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- Bjermer, Leif, et al.
(författare)
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The use of leukotriene receptor antagonists (LTRAs) as complementary therapy in asthma
- 2002
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Ingår i: Monaldi Archives for Chest Disease. - 1122-0643. ; 57:1, s. 76-83
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Tidskriftsartikel (refereegranskat)abstract
- The cysteinyl-leukotrienes (cysLTs: LTC4, LTD4 and LTE4) have an important pathophysiological role in asthma. They are not only extremely potent bronchoconstrictors, but are also involved in the central mechanisms of the asthmatic inflammation and the subsequent remodelling of the airways. Allergen-induced bronchoconstriction as well as spontaneous exacerbations of asthma are associated with increased secretion of LTE4 in urine. This increase does not seem to be affected by high doses of inhaled or systemic corticosteroids. On the contrary, both in vivo and in vitro experiments indicate that corticosteroids to a certain degree may even upregulate the cysLTs synthesis. Moreover, inhaled medication may not get as far as the small airways, which are affected by inflammatory changes in asthma. Hence, the combination of an oral leukotriene receptor antagonist (LTRA) with an inhaled corticosteroid (ICS) seems a rational therapeutic approach to achieve a more complete control of the inflammatory mechanisms in asthma. The additive effects by combining an LTRA with an ICS have been investigated in adults as well as in children from 6-14 years of age. The addition of LTRA improves lung function, and reduces day and night time symptoms in all age groups. More importantly, the combination has also been found to decrease the exacerbation rates in all age groups. More recently, a few studies have compared the effect of additive therapy with LTRA and ICS versus long-acting beta 2-agonists (LABAs) and ICS in asthmatics. Depending on the patient and outcome parameters preselection, some studies found that addition of LABA to ICS resulted in a better lung function and a better overall disease control. Yet one--unsponsored-study, comparing the protective effects of LABA versus LTRA on inflammatory outcome parameters in asthma, found a significant protection against airway hyperresponsiveness to adenosine monophosphate (AMP), together with significant decreases in exhaled nitric oxide (NO) and sputum eosinophils following one week treatment with LTRA, whereas the initial protection by LABA on the AMP responsiveness was lost after one week, and no anti-inflammatory effects could be observed. Similar beneficial effects from LTRA therapy are expected in patients with nocturnal asthma, in whom a decreased responsiveness to corticosteroids has been demonstrated. The choice of either combination therapy has clinical implications. It seems that especially patients with a suboptimal lung function and a significant beta 2-agonist reversibility will benefit from the addition of a LABA, whereas asthmatics with mainly exercise-induced asthma, nocturnal symptoms, or a frequent worsening due to low tolerance to provocative stimuli, may mostly benefit by adding an LTRA to ICS. However, it remains to be determined which combination has the most profound effect on the inflammatory process and the structural changes in asthma.
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- De Prins, L, et al.
(författare)
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White Paper on European Patient Needs and Suggestions on Chronic Type 2 Inflammation of Airways and Skin by EUFOREA
- 2022
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Ingår i: Frontiers in allergy. - : Frontiers Media SA. - 2673-6101. ; 3, s. 889221-
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 inflammation underlies the chronicity of disease in subgroups of patients with asthma, chronic rhinosinusitis with nasal polyps (CRSwNP) and atopic dermatitis (AD), that often co-exist. Although several studies have investigated the unmet needs of asthma, AD and CRSwNP as such, little is known about the similarities and differences in experiences and perspectives of the current management of patients with comorbid Type 2 inflammatory diseases.AimsTo improve insight into the common and organ-specific needs of patients with Type 2 inflammation and comorbidities, allowing the formulation of recommendations to better address these needs in the future.MethodologyThis qualitative study was conducted between July 2021 and December 2021 using semi-structured face-to-face or telephone interviews with patients suffering from year-long severe chronic Type 2 inflammation and at least one co-morbid inflammatory condition. Seven participating academic centers in Europe interviewed asthma (Copenhagen and Leuven), CRSwNP (London, Amsterdam and Crete) and/or AD (Oldenburg and Zurich) patients on patient characteristics, disease severity, shortcomings of current care pathways and suggestions for improvement of care. Transcripts were analyzed using an inductive thematic analysis approach.ResultsEighty-one patients with severe Type 2 inflammation and comorbidities were interviewed. Similar needs were recognized by patients with Type 2 inflammation, with both a lack of coordination in care and a lack of a real cure reported as being most frustrating. However, several needs are specific to asthma, CRSwNP and AD. Suggestions for improvement of care were generic across diseases, such as the implementation of a multidisciplinary approach, the improved facilitation of access to better treatments, the increase of general awareness on disease burden, and better educational programs for healthcare providers and patients. Of note, patients with CRSwNP also stated the need for alternatives to sinus surgery, whereas patients with asthma requested better medical care to prevent exacerbations and patients with AD would warmly welcome the reimbursement of emollients.ConclusionPatients with asthma, CRSwNP and AD have shared unmet needs that need to be addressed by physicians, the academic community and health policy makers. This survey provides unique recommendations made by patients for the implementation of better care.
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| 7. |
- Del Giacco, S. R., et al.
(författare)
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Allergy in severe asthma
- 2017
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538. ; 72:2, s. 207-220
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Tidskriftsartikel (refereegranskat)abstract
- It is well recognized that atopic sensitization is an important risk factor for asthma, both in adults and in children. However, the role of allergy in severe asthma is still under debate. The term 'Severe Asthma' encompasses a highly heterogeneous group of patients who require treatment on steps 4-5 of GINA guidelines to prevent their asthma from becoming 'uncontrolled', or whose disease remains 'uncontrolled' despite this therapy. Epidemiological studies on emergency room visits and hospital admissions for asthma suggest the important role of allergy in asthma exacerbations. In addition, allergic asthma in childhood is often associated with severe asthma in adulthood. A strong association exists between asthma exacerbations and respiratory viral infections, and interaction between viruses and allergy further increases the risk of asthma exacerbations. Furthermore, fungal allergy has been shown to play an important role in severe asthma. Other contributing factors include smoking, pollution and work-related exposures. The 'Allergy and Asthma Severity' EAACI Task Force examined the current evidence and produced this position document on the role of allergy in severe asthma.
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- Hellings, P. W., et al.
(författare)
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EUFOREA summit in Brussels 2023 : inspiring the future of allergy & respiratory care
- 2023
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Ingår i: Frontiers in Allergy. - 2673-6101. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.
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| 12. |
- Kortekaas Krohn, I., et al.
(författare)
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Emerging roles of innate lymphoid cells in inflammatory diseases : Clinical implications
- 2018
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 73:4, s. 837-850
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Forskningsöversikt (refereegranskat)abstract
- Innate lymphoid cells (ILC) represent a group of lymphocytes that lack specific antigen receptors and are relatively rare as compared to adaptive lymphocytes. ILCs play important roles in allergic and nonallergic inflammatory diseases due to their location at barrier surfaces within the airways, gut, and skin, and they respond to cytokines produced by activated cells in their local environment. Innate lymphoid cells contribute to the immune response by the release of cytokines and other mediators, forming a link between innate and adaptive immunity. In recent years, these cells have been extensively characterized and their role in animal models of disease has been investigated. Data to translate the relevance of ILCs in human pathology, and the potential role of ILCs in diagnosis, as biomarkers and/or as future treatment targets are also emerging. This review, produced by a task force of the Immunology Section of the European Academy of Allergy and Clinical Immunology (EAACI), encompassing clinicians and researchers, highlights the role of ILCs in human allergic and nonallergic diseases in the airways, gastrointestinal tract, and skin, with a focus on new insights into clinical implications, therapeutic options, and future research opportunities.
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| 13. |
- Mathioudakis, AG, et al.
(författare)
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Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:7, s. e048338-
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Tidskriftsartikel (refereegranskat)abstract
- Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted.Methods and analysisStandard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence.Ethics and disseminationEthics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank.PROSPERO registration numbersCRD42020132990, CRD42020171624.
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| 16. |
- Roth-Walter, F., et al.
(författare)
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Metabolic pathways in immune senescence and inflammaging : Novel therapeutic strategy for chronic inflammatory lung diseases. An EAACI position paper from the Task Force for Immunopharmacology
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Ingår i: Allergy: European Journal of Allergy and Clinical Immunology. - 0105-4538.
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Tidskriftsartikel (refereegranskat)abstract
- The accumulation of senescent cells drives inflammaging and increases morbidity of chronic inflammatory lung diseases. Immune responses are built upon dynamic changes in cell metabolism that supply energy and substrates for cell proliferation, differentiation, and activation. Metabolic changes imposed by environmental stress and inflammation on immune cells and tissue microenvironment are thus chiefly involved in the pathophysiology of allergic and other immune-driven diseases. Altered cell metabolism is also a hallmark of cell senescence, a condition characterized by loss of proliferative activity in cells that remain metabolically active. Accelerated senescence can be triggered by acute or chronic stress and inflammatory responses. In contrast, replicative senescence occurs as part of the physiological aging process and has protective roles in cancer surveillance and wound healing. Importantly, cell senescence can also change or hamper response to diverse therapeutic treatments. Understanding the metabolic pathways of senescence in immune and structural cells is therefore critical to detect, prevent, or revert detrimental aspects of senescence-related immunopathology, by developing specific diagnostics and targeted therapies. In this paper, we review the main changes and metabolic alterations occurring in senescent immune cells (macrophages, B cells, T cells). Subsequently, we present the metabolic footprints described in translational studies in patients with chronic asthma and chronic obstructive pulmonary disease (COPD), and review the ongoing preclinical studies and clinical trials of therapeutic approaches aiming at targeting metabolic pathways to antagonize pathological senescence. Because this is a recently emerging field in allergy and clinical immunology, a better understanding of the metabolic profile of the complex landscape of cell senescence is needed. The progress achieved so far is already providing opportunities for new therapies, as well as for strategies aimed at disease prevention and supporting healthy aging.
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| 17. |
- Scadding, G. K., et al.
(författare)
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Pre-asthma : a useful concept for prevention and disease-modification? A EUFOREA paper. Part 1—allergic asthma
- 2023
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Ingår i: Frontiers in Allergy. - 2673-6101. ; 4
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Forskningsöversikt (refereegranskat)abstract
- Asthma, which affects some 300 million people worldwide and caused 455,000 deaths in 2019, is a significant burden to suffers and to society. It is the most common chronic disease in children and represents one of the major causes for years lived with disability. Significant efforts are made by organizations such as WHO in improving the diagnosis, treatment and monitoring of asthma. However asthma prevention has been less studied. Currently there is a concept of pre- diabetes which allows a reduction in full blown diabetes if diet and exercise are undertaken. Similar predictive states are found in Alzheimer's and Parkinson's diseases. In this paper we explore the possibilities for asthma prevention, both at population level and also investigate the possibility of defining a state of pre-asthma, in which intensive treatment could reduce progression to asthma. Since asthma is a heterogeneous condition, this paper is concerned with allergic asthma. A subsequent one will deal with late onset eosinophilic asthma.
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| 20. |
- Stenberg, H., et al.
(författare)
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Small airway involvement in the late allergic response in asthma
- 2017
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894. ; 47:12, s. 1555-1565
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Tidskriftsartikel (refereegranskat)abstract
- Background: Allergy and asthma are closely linked. Inhalation of allergen induces an early allergic response (EAR) within the airways of allergic asthmatic subjects, which is followed by a late allergic response (LAR) in approximately 50% of the subjects. The LAR is defined as a drop in forced expiratory volume in 1 second (FEV1) from baseline usually occurring 4-8 hours after exposure and is believed to affect small airways. However, FEV1 is insensitive to changes in small airway physiology. Objective: Our aim was to investigate and compare the pathophysiological processes in large and small airways during the EAR and the LAR and to characterize subjects with both an EAR and a LAR (dual responders) versus those with an EAR only (single responders). Methods: Thirty-four subjects with allergic asthma underwent an inhaled allergen challenge. Lung physiology was assessed by spirometry, impulse oscillometry (IOS), body plethysmography, inert gas washout, single breath methane dilution carbon monoxide diffusion and exhaled breath temperature (EBT), at baseline and repeatedly for 23 hours post-allergen challenge. Results: Peripheral airway resistance, air trapping and ventilation heterogeneity were significantly increased in dual responders (n = 15) compared to single responders (n = 19) 6-8 hours post-challenge. Parameters of peripheral airway resistance and ventilation heterogeneity, measured with IOS and inert gas washout, respectively, correlated at baseline and during the allergic airway response in all subjects. Conclusion: The LAR involves increased resistance and ventilation defects within the peripheral airways. Alternative definitions of the LAR including small airways pathophysiology could be considered. Clinical relevance: Small airway dysfunction during the LAR suggests that dual responders may have more extensive airway pathology and underscores the relevance of small airways assessment in asthma.
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