scholarly journals Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis

2022 ◽  
Vol 50 (1) ◽  
pp. 030006052110704
Author(s):  
Mitsuru Tsuge ◽  
Masanori Ikeda ◽  
Yoichi Kondo ◽  
Hirokazu Tsukahara
Keyword(s):  
Severe Asthma ◽  
Wall Thickness ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Three Dimensional ◽  
Treatment Resistance ◽  
Poor Response ◽  
Airway Wall ◽  
Bronchial Wall ◽  
Severe Allergic Asthma

Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma.

scholarly journals Immunologic Pathophysiology and Airway Remodeling Mechanism in Severe Asthma: Focused on IgE-Mediated Pathways

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 83
Author(s):  
Shih-Lung Cheng
Keyword(s):  
Severe Asthma ◽  
Immunoglobulin E ◽  
Airway Remodeling ◽  
Real Life ◽  
Allergic Diseases ◽  
Proinflammatory Mediators ◽  
Small Subgroup ◽  
Humanized Monoclonal Antibody ◽  
Severe Allergic Asthma ◽  
Ige Mediated

Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remains partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E (IgE) and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating IgE, which in turn impedes and reduces subsequent releases of the proinflammatory mediators. In the past decade, omalizumab has been proven to be efficacious and well-tolerated in the treatment of moderate-to-severe asthma in both trials and real-life studies, most notably in reducing exacerbation rates and corticosteroid use. While growing evidence has demonstrated that omalizumab may be potentially beneficial in treating other allergic diseases, its indication remains confined to treating severe allergic asthma and chronic idiopathic urticaria. Future efforts may be bestowed on determining the optimal length of omalizumab treatment, seeking biomarkers that could better predict treatment response and as well as extending its indications.

Correlation of matrix‐related airway remodeling and bradykinin B1 receptor expression with fixed airflow obstruction in severe asthma

Allergy ◽  
2020 ◽  
Author(s):  
Francesca Bertolini ◽  
Vitina Carriero ◽  
Michela Bullone ◽  
Andrea Elio Sprio ◽  
Ilaria Defilippi ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Receptor Expression ◽  
B1 Receptor ◽  
Bradykinin B1 Receptor ◽  
Fixed Airflow Obstruction

Airway Wall Thickness On Computerized Tomography Correlates With Increased Mast Cell Markers In Severe Asthma

2012 ◽  
Author(s):  
Hrishikesh S. Kulkarni ◽  
Merritt L. Fajt ◽  
Crystal E. Uvalle ◽  
Eric A. Hoffman ◽  
Janice Cook-Granroth ◽  
...  
Keyword(s):  
Mast Cell ◽  
Computerized Tomography ◽  
Severe Asthma ◽  
Wall Thickness ◽  
Airway Wall ◽  
Cell Markers ◽  
Airway Wall Thickness

Reduction of bronchial wall thickness and hyperinflation on quantitative CT after bronchial thermoplasty for severe asthma

2017 ◽  
Author(s):  
Maren Schuhmann ◽  
Philip Konietzke ◽  
Mark Wielpütz ◽  
Oliver Weinheimer ◽  
Philine Kaukel ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Wall Thickness ◽  
Quantitative Ct ◽  
Bronchial Wall ◽  
Bronchial Thermoplasty

Evaluation of Airway Wall Thickness in Severe Asthma with monoclonal antibody therapy

2019 ◽  
Author(s):  
Junko Saji ◽  
Yuki Kanno ◽  
Akihito Tsunoda ◽  
Eriko Koda ◽  
Shinya Azagami ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Severe Asthma ◽  
Wall Thickness ◽  
Antibody Therapy ◽  
Monoclonal Antibody Therapy ◽  
Airway Wall ◽  
Airway Wall Thickness

scholarly journals Predictors of reversible airway obstruction with omalizumab in severe asthma: a real-life study

2019 ◽  
Vol 13 ◽  
pp. 175346661984127 ◽  
Author(s):  
Paolo Solidoro ◽  
Filippo Patrucco ◽  
Francesca de Blasio ◽  
Luisa Brussino ◽  
Michela Bellocchia ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Allergic Asthma ◽  
Severe Asthma ◽  
Airway Remodeling ◽  
Real Life ◽  
Forced Expiratory Volume ◽  
Life Study ◽  
Reversible Airway Obstruction ◽  
Number Of Patients ◽  
Severe Allergic Asthma

Background: Omalizumab may modulate airway remodeling in severe asthma. Using forced expiratory volume in 1 second (FEV1) as a surrogate of airway remodeling, we aimed to investigate if an omalizumab add-on in severe allergic asthma may lead to a persistent reversal of airway obstruction and to evaluate the potential biomarkers of airway obstruction reversibility. Methods: Data were collected before (T0) and after omalizumab add-on for 1 year (T1, 32 patients), 2 years (T2, 26 patients) and 4 years (T4, 13 patients). All patients had baseline FEV1 below 80 % predicted (60.5 ± 12.5 %). After omalizumab, 18 patients showed FEV1 normalization (reversible airway obstruction; RAO+) already at T1 (88.7 ± 14.9 %, p < 0.0001) that persisted up to T4 (83.2 ± 7.9, p < 0.01), while 14 patients (RAO−) had FEV1 persistently decreased, from T1 (65.2 ± 8.4%, p < 0.05) up to T4 (61.4 ± 6.2%, not significant). Both groups had significant improvement of symptoms and exacerbations after omalizumab at T1, which persisted up to T4. The comparison between pretreatment characteristics of the two groups showed that RAO+ patients, had higher values of circulating eosinophils, exhaled nitric oxide (FENO), prevalence of rhinitis and nasal polyps, need of oral corticosteroids, shorter asthma duration, higher FEV1 and response to albuterol test. The optimal cut-off points predicting FEV1 normalization after omalizumab add-on were 30.5 ppb for FENO and 305 cells/µl for eosinophils. Conclusions: This study suggests that omalizumab add-on contributes to the persistent reversal of airway obstruction in a consistent number of patients with severe allergic asthma, and this beneficial effect is predicted by elevated pretreatment FENO and circulating eosinophils.

Impact of bronchial wall thickness on airflow obstruction in bronchiectasis

2022 ◽  
Vol 295 ◽  
pp. 103788
Author(s):  
Yuji Yamamoto ◽  
Tomoki Kuge ◽  
Keisuke Miki ◽  
Kazuyuki Tsujino ◽  
Takahiro Kawasaki ◽  
...  
Keyword(s):  
Wall Thickness ◽  
Airflow Obstruction ◽  
Bronchial Wall

Proposed nomenclature for quantifying subdivisions of the bronchial wall

1994 ◽  
Vol 77 (2) ◽  
pp. 1011-1014 ◽  
Author(s):  
A. Bai ◽  
D. H. Eidelman ◽  
J. C. Hogg ◽  
A. L. James ◽  
R. K. Lambert ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cross Sections ◽  
Airway Remodeling ◽  
Chronic Obstructive ◽  
Structural Components ◽  
Airway Wall ◽  
Morphometric Measurements ◽  
Obstructive Pulmonary Disease ◽  
Bronchial Wall ◽  
Airway Mechanics

There is increasing interest in the structural components of the airway wall because of the airway remodeling that is observed in conditions such as asthma and chronic obstructive pulmonary disease and because of their contribution to changes in airway mechanics. This interest has stimulated several groups to make morphometric measurements on airway cross sections, and their results have been reported using a variety of nomenclature. We propose the adoption of a standard system of nomenclature that is based on accepted terms for subdivisions of the airway wall and has been agreed to by several groups working in this field.

scholarly journals Heterogeneity of airway wall dimensions in humans: a critical determinant of lung function in asthmatics and nonasthmatics

2017 ◽  
Vol 312 (3) ◽  
pp. L425-L431 ◽  
Author(s):  
Christopher D. Pascoe ◽  
Chun Y. Seow ◽  
Tillie L. Hackett ◽  
Peter D. Paré ◽  
Graham M. Donovan
Keyword(s):  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Small Airways ◽  
Airway Wall ◽  
Critical Determinant ◽  
Mean Values ◽  
Airway Narrowing ◽  
Wall Area ◽  
First Time ◽  
Fixed Airflow Obstruction

Airway remodeling, a key feature of asthma, alters every layer of the airway wall but most strikingly the airway smooth muscle (ASM) layer. Airway remodeling in asthmatics contributes to fixed airflow obstruction and can amplify airway narrowing caused by ASM activation. Previous modeling studies have shown that the increase in ASM mass has the largest effect on increasing maximal airway narrowing. Simulated heterogeneity in the dimensions and properties of the airway wall can further amplify airway narrowing. Using measurements made on histological sections from donor lungs, we show for the first time that there is profound heterogeneity of ASM area and wall area in both nonasthmatics and asthmatics. Using a mathematical model, we found that this heterogeneity, together with changes in the mean values, contributes to an increased baseline resistance and elastance in asthmatics as well as a leftward shift in the responsiveness of the airways to a simulated agonist in both nonasthmatics and asthmatics. The ability of heterogeneous wall dimensions to shift the dose-response curve is largely due to an increased susceptibility for the small airways to close. This research confirms that heterogeneity of airway wall dimensions can contribute to exaggerated airway narrowing and provides an actual assessment of the magnitude of these effects.

scholarly journals Genetic Determinants of Poor Response to Treatment in Severe Asthma

2021 ◽  
Vol 22 (8) ◽  
pp. 4251
Author(s):  
Ricardo G. Figueiredo ◽  
Ryan S. Costa ◽  
Camila A. Figueiredo ◽  
Alvaro A. Cruz
Keyword(s):  
Severe Asthma ◽  
Inhaled Corticosteroids ◽  
Association Studies ◽  
Airway Remodeling ◽  
Expression Patterns ◽  
Poor Response ◽  
Response To Treatment ◽  
Genome Wide Association Studies ◽  
Genetic Determinants ◽  
Increased Risk

Severe asthma is a multifactorial disorder with marked phenotypic heterogeneity and complex interactions between genetics and environmental risk factors, which could, at least in part, explain why during standard pharmacologic treatment, many patients remain poorly controlled and at an increased risk of airway remodeling and disease progression. The concept of “precision medicine” to better suit individual unique needs is an emerging trend in the management of chronic respiratory diseases. Over the past few years, Genome-Wide Association Studies (GWAS) have revealed novel pharmacogenetic variants related to responses to inhaled corticosteroids and the clinical efficacy of bronchodilators. Optimal clinical response to treatment may vary between racial/ethnic groups or individuals due to genetic differences. It is also plausible to assume that epigenetic factors play a key role in the modulation of gene expression patterns and inflammatory cytokines. Remarkably, specific genetic variants related to treatment effectiveness may indicate promising pathways for novel therapies in severe asthma. In this review, we provide a concise update of genetic determinants of poor response to treatment in severe asthma and future directions in the field.

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