| 1. |
- Eger, Katrien, et al.
(författare)
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The effect of the COVID-19 pandemic on severe asthma care in Europe : will care change for good?
- 2022
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Ingår i: ERJ Open Research. - : European Respiratory Society (ERS). - 2312-0541. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Background The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.
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| 2. |
- Janson, Christer, et al.
(författare)
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Eosinophilic airway diseases : basic science, clinical manifestations and future challenges
- 2022
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Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 9:1
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Forskningsöversikt (refereegranskat)abstract
- Eosinophils have a broad range of functions, both homeostatic and pathological, mediated through an array of cell surface receptors and specific secretory granules that promote interactions with their microenvironment. Eosinophil development, differentiation, activation, survival and recruitment are closely regulated by a number of type 2 cytokines, including interleukin (IL)-5, the key driver of eosinophilopoiesis. Evidence shows that type 2 inflammation, driven mainly by interleukin (IL)-4, IL-5 and IL-13, plays an important role in the pathophysiology of eosinophilic airway diseases, including asthma, chronic rhinosinusitis with nasal polyps, eosinophilic granulomatosis with polyangiitis and hypereosinophilic syndrome. Several biologic therapies have been developed to suppress type 2 inflammation, namely mepolizumab, reslizumab, benralizumab, dupilumab, omalizumab and tezepelumab. While these therapies have been associated with clinical benefits in a range of eosinophilic diseases, their development has highlighted several challenges and directions for future research. These include the need for further information on disease progression and identification of treatable traits, including clinical characteristics or biomarkers that will improve the prediction of treatment response. The Nordic countries have a long tradition of collaboration using patient registries and Nordic asthma registries provide unique opportunities to address these research questions. One example of such a registry is the NORdic Dataset for aSThmA Research (NORDSTAR), a longitudinal population-based dataset containing all 3.3 million individuals with asthma from four Nordic countries (Denmark, Finland, Norway and Sweden). Large-scale, real-world registry data such as those from Nordic countries may provide important information regarding the progression of eosinophilic asthma, in addition to clinical characteristics or biomarkers that could allow targeted treatment and ensure optimal patient outcomes.
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| 3. |
- Yasinska, Valentyna, et al.
(författare)
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Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids
- 2023
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Ingår i: ERJ Open Research. - : European Respiratory Society. - 2312-0541. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure.Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study.Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months.Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.
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| 4. |
- Yasinska, Valentyna
(författare)
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Phenotyping of severe asthma in a clinical context
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Severe asthma is a chronic heterogeneous inflammatory disease characterized by several clinical phenotypes and molecular endotypes. Although it affects a relatively small proportion of the asthma population (approximately 4%-10%), with an even smaller proportion of these having severe uncontrolled eosinophilic asthma, it accounts for > 50% of the costs attributed to the disease. Despite the availability of modern medicines and improvements in certain outcomes, severe asthma is still a cause of mortality. Although it is known that severe asthma is driven by type 2 inflammation in most cases, and we now have the possibility to use specific biological therapies targeting this particular type of inflammation, many patients are still suboptimally controlled due to the heterogenous nature of this disease with its multiple subphenotypes. There is, therefore, an unmet need to characterize and classify these patients with a view to improve therapy and reduce costs on a global scale. Furthermore, selection of the most appropriate biologic and the best clinical outcomes and biomarkers with which to monitor response to therapy, are still issues of debate and the subject of ongoing research. Three clinical severe asthma studies are included in this thesis, the overall aim of which was to provide an increased understanding of the clinical features and treatment effects associated with the different sub-phenotypes of severe asthma. A specific focus was also to validate different clinical outcomes and assess their importance for the management of asthma. The three studies address these aims in different ways including an epidemiological investigation (Paper I), a pharmacological assessment of the drugs used to treat asthma as well as their side effects and relationship with asthma severity (Paper II) and a clinical intervention applied in a “real-life” setting, including a preliminary meta-analysis with the objective to develop a new method for assessment of response to therapy (Paper III). Several important observations were made in Paper I. The results of this study revealed differences in clinical characteristics, lifestyle factors and treatment patterns among severe asthmatics in Europe, confirming the heterogeneity of this disease. Moreover, the severe asthma definition in current guidelines did not correspond to the characteristics of real-world severe asthmatics, and the definitions also differed between countries. Finally, Paper I emphasized the importance of harmonizing severe asthma registries throughout Europe, and the need for long-term follow-up of this group of patients. In Paper II was done analysis of data from 478 well characterized asthmatics and 98 healthy controls in the U-BIOPRED study. Paper II shows that severe asthmatics have significant suppression of androgens and cortisol compared to patients with mild-to-moderate asthma and healthy control according to extensive analysis of urinary endogenous and exogenous steroids. This suppression is more pronounced in women compared to men. Moreover, the data show that this adrenal suppression is depended on the level of treatment with exogenous corticosteroids. Thus, our results provide support to the hypothesis that this relative deficiency in androgen levels during steroid treatment that is disproportional greater in women compared to men may partly explain gender differences in the severity of asthma and prevalence. Finally, our study supports that reduction of high dose inhaled corticosteroids (ICS), and especially the taper of oral corticosteroids (OCS) should be a clinical goal in order to reduce the side effects of corticosteroids. In Paper III, we modified a quantitative algorithm that was originally developed in a European collaboration to assess response to therapy and evaluate efficacy, and then tested this strategy in patients with severe asthma undergoing treatment with the biologic mepolizumab. The method was able to quantify response to an expensive biological treatment and identify four groups with different degrees of response to mepolizumab: super response, substantial response, sufficient response, and non-response. The super responder group had the greatest improvement in lung function, asthma quality of life questionnaire, asthma control questionnaire and the highest reductions in exacerbations and OCS use, whereas the nonresponders lost asthma control, discontinued mepolizumab treatment and switched to other biologics. This new, quantitative algorithm was shown to provide a more individualized assessment of treatment response and identified non-responders in need of revised treatment. Further, this method can be implemented in clinical practice for greater precision in early clinical decision-making regarding the use of biological therapy. In conclusion, the three clinical studies included in the thesis have contributed to an increased understanding of the clinical phenotypes of severe asthma. The experiences accumulated during this work allow for some general implications. For example, longitudinal, prospective studies carried out in a real-world setting are important for evaluation of response to treatment with new drugs since the differing responses of well-characterized and phenotyped patients can reveal clinical sub-phenotypes and their relationship to underlying molecular mechanisms. The utility of different clinical outcomes could be validated and their importance for asthma management assessed. Clinical studies also provide an opportunity to investigate requirements for improved management and care of severe asthmatics. Patient-centred research contributes to a better understanding of patient needs, and thereby facilitates refined assessment of clinical response to treatment.
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