Novel Tools in an Effort to Increase Treatment for Asthma

RSI out of Dublin Ireland, Stanford University, and Oregon Health Sciences University have located a marker that can help tell which asthma patients are likely to benefit from a new treatment that targets inflammatory cells. Asthma affects approximately 470,000 people in Ireland. thus finding a novel treatment is now available and it is important to match the treatment to the patient who will benefit the most

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Breathing pattern disorder (BPD) can co-exist with and mimic asthma acting to amplify symptoms and confound assessment of disease control. This results in inappropriate treatment escalation. Adult patients need to be referred with an unmanageable treatment of asthma to undergo respiratory physiotherapy assessment to diagnose BPD. After this, the respiratory illness can be better classified and a more personalized treatment can be given. Breathing pattern irregularities are highly prevalent in the referred with difficult to manage asthma. By making use of a novel breathing pattern assessment tool (BPAT), their treatment can be more individualized variability of those studied to ensure BPAT is a robust clinical tool (Todd, 2018).

To evaluate the reliability of medication identification (MED ID), a novel survey assessing caregivers perceived ability to identify inhaled asthma meds. Caregivers of adolescents with persistent asthma indicated name of the medication used as inhaled. Then caregivers answered the MED ID survey of questions and perceived ability to identified inhaled medications. The study found that 76% of 126 enrolled caregivers were able to identify at least one inhaled asthma medications. The statistics used proved that a two-question MED ID survey is reliable and a valid way to assess caregivers ability to identify asthma medications (Frey, 2017).

Asthma is a patchwork of chronic inflammatory disease affecting their airways. Worldwide over 300 million children and adults suffer from asthma. It is considered to be the most common chronic disease among children. Poor control and exacerbations have a substantial impact on quality of life of patients. It also has a large impact on society because of direct and indirect costs. The EU has estimated that annual costs and loss of productivity due to asthma is € 33.9 billion Euros (approx. $39.5 billion) with hospital care and healthcare visits due to uncontrolled asthma substantially contributing to direct medical costs.

There is a large variation in the magnitude of the response to asthma medication management. A 16 week cross-over trial showed children with mild to moderate asthma show a large distribution in improvement in asthma control days per week. There is also an increase in lung function with the addition of low dose inhaled corticosteroids. Even in clinical trials where adherence to treatment is closely monitored and patients remain symptomatic despite maintenance therapy. Rapidly evolving genotyping technologies have led to the identification of various genetic variants associated with poor asthma treatment outcomes.

Although various genetics have been reported to influence response to short and long-acting beta-2 antagonists inhaled corticosteroids results remain largely inconsistent or the size of the effect was small. And while various novel genetic variants have been identified, they often don’t reach the threshold needed to say there is a genome-wide significance. This study did find a genetic variant that may change clinical asthma practice in children. Various studies have found children carrying this variation respond poorly to long-acting beta-2 agonists and would be best to try an alternative treatment. This study also found that up to 80% of the variance in lung function response from treatment in asthma patients is due to genetic variations. In future, precision-medicine guided trials are needed to pave the way for clinical implementation of biomarker-guided treatment (Vijverberg et al. 2018).

Severe asthma in therapy-resistant asthma in children is a patchwork disease that affects all age groups. Due to this, a precise diagnosis and treatment have been imperative to have better outcomes. There seems to be a huge diagnosis gap in severe asthma; there is no single test to accurately determine disease phenotype. Bronchial asthma is a chronic inflammatory tissue characterized by bronchial hyperactivity, reversible airway obstruction, and excessive mucus production.

Bronchial asthma more closely resembles a complex of clinical diseases than a single condition. In the past five years, it has emerged as the most common incommunicable respiratory disease affecting children worldwide. Asthma is further distinguished by multiple phenotypes that may differ based on age of onset, trigger factors and pattern of severity as shown by the reversible loss of lung function. Severe asthma is a clinically and etiologically patchwork of respiratory disorders that affects approximately 5% to 10% of patients with bronchial asthma.

Studies are currently being conducted to define phenotypic biomarkers and biomarker therapies in an effort to treat and manage severe asthma. There is no single test available to accurately determine these phenotypes. Reliable markers in severe asthma in children as predicated upon the prospect of using noninvasive methods to obtain an estimate ideal biomarkers and confirming diagnosis. Identification and utilization of ideal and defined biomarkers in severe asthma remains inconclusive. Apart from the disease varieties, the reason for this includes the diverse and overlapping biological aspects of each prospective biomarker, its changing concentrations depending on disease pathobiology and methods of sample collection/evaluation, and the invasiveness of sampling techniques that need specific tools and skills. Thus this study has shown the biomarkers from sputum (mucus) testing (Uwaezuoke et al. (2018).

Inhaled allergen challenges are often used to evaluate novel asthma treatments in early clinical trials. This is because inhaled allergens allow for rapid evaluation of the potential to suppress allergic inflammation before later phase studies focusing on clinical endpoints. In the allergen challenge studies, the endpoint is usually the fall in lung function caused by allergen inhalation. This study used baseline induced sputum and bronchoscopy samples were collected. In addition, they made use of bronchial biopsies from the lower lobes of one of the lungs.

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Only one of the original test subjects was removed due to intoleration of the baseline bronchoscopy. The observations of the study support the involvement of specific kinase pathways in the allergic response. This study also found that epithelial activation contributes to the inflammatory cascade in asthma caused by environmental triggers. They also found that the allergic response involves T-helper 2 cell activation. There were inconsistent reports of changes in leukocyte numbers (a white blood cell that responds to invading organisms) in bronchial mucosa after allergen challenge, probably due to differences in time-point of sampling.

And while the sample numbers were few, the study felt they had enough tissue samples to perform validation experiments. This study showed biomarkers of kinase activation during an asthmatic allergic response. Future clinical trials of novel kinase inhibitors could consider using the allergen challenge model in proof of concept studies while employing these biomarkers to understand the pharmacological effects of kinase inhibition in the lungs (Southworth et al. 2018).

Asthma is a chronic inflammatory disease characterized by reversible airway obstruction, airway hyper-responsiveness mucous hypersecretion and airway remodeling caused by many stimuli including genetic and environmental factors. It affects approximately 300 million individuals worldwide with a prevalence ranging from 1% to 18% of the population in different countries. Standard therapies include inhaled corticosteroids in combination with long-acting beta-2 agonists to reduce symptoms. This study has found that two herbal preparations when used together can help asthma patients as well as osteoarthritis patients. It is known as AlvioLife® and is also known as Respicor (Yugandhar et al. 2017).

Work Cited
Frey, S.M. et al. (2017). Medication identification in pediatric asthma (MED ID): The reliability and validity of a novel screening tool. Journal of Asthma,55(2). https://doi.org/10.1080/02770903.2016.1258078

Southworth, T. et al. (2018). P13K, p38, and JAK/STAT signaling in bronchial tissue from patients with asthma following allergen challenge. Biomarker Research,6(14). https://doi.org/10.1186/s40364-018-0128-9

Todd, S. et al. (2018). Novel assessment tool to detect breathing pattern disorder in patients with refractory asthma. Respirology,23(3). Wiley Online Library. https://doi.org/10.111/resp.13173

Uwaezuoke, S.N. et al. (2018). Severe bronchial asthma in children: A review of novel biomarkers used as predictors of the disease. Journal of Asthma and Allergy. Dove Press. https://dx.doi.org/10.2147/JAA.S149577

Vijverberg, S.J.H. et al. (2018). Treatment response heterogeneity in asthma: The role of genetic variation. Expert Review of Respiratory Medicine,12(1). Taylor & Francis. https://doi.org/10.1080/17476348.2018.1403318

Yugandhar, P. et al. (2017). A novel herbal composition containing extracts of Boswellia Serrata gum resin and Aegle marmelos fruit double-blind clinical study. Phytotherapy Research. Doi:10.1002/ptr.5963

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