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- Kolmert, Johan, et al.
(author)
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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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In: 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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Journal article (peer-reviewed)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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| 2. |
- Mathioudakis, Alexander G., et al.
(author)
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ERS/EAACI statement on adherence to international adult asthma guidelines
- 2021
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In: European Respiratory Review. - : European Respiratory Society (ERS). - 0905-9180 .- 1600-0617. ; 30:161
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Research review (peer-reviewed)abstract
- Guidelines aim to standardise and optimise asthma diagnosis and management. Nevertheless, adherence to guidelines is suboptimal and may vary across different healthcare professional (HCP) groups. Further to these concerns, this European Respiratory Society (ERS)/European Academy of Allergy and Clinical Immunology (EAACI) statement aims to: 1) evaluate the understanding of and adherence to international asthma guidelines by HCPs of different specialties via an international online survey; and 2) assess strategies focused at improving implementation of guideline-recommended interventions, and compare process and clinical outcomes in patients managed by HCPs of different specialties via systematic reviews. The online survey identified discrepancies between HCPs of different specialties which may be due to poor dissemination or lack of knowledge of the guidelines but also a reflection of the adaptations made in different clinical settings, based on available resources. The systematic reviews demonstrated that multifaceted quality improvement initiatives addressing multiple challenges to guidelines adherence are most effective in improving guidelines adherence. Differences in outcomes between patients managed by generalists or specialists should be further evaluated. Guidelines need to consider the heterogeneity of real-life settings for asthma management and tailor their recommendations accordingly. Continuous, multifaceted quality improvement processes are required to optimise and maintain guidelines adherence. Validated referral pathways for uncontrolled asthma or uncertain diagnosis are needed.
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| 3. |
- Roth-Walter, Franziska, et al.
(author)
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Immune modulation via T regulatory cell enhancement : Disease-modifying therapies for autoimmunity and their potential for chronic allergic and inflammatory diseases—An EAACI position paper of the Task Force on Immunopharmacology (TIPCO)
- 2021
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In: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 76:1, s. 90-113
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Journal article (peer-reviewed)abstract
- Therapeutic advances using targeted biologicals and small-molecule drugs have achieved significant success in the treatment of chronic allergic, autoimmune, and inflammatory diseases particularly for some patients with severe, treatment-resistant forms. This has been aided by improved identification of disease phenotypes. Despite these achievements, not all severe forms of chronic inflammatory and autoimmune diseases are successfully targeted, and current treatment options, besides allergen immunotherapy for selected allergic diseases, fail to change the disease course. T cell–based therapies aim to cure diseases through the selective induction of appropriate immune responses following the delivery of engineered, specific cytotoxic, or regulatory T cells (Tregs). Adoptive cell therapies (ACT) with genetically engineered T cells have revolutionized the oncology field, bringing curative treatment for leukemia and lymphoma, while therapies exploiting the suppressive functions of Tregs have been developed in nononcological settings, such as in transplantation and autoimmune diseases. ACT with Tregs are also being considered in nononcological settings such as cardiovascular disease, obesity, and chronic inflammatory disorders. After describing the general features of T cell–based approaches and current applications in autoimmune diseases, this position paper reviews the experimental models testing or supporting T cell–based approaches, especially Treg-based approaches, in severe IgE-mediated responses and chronic respiratory airway diseases, such as severe asthma and COPD. Along with an assessment of challenges and unmet needs facing the application of ACT in these settings, this article underscores the potential of ACT to offer curative options for patients with severe or treatment-resistant forms of these immune-driven disorders.
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