allergy supplemented by analysis of specific IgE to the foods in question. Seventy-nine patients participated (28 males, 51 females, mean-age 41 years).ResultsThe domain with the most negative impact on HRQL was AADR, assessing the patients’ experience of dietary restrictions. The domain with the least negative impact on HRQL was FAH, relating to health concerns due to the food allergy. One third of the patients had four concomitant allergic disorders, which had a negative impact on HRQL. Furthermore, asthma in combination with food allergy had a strong impact. Anaphylaxis, and particularly prescription of an epinephrine auto-injector, was associated with low HRQL. These effects were not seen using EQ-5D. Analyses of the symptoms revealed that oral allergy syndrome and cardiovascular symptoms had the greatest impact on HRQL. In contrast, no significant effect on HRQL was seen by the number of food allergies.ConclusionsThe FAQLQ-AF is a valid instrument, and more accurate among patients with allergy to staple foods in comparison to the commonly used generic EQ-5D. It adds important information on HRQL in food allergic adults. We found that the restrictions imposed on the patients due to the diet had the largest negative impact on HRQL. Both severity of the food allergy and the presence of concomitant allergic disorders had a profound impact on HRQL.
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| 15. |
- Jansson, Sven-Arne, et al.
(författare)
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Okänt hur mycket astma och allergier kostar samhället : kostnadsstudier kan ge bättre planering av vård och forskning
- 2007
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Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 104:39, s. 2792-2796
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Tidskriftsartikel (refereegranskat)abstract
- Få studier av kostnader för allergisjukdomar är genomförda nationellt och internationellt. I Sverige är det endast astma som är studerat, och för rinit och eksem finns endast ett fåtal internationella studier. Inom födoämnesöverkänslighet finns över huvud taget inga sjukdomskostnadsstudier publicerade. Det är svårt att jämföra olika studier, såväl nationellt som internationellt, på grund av olika studiedesign, hälso- och sjukvårdssystem och behandlingstraditioner. De svenska kostnaderna för de studerade allergisjukdomarna har skattats och uppgår sannolikt till över 10 miljarder kronor totalt per år, varav kostnaden för astma uppgår till cirka 7 miljarder kronor. Det är viktigt att studier kommer till stånd i Sverige för att få en uppfattning om de faktiska svenska kostnaderna för allergisjukdomarna.
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| 16. |
- Johnsson, Anna-Karin, et al.
(författare)
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COX-1 dependent biosynthesis of 15-hydroxyeicosatetraenoic acid in human mast cells
- 2021
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Ingår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. - : Elsevier. - 1388-1981 .- 1879-2618. ; 1866:5
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Tidskriftsartikel (refereegranskat)abstract
- 15-hydroxyeicosatetraenoic acid (15-HETE) is an arachidonic acid derived lipid mediator which can originate both from 15-lipoxygenase (15-LOX) activity and cyclooxygenase (COX) activity. The enzymatic source determines the enantiomeric profile of the 15-HETE formed. 15-HETE is the most abundant arachidonic acid metabolite in the human lung and has been suggested to influence the pathophysiology of asthma. Mast cells are central effectors in asthma, but there are contradictory reports on whether 15-HETE originates from 15-LOX or COX in human mast cells. This prompted the current study where the pathway of 15-HETE biosynthesis was examined in three human mast cell models; the cell line LAD2, cord blood derived mast cells (CBMC) and tissue isolated human lung mast cells (HLMC). Levels and enantiomeric profiles of 15-HETE and levels of the downstream metabolite 15-KETE, were analyzed by UPLC-MS/MS after stimulation with anti-IgE or calcium ionophore A23187 in the presence and absence of inhibitors of COX isoenzymes. We found that 15-HETE was produced by COX-1 in human mast cells under these experimental conditions. Unexpectedly, chiral analysis showed that the 15(R) isomer was predominant and gradually accumulated, whereas the 15(S) isomer was metabolized by the 15hydroxyprostaglandin dehydrogenase. We conclude that during physiological conditions, i.e., without addition of exogenous arachidonic acid, both enantiomers of 15-HETE are produced by COX-1 in human mast cells but that the 15(S) isomer is selectively depleted by undergoing further metabolism. The study highlights that 15-HETE cannot be used as an indicator of 15-LOX activity for cellular studies, unless chirality and sensitivity to pharmacologic inhibition is determined.
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| 17. |
- Johnsson, Anna-Karin, et al.
(författare)
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Selective inhibition of prostaglandin D-2 biosynthesis in human mast cells to overcome need for multiple receptor antagonists : Biochemical consequences
- 2021
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Ingår i: Clinical and Experimental Allergy. - : John Wiley & Sons. - 0954-7894 .- 1365-2222. ; 51:4, s. 594-603
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Tidskriftsartikel (refereegranskat)abstract
- Background The major mast cell prostanoid PGD(2) is targeted for therapy of asthma and other diseases, because the biological actions include bronchoconstriction, vasodilation and regulation of immune cells mediated by three different receptors. It is not known if the alternative to selectively inhibit the biosynthesis of PGD(2) affects release of other prostanoids in human mast cells. Objectives To determine the biochemical consequences of inhibition of the hematopoietic prostaglandin D synthase (hPGDS) PGD(2) in human mast cells. Methods Four human mast cell models, LAD2, cord blood derived mast cells (CBMC), peripheral blood derived mast cells (PBMC) and human lung mast cells (HLMC), were activated by anti-IgE or ionophore A23187. Prostanoids were measured by UPLC-MS/MS. Results All mast cells almost exclusively released PGD(2) when activated by anti-IgE or A23187. The biosynthesis was in all four cell types entirely initiated by COX-1. When pharmacologic inhibition of hPGDS abolished formation of PGD(2), PGE(2) was detected and release of TXA(2) increased. Conversely, when the thromboxane synthase was inhibited, levels of PGD(2) increased. Adding exogenous PGH(2) confirmed predominant conversion to PGD(2) under control conditions, and increased levels of TXB2 and PGE(2) when hPGDS was inhibited. However, PGE(2) was formed by non-enzymatic degradation. Conclusions Inhibition of hPGDS effectively blocks mast cell dependent PGD(2) formation. The inhibition was associated with redirected use of the intermediate PGH(2) and shunting into biosynthesis of TXA(2). However, the levels of TXA(2) did not reach those of PGD(2) in naive cells. It remains to determine if this diversion occurs in vivo and has clinical relevance.
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| 18. |
- Kolmert, Johan, et al.
(författare)
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Urinary Leukotriene E-4 and Prostaglandin D-2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation A Clinical Observational Study
- 2021
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - NEW YORK, USA : AMER THORACIC SOC. - 1073-449X .- 1535-4970. ; 203:1, s. 37-53
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: New approaches are needed to guide personalized treatment of asthma. Objectives: To test if urinary eicosanoid metabolites can direct asthma phenotyping. Methods: Urinary metabolites of prostaglandins (PGs), cysteinyl leukotrienes (CysLTs), and isoprostanes were quantified in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy control participants. Validation was performed internally in 302 participants with SA followed up after 12-18 months and externally in 95 adolescents with asthma. Measurement and Main Results: Metabolite concentrations in healthy control participants were unrelated to age, body mass index, and sex, except for the PGE(2) pathway. Eicosanoid concentrations were generally greater in participants with MMA relative to healthy control participants, with further elevations in participants with SA. However, PGE(2) metabolite concentrations were either the same or lower in male nonsmokers with asthma than in healthy control participants. Metabolite concentrations were unchanged in those with asthma who adhered to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas those with SA treated with omalizumab had lower concentrations of LTE4 and the PGD(2) metabolite 2,3-dinor-11 beta-PGF(2 alpha). High concentrations of LTE4 and PGD(2) metabolites were associated with lower lung function and increased amounts of exhaled nitric oxide and eosinophil markers in blood, sputum, and urine in U-BIOARED participants and in adolescents with asthma. These type 2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study and were found to be as sensitive to detect T2 inflammation as the established biomarkers. Conclusions: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new noninvasive approach for molecular phenotyping of adult and adolescent asthma.
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| 19. |
- Kuo, Chih-Hsi Scott, et al.
(författare)
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A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED
- 2017
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1073-449X .- 1535-4970. ; 194:4, s. 443-455
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Tidskriftsartikel (refereegranskat)abstract
- RATIONALE AND OBJECTIVES: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. We used transcriptomic profiling of airway tissues to help define asthma phenotypes.METHODS: The transcriptome from bronchial biopsies and epithelial brushings of 107 moderate-to-severe asthmatics were annotated by gene-set variation analysis (GSVA) using 42 gene-signatures relevant to asthma, inflammation and immune function. Topological data analysis (TDA) of clinical and histological data was used to derive clusters and the nearest shrunken centroid algorithm used for signature refinement.RESULTS: 9 GSVA signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper type 2 (Th-2) cytokines and lack of corticosteroid response (Group 1 and Group 3). Group 1 had the highest submucosal eosinophils, high exhaled nitric oxide (FeNO) levels, exacerbation rates and oral corticosteroid (OCS) use whilst Group 3 patients showed the highest levels of sputum eosinophils and had a high BMI. In contrast, Group 2 and Group 4 patients had an 86% and 64% probability of having non-eosinophilic inflammation. Using machine-learning tools, we describe an inference scheme using the currently-available inflammatory biomarkers sputum eosinophilia and exhaled nitric oxide levels along with OCS use that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity.CONCLUSION: This analysis demonstrates the usefulness of a transcriptomic-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target Th2-mediated inflammation and/or corticosteroid insensitivity.
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| 20. |
- Mazzurana, Luca, et al.
(författare)
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Tissue-specific transcriptional imprinting and heterogeneity in human innate lymphoid cells revealed by full-length single-cell RNA-sequencing
- 2021
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Ingår i: Cell Research. - : Springer Science and Business Media LLC. - 1748-7838 .- 1001-0602. ; 31:5, s. 554-568
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Tidskriftsartikel (refereegranskat)abstract
- The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127+ ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2+ and CRTH2− ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.
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| 21. |
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| 22. |
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| 23. |
- Protudjer, Jennifer L. P., et al.
(författare)
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Household Costs Associated with Objectively Diagnosed Allergy to Staple Foods in Children and Adolescents
- 2015
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Ingår i: Journal of Allergy and Clinical Immunology-In Practice. - : Elsevier BV. - 2213-2198 .- 2213-2201. ; 3:1, s. 68-75
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We previously reported that indirect and intangible costs burden households with a food allergic adult. We now extend our investigation to households with food allergic children and adolescents. OBJECTIVE: The objective of this study was to estimate direct, indirect, and intangible costs of food allergy in households with a child and/or adolescent with objectively diagnosed allergy to staple foods (cow's milk, hen's egg, and/or wheat), and to compare these costs with age-and sex-matched controls. METHODS: Direct and indirect cost parent-reported data collected via the Food Allergy Socio-Economic Questionnaire of 84 children (0-12 years) and 60 adolescents (13-17 years) with objectively diagnosed allergy to staple foods ("cases") and age- and sex-matched controls (n = 94 children; n = 56 adolescents) were compared. Annual household costs were calculated. Total household costs included direct plus indirect costs. Intangible costs included parent-reported health of their child and/or adolescent, standard of living, and perceptions of well-being. RESULTS: Amongst cases, total household costs were higher by (sic)3961 for children and (sic)4792 for adolescents versus controls (P < .05), and were driven by direct (eg, medications) and indirect (eg, time with health care professionals) costs. For children only, a history of anaphylaxis was associated with higher direct costs than no anaphylaxis ((sic)13,016 vs (sic)10,044, P < .05). Intangible costs (eg, parent-reported health of a child and/or adolescent) were significantly impacted amongst cases versus controls (P < .01). CONCLUSION: Households with a child and/or adolescent with objectively diagnosed allergy to staple foods have higher total household costs than controls. Direct and indirect costs were significantly higher for cases versus controls amongst children only. Amongst both age groups, such allergy adversely impacted intangible costs. (C) 2015 The Authors. Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology.
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| 24. |
- Protudjer, Jennifer Lisa Penner, et al.
(författare)
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Impaired health-related quality of life in adolescents with allergy to staple foods
- 2016
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Ingår i: Clinical and Translational Allergy. - : Wiley. - 2045-7022. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cow's milk, hen's egg and wheat are staple foods in a typical western diet. Despite the ubiquity of these foods, the impact of staple food allergy on health-related quality of life (HRQL) amongst adolescents is incompletely understood. The aims of this study were to make use of the Swedish version of EuroPrevall's disease-specific food allergy quality of life questionnaire-teenager form (FAQLQ-TF) and to investigate the association between objectively-diagnosed staple food allergy and HRQL amongst adolescents. Methods: In this cross-sectional study, 58 adolescents aged 13-17 years [n = 40 (69 %) boys] with objectively-diagnosed allergy to the staple foods cow's milk, hen's egg and/or wheat and living in Stockholm, Sweden were included. Adolescents completed the FAQLQ-TF, which has a corresponding scale of 1 = best HRQL, and 7 = worst HRQL. Overall HRQL and domain-specific HRQL were established. Adolescents also reported symptoms, adrenaline auto injector (AAI) prescription and presence of other food allergies. A history of anaphylaxis was defined among those reporting difficulty breathing, inability to stand/collapse, and/or loss of consciousness. Clinically different HRQL was set at a mean difference of >= 0.5. Results: Overall mean HRQL was poorer than average [mean: 4.70/7.00 (95 % CI 4.30-5.01)]. The domain risk of accidental exposure was significantly associated with clinically better HRQL than the domain allergen avoidance and dietary restrictions (mean difference = 0.76; p < 0.001). Girls had clinically worse, but not statistically significantly different mean HRQL than boys (mean difference = 0.71; p < 0.07). HRQL tended to be worse amongst those with allergies to more than three foods or an AAI prescription. The number and types of symptoms, including a history of anaphylaxis were not associated with worse HRQL. Conclusions: As ascertained via a food allergy-specific questionnaire, adolescents with staple food allergy report poorer than average HRQL, specifically in relation to emerging independence and the need for support. Girls have clinically worse HRQL than boys. The number and type of previous symptoms and history of anaphylaxis were not associated with worse HRQL.
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| 25. |
- Yasinska, Valentyna, et al.
(författare)
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Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months.Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.
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