scholarly journals Biomarkers in the context of managing severe asthma

2019 ◽  
Vol 2 (1) ◽  
pp. 10-18
Author(s):  
Stanley J. Szefler
Keyword(s):  
Nitric Oxide ◽  
Severe Asthma ◽  
Clinical Application ◽  
Biologic Therapy ◽  
Asthma Management ◽  
Response To Treatment ◽  
Biologic Therapies ◽  
Uncontrolled Asthma ◽  
The Cost ◽  
Blood Eosinophils

Only recently have asthma strategies addressed biomarkers in asthma management, for example, as applied in the identification of severe asthmatics likely to respond to biologic therapy. Three biomarkers are readily available for clinical application in managing severe asthma including blood eosinophils, exhaled nitric oxide and serum IgE. While we have a limited number of biomarkers for clinical application, the available biomarkers have ushered in the era of personalized medicine for asthma. These three biomarkers are readily available for application in the clinic setting to select medications and to monitor response to treatment as well as medication adherence. These biomarkers can be used to modify the cost of uncontrolled asthma and also used to select those patients likely to respond to the available biologic therapies for severe asthma.

Applying personalized medicine to adult severe asthma

2021 ◽  
Vol 42 (1) ◽  
pp. e8-e16 ◽  
Author(s):  
Angelica Tiotiu
Keyword(s):  
Personalized Medicine ◽  
Severe Asthma ◽  
Negative Impact ◽  
Target Therapy ◽  
Asthma Management ◽  
Future Research ◽  
Biologic Therapies ◽  
Eosinophilic Asthma ◽  
Definition Of ◽  
Structured Approach

Background: Severe asthma is a heterogeneous disease that consists of various phenotypes driven by different pathways. Associated with significant morbidity, an important negative impact on the quality of life of patients, and increased health care costs, severe asthma represents a challenge for the clinician. With the introduction of various antibodies that target type 2 inflammation (T2) pathways, severe asthma therapy is gradually moving to a personalized medicine approach. Objective: The purpose of this review was to emphasize the important role of personalized medicine in adult severe asthma management. Methods: An extensive research was conducted in medical literature data bases by applying terms such as “severe asthma” associated with “structured approach,” “comorbidities,” “biomarkers,” “phenotypes/endotypes,” and “biologic therapies.” Results: The management of severe asthma starts with a structured approach to confirm the diagnosis, assess the adherence to medications and identify confounding factors and comorbidities. The definition of phenotypes or endotypes (phenotypes defined by mechanisms and identified through biomarkers) is an important step toward the use of personalized medicine in asthma. Severe allergic and nonallergic eosinophilic asthma are two defined T2 phenotypes for which there are efficacious targeted biologic therapies currently available. Non-T2 phenotype remains to be characterized, and less efficient target therapy exists. Conclusion: Despite important progress in applying personalized medicine to severe asthma, especially in T2 inflammatory phenotypes, future research is needed to find valid biomarkers predictive for the response to available biologic therapies to develop more effective therapies in non-T2 phenotype.

Cost Utility of Fractional Exhaled Nitric Oxide Monitoring for the Management of Children Asthma

2020 ◽  
Author(s):  
Jefferson Antonio Buendia ◽  
Rannery Acuña ◽  
carlos rodriguez
Keyword(s):  
Nitric Oxide ◽  
Markov Model ◽  
Standard Therapy ◽  
Asthma Management ◽  
Cost Effective ◽  
Cost Utility ◽  
Exhaled Nitric Oxide ◽  
Fractional Exhaled Nitric Oxide ◽  
Tertiary Center ◽  
The Cost

Abstract IntroductionFractional exhaled nitric oxide is a simple, non-invasive measurement of airway inflammation with minimal discomfort to the patient and with results available within a few minutes. This study aimed to evaluate the cost-effectiveness of asthma management using fractional exhaled nitric oxide monitoring in patients between 4 and 18 years of age.Methods A Markov model was used to estimate the cost-utility of asthma management using fractional exhaled nitric oxide monitoring versus asthma management without using fractional exhaled nitric oxide monitoring (standard therapy) in patients between 4 and 18 years of age. Cost data were obtained from a retrospective study on asthma from a tertiary center, in Medellin, Colombia, while probabilities of the Markov model and utilities were obtained from the systematic review of published randomized clinical trials. The analysis was carried out from a societal perspective.ResultsThe model showed that fractional exhaled nitric oxide monitoring was associated with a lower total cost than standard therapy (US $1,333 vs. US $1,452 average cost per patient) and higher QALYs (0.93 vs. 0.92 average per patient). The probability that fractional exhaled nitric oxide monitoring provides a more cost-effective use of resources compared with standard therapy exceeds 99% for all willingness-to-pay thresholds.Conclusion Asthma management using fractional exhaled nitric oxide monitoring was cost-effective for treating patients between 4 and 18 years of age with mild to moderate allergic asthma. Our study suggests evidence that could be used by decision-makers to improve clinical practice guidelines, but this should be replicated in different clinical settings.

scholarly journals Characterisation of patients with severe asthma in the UK Severe Asthma Registry in the biologic era

Thorax ◽  
2020 ◽  
pp. thoraxjnl-2020-215168
Author(s):  
David J Jackson ◽  
John Busby ◽  
Paul E Pfeffer ◽  
Andrew Menzies-Gow ◽  
Thomas Brown ◽  
...  
Keyword(s):  
Asthma Control ◽  
Severe Asthma ◽  
Symptom Control ◽  
Unmet Need ◽  
High Dose ◽  
Blood Eosinophil ◽  
Biologic Therapies ◽  
Exacerbation Rate ◽  
The Uk ◽  
Blood Eosinophils

BackgroundThe UK Severe Asthma Registry (UKSAR) is the world’s largest national severe asthma registry collecting standardised data on referrals to UK specialist services. Novel biologic therapies have transformed the management of type 2(T2)-high severe asthma but have highlighted unmet need in patients with persisting symptoms despite suppression of T2-cytokine pathways with corticosteroids.MethodsDemographic, clinical and treatments characteristics for patients meeting European Respiratory Society / American Thoracic Society severe asthma criteria were examined for 2225 patients attending 15 specialist severe asthma centres. We assessed differences in biomarker low patients (fractional exhaled nitric oxide (FeNO) <25 ppb, blood eosinophils <150/μL) compared with a biomarker high population (FeNO ≥25 ppb, blood eosinophils ≥150/µL).ResultsAge (mean 49.6 (14.3) y), age of asthma onset (24.2 (19.1) y) and female predominance (62.4%) were consistent with prior severe asthma cohorts. Poor symptom control (Asthma Control Questionnaire-6: 2.9 (1.4)) with high exacerbation rate (4 (IQR: 2, 7)) were common despite high-dose treatment (51.7% on maintenance oral corticosteroids (mOCS)). 68.9% were prescribed biologic therapies including mepolizumab (50.3%), benralizumab (26.1%) and omalizumab (22.6%). T2-low patients had higher body mass index (32.1 vs 30.2, p<0.001), depression/anxiety prevalence (12.3% vs 7.6%, p=0.04) and mOCS use (57.9% vs 42.1%, p<0.001). Many T2-low asthmatics had evidence of a historically elevated blood eosinophil count (0.35 (0.13, 0.60)).ConclusionsThe UKSAR describes the characteristics of a large cohort of asthmatics referred to UK specialist severe asthma services. It offers the prospect of providing novel insights across a range of research areas and highlights substantial unmet need with poor asthma control, impaired lung function and high exacerbation rates. T2-high phenotypes predominate with significant differences apparent from T2-low patients. However, T2-low patients frequently have prior blood eosinophilia consistent with possible excessive corticosteroid exposure.

scholarly journals Unmet need in severe, uncontrolled asthma: can anti-TSLP therapy with tezepelumab provide a valuable new treatment option?

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Michael E. Wechsler ◽  
Chris E. Brightling
Keyword(s):  
Inflammatory Response ◽  
Airway Inflammation ◽  
Asthma Control ◽  
Severe Asthma ◽  
Human Monoclonal Antibody ◽  
Unmet Need ◽  
Blood Eosinophil ◽  
Biologic Therapies ◽  
Uncontrolled Asthma ◽  
Asthma Exacerbations

Abstract Despite treatment with standard-of-care medications, including currently available biologic therapies, many patients with severe asthma have uncontrolled disease, which is associated with a high risk of hospitalization and high healthcare costs. Biologic therapies approved for severe asthma have indications limited to patients with either eosinophilic or allergic phenotypes; there are currently no approved biologics for patients with eosinophil-low asthma. Furthermore, existing biologic treatments decrease exacerbation rates by approximately 50% only, which may be because they target individual, downstream elements of the asthma inflammatory response, leaving other components untreated. Targeting an upstream mediator of the inflammatory response may have a broader effect on airway inflammation and provide more effective asthma control. One such potential target is thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine released in response to multiple triggers associated with asthma exacerbations, such as viruses, allergens, pollutants and other airborne irritants. Mechanistic studies indicate that TSLP drives eosinophilic (including allergic) inflammation, neutrophilic inflammation and structural changes to the airway in asthma through actions on a wide variety of adaptive and innate immune cells and structural cells. Tezepelumab is a first-in-class human monoclonal antibody that blocks the activity of TSLP. In the phase 2b PATHWAY study (NCT02054130), tezepelumab reduced asthma exacerbations by up to 71% compared with placebo in patients with severe, uncontrolled asthma across the spectrum of inflammatory phenotypes, and improved lung function and asthma control. Phase 3 trials of tezepelumab are underway. NAVIGATOR (NCT03347279), a pivotal exacerbation study, aims to assess the potential efficacy of tezepelumab further in patients with a broad range of severe asthma phenotypes, including those with low blood eosinophil counts. SOURCE (NCT03406078) aims to evaluate the oral corticosteroid-sparing potential of tezepelumab. DESTINATION (NCT03706079) is a long-term extension study. In addition, an ongoing phase 2 bronchoscopy study, CASCADE (NCT03688074), aims to evaluate the effect of tezepelumab on airway inflammation and airway remodelling in patients across the spectrum of type 2 airway inflammation. Here, we summarize the unmet therapeutic need in severe asthma and the current treatment landscape, discuss the rationale for targeting TSLP in severe asthma therapy and describe the current development status of tezepelumab.

scholarly journals Targeting dynamic hyperinflation in moderate to severe asthma – a randomised controlled trial

2021 ◽  
pp. 00738-2020
Author(s):  
A. N. van der Meer ◽  
K. de Jong ◽  
A. Hoekstra-Kuik ◽  
E. H. Bel ◽  
A. ten Brinke
Keyword(s):  
Nitric Oxide ◽  
Severe Asthma ◽  
Respiratory Health ◽  
Controlled Trial ◽  
Exhaled Nitric Oxide ◽  
Dynamic Hyperinflation ◽  
Small Airways ◽  
Asthma Patients ◽  
Anti Inflammatory ◽  
Blood Eosinophils

BackgroundDynamic hyperinflation (DH) is highly prevalent in moderate to severe asthma, which may significantly impede activities of daily life. We hypothesised that DH in asthma is due to inflammation of large and small airways and can be reduced by systemic anti-inflammatory treatment. Therefore, we investigated the effect of systemic glucocorticoids on DH in moderate to severe asthma patients and explored the relationships between inflammatory markers and changes in DH.MethodsIn this randomised placebo-controlled trial we included 32 asthma patients on inhaled glucocorticoid therapy showing DH, defined by a ≥10% reduction in inspiratory capacity measured by standardised metronome-paced tachypnea test. Patients received either triamcinolone (80 mg) or placebo intramuscularly. Before and 2 weeks after treatment, patients completed respiratory health questionnaires, had blood eosinophils and exhaled nitric oxide levels measured and underwent lung function and DH testing.ResultsAfter adjustment for potential confounders, DH was significantly reduced by 28.1% in the triamcinolone group, and increased by 9.4% in the placebo group (p=0.027). In the triamcinolone-treated patients, the reduction in DH was greater in patients with higher blood eosinophils at baseline (r=−0.592, p=0.020) and tended to be associated with a reduction in blood eosinophils (r=0.412, p=0.127) and exhaled nitric oxide (r=0.442, p=0.099).ConclusionsThis exploratory study suggests that dynamic hyperinflation in asthma can be reduced by systemic anti-inflammatory treatment, particularly in patients with elevated blood eosinophils. This supports the hypothesis that dynamic hyperinflation in asthma is due to airway inflammation and should be considered an important target for treatment.

scholarly journals Clinical utility of fractional exhaled nitric oxide in severe asthma management

2020 ◽  
Vol 55 (3) ◽  
pp. 1901633 ◽  
Author(s):  
Andrew Menzies-Gow ◽  
Adel H. Mansur ◽  
Christopher E. Brightling
Keyword(s):  
Nitric Oxide ◽  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Healthcare Providers ◽  
Asthma Management ◽  
Cost Effective ◽  
Chronic Inflammatory Disease ◽  
Initial Diagnosis ◽  
Increased Risk ◽  
The Usa

Asthma is a chronic inflammatory disease of the airways, affecting over 350 million people worldwide and placing a significant burden on healthcare providers and wider society. Approximately 5–10% of asthma patients are diagnosed with severe asthma and typically are associated with increased risk of hospitalisation from exacerbations, increased morbidity, mortality and higher asthma-associated healthcare costs. Nitric oxide (NO) is an important regulator of immune responses and is a product of inflammation in the airways that is over-produced in asthma. Fractional exhaled NO (FeNO) is predominantly used as a predictor of response to inhaled corticosteroids (ICSs), to monitor adherence and as a diagnostic tool in ICS-naïve patients. In the UK, the National Institute for Health and Care Excellence (NICE) guidelines recommend the use of FeNO for the initial diagnosis of patients with suspected asthma. In the USA, American Thoracic Society (ATS) guidelines recommend FeNO as part of the initial diagnosis of asthma and for monitoring of airway inflammation. FeNO has also been shown to be a predictive factor for asthma exacerbations, with higher levels being associated with a greater number of exacerbations. In addition, higher levels of FeNO have been shown to be associated with a decline in lung function. FeNO testing is a cost-effective procedure and has been shown to improve patient management when combined with standard assessment methods. Recent evidence suggests that FeNO may also be useful as a surrogate biomarker for the assessment and management of severe asthma and to predict responsiveness to some biological therapies.

scholarly journals Biologic Therapy and Severe Asthma in Children

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 760
Author(s):  
Daniele Russo ◽  
Paola Di Filippo ◽  
Marina Attanasi ◽  
Mauro Lizzi ◽  
Sabrina Di Pillo ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Biologic Therapy ◽  
Pediatric Population ◽  
Adult Population ◽  
Allergic Diseases ◽  
Molecular Pathways ◽  
Efficacy And Safety ◽  
Biologic Therapies ◽  
Asthma In Children

Severe asthma is a heterogeneous, complex and chronic disease widespread in the pediatric population. According to the recent findings about the different endotypes of asthma in children, each one characterized by specific intracellular molecular pathways, several innovative biologic therapies have been developed. Due to their precise ability to target specific inflammatory type 2 mediators, biologics have revolutionized the care of chronic allergic diseases in the pediatric and adult population. In this review, we aim to provide the latest evidence about the use, indications, efficacy and safety of biologic therapies to treat severe asthma in children and adolescents.

scholarly journals Cost utility of fractional exhaled nitric oxide monitoring for the management of children asthma

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jefferson Antonio Buendía ◽  
Ranniery Acuña-Cordero ◽  
Carlos E. Rodriguez-Martinez
Keyword(s):  
Nitric Oxide ◽  
Markov Model ◽  
Standard Therapy ◽  
Asthma Management ◽  
Cost Effective ◽  
Cost Utility ◽  
Exhaled Nitric Oxide ◽  
Fractional Exhaled Nitric Oxide ◽  
Tertiary Center ◽  
The Cost

Abstract Introduction Fractional exhaled nitric oxide is a simple, non-invasive measurement of airway inflammation with minimal discomfort to the patient and with results available within a few minutes. This study aimed to evaluate the cost-effectiveness of asthma management using fractional exhaled nitric oxide monitoring in patients between 4 and 18 years of age. Methods A Markov model was used to estimate the cost-utility of asthma management using fractional exhaled nitric oxide monitoring versus asthma management without using fractional exhaled nitric oxide monitoring (standard therapy) in patients between 4 and 18 years of age. Cost data were obtained from a retrospective study on asthma from a tertiary center, in Medellin, Colombia, while probabilities of the Markov model and utilities were obtained from the systematic review of published randomized clinical trials. The analysis was carried out from a societal perspective. Results The model showed that fractional exhaled nitric oxide monitoring was associated with a lower total cost than standard therapy (US $1333 vs. US $1452 average cost per patient) and higher QALYs (0.93 vs. 0.92 average per patient). The probability that fractional exhaled nitric oxide monitoring provides a more cost-effective use of resources compared with standard therapy exceeds 99% for all willingness-to-pay thresholds. Conclusion Asthma management using fractional exhaled nitric oxide monitoring was cost-effective for treating patients between 4 and 18 years of age with mild to moderate allergic asthma. Our study suggests evidence that could be used by decision-makers to improve clinical practice guidelines, but this should be replicated in different clinical settings.

Biomarkers in asthma - interpretation and utility in current asthma management

2021 ◽  
Vol 17 ◽  
Author(s):  
Polliana Mihaela Leru
Keyword(s):  
Severe Asthma ◽  
Asthma Management ◽  
Initial Therapy ◽  
Variable Response ◽  
Clinical Criteria ◽  
Disease Biology ◽  
Therapeutic Choice ◽  
Blood Eosinophils

: Asthma is a complex and highly heterogeneous disorder, having many clinical phenotypes and underlining mechanisms, a broad spectrum of severity and variable response to controller therapy. Intensive research has been focused on identification and validation of the most appropriate biomarkers in the clinical management of asthma, mostly addressed to severe and refractory cases. The use of reliable biomarkers in severe asthma can contribute to better understanding of disease biology, diagnosis and screening, by a refined characterization of particular phenotypes and endotypes, assessment of severity, control and prognosis. There is an increasing interest to validate biomarkers able to indicate the adequate therapeutic choice from the class of biological agents, most of them targeting T2 inflammation. Using a reliable and validated biomarker, the clinician can monitor the response to initial therapy and early identify a severe phenotype. The aim of this paper is to review the clinical utility of relevant biomarkers currently used in asthma management. Indication for a more advanced and efficient therapy, such as monoclonal antibodies and selection of the optimal molecule is based on biomarkers and clinical criteria, according to the most recent experts’ recommendations. Peripheral blood eosinophils is considered an important biomarker for selection and identification of responders to anti-eosinophil biological therapy. Reallife long-term studies to confirm the precise use and cutoffs of the already approved biomarkers for T2 phenotypes and to identify reliable biomarkers for non- T2 severe asthma are still unmet needs in asthma management.

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