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Opis: Biologics use in severe paediatric asthma The global prevalence of severe asthma among adolescents ranges from 4% to 11%; and up to 7% of children with asthma display an uncontrolled and severe form that is often associated with a substantial burden on the quality of life of patients and their families, and increasing costs of healthcare [1, 2]. “Childhood asthma” is an umbrella term describing a heterogeneous disease comprising different phenotypes and a wide range of symptoms [3–5]. Despite decades of basic and clinical research, tailored strategies to modify the natural course of asthma, prevent severe exacerbations and inhibit lung function decline are still lacking. In addition, clinical phenotypes are only moderately reliable in the prediction of treatment responses and our current understanding of asthma endotypes is limited. Most asthma endotypes involve concomitant inflammatory pathways and distorted immune parameters. Advances in understanding severe paediatric asthma pathophysiological mechanisms and immunological pathways mediating the airway inflammation would allow better characterisation of these patients as well as optimised intervention, guided by treatable traits and biomarkers [6, 7]. Recent studies have demonstrated the effectiveness of monoclonal antibodies (mAbs), also known as biologics, targeting type 2 inflammation in controlling the symptoms of severe asthma. Currently, four human mAbs are approved for use in children: mAbs that target interleukin (IL)-5 or IL-5 receptor (R) (mepolizumab and benralizumab), mAbs that target IL-4R (dupilumab), and mAbs that target immunoglobulin E (omalizumab). Omalizumab was the first biologic approved to treat moderate-to-severe allergic asthma (≥6 years of age). Mepolizumab and dupilumab have been approved for severe eosinophilic asthma (≥6 and ≥12 years of age, respectively), while benralizumab has been approved in the USA to treat children (≥12 years of age) with severe eosinophilic asthma [8–13]. The introduction of mAb agents in asthma treatment is a milestone in the application of personalised medicine. However, comparative studies and standardised algorithms for the management of paediatric severe asthma to guide the best therapeutic option for paediatric patients with severe asthma are lacking [14]. More personalised medicine approaches may benefit the patient by better matching patients with the most appropriate therapy. Risk stratification, remote monitoring and the integration of multiple data sources could help tailor management for the individual child with severe asthma. A digital multidisciplinary European expert meeting took place on 9 July 2020. In this workshop, we brought together European respiratory/allergy paediatricians, immunologists, epidemiologists and basic scientists to identify the unmet needs of paediatric severe asthma patients, and set the priorities for clinical and research activities ahead. The participants discussed ongoing initiatives and knowledge gaps, and formulated proposals on how to address these challenges. In this report, we describe the main findings of this expert meeting.
Ključne besede: asthma, paediatric asthma, severe asthma, children, biologics, monoclonal antibodies, biologic therapy, therapy
Objavljeno v DKUM: 14.08.2024; Ogledov: 84; Prenosov: 6
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Opis: Background Uncontrolled pediatric asthma has a large impact on patients and their caregivers. More insight into determinants of uncontrolled asthma is needed. We aim to compare treatment regimens, inhaler techniques, medication adherence and other characteristics of children with controlled and uncontrolled asthma in the: Systems Pharmacology approach to uncontrolled Paediatric Asthma (SysPharmPediA) study. Material and methods 145 children with moderate to severe doctor-diagnosed asthma (91 uncontrolled and 54 controlled) aged 6–17 years were enrolled in this multicountry, (Germany, Slovenia, Spain, and the Netherlands) observational, case-control study. The definition of uncontrolled asthma was based on asthma symptoms and/or exacerbations in the past year. Patient-reported adherence and clinician-reported medication use were assessed, as well as lung function and inhalation technique. A logistic regression model was fitted to assess determinants of uncontrolled pediatric asthma. Results Children in higher asthma treatment steps had a higher risk of uncontrolled asthma (OR (95%CI): 3.30 (1.56–7.19)). The risk of uncontrolled asthma was associated with a larger change in FEV1% predicted post and pre-salbutamol (OR (95%CI): 1.08 (1.02–1.15)). Adherence and inhaler techniques were not associated with risk of uncontrolled asthma in this population. Conclusion This study showed that children with uncontrolled moderate-to-severe asthma were treated in higher treatment steps compared to their controlled peers, but still showed a higher reversibility response to salbutamol. Self-reported adherence and inhaler technique scores did not differ between controlled and uncontrolled asthmatic children. Other determinants, such as environmental factors and differences in biological profiles, may influence the risk of uncontrolled asthma in this moderate to severe asthmatic population.
Ključne besede: pediatric asthma, asthma control, uncontrolled asthma, medication, adherence, inhaler technique
Objavljeno v DKUM: 16.08.2023; Ogledov: 472; Prenosov: 44
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Opis: Introduction: We studied the diagnostic accuracy of bedside lung ultrasound (the presence of a comet tail sign), N-terminal pro-brain natriuretic peptide (NT-proBNP), and clinical assessment (modified Boston criteria) in differentiating heart failure (HF)- related acute dyspnea from pulmonary (COPD/asthma) related acute dyspnea in the prehospital setting. Methods: Prospective study was performed at the Center for Emergency Medicine Maribor, Slovenia, between July 2007 and April 2010. Two groups of patients were compared: HF-related acute dyspnea group (n = 129) vs pulmonary-related (asthma/COPD) acute dyspnea group (n = 89). All patients underwent lung ultrasound examination, along with basic laboratory, rapid NT-proBNP testing and chest X-ray. Results: Ultrasound comet tail sign has 100% sensitivity, 95% specificity, 100% negative predictive value (NPV) and 96% positive predictive value (PPV) for the diagnosis of HF. NT-proBNP (cut-off point 1000 pg/ml) has 92% sensitivity, 89% specificity, 86% NPV and 90% PPV. Boston modified criteria have 85% sensitivity, 86% specificity, 80% NPV and 90% PPV. Comparing the three methods, we found significant differences between ultrasound sign vs NT-proBNP (P<0.05) and Boston modified criteria (P<0.05). Combination of ultrasound sign and NT-proBNP has 100% sensitivity, 100% specificity, 100% NPV and 100% PPV. With ultrasound we can exclude HF in patients with pulmonary related dyspnea who have positive NT-proBNP (> 1000 pg/ml) and previous history of HF. Conclusions: Ultrasound comet tail sign alone or in combination with NT-proBNP has a high diagnostic accuracy in differentiating between acute HF and COPD/asthma causes of acute dyspnea in prehospital emergency setting.
Ključne besede: lungs, ultrasound, N-terminal pro-brain natriuretic peptide, acute heart failure, chronic obstructive pulmonary disease, asthma, acute dyspnea
Objavljeno v DKUM: 29.06.2017; Ogledov: 2008; Prenosov: 405
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