| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Balgoma, D, et al.
(författare)
-
Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD
- 2016
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 47:6, s. 1645-1656
-
Tidskriftsartikel (refereegranskat)abstract
- Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality; however, the role of inflammatory mediators in its pathobiology remains unclear. The aim of this study was to investigate the influence of gender in COPD on lipid mediator levels.Bronchoalveolar lavage fluid (BALF) and serum were obtained from healthy never-smokers, smokers and COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage I–II/A–B) (n=114). 94 lipid mediators derived from the cytochrome-P450, lipoxygenase, and cyclooxygenase pathways were analysed by liquid chromatography-mass spectrometry.Multivariate modelling identified a 9-lipid panel in BALF that classified female smokers with COPD from healthy female smokers (p=6×10−6). No differences were observed for the corresponding male population (p=1.0). These findings were replicated in an independent cohort with 92% accuracy (p=0.005). The strongest drivers were the cytochrome P450-derived epoxide products of linoleic acid (leukotoxins) and their corresponding soluble epoxide hydrolase (sEH)-derived products (leukotoxin-diols). These species correlated with lung function (r=0.87; p=0.0009) and mRNA levels of enzymes putatively involved in their biosynthesis (r=0.96; p=0.003). Leukotoxin levels correlated with goblet cell abundance (r=0.72; p=0.028).These findings suggest a mechanism by which goblet cell-associated cytochrome-P450 and sEH activity produce elevated leukotoxin-diol levels, which play a putative role in the clinical manifestations of COPD in a female-dominated disease sub-phenotype.
|
|
| 8. |
|
|
| 9. |
- Bood, JR, et al.
(författare)
-
Urinary excretion of lipid mediators in response to repeated eucapnic voluntary hyperpnea in asthmatic subjects
- 2015
-
Ingår i: Journal of applied physiology (Bethesda, Md. : 1985). - : American Physiological Society. - 1522-1601 .- 8750-7587. ; 119:3, s. 272-279
-
Tidskriftsartikel (refereegranskat)abstract
- Exercise-induced bronchoconstriction displays refractoriness manifested as a decreased response to repeated exercise challenge within hours. The refractoriness may be attenuated by inhibition of the biosynthesis of prostaglandins (PG). The aim of the study was to determine which PGs and other lipid mediators are excreted during the refractory period. First, 16 subjects with mild stable asthma performed two repeated 4-min challenges with eucapnic voluntary hyperpnea (EVH) 1 and 3 h apart. There was a similar degree of refractoriness in both protocols (∼15% protection). The 1-h interval was too short to study mediator excretion because the urinary levels did not return to baseline before the second challenge. With the 3-h protocol, there was increased urinary excretion of cysteinyl-leukotrienes and metabolites of the mast cell product PGD2after both challenges. Next, another eight subjects performed two 6-min challenges with EVH 3 h apart, which produced a greater bronchoconstrictor response than the 4-min protocol (30.0 ± 5.4 vs. 17.7 ± 1.5%; P = 0.0029) and a greater degree of refractoriness (∼30%). Analysis by ultra-performance liquid chromatography triple quadrupole mass spectrometry confirmed excretion of the bronchoconstrictor cysteinyl-leukotrienes and PGD2during both challenges. In addition, there was increased excretion of the bronchoprotective PGE2, and also of the main metabolite of PGI2. This is the first report of excretion of PGE2and PGI2during the refractory period to EVH challenge, suggesting that they may mediate the refractoriness. Maintained excretion of PGD2and leukotriene E4following the repeat challenge argues against mast cell mediator depletion as the mechanism of refractoriness.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Chung, KF, et al.
(författare)
-
International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma
- 2014
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 43:2, s. 343-373
-
Tidskriftsartikel (refereegranskat)abstract
- Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults.A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations.When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided.Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.
|
|
| 14. |
|
|
| 15. |
- Daham, K, et al.
(författare)
-
Effects of celecoxib on major prostaglandins in asthma
- 2011
-
Ingår i: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - : Wiley. - 1365-2222. ; 41:1, s. 36-45
-
Tidskriftsartikel (refereegranskat)
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
|
|
| 27. |
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
|
|
| 34. |
- Eriksson, Jonas, 1984, et al.
(författare)
-
Update of prevalence of self-reported allergic rhinitis and chronic nasal symptoms among adults in Sweden
- 2012
-
Ingår i: The Clinical Respiratory Journal. - 1752-699X .- 1752-6981. ; 6:3, s. 159-168
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Allergic rhinitis (AR) is the most common immunologic disease, and it renders a considerable burden on both sufferers and society. The prevalence of AR has been increasing worldwide over the past century. The aim of this study was to assess the present prevalence, risk factor patterns and comorbidity of self-reported AR and chronic nasal symptoms in different age groups in Stockholm, Sweden. Methods: A postal questionnaire was sent on two occasions, in 2006 to a population aged 30-80 years, randomly selected 10 years previously, and in 2007 to a randomly selected sample of subjects aged 20-69 years. The response rates were 83% and 68%, respectively, and in total, 9792 subjects participated. The questionnaire included questions on self-reported AR, asthma, respiratory and nasal symptoms and possible determinants. Results: The prevalence of self-reported AR was 28.0% (men 26.6%, women 29.1%, P<0.01) similar to 10 years previously and 33.6% in ages 30-40 years. Allergic heredity [odds ratio (OR) 4.76, confidence interval (CI) 95% 4.25-5.33], physician-diagnosed asthma (OR 5.29, CI 95% 4.49-6.24) and occupational exposure to dust, gases and fumes (OR 1.49, CI 95% 1.30-1.72) were determinants for AR. Prevalence of chronic nasal congestion was 16.1% and of chronic rhinorrhea 14.1%. Conclusions: As a basis for understanding the disease, as well as in planning and prioritising health-care resources, the study provides information about the current prevalence and determinants of self-reported AR and chronic nasal symptoms. Further, comparing with previous studies, the present study suggests that a plateau in the prevalence of AR may have been reached in Sweden. Please cite this paper as: Eriksson J, Ekerljung L, Rönmark E, Dahlén B, Ahlstedt S, Dahlén S-E and Lundbäck B. Update of prevalence of self-reported allergic rhinitis and chronic nasal symptoms among adults in Sweden
|
|
| 35. |
- Gafvelin, G, et al.
(författare)
-
Selective COX-2 Inhibition Exerts No Negative Effects on Peripheral Blood Lymphocytes in Allergic Asthmatics
- 2016
-
Ingår i: International archives of allergy and immunology. - : S. Karger AG. - 1423-0097 .- 1018-2438. ; 170:1, s. 57-61
-
Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> Selective inhibition of cyclooxygenase-2 (COX-2) reduces the production of prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), which can have both pro- and anti-inflammatory effects on allergic inflammation. Moreover, in vitro PGE<sub>2</sub> has been shown to affect inflammation through the modulation of lymphocyte responses. <b><i>Methods:</i></b> Sixteen subjects with mild allergic asthma were recruited to a two-period cross-over study: one treatment period with the selective COX-2 inhibitor etoricoxib and one without. Each treatment period ended with an airway challenge with the patient's relevant allergen. Antigen-specific proliferation with the major cat allergen, Fel d 1, was analysed in PBMCs. CD4+ T cells were phenotyped using flow cytometry, and mRNA expression of FOXP3 in anti-CD3-stimulated CD4+ cells were analysed. <b><i>Results:</i></b> No significant impact of in vivo inhibition of COX-2 was detected on the proportion of Th1, Th2, or Treg cells in peripheral blood. Likewise, the treatment had minor effects on the stimulated expression of FOXP3 mRNA in CD4+ T cells. Proliferation of PBMCs to the major cat allergen Fel d 1 was slightly reduced by etoricoxib treatment in cat-allergic patients. <b><i>Conclusions:</i></b> Short-term treatment with the COX-2 inhibitor etoricoxib had a minor impact on T-cell responses, supporting its safe use also in subjects exposed to triggers of lymphocyte activation.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
|
|
| 39. |
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
- Khaleva, E, et al.
(författare)
-
Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
- 2023
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
-
Tidskriftsartikel (refereegranskat)abstract
- Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
|
|
| 49. |
- Khaleva, E, et al.
(författare)
-
Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA)
- 2023
-
Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 61:4
-
Tidskriftsartikel (refereegranskat)abstract
- Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) working group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies.MethodsCOMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult, and paediatric clinicians, pharmaceutical representatives and health regulators from across Europe. Evidence included a systematic review of development, validity, and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients’ and carers’ views about outcome measures. It was discussed using a modified GRADE Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria.ResultsBoth adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire, and Asthma Control Test (ACT) or Childhood-ACT while the adult COM includes the Severe Asthma Questionnaire and the Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately).ConclusionsThis patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.
|
|
| 50. |
|
|
