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Lage Aksnes - One of the best experts on this subject based on the ideXlab platform.
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Increased levels of urinary Leukotriene E4 in children with severe atopic eczema/dermatitis syndrome
Allergy, 2005Co-Authors: Knut Øymar, Lage AksnesAbstract:Background: Leukotrienes are thought to play a role in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS). Urinary Leukotriene E4 (U-LTE4) is a marker of whole-body cysteinyl-Leukotriene production. Aims of the study: To evaluate the role of Leukotrienes in children with AEDS by measuring levels of U-LTE4, and to evaluate whether levels of U-LTE4 may reflect disease activity and allergic sensitization in AEDS. Methods: U-LTE4 was measured by enzyme-linked immunosorbent assay in 87 children with mild (n = 32), moderate (n = 34) and severe (n = 21) AEDS, as well as in 72 nonatopic healthy controls. Fifty-eight of the children with AEDS were sentitized to common allergens, and 29 were not. Results: Levels of U-LTE4 were higher in children with severe AEDS (140; 66–166 μg/mmol creatinine, median; quartiles) than in controls (52; 30–90, P
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increased levels of urinary Leukotriene E4 in children with severe atopic eczema dermatitis syndrome
Allergy, 2005Co-Authors: Knut Øymar, Lage AksnesAbstract:Background: Leukotrienes are thought to play a role in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS). Urinary Leukotriene E4 (U-LTE4) is a marker of whole-body cysteinyl-Leukotriene production. Aims of the study: To evaluate the role of Leukotrienes in children with AEDS by measuring levels of U-LTE4, and to evaluate whether levels of U-LTE4 may reflect disease activity and allergic sensitization in AEDS. Methods: U-LTE4 was measured by enzyme-linked immunosorbent assay in 87 children with mild (n = 32), moderate (n = 34) and severe (n = 21) AEDS, as well as in 72 nonatopic healthy controls. Fifty-eight of the children with AEDS were sentitized to common allergens, and 29 were not. Results: Levels of U-LTE4 were higher in children with severe AEDS (140; 66–166 μg/mmol creatinine, median; quartiles) than in controls (52; 30–90, P < 0.05), whereas levels of U-LTE4 in moderate and mild disease were similar to controls. U-LTE4 levels were similar in children with or without sensitization to common allergens, but severe AEDS children with sensitization had higher levels of U-LTE4 than those without sensitization. Conclusion: The results suggest a role for Leukotrienes in the pathogenesis of severe AEDS, and may support a role for Leukotriene-antagonists in the treatment of this disorder. Levels of U-LTE4 may reflect the disease severity and sensitization to allergens in AEDS.
Rohit Divekar - One of the best experts on this subject based on the ideXlab platform.
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Elevated Urine Leukotriene E4 Is Associated With Worse Objective Markers in Nasal Polyposis Patients.
The Laryngoscope, 2020Co-Authors: Garret Choby, Erin K. O'brien, Alyssa J. Smith, Jason H. Barnes, John B. Hagan, Janalee K. Stokken, Andrew Strumpf, Jose L. Mattos, Spencer C. Payne, Rohit DivekarAbstract:OBJECTIVES Urine Leukotriene E4 (uLTE4) is a biomarker of Leukotriene synthesis and is elevated in patients with aspirin-exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin-tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP. METHODS A retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund-Mackay CT score, spirometry and lab values) were collected. RESULTS Among the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P
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elevated urine Leukotriene E4 is associated with worse objective markers in nasal polyposis patients
Laryngoscope, 2020Co-Authors: Garret Choby, Alyssa J. Smith, Jason H. Barnes, John B. Hagan, Janalee K. Stokken, Andrew Strumpf, Jose L. Mattos, Spencer C. Payne, Erin K Obrien, Rohit DivekarAbstract:OBJECTIVES Urine Leukotriene E4 (uLTE4) is a biomarker of Leukotriene synthesis and is elevated in patients with aspirin-exacerbated respiratory disease (AERD). It can also be useful to help delineate aspirin-tolerant chronic rhinosinusitis with nasal polyposis (CRSwNP) patients from AERD patients. The purpose of this study is to determine if uLTE4 biomarker levels are associated with objective and subjective markers of disease severity in patients with CRSwNP. METHODS A retrospective analysis of CRSwNP patients who underwent uLTE4 testing was completed to determine the association of uLTE4 levels to markers of disease severity. uLTE4 levels, as well as presenting subjective (Sinonasal Outcome Test 22 [SNOT22] scores, asthma control test [ACT] scores) and objective data (Lund-Mackay CT score, spirometry and lab values) were collected. RESULTS Among the 157 CRSwNP patients who met inclusion criteria, uLTE4 levels were associated with history of asthma (P < .001), aspirin sensitivity (P < .001), worse Lund-Mackay CT scores (P = .002) and other objective markers of disease severity including serum IgE (P = .05), presenting blood eosinophil level (P < .001), and the highest recorded eosinophil level (P < .001). In subgroup analysis, associations of uLTE4 to disease markers had stronger correlations in the aspirin sensitive CRSwNP group (R range 0.31-0.52) than the aspirin tolerant CRSwNP group (R range -0.30-0.24). uLTE4 levels were not associated with subjective symptom scores (SNOT22 and ACT scores). CONCLUSION Elevated uLTE4 biomarker levels are associated with worsened objective markers of disease severity in CRSwNP patients but not patient-reported symptom measures. LEVEL OF EVIDENCE 3 Laryngoscope, 2020.
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Urinary Leukotriene E4 to Determine Aspirin Intolerance in Asthma: A Systematic Review and Meta-Analysis
The journal of allergy and clinical immunology. In practice, 2017Co-Authors: John B. Hagan, Erin K. O'brien, Rohit Divekar, Tanya M. Laidlaw, Hirohito Kita, Gerald W. Volcheck, Christina R. Hagan, Devyani Lal, Harry G. Teaford, Patricia J. ErwinAbstract:Background Urinary Leukotriene E4 (ULTE4) may be a biomarker that distinguishes aspirin-intolerant asthma from other asthma subtypes. Objective To estimate the diagnostic testing accuracy of ULTE4 as a marker of aspirin intolerance in patients with asthma using previously published studies. Methods We identified relevant clinical studies from a systematic review of English and non-English articles using MEDLINE, EMBASE, and CENTRAL (inception to February 10, 2015). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included previously published studies that analyzed ULTE4 in human subjects with asthma characterized as having or not having aspirin intolerance on the basis of a specified definition: convincing history of aspirin intolerance, positive aspirin challenge, or both as the criterion standard. Individual-level data points from all included studies were obtained and analyzed. Results The search strategy identified 867 potential articles, of which 86 were reviewed at the full-text level and 10 met criteria for inclusion. The sensitivity, specificity, positive predictive value, and negative predictive values of ULTE4 to determine aspirin intolerance in subjects with asthma were 0.55, 0.82, 0.75, and 0.66 (Amersham-enzyme immunoassay); 0.76, 0.77, 0.70, and 0.78 (Cayman-enzyme immunoassay); 0.70, 0.81, 0.86, and 0.79 (mass spectrometry); and 0.81,0.79, 0.65, and 0.88 (radioimmunoassay) at optimal thresholds of 192, 510, 167 to 173, and 66 to 69 pg/mg Cr, respectively. The diagnostic odds ratio for each methodology was 6.0, 11.9, 10.5, and 19.1, respectively. Conclusions ULTE4 is a marker for aspirin-intolerant asthma and could potentially be used as a clinical test to identify the risk of aspirin intolerance in subjects with asthma.
Knut Øymar - One of the best experts on this subject based on the ideXlab platform.
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Increased levels of urinary Leukotriene E4 in children with severe atopic eczema/dermatitis syndrome
Allergy, 2005Co-Authors: Knut Øymar, Lage AksnesAbstract:Background: Leukotrienes are thought to play a role in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS). Urinary Leukotriene E4 (U-LTE4) is a marker of whole-body cysteinyl-Leukotriene production. Aims of the study: To evaluate the role of Leukotrienes in children with AEDS by measuring levels of U-LTE4, and to evaluate whether levels of U-LTE4 may reflect disease activity and allergic sensitization in AEDS. Methods: U-LTE4 was measured by enzyme-linked immunosorbent assay in 87 children with mild (n = 32), moderate (n = 34) and severe (n = 21) AEDS, as well as in 72 nonatopic healthy controls. Fifty-eight of the children with AEDS were sentitized to common allergens, and 29 were not. Results: Levels of U-LTE4 were higher in children with severe AEDS (140; 66–166 μg/mmol creatinine, median; quartiles) than in controls (52; 30–90, P
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increased levels of urinary Leukotriene E4 in children with severe atopic eczema dermatitis syndrome
Allergy, 2005Co-Authors: Knut Øymar, Lage AksnesAbstract:Background: Leukotrienes are thought to play a role in the pathogenesis of atopic eczema/dermatitis syndrome (AEDS). Urinary Leukotriene E4 (U-LTE4) is a marker of whole-body cysteinyl-Leukotriene production. Aims of the study: To evaluate the role of Leukotrienes in children with AEDS by measuring levels of U-LTE4, and to evaluate whether levels of U-LTE4 may reflect disease activity and allergic sensitization in AEDS. Methods: U-LTE4 was measured by enzyme-linked immunosorbent assay in 87 children with mild (n = 32), moderate (n = 34) and severe (n = 21) AEDS, as well as in 72 nonatopic healthy controls. Fifty-eight of the children with AEDS were sentitized to common allergens, and 29 were not. Results: Levels of U-LTE4 were higher in children with severe AEDS (140; 66–166 μg/mmol creatinine, median; quartiles) than in controls (52; 30–90, P < 0.05), whereas levels of U-LTE4 in moderate and mild disease were similar to controls. U-LTE4 levels were similar in children with or without sensitization to common allergens, but severe AEDS children with sensitization had higher levels of U-LTE4 than those without sensitization. Conclusion: The results suggest a role for Leukotrienes in the pathogenesis of severe AEDS, and may support a role for Leukotriene-antagonists in the treatment of this disorder. Levels of U-LTE4 may reflect the disease severity and sensitization to allergens in AEDS.
Tak H. Lee - One of the best experts on this subject based on the ideXlab platform.
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Leukotriene E4 is a full functional agonist for human cysteinyl Leukotriene type 1 receptor-dependent gene expression
Scientific reports, 2016Co-Authors: Holly R. Foster, Tak H. Lee, Elisabeth Fuerst, William J. Branchett, David J. Cousins, Grzegorz WoszczekAbstract:Leukotriene E4 (LTE4) the most stable of the cysteinyl Leukotrienes (cysLTs) binds poorly to classical type 1 (CysLT1) and 2 (CysLT2) receptors although it induces potent responses in human airways in vivo, such as bronchoconstriction, airway hyperresponsiveness and inflammatory cell influx suggesting the presence of a novel receptor that preferentially responds to LTE4. To identify such a receptor two human mast cell lines, LAD2 and LUVA, were selected that differentially responded to LTE4 when analysed by intracellular signalling and gene expression. Comparative transcriptome analysis and recombinant gene overexpression experiments revealed CysLT1 as a receptor responsible for potent LTE4-induced response in LAD2 but not in LUVA cells, an observation confirmed further by gene knockdown and selective inhibitors. Lentiviral overexpression of CysLT1 in LUVA cells augmented intracellular calcium signalling induced by LTE4 but did not restore full agonist responses at the gene expression level. Our data support a model where both an increased expression of Gαq-coupled CysLT1, and sustained intracellular calcium mobilisation and extracellular signal-regulated kinase (Erk) activation, are required for LTE4-mediated regulation of gene expression in human cells. Our study shows for the first time that CysLT1 expression is critically important for responsiveness to LTE4 within a human cell system.
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The effect of aspirin desensitization on urinary Leukotriene E4 concentrations in aspirin-sensitive asthma.
American journal of respiratory and critical care medicine, 1995Co-Authors: S. M. Shuaib Nasser, Manish Patel, G. S. Bell, Tak H. LeeAbstract:Patients with aspirin sensitive asthma (ASA) can be desensitized to aspirin but the mechanisms by which this happens are unknown. To test the hypothesis that there may be a reduction in aspirin-induced Leukotriene release following aspirin desensitization, we studied nine patients with ASA, 37 +/- 2.3 yr of age (mean +/- SEM) with a baseline FEV1 of 94 +/- 3.5%. Urinary Leukotriene E4 (LTE4) and FEV1 were measured before and after ingestion of a threshold dose of aspirin leading to a 15% decrease in FEV1, and then at intervals following desensitization, when a maintenance dose of 600 mg aspirin was ingested. Prior to desensitization, the maximum decrease in FEV1 following ingestion of a threshold dose of aspirin was 15.3 +/- 3.9%, and urinary LTE4 rose from a baseline value of 235 +/- 79.4 pg/mg creatinine to 1,714 +/- 783 pg/mg creatinine at 3 h. Immediately after acute desensitization, which was performed over several days, 600 mg aspirin provoked a maximum decrease in FEV1 of only 3.3 +/- 2.4%, and urinary LTE4 increased from a baseline of 645 +/- 223 pg/mg creatinine to 1,256 +/- 456 pg/mg creatinine. Following ingestion of 600 mg aspirin for 9 +/- 3.2 mo (n = 5; chronic desensitization), urinary LTE4 rose from a basal level of 432 +/- 127 pg/mg creatinine to 749 +/- 257 pg/mg creatinine at 3 h after 600 mg aspirin, and this was accompanied by a maximum decrease in FEV1 of 7.4 +/- 4.5%. Although there was significantly less aspirin-induced LTE4 excretion after acute desensitization, substantial amounts of LTE4 were still produced without any significant change in lung function.(ABSTRACT TRUNCATED AT 250 WORDS)
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Airway responsiveness to Leukotriene C4 (LTC4), Leukotriene E4 (LTE4) and histamine in aspirin-sensitive asthmatic subjects
The European respiratory journal, 1993Co-Authors: Pandora E. Christie, M. Schmitz-schumann, Bernd W. Spur, Tak H. LeeAbstract:We wanted to determine whether the airway response to inhaled Leukotriene C4 (LTC4) is similar to inhaled Leukotriene E4 (LTE4) in aspirin-sensitive asthma and, therefore, determined airway responsiveness to histamine, LTC4 and LTE4 in seven aspirin-sensitive subjects and 13 control asthmatic subjects, who were tolerant of aspirin. The concentration of inhaled lysine-aspirin which produced a 15% fall in forced expiratory volume in one second (FEV1) (PC15) was determined in aspirin-sensitive asthmatic subjects. The dose of histamine, LTC4 and LTE4 which produced a 35% fall in specific airways conductance (PD35sGaw) was determined by linear interpolation from the log dose response curve. There was no correlation between the PC15 for lysine-aspirin and the airway reactivity to inhaled LTC4 or LTE4. There was no difference in airway response to histamine and LTC4 between any of the groups of asthmatic subjects. There was a rank order of potency LTC4 > LTE4 > histamine in both groups, with LTC4 approximately 1,000 fold more potent than histamine in both groups. Aspirin-sensitive asthmatic subjects were significantly more responsive to LTE4 (p = 0.02) than aspirin-tolerant asthmatic subjects. The relative responsiveness of LTE4 to histamine (PD35 histamine/PD35 LTE4) was significantly greater in aspirin-sensitive asthmatic subjects compared to aspirin-tolerant asthmatic subjects (p = 0.05). There was no difference in relative responsiveness of LTC4 to histamine between aspirin-sensitive or aspirin-tolerant asthmatic subjects. We conclude that the airways of aspirin-sensitive asthmatic subjects demonstrate a selective hyperresponsiveness to LTE4, which is not observed for LTC4.
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Urinary Leukotriene E4 after lysine-aspirin inhalation in asthmatic subjects.
The American review of respiratory disease, 1992Co-Authors: Pandora E. Christie, P. Tagari, Anthony W. Ford-hutchinson, Cheryl Black, Andre Markendorf, M. Schmitz-schumann, Tak H. LeeAbstract:The FEV1 and urinary Leukotriene E4 (LTE4) concentrations were determined in six aspirin-sensitive and six non-aspirin-sensitive asthmatic subjects before and after inhalation challenge with lysine-aspirin or placebo solution. Lysine-aspirin produced a mean fall in FEV1 of 26.7 ± 4.9% (mean ± SEM) in subjects with aspirin sensitivity and of 8.5 ± 6.5% (mean ± SEM) in non-aspirin-sensitive asthmatic subjects. The mean baseline urinary LTE4 concentration of 83 pg/mg creatinine (geometric mean [GM], range 15 to 326 pg/mg creatinine) in aspirin-sensitive subjects was significantly higher than the 33.8 pg/mg creatinine (GM, range 10 to 111 pg/mg creatinine) in non-aspirin-sensitive subjects (p = 0.02). In aspirin-sensitive subjects, inhalation challenge with lysine-aspirin produced a significant increase in urinary LTE4 concentration to 240 pg/mg creatinine (GM, range 60 to 1,113 pg/mg creatinine), which was not observed after placebo challenge. There was no significant change in urinary LTE4 concentration aft...
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Urinary Leukotriene E4 in bronchial asthma.
The European respiratory journal, 1992Co-Authors: Christine M. Smith, Pandora E. Christie, Richard J. Hawksworth, Francis Thien, Tak H. LeeAbstract:Leukotriene E4 (LTE4) is excreted into the urine in a relatively constant proportion of 4-7% when either Leukotriene C4 (LTC4) or LTE4 is intravenously infused, regardless of the magnitude of the infused dose. Measurement of LTE4 in urine is, therefore, a convenient and non-invasive method for assessing changes in the rate of total body sulphidopeptide Leukotriene production. We assayed urinary LTE4 in 17 normal subjects, 31 subjects with asthma without aspirin sensitivity, and 10 aspirin-sensitive subjects. The relationship between urinary LTE4 and nonspecific bronchial hyperresponsiveness, as assessed by the provocative dose producing a 20% fall in forced expiratory volume in one second (PD20) to inhaled histamine, was examined in 19 non-aspirin-sensitive asthmatic subjects. The urinary LTE4 values were log-normally distributed. Urinary LTE4 was detected in 28 of the 31 non-aspirin-sensitive asthmatic subjects, and the geometric mean (95% confidence interval (CI) of 43 (32-57) pg.mg-1 creatinine was no different to that of 34 (25-48) pg.mg-1 creatinine measured in the normal subjects. The geometric mean of 101 (55-186) pg.mg-1 creatinine measured in the aspirin-sensitive asthmatics was significantly higher than that measured in the normal subjects (p less than 0.005) and in the asthmatic subjects who were non-aspirin-sensitive (p less than 0.002), but there was considerable overlap between the three groups. There was no relationship between urinary LTE4 and PD20, or between urinary LTE4 and baseline forced expiratory volume in one second (FEV1) (% predicted). Thus, measurement of LTE4 in a single sample of urine will not predict the extent of bronchial hyperresponsiveness or degree of airflow obstruction.
Michael R. Debaun - One of the best experts on this subject based on the ideXlab platform.
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Urinary cysteinyl Leukotriene E4 significantly increases during pain in children and adults with sickle cell disease
American journal of hematology, 2009Co-Authors: Joshua J. Field, Robert C. Strunk, Jessica Knight-perry, Morey A. Blinder, Raymond R. Townsend, Michael R. DebaunAbstract:Baseline level of the cysteinyl Leukotriene (CysLT), Leukotriene E4 (LTE4), is associated with an increased pain rate in children and adults with sickle cell disease (SCD). To provide additional evidence for a role of CysLTs in the pathogenesis of vaso-occlusion, we tested the hypothesis that LTE4 levels will increase within an individual during painful episodes compared to baseline. In a cohort of 19 children and adults with SCD, median LTE4 levels increased from 82.36 pg/mg creatinine at baseline to 162.81 pg/mg creatinine during a painful episode (P < 0.001). These data further support a contribution of CysLTs to the process of vaso-occlusion.
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Urinary cysteinyl Leukotriene E4 is associated with increased risk for pain and acute chest syndrome in adults with sickle cell disease
American journal of hematology, 2009Co-Authors: Joshua J. Field, Robert C. Strunk, Morey A. Blinder, James G. Krings, Nicole L. White, Yan Yan, Michael R. DebaunAbstract:Leukotriene E4 (LTE4) levels are associated with rate of pain episodes in children with sickle cell disease (SCD). Because complications of SCD manifest differently in adults than children, we examined a cohort of adults with SCD to determine the relationship between baseline LTE4 and SCD-related morbidity. Baseline LTE4 levels were associated with increased rates of pain and acute chest syndrome (ACS) episodes, when those with LTE4 values in the highest tertile were compared with those in the lowest tertile (pain: risk ratio 7.1, 95% CI 1.8–27.5, P = 0.005; ACS: risk ratio 12.2, 95% CI 2.1–69.8, P = 0.005). Am. J. Hematol., 2009. © 2009 Wiley-Liss, Inc.
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Elevated Urinary Leukotriene E4 Levels Are Associated with Hospitalization for Pain in Children with Sickle Cell Disease.
Blood, 2007Co-Authors: Jeanine E. Jennings, Robert C. Strunk, Thiruvamoor Ramkumar, Jingnan Mao, Jessica H. Boyd, Mario Castro, Michael R. DebaunAbstract:Introduction: Sickle cell disease (SCD) is associated with an inflammatory state. Luekotrienes are inflammatory mediators derived from arachidonic acid and produced by white blood cells in response to inflammatory stimuli. We tested two hypotheses among children with SCD: Baseline Leukotriene levels are elevated in SCD when compared to controls children without SCD, Baseline Leukotriene levels are associated with an increased incidence rate of hospitalization for pain. Methods: During routine clinical visits, baseline urinary Leukotriene E4 (LTE4) levels were measured in children with SCD (cases) and age, and ethnic, matched children without SCD (controls). Medical records of the cases were reviewed to assess the frequency of hospitalization for pain within three years of entering the study. Results: LTE4 levels were obtained in 71 cases and 22 controls. LTE4 levels were higher in the cases compared to controls (median LTE4: 100 vs.57 pg/mg creatinine); P Conclusion: LTE4 levels are elevated in children with SCD when compared to controls without SCD and are associated with an increased rate of hospitalizations for pain.