scholarly journals Bronchial Thermoplasty in the Treatment of Severe Asthma

2020 ◽  
pp. 1-9
Author(s):  
Nightingale Syabbalo ◽  
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Airway Disease ◽  
Airflow Limitation ◽  
Response To Treatment ◽  
High Dose ◽  
Eosinophilic Asthma ◽  
Bronchial Thermoplasty ◽  
Long Acting ◽  
Refractory Asthma

Asthma is a chronic inflammatory airway disease with several distinct phenotypes, characterized by different immunopathological pathways, clinical presentation, severity of the disease, and response to treatment. The phenotypes of asthma include eosinophilic, neutrophilic, mixed granulocytic, and paucigranulocytic asthma. Approximately 3.6-10% of patients with asthma have severe refractory disease, which is unresponsive to high dose inhaled corticosteroids (ICS), and long-acting β2-agonists (LABA). Most patients with eosinophilic asthma are responsive to corticosteroids, and interleukintargeted biologics, whereas, patients from other phenotypes, such as neutrophillic and paucigranullocytic asthma are resistant to treatment with ICS and biotherapeutics. The hallmark of severe refractory asthma is airway hyperresponsiveness, and remodeling. Histopathologically, patients with severe asthma have airway smooth muscle (ASM) hyperplasia and hypertrophy; subepithelial basement membrane thickening and fibrosis; all which contribute to fixed airflow limitation. Severe refractory asthma is very difficult to treat pharmacologically. It requires innovative therapies, such as bronchial thermoplasty which reduces the hypertrophied ASM mass and relieves the AHR, and broncoconstriction. Bronchial thermoplasty has been shown to improve asthma control, reduce severe exacerbations, hospitalizations, emergency room visits, and improve the quality of life, which persist up to 5 years following the procedure

Diagnosis and Management of Severe Asthma

2018 ◽  
Vol 39 (01) ◽  
pp. 091-099 ◽  
Author(s):  
Kian Fan Chung
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
High Dose ◽  
Blood Eosinophil ◽  
Exhaled Breath ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Asthma Patients ◽  
Long Acting

AbstractSevere therapy-resistant asthma has been defined as “asthma which requires treatment with high dose inhaled corticosteroids (ICSs) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy”. Patients who usually present with ‘difficult-to-treat asthma’ should first be assessed to determine whether he/she has asthma with the exclusion of other diagnoses and if so, whether the asthma can be classified as severe therapy-resistant. This necessitates an assessment of adherence to medications, confounding factors, and comorbidities. Increasingly, management of severe therapy-resistant asthma will be helped by the determination of phenotypes to optimize responses to existing and new therapies. Severe asthma patients are usually on a combination of high dose ICS and long-acting β-agonist (LABA) and, in addition, are often on a maintenance dose of oral corticosteroids. Phenotyping can be informed by measuring blood eosinophil counts and the level of nitric oxide in exhaled breath, and the use of sputum granulocytic counts. Severe allergic asthma and severe eosinophilic asthma are two defined phenotypes for which there are efficacious targeted biologic therapies currently available, namely anti-immunoglobulin E (IgE) and anti-interleukin (IL)-5 antibodies, respectively. Further progress will be realized with the definition of noneosinophilic or non-T2 phenotypes. It will be important for patients with severe asthma to be ultimately investigated and managed in specialized severe asthma centers.

scholarly journals Eosinophils Target Therapy for Severe Asthma: Critical Points

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
L. Brussino ◽  
E. Heffler ◽  
C. Bucca ◽  
S. Nicola ◽  
G. Rolla
Keyword(s):  
Severe Asthma ◽  
Eosinophil Count ◽  
Inhaled Corticosteroids ◽  
Response To Treatment ◽  
High Dose ◽  
Blood Eosinophil ◽  
Moderate Increase ◽  
Eosinophilic Asthma ◽  
Peripheral Blood Eosinophil ◽  
Blood Eosinophil Count

Asthma is a chronic and heterogeneous disease, which is defined as severe disease whenever it requires treatment with a high dose of inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming ‘‘uncontrolled’’ or if it remains ‘‘uncontrolled’’ despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma, which is characterized by sputum eosinophilia, associated with mild to moderate increase in blood eosinophil count, frequently adult-onset, and associated with chronic rhinosinusitis with nasal polyps in half of the cases. Eosinophilic asthma is driven by T2 inflammation, characterized, among the others, by interleukin-5 production. IL-5 plays a key role in the differentiation, survival, migration, and activation of eosinophils, and it has become an appealing therapeutic target for eosinophilic asthma. In recent years two monoclonal antibodies (mepolizumab and reslizumab) directed against IL-5 and one monoclonal antibody directed against the alpha-subunit of the IL-5 receptor (benralizumab) have been developed. All these IL-5 target drugs have been shown to reduce the number of exacerbation in patients with severe asthma selected on the basis of peripheral blood eosinophil count. There are still a number of unresolved issues related to the anti-IL5 strategy in eosinophilic asthma, which are here reviewed. These issues include the effects of such therapy on airway obstruction and asthmatic symptoms, the level of baseline eosinophils that predicts a response to treatment, the relationship between blood and airway eosinophilia, and, perhaps most importantly, how to elucidate the pathogenetic role played by eosinophils in the individual patient with severe eosinophilic asthma.

scholarly journals The Role of Omalizumab in the Treatment of Severe Allergic Asthma

2006 ◽  
Vol 13 (suppl b) ◽  
pp. 1B-9B ◽  
Author(s):  
Kenneth R Chapman ◽  
Andre Cartier ◽  
Jacques Hébert ◽  
R Andrew McIvor ◽  
R Robert Schellenberg
Keyword(s):  
Severe Asthma ◽  
Adjunctive Therapy ◽  
Conventional Therapy ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
Severe Disease ◽  
Phase Iii ◽  
High Dose ◽  
Two Phase ◽  
Long Acting

BACKGROUND: A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.OBJECTIVE: To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.METHODS: A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use.RESULTS: Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or fourweek intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumabtreated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment.RECOMMENDATIONS: Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.

Dual biologic therapy in a patient with severe asthma and other allergic disorders

2021 ◽  
Vol 14 (5) ◽  
pp. e242211
Author(s):  
Joshua Ray Caskey ◽  
David Kaufman
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Chronic Idiopathic Urticaria ◽  
High Dose ◽  
Dramatic Improvement ◽  
Eosinophilic Asthma ◽  
Severe Eosinophilic Asthma ◽  
Systemic Corticosteroids ◽  
Acute Exacerbations ◽  
H1 Antihistamines

Severe asthma is very difficult to manage in many individuals, and systemic corticosteroids are often used to prevent or manage acute exacerbations. Furthermore, comorbid allergic conditions may render standard therapies inadequate. A 51-year-old man presented with severe eosinophilic asthma requiring nearly constant oral corticosteroid usage despite using high-dose inhaled corticosteroids and secondary asthma controllers. His condition was complicated by aspirin-exacerbated respiratory disease, including severe nasal polyposis, chronic rhinosinusitis, as well as chronic idiopathic urticaria. Mepolizumab was initiated and led to dramatic improvement of asthma over 6 months. However, he continued to experience exacerbations of chronic idiopathic urticaria not responsive to H1-antihistamines. Omalizumab was added, and the patient’s urticaria attained marked improvement with only an occasional breakthrough rash. Dual biologic therapies can be a unique and useful steroid-sparing treatment option for patients with uncontrolled severe asthma and chronic idiopathic urticaria.

scholarly journals The Role of Omalizumab in the Treatment of Severe Allergic Asthma

2006 ◽  
Vol 13 (suppl b) ◽  
pp. 1B-9B ◽  
Author(s):  
Kenneth R Chapman ◽  
Andre Cartier ◽  
Jacques Hébert ◽  
R Andrew McIvor ◽  
R Robert Schellenberg
Keyword(s):  
Severe Asthma ◽  
Adjunctive Therapy ◽  
Conventional Therapy ◽  
Inhaled Corticosteroids ◽  
Immunoglobulin E ◽  
Severe Disease ◽  
Phase Iii ◽  
High Dose ◽  
Two Phase ◽  
Long Acting

BACKGROUND: A novel anti-immunoglobulin E (anti-IgE) therapy for asthma, omalizumab, has been approved for use in Canada.OBJECTIVE: To review the basic and clinical data for omalizumab, and to examine its possible role for asthma management in Canada.METHODS: A literature search from 1960 to 2006 was conducted in MEDLINE to identify studies of omalizumab. In addition, abstracts from recent respiratory and allergy scientific meetings were sought, and any unpublished data were requested from the manufacturer. A consensus panel of respiratory and allergy specialists reviewed and summarized the data, and derived a set of recommendations for omalizumab use.RESULTS: Omalizumab is a humanized monoclonal antibody designed to bind to the C epsilon 3 domain of the IgE molecule, forming soluble immune complexes that are cleared by the reticuloendothelial system. Subcutaneous injections, given at two- or fourweek intervals at the recommended dose, result in a rapid decrease in free circulating IgE levels. In two phase III clinical trials of 1405 adult and adolescent patients with moderate to severe asthma maintained on moderate doses of inhaled corticosteroids (ICS), omalizumab reduced exacerbation rates compared with placebo, and was associated with improved symptoms and a greater corticosteroid-sparing effect. In a trial of 419 patients with severe disease that was uncontrolled despite the use of high-dose ICS and concurrent long-acting beta2-agonists, severe exacerbations were 50% less frequent in omalizumab-treated patients than in control subjects. Retrospective analyses have identified the characteristics of patients most likely to respond to omalizumab treatment.RECOMMENDATIONS: Omalizumab may be considered as a potential adjunctive therapy in atopic patients with severe asthma uncontrolled by conventional therapy with optimal doses of ICS and appropriate adjunctive therapy (eg, long-acting beta2-agonists). Typically, patients are identified by the need for frequent short course or continuous oral corticosteroids. Therapy should be initiated only after review by a specialist to confirm the diagnosis and that conventional therapy is optimal.

scholarly journals Severe Neutrophilic Asthma: Pathogenesis and Treatment

2022 ◽  
Vol 3 (1) ◽  
pp. 01-13
Author(s):  
Nightingale Syabbalo
Keyword(s):  
Cell Injury ◽  
Inhaled Corticosteroids ◽  
Fungal Infections ◽  
Unmet Need ◽  
Airway Disease ◽  
Airway Epithelial Cells ◽  
High Dose ◽  
Interleukin 17 ◽  
Airway Epithelial ◽  
Eosinophilic Asthma

Asthma is a common chronic airway disease affecting about 358 million people worldwide, and an estimated 7 million children globally. Approximately 10% of patients with asthma have severe refractory disease, which is difficult to control on high doses of inhaled corticosteroids and other modifiers. Among these, are patients with severe neutrophilic asthma. Neutrophilic asthma is a severe phenotype of asthma, characterized by frequent exacerbations, persistent airway obstruction, and poor lung function. Immunopathologically, it is characterized by the presence of high levels of neutrophils in the airways and lungs. Interleukin-17 produced by Th17 cells, plays a key role in the pathogenesis of neutrophilic asthma by expressing the secretion of chemoattractant cytokines and chemokines for the recruitment, and activation of neutrophils. Interleukin-8 is a powerful chemoattractant and activator of neutrophils. Activated neutrophils produce an oxidative burst, releasing multiple reactive oxygen species, proteinases, cytokines, which cause airway epithelial cell injury, inflammation, airway hyperresponsiveness, and remodeling. Furthermore, exasperated neutrophils due to viral, bacterial or fungal infections, and chemical irritants can release extracellular nucleic acids (DNA), designated as NETs (neutrophil extracellular traps), which are more toxic to the airway epithelial cells, and orchestrate airway inflammation, and release alarmin cytokines. Dysregulated NETs formation is associated with severe asthma. Most patients with neutrophilic asthma are unresponsive to the standard of care, including high dose inhaled corticosteroids, and to targeted biologics, such as mepolizumab, and dupilumab, which are very effective in treating eosinophilic asthma. There is unmet need to explore for novel biologics for the treatment of neutrophilic asthma, and in refining therapies, such as bronchial thermoplasty.

scholarly journals Systems Approaches to Treatment Response to Imatinib in Severe Asthma: A Pilot Study

2021 ◽  
Vol 11 (4) ◽  
pp. 240
Author(s):  
Seung Han Baek ◽  
Dinah Foer ◽  
Katherine N. Cahill ◽  
Elliot Israel ◽  
Enrico Maiorino ◽  
...  
Keyword(s):  
Gene Expression ◽  
Clinical Trial ◽  
Systems Biology ◽  
Pilot Study ◽  
Severe Asthma ◽  
Treated Patient ◽  
Expression Patterns ◽  
Airflow Limitation ◽  
Response To Treatment ◽  
Imatinib Treatment

There is an acute need for advances in pharmacologic therapies and a better understanding of novel drug targets for severe asthma. Imatinib, a tyrosine kinase inhibitor, has been shown to improve forced expiratory volume in 1 s (FEV1) in a clinical trial of patients with severe asthma. In a pilot study, we applied systems biology approaches to epithelium gene expression from these clinical trial patients treated with imatinib to better understand lung function response with imatinib treatment. Bronchial brushings from ten imatinib-treated patient samples and 14 placebo-treated patient samples were analyzed. We used personalized perturbation profiles (PEEPs) to characterize gene expression patterns at the individual patient level. We found that strong responders—patients with greater than 20% increase in FEV1—uniquely shared multiple downregulated mitochondrial-related pathways. In comparison, weak responders (5–10% FEV1 increase), and non-responders to imatinib shared none of these pathways. The use of PEEP highlights its potential for application as a systems biology tool to develop individual-level approaches to predicting disease phenotypes and response to treatment in populations needing innovative therapies. These results support a role for mitochondrial pathways in airflow limitation in severe asthma and as potential therapeutic targets in larger clinical trials.

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