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- Gyllfors, Per, et al.
(author)
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Relation between bronchial responsiveness to inhaled leukotriene D4 and markers of leukotriene biosynthesis
- 2005
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In: Thorax. - : BMJ. - 0040-6376 .- 1468-3296. ; 60:11, s. 902-8
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Journal article (peer-reviewed)abstract
- 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.
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| 2. |
- Badi, Yusef Eamon, et al.
(author)
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Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma
- 2022
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In: Journal of Allergy and Clinical Immunology. - : Elsevier. - 0091-6749 .- 1097-6825. ; 149:1, s. 89-101
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Journal article (peer-reviewed)abstract
- Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases.Objective: We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti–IL-22 (fezakinumab [FZ]) is enriched in severe asthma.Methods: An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort.Results: The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, TH2, and TH17/TH22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P <.05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P <.05) and particularly in neutrophilic and mixed granulocytic sputum (P <.05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with TH22/IL-22 pathways.Conclusions: The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.
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| 4. |
- Ekerljung, Linda, 1979, et al.
(author)
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Has the increase in the prevalence of asthma and respiratory symptoms reached a plateau in Stockholm, Sweden?
- 2010
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In: The International Journal of Tuberculosis and Lung Disease. - 1027-3719 .- 1815-7920. ; 14:6, s. 764-771
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Journal article (peer-reviewed)abstract
- SETTING: An increase in the prevalence of asthma has previously been reported worldwide. However, the current trend is debatable. OBJECTIVE: To assess changes in the prevalence of asthma and respiratory symptoms in a defined study area in Stockholm, Sweden, using identical methods. DESIGN: A questionnaire was sent by mail in 1996 and 2007 to randomly selected subjects aged 20-69 years. On both occasions, 8000 subjects received the questionnaire, with response rates of 72% and 68%, respectively. Questions on asthma, respiratory symptoms, asthma medication and possible determinants were included. Logistic regression analysis was used to assess determinants. RESULTS: Ever asthma increased from 8.7% in 1996 to 11.0% in 2007 and physician-diagnosed asthma from 7.6% to 9.3%. The proportion of asthma patients reporting one to two symptoms increased by 14% during the study period. There were few significant changes in the prevalence of respiratory symptoms: wheeze in the previous 12 months (15.9-17.3%), wheezing with breathlessness apart from cold (3.2-4.1%) and recurrent wheeze (8.3-6.8%). There was no major difference in the risk factor pattern between the surveys. CONCLUSION: An increase in the prevalence of asthma with few symptoms as well as an unchanged prevalence of symptoms was demonstrated, which may indicate a change in diagnostic practices.
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| 5. |
- Gaber, Flora, et al.
(author)
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Saliva is one likely source of leukotriene B4 in exhaled breath condensate
- 2006
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In: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 28:6, s. 1229-35
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Journal article (peer-reviewed)abstract
- 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.
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