New Drugs For Asthma Research Articles

Mapping knowledge structure and research of the biologic treatment of asthma: A bibliometric study.

Bronchial asthma (asthma) is a chronic inflammatory disease of the airways, involving a variety of cells and cellular components, that manifests clinically as recurrent episodes of wheezing, shortness of breath, with or without chest tightness or cough, airway hyperresponsiveness, and variable airflow limitation. The number of people with asthma has reached 358 million worldwide and asthma causes huge economic loss. However, there is a subset of patients who are not sensitive to existing drugs and the existing drugs have many adverse effects. Therefore, it's important to find new drugs for asthma patients. Publications related to biologics in asthma published from 2000 to 2022 were retrieved from Web of Science Core Collection. The search strategies were as follows: topic: TS=(biologic* OR "biologic* product*" OR "biologic* therap*" OR biotherapy* OR "biologic* agent*" OR Benralizumab OR "MEDI-563" OR Fasenra OR "BIW-8405" OR Dupilumab OR SAR231893 OR "SAR-231893" OR Dupixent OR REGN668 OR "REGN-668" OR Mepolizumab OR Bosatria OR "SB-240563" OR SB240563 OR Nucala OR Omalizumab OR Xolair OR Reslizumab OR "SCH-55700" OR SCH55700 OR "CEP-38072" OR CEP38072 OR Cinqair OR "DCP-835" OR DCP835 OR Tezspire OR "tezepelumab-ekko" OR "AMG-157" OR tezspire OR "MEDI-9929" OR "MEDI-19929" OR MEDI9929 OR Itepekimab OR "REGN-3500"OR REGN3500 OR "SAR-440340"OR SAR440340 OR Tralokinumab OR "CAT-354" OR Anrukinzumab OR "IMA-638" OR Lebrikizumab OR "RO-5490255"OR "RG-3637"OR "TNX-650"OR "MILR1444A"OR "MILR-1444A"OR"PRO301444"OR "PRO-301444"OR Pitrakinra OR altrakincept OR "AMG-317"OR"AMG317" OR Etokimab OR Pascolizumab OR "IMA-026"OR Enokizumab OR "MEDI-528"OR "7F3COM-2H2" OR 7F3COM2H2 OR Brodalumab OR "KHK-4827" OR "KHK4827"OR "AMG-827"OR Siliq OR Ligelizumab OR "QGE-031" OR QGE031 OR Quilizumab OR Talizumab OR "TNX-901" OR TNX901 OR Infliximab OR Etanercept OR "PRS-060") AND TS=asthma*. The document type was set to articles and review articles and the language restriction was set to English. Three different analysis tools including one online platform, VOS viewer1.6.18, and CiteSpace V 6.1.R1 software were used to conduct this bibliometric study. This bibliometric study included 1,267 English papers published in 244 journals from 2,012 institutions in 69 countries/regions. Omalizumab, benralizumab, mepolizumab, and tezepelumab in relation to asthma were the research hotspots in the field. This study systematically uncovers a holistic picture of existing literature related to the biologic treatment of asthma over the past 20 years. We consulted scholars in order to understand key information in this field from the perspective of bibliometrics, which we believe may greatly facilitate future research in this field.

A Network Pharmacology Approach to Reveal the Underlying Mechanisms of Rhizoma Dioscoreae Nipponicae in the Treatment of Asthma.

Background In this study, network pharmacological methods were used to analyze the targets of Rhizoma Dioscoreae Nipponicae (RDN) and investigate the potential underlying mechanism of RDN in the treatment of asthma. Methods Asthma-related targets were obtained from the GeneCards and DisGeNET databases. The bioactive components of RDN were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform database, and the targets of these compounds were predicted using the BATMAN-TCM database. The network of RDN component targets was constructed using Cytoscape. A protein-protein interaction (PPI) network was constructed in Cytoscape to determine the potential targets of RDN for the treatment of asthma. The hub genes of RDN in the treatment of asthma were screened using network topological parameters. Gene ontology (GO) and the KEGG pathways were analyzed. Molecular docking and in vivo experiments were performed to validate the network pharmacology results. Results A total of four bioactive components and 55 targets were identified. The results of the enrichment analysis suggested that the treatment of asthma with RDN involved signaling pathways, such as those related to systemic lupus erythematosus, alcoholism, viral carcinogenesis, the cell cycle, prostate cancer, transcriptional misregulation in cancer, hepatitis B, thyroid hormone signaling, and PI3K-AKT signaling, as well as other signaling pathways. Molecular docking showed that the active components of RDN could stably bind to the predicted target. In vivo experiments showed that RDN could regulate the expression of target genes and inhibit the activation of the PI3K-AKT signaling pathway. Conclusion To a certain extent, this study reveals the potential bioactive components and molecular mechanisms of RDN in the treatment of asthma and provides new insights for the development of new drugs for asthma.

Pathogenic changes in group 2 innate lymphoid cells (ILC2) in intractable asthma

There is a certain population of intractable asthma patients, who can not be controlled by corticosteroid therapy. It has been suggested that 5-10% of asthma patients have been suffered from steroid resistance. Since it has been difficult to develop a steroid-resistant asthma model, the detailed mechanisms have been unclear. Recently, an intractable asthma model showing steroid insensitivity was developed by the author and colleagues. We found that pathogenic changes in type 2 innate lymphoid cells (ILC2) were induced in the intractable asthma. When ovalbumin (OVA) + Al(OH)3-sensitized BALB/c mice were intratracheally challenged with OVA at 5 μg/animal, development of airway remodeling as well as lung eosinophilia and neutrophilia were markedly suppressed by treatment with dexamethasone. In contrast, when increasing the dose of OVA for challenges to 500 μg/animal, those asthmatic responses turned to be steroid insensitive. When Th2 cells and ILC2 in the lung were stimulated in vitro, ILC2 produced larger amounts of type 2 cytokines than Th2 cells. Interestingly, amounts of type 2 cytokines produced by the steroid-insensitive model-derived ILC2 were significantly larger than those by the steroid-sensitive, and that the former ILC2 exhibited higher expression of thymic stromal lymphopoietin (TSLP) receptor and signal transducer and activator of transcription (STAT) 5a gene. Treatment with anti-IL-5 antibody improved the steroid sensitivity. Taken together, ILC2 have been transformed to be pathogenic in the intractable asthma. IL-5 hyper-produced from ILC2 may be involved in the development of steroid resistance. The molecules related to the above mentioned are expected to be targets for development of new therapeutic drugs for intractable asthma.

New drugs for asthma

New drugs for asthma

New Drugs for Pediatric Asthma.

Asthma is the most common chronic disease in children. As suggested by international guidelines, the main goals of asthma treatment are symptoms control and lung function preservation, through a stepwise and control-based approach. The first line therapy based on inhaled corticosteroids may fail to reach control in more than one third of patients, especially adolescents, and in these lung function and quality of life may progressively worsen. Treatment with omalizumab, the first anti-immunoglobulin E recombinant humanized monoclonal antibody, has been definitely approved in pediatric uncontrolled asthma. In this review, we discuss the mechanisms and potential roles of emerging therapies for pediatric severe asthma. Novel biologic drugs (i.e., dupilumab, mepolizumab, reslizumab, and benralizumab) seem to be promising in reducing annual exacerbation rates and steroid-use in glucocorticoid-dependent cases, but available data are few and limited to adolescents and adults. Evidences on the use of the muscarinic antagonist tiotropium as controller medication in pediatric settings are progressively growing, sustaining an application as asthma maintenance treatment in children aged >6 years and in preschool children with persistent asthmatic symptoms, but well powered trials are needed to confirm its safety and efficacy. New inhaled corticosteroids (i.e., ciclesonide and mometasone) are effective as once-daily controller therapy, but long-term studies in the different pediatric ages are needed to compare effectiveness and safety to usual treatments. At present, the role of macrolides in pediatric severe asthma is controversial and their administration is not recommended routinely, but may be considered in children with neutrophilic asthma for reducing daily oral steroids administration and improving lung function. Despite the availability of several novel therapeutic strategies for uncontrolled asthma, future trials targeted at specific pediatric age subgroups are needed to support evidences of safety and efficacy also in children.

Uncovering the mechanism of Maxing Ganshi Decoction on asthma from a systematic perspective: A network pharmacology study

Maxing Ganshi Decoction (MXGSD) is used widely for asthma over thousands of years, but its underlying pharmacological mechanisms remain unclear. In this study, systematic and comprehensive network pharmacology was utilized for the first time to reveal the potential pharmacological mechanisms of MXGSD on asthma. Specifically, we collected 141 bioactive components from the 600 components in MXGSD, which shared 52 targets common to asthma-related ones. In-depth network analysis of these 52 common targets indicated that asthma might be a manifestation of systemic neuro-immuno-inflammatory dysfunction in the respiratory system, and MXGSD could treat asthma through relieving airway inflammation, improving airway remodeling, and increasing drug responsiveness. After further cluster and enrichment analysis of the protein-protein interaction network of MXGSD bioactive component targets and asthma-related targets, we found that the neurotrophin signaling pathway, estrogen signaling pathway, PI3K-Akt signaling pathway, and ErbB signaling pathway might serve as the key points and principal pathways of MXGSD gene therapy for asthma from a systemic and holistic perspective, and also provides a novel idea for the development of new drugs for asthma.

Evaluation of the use of Swedish integrated electronic health records and register health care data as support clinical trials in severe asthma: the PACEHR study.

BackgroundIn the development of new drugs for severe asthma, it is a challenge from an ethical point of view to randomize severe asthma patients to placebo, and to obtain long-term safety data due to discontinuations. The aim of this study was to evaluate the feasibility of using electronic health record (EHR) data to create a real-world reference population of uncontrolled asthmatic patients to supplement the concurrent control/placebo group in long-term studies of asthma.MethodsEHR data from 36 primary care centres and a University hospital in Sweden were linked to Swedish mandatory health registers (2005–2013), creating a population covering 33 890 asthma patients, including data on co-morbidities, risk factors and laboratory/respiratory measurements. A severe asthma EHR reference cohort was established. We used logistic regression to estimate the propensity score (probability) of each RCT or EHR patient existing in the EHR cohort given their covariates.ResultsWe created an EHR-derived reference cohort of 240 patients, matching the placebo group (N = 151) in an RCT of severe asthma. The exacerbation rate during follow-up in the EHR study population was 1.24 (weighted) compared to 0.9 in the RCT placebo group. Patients in the EHR cohort were of similar age as in the RCT placebo group, 50.6 years versus 50.1 years; had slightly higher body mass index 27.0 kg/m2 versus 27.3 kg/m2; and consisted of 40% versus 34% males.ConclusionsThe results indicate that EHRs provide an opportunity to supplement the control group in RCTs of severe diseases.

The assessment of new drugs for asthma and COPD: a Delphi study examining the perspectives of Italian payers and clinicians

Background: Asthma and chronic obstructive pulmonary disease (COPD) are disorders of the lungs characterized by airflow obstruction, inflammation and tissue remodeling. Management of patients with these diseases is complex and the improvement of diagnostic-therapeutic strategies represents a critical challenge for the healthcare system. In this context, investigating the criteria and information needed for an appropriate and effective evaluation of incoming treatment options is crucial to ensure that clinicians and policy-makers are provided with the best available evidence to make decisions aimed at improving patient outcomes. Therefore, the objective of this study was to investigate the degree of agreement among Health Technology Assessment (HTA) experts on issues crucial to the evaluation of new drugs for asthma and COPD and to appropriately manage the clinical pathway for patients.
 Methods: This research was conducted using an e-Delphi technique organized in three subsequent rounds and involving a panel of ten experts (six regional and local payers and four clinicians). Panelists were asked to comment in written form on a set of statements, explaining qualitatively the extent to which they agreed or disagreed with the assertions. Statements were subsequently modified and resubmitted for assessment.
 Results: Panelists expressed their opinions during each round and, after round III, a consensus document was finalized. The degree of consensus was high among experts and concerned five main topics: (a) the need to address current unmet needs of patients with asthma or COPD, (b) the importance of further studies and real-life information in the evaluation of treatments, (c) existing evidence and evidence needed to assess drugs, (d) critical issues in obtaining a positive evaluation from regional and local authorities for new treatments to be included in regional formularies and to have an important place in therapeutic categories, and (e) the major obstacles to the appropriate administration of drugs and management of patients.
 Conclusion: The final document highlights that no proof of difference among drugs exists, that evidence on final endpoints (and particularly on mortality) should be strengthened and that actions regarding risk factors, appropriate diagnosis, patient staging and adherence to therapy are particularly important for a better clinical management.

Evaluation of New Drugs for Asthma and COPD: Endpoints, Biomarkers and Clinical Trial Design.

There remains a considerable need to develop novel therapies for patients with asthma and chronic obstructive pulmonary disease (COPD). The greatest challenge at the moment is measuring the effects of novel anti-inflammatory drugs, as these drugs often cause only small effects on lung function. Measurements that demonstrate the pharmacological and clinical effects of these drugs are needed. Furthermore, we now recognise that only subgroups of patients are likely to respond to these novel drugs, so using biomarkers to determine the clinical phenotype most suitable for such therapies is important. An endotype is a subtype of a (clinical) condition defined by a distinct pathophysiological mechanism. An endotype-driven approach may be more helpful in drug development, enabling drugs to be targeted specifically towards specific biological mechanisms rather than clinical characteristics. This requires the development of biomarkers to define endotypes and/or to measure drug effects. This newer approach should continue alongside efforts to optimise the measurement of clinical endpoints, including patient-reported outcome measurements, required by drug regulatory authorities.

The assessment of new drugs for asthma and COPD: a Delphi study examining the perspectives of Italian payers and clinicians.

BackgroundAsthma and chronic obstructive pulmonary disease (COPD) are disorders of the lungs characterized by airflow obstruction, inflammation and tissue remodeling. Management of patients with these diseases is complex and the improvement of diagnostic-therapeutic strategies represents a critical challenge for the healthcare system. In this context, investigating the criteria and information needed for an appropriate and effective evaluation of incoming treatment options is crucial to ensure that clinicians and policy-makers are provided with the best available evidence to make decisions aimed at improving patient outcomes. Therefore, the objective of this study was to investigate the degree of agreement among Health Technology Assessment (HTA) experts on issues crucial to the evaluation of new drugs for asthma and COPD and to appropriately manage the clinical pathway for patients.MethodThis research was conducted using an e-Delphi technique organized in three subsequent rounds and involving a panel of ten experts (six regional and local payers and four clinicians). Panelists were asked to comment in written form on a set of statements, explaining qualitatively the extent to which they agreed or disagreed with the assertions. Statements were subsequently modified and resubmitted for assessment.ResultsPanelists expressed their opinions during each round and, after round III, a consensus document was finalized. The degree of consensus was high among experts and concerned five main topics: (a) the need to address current unmet needs of patients with asthma or COPD, (b) the importance of further studies and real-life information in the evaluation of treatments, (c) existing evidence and evidence needed to assess drugs, (d) critical issues in obtaining a positive evaluation from regional and local authorities for new treatments to be included in regional formularies and to have an important place in therapeutic categories, and (e) the major obstacles to the appropriate administration of drugs and management of patients.ConclusionThe final document highlights that no proof of difference among drugs exists, that evidence on final endpoints (and particularly on mortality) should be strengthened and that actions regarding risk factors, appropriate diagnosis, patient staging and adherence to therapy are particularly important for a better clinical management.Electronic supplementary materialThe online version of this article (doi:10.1186/s40248-016-0038-3) contains supplementary material, which is available to authorized users.

Balancing options for health research and development

Balancing options for health research and development

New Drugs for Asthma

Current therapy for asthma with inhaled corticosteroids and long-acting inhaled β(2)-agonists is highly effective, safe, and relatively inexpensive, but many patients remain poorly controlled. Most advances have been through improving these drug classes and a major developmental hurdle is to improve existing drug classes. Major unmet needs include better treatment of severe asthma (which has some similarity to chronic obstructive pulmonary disease), as well as curative therapies for mild to moderate asthma that do not result in the return of symptoms when the treatment is stopped. Several new treatments are in development, but many are specific, targeting a single mediator or receptor, and are unlikely to have a major clinical impact, although they may be effective in specific asthma phenotypes (endotypes). Drugs with more widespread effects, such as kinase inhibitors, may be more effective but have a greater risk of side effects so inhaled delivery may be needed. Several new treatments target the underlying allergic/immune process and would treat concomitant allergic diseases. Improved immunotherapy approaches have the potential for disease modification, although prospects for a cure are currently remote.

New drugs for asthma

New drugs for asthma

Provoked models of asthma: what have we learnt?

Asthma is a chronic inflammatory disease of the airways characterized by physiological abnormalities of variable airflow obstruction and airway hyperresponsiveness (AHR) to a wide variety of physical and inhaled chemical stimuli and the presence of symptoms. AHR is measured by challenging the airways with a variety of agonists and naturally occurring stimuli, which results in constriction of the airway smooth muscle, leading to airway narrowing and airflow limitation. There are two distinct mechanisms by which the airways can narrow to a constrictor stimulus and these are defined by the pathways they take to induce AHR. Direct stimuli are pharmacological agents administered exogenously (such as histamine or methacholine) that act 'directly' on specific receptors on the bronchial smooth muscle to cause constriction. The other mechanism by which the airway can narrow is via the inhalation of indirect stimuli, which include natural stimuli, such as allergen or exercise, and pharmacological agents such as adenosine monophosphate and hyper-osmotic agents (e.g. hypertonic saline or dry powder mannitol). These stimuli induce airway narrowing 'indirectly' by causing the endogenous release of mediators of bronchoconstriction from airway inflammatory cells. Provoked models of asthma have been extremely valuable in understanding the pathobiology of asthma, in aiding diagnosis, in helping to clarify the mechanisms of actions of effective drugs and in the development of new entities to treat asthma. Some provoked models are valuable clinically, particularly those that measure direct AHR, while others, particularly allergen challenge, have been used in animal models and in humans to study the mechanisms of allergen-induced airway inflammation and the associated physiological changes, as well in the development of new drugs for asthma. An emerging role for measurements of AHR is in the evaluation of the optimal treatment for patients with asthma.

Are there any realistic chances to develop new drugs for asthma?

Asthma bronchiale, an inflammatory airway disease, imposes a significant health care problem worldwide. It is characterized by three critical phenotypic traits: intermittent and reversible bronchoconstriction, bronchial hyperresponsiveness and airway inflammation. Conventional therapy basically consists of beta(2)-adrenoceptor agonists in combination with glucocorticoids. Nevertheless, there is an urgent need for novel therapies, both for patients with uncontrollable disease symptoms and for those suffering from glucocorticoid-insensitive asthma. Monotherapy seems to be relatively ineffective against this complex and multifaceted disease, which is evident by the variety of disappointing treatment strategies. Thus, we should instead concentrate on multiple target strategies, such as novel and more potent glucocorticoids or phosphodiesterase type 4 (PDE4) inhibitors with isozyme selectivity. In addition, an examination of the application method should not be neglected, with emphasis on inhalative approaches. To summarize, research into asthma's pathophysiology is of critical importance, concentrating on human-relevant targets and conducting preliminary studies. With these imperatives in mind, we can hope to better manage this multifactor disease in the near future.

ILV1 New drugs for asthma and COPD

ILV1 New drugs for asthma and COPD

1 NEW DRUGS FOR ASTHMA, ALLERGY AND COPD

1 NEW DRUGS FOR ASTHMA, ALLERGY AND COPD

New drugs for asthma.

Asthma is a major and increasing global health problem and, despite major advances in therapy, many patients' symptoms are not adequately controlled. Treatment with combination inhalers, which contain a corticosteroid and long-acting beta(2) adrenoceptor agonist, is the most effective current therapy. There is therefore a search for new therapies, particularly safe and effective oral treatments and those that are more efficacious in severe asthma. New therapies in development include mediator antagonists and inhibitors of cytokines, although these therapies might be too specific to be very effective. New anti-inflammatory therapies include corticosteroids and inhibitors of phosphodiesterase-4, p38 mitogen-activated protein kinase and nuclear factor-kappaB. The prospects for a curative treatment are on the horizon.

Neurogenic mechanisms in bronchial inflammatory diseases.

Neurogenic inflammation encompasses the release of neuropeptides from airway nerves leading to inflammatory effects. This neurogenic inflammatory response of the airways can be initiated by exogenous irritants such as cigarette smoke or gases and is characterized by a bi-directional linkage between airway nerves and airway inflammation. The event of neurogenic inflammation may participate in the development and progression of chronic inflammatory airway diseases such as allergic asthma or chronic obstructive pulmonary disease (COPD). The molecular mechanisms underlying neurogenic inflammation are orchestrated by a large number of neuropeptides including tachykinins such as substance P and neurokinin A, or calcitonin gene-related peptide. Also, other biologically active peptides such as neuropeptide tyrosine, vasoactive intestinal polypeptide or endogenous opioids may modulate the inflammatory response and recently, novel tachykinins such as virokinin and hemokinins were identified. Whereas the different aspects of neurogenic inflammation have been studied in detail in laboratory animal models, only little is known about the role of airway neurogenic inflammation in human diseases. However, different functional properties of airway nerves may be used as targets for future therapeutic strategies and recent clinical data indicates that novel dual receptor antagonists may be relevant new drugs for bronchial asthma or COPD.

1 New drugs for asthma

1 New drugs for asthma