Biological Therapies in Children and Adolescents with Severe Uncontrolled Asthma: A Practical Review.
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ABSTRACT:
SUBMITTER: Votto M
PROVIDER: S-EPMC8107006 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC8360078 | biostudies-literature
Project description:Asthma is a variable chronic respiratory disease characterized by airway inflammation and hyperresponsiveness, bronchoconstriction, and mucus hypersecretion. While most patients with asthma achieve good control of the disease, 5-10% experience severe symptoms and recurrent exacerbation despite the maximal offered therapy with inhaled corticosteroids and long acting bronchodilators. In previous years, novel biological therapies have become available, and various asthma phenotypes that are characterized by specific biomarkers have been identified. Currently approved biological agents target inflammatory molecules of the type 2 inflammatory pathway, and are effective at decreasing the frequency of asthma attacks, controlling symptoms and decreasing use of systemic steroids. The present study reviewed the effectiveness and safety profile of the currently approved biological drugs and provided an overview of the assessment of patients with severe asthma who are potentially suitable for biological therapy, in order to help clinicians to select the most appropriate biological agent.
| S-EPMC8453334 | biostudies-literature
Project description:Severe asthma accounts for only a small proportion of the children with asthma but a disproportionately high amount of resource utilization and morbidity. It is a heterogeneous entity and requires a step-wise, evidence-based approach to evaluation and management by pediatric subspecialists. The first step is to confirm the diagnosis by eliciting confirmatory history and objective evidence of asthma and excluding possible masquerading diagnoses. The next step is to differentiate difficult-to-treat asthma, asthma that can be controlled with appropriate management, from asthma that requires the highest level of therapy to maintain control or remains uncontrolled despite management optimization. Evaluation of difficult-to-treat asthma includes an assessment of medication delivery, the home environment, and, if possible, the school and other frequented locations, the psychosocial situation, and comorbid conditions. Once identified, aggressive management of issues related to poor adherence and drug delivery, remediation of environmental triggers, and treatment of comorbid conditions is necessary to characterize the degree of control that can be achieved with standard therapies. For the small proportion of patients whose disease remains poorly controlled with these interventions, the clinician may assess steroid responsiveness and determine the inflammatory pattern and eligibility for biologic therapies. Management of severe asthma refractory to traditional therapies involves considering the various biologic and other newly approved treatments as well as emerging therapies based on the individual patient characteristics.
| S-EPMC5879140 | biostudies-literature
Project description:Asthma is the most common chronic lower respiratory tract disease in childhood throughout the world. Despite advances in asthma management, acute exacerbations continue to be a major problem in patients and they result in a considerable burden on direct/indirect health care providers. A severe exacerbation occurring within 1 year is an independent risk factor. Respiratory tract viruses have emerged as the most frequent triggers of exacerbations in children. It is becoming increasingly clear that interactions may exist between viruses and other triggers, increasing the likelihood of an exacerbation. In this study, we provide an overview of current knowledge about asthma exacerbations, including its definition, impact on health care providers, and associated factors. Prevention management in intermittent asthma as well as intermittent wheeze in pre-school children and those with persistent asthma are discussed. Our review findings support the importance of controlling persistent asthma, as indicated in current guidelines. In addition, we found that early episodic intervention appeared to be crucial in preventing severe attacks and future exacerbations. Besides the use of medication, timely education after an exacerbation along with a comprehensive plan in follow up is also vitally important.
| S-EPMC7102856 | biostudies-literature
Project description:Recognition of phenotypic variability in pediatric asthma allows for a more personalized therapeutic approach. Knowledge of the underlying pathophysiological and molecular mechanisms (endotypes) of corresponding biomarkers and new treatments enables this strategy to progress. Biologic therapies for children with severe asthma are becoming more relevant in this sense. The T2 phenotype is the most prevalent in childhood and adolescence, and non-T2 phenotypes are usually rare. This document aims to review the mechanism of action, efficacy, and potential predictive and monitoring biomarkers of biological drugs, focusing on the pediatric population. The drugs currently available are omalizumab, mepolizumab, benralizumab, dupilumab, and 1ezepelumab, with some differences in administrative approval prescription criteria between the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Previously, we described the characteristics of severe asthma in children and its diagnostic and therapeutic management.
| S-EPMC10532431 | biostudies-literature
Project description:Transcriptional profiling of lung epithelial brushing mRNA from severe uncontrolled asthmatics
2017-06-06 | GSE65584 | GEO
Project description:Congenital laryngomalacia is the most common cause of stridor in infants and usually resolves without therapy by 12-18?months of age. However, a recent study found that laryngomalacia may leave structural and functional traces with increased risk of later respiratory symptoms, suggesting that late-onset laryngomalacia may represent long-term consequences of milder or even undiagnosed forms. Unusual cases demonstrated that inspiratory stridor developed subsequent to upper respiratory tract infections. The lack of airway hyperresponsiveness in adulthood also raised questions regarding the diagnosis of childhood asthma. Laryngomalacia should be distinguished from severe asthma.
| S-EPMC5879029 | biostudies-literature
Project description:Asthma is a heterogeneous respiratory disease characterized by usually reversible bronchial obstruction, which is clinically expressed by different phenotypes driven by complex pathobiological mechanisms (endotypes). In recent years several molecular effectors and signaling pathways have emerged as suitable targets for biological therapies of severe asthma, refractory to standard treatments. Indeed, various therapeutic mono-clonal antibodies currently allow one to intercept at different levels the chain of pathogenic events leading to type 2 (T2) airway inflammation. Pro-allergic immunoglobulin E (IgE) is the first molecule against which an anti-asthma monoclonal antibody (omalizumab) was developed; today other targets are successfully being exploited by biological treatments for severe asthma. In particular, pro-eosinophilic interleukin 5 (IL-5) can be targeted by mepolizumab or reslizumab, whereas benralizumab is a selective blocker of IL-5 receptor, and IL-4 and IL-13 can be targeted by dupilumab. Besides these drugs, which are already available in medical practice, other biologics are under clinical development such as those targeting innate cytokines, including the alarmin thymic stromal lymphopoietin (TSLP), which plays a key role in the pathogenesis of type 2 asthma. Therefore, ongoing and future biological therapies are significantly changing severe asthma management on a global level. These new therapeutic options make it possible to implement phenotype/endotype-specific treatments, which are delineating personalized approaches precisely addressing the individual traits of asthma pathobiology. The aim of the study is to review the immunopathology and treatment efficacy for severe asthma and focused on new biological agents with benralizumab (anti-IL-5) and tezepelumab (anti-TSLP).
| S-EPMC8399988 | biostudies-literature
Project description:BackgroundPatients with severe refractory asthma (SRA), even when using high doses of multiple controller medications in a regular and appropriate way, can have persistent complaints of exercise limitation.MethodsThis was a cross-sectional study involving patients with SRA (treated with ≥ 800 μg of budesonide or equivalent, with ≥ 80% adherence, appropriate inhaler technique, and comorbidities treated), who presented no signs of a lack of asthma control other than exercise limitation. We also evaluated healthy controls, matched to the patients for sex, age, and body mass index. All participants underwent cardiopulmonary exercise testing (CPET) on a cycle ergometer, maximum exertion being defined as ≥ 85% of the predicted heart rate, with a respiratory exchange ratio ≥ 1.0 for children and ≥ 1.1 for adolescents. Physical deconditioning was defined as oxygen uptake (VO2) < 80% of predicted at peak exercise, without cardiac impairment or ventilatory limitation. Exercise-induced bronchoconstriction (EIB) was defined as a forced expiratory volume in one second ≥ 10% lower than the baseline value at 5, 10, 20, and 30 minutes after CPET.ResultsWe evaluated 20 patients with SRA and 19 controls. In the sample as a whole, the mean age was 12.9 ± 0.4 years. The CPET was considered maximal in all participants. In terms of the peak VO2 (VO2 peak), there was no significant difference between the patients and controls, (P = 0.10). Among the patients, we observed isolated EIB in 30%, isolated physical deconditioning in 25%, physical deconditioning accompanied by EIB in 25%, and exercise-induced symptoms not supported by the CPET data in 15%.Conclusion and clinical relevancePhysical deconditioning, alone or accompanied by EIB, was the determining factor in reducing exercise tolerance in patients with SRA and was not therefore found to be associated with a lack of asthma control.
| S-EPMC7870485 | biostudies-literature
Project description:ObjectivesTo describe internet use for health information among adolescents with uncontrolled persistent asthma, and to examine whether health-related internet use is associated with responsibility for home asthma management.MethodsWe analyzed baseline data from the School-Based Asthma Care for Teens (SB-ACT) Trial, which included adolescents (12-16 years) in an urban school district who had uncontrolled persistent asthma per caregiver report. We asked adolescents whether they had ever used the Internet to look for health or medical information (Y/N). Teens then described family responsibility for 9 asthma management tasks (e.g. full caregiver responsibility, shared responsibility, or full teen responsibility). We examined responsibility sum scores in addition to responsibility for individual management tasks. We used bivariate and multivariate analyses to compare health-related internet use with participant characteristics, teen-reported asthma symptoms, and management responsibility.ResultsWe examined data for 425 adolescents (mean age 13.4 years). Almost half (45%) reported seeking health information on the Internet. In adjusted analyses, health-related internet use was strongly associated with teen responsibility (sum score and tasks relating to carrying and using medications); internet use was also more likely among teens who were older, female, or reported uncontrolled disease.ConclusionsAdolescents with persistent asthma who share responsibility for home management or report uncontrolled disease are more likely to seek health information online. Future interventions to support teens who co-manage asthma should work to engage patients in both clinical and digital spaces, and ensure that all patients can access accurate, patient-centered asthma information when needed.
| S-EPMC8274383 | biostudies-literature