Dataset Information

Characteristics of the European Thoracic Society/American Thoracic Society severe asthma definition as a determinant of future use of biologics/bronchial thermoplasty.

ABSTRACT:

Background

International guidelines define severe uncontrolled asthma. Biologics or bronchial thermoplasty (Bio/BT) are recommended for such patients.

Objectives

To determine which definitions of severe uncontrolled asthma are associated with an additional Bio/BT treatment in patients with severe uncontrolled asthma.

Methods

Consecutive 107 asthmatics (including 15 patients for whom Bio/BT was introduced within 3 months after examination), classified as treatment step 4 according to the Global Initiative for Asthma 2015 guideline, were eligible for this analysis. Patients were assessed using the European Thoracic Society/American Thoracic Society (ERS/ATS) severe uncontrolled asthma guideline as defined by these 4 characteristics: poor control (ACT < 20), frequent exacerbations (≥2/yr), admissions (≥1/yr), and airflow limitation (forced expiratory volume in 1 second < 80% of predicted), along with comorbidities, and biomarkers, including blood granulocytes, fractional nitric oxide, and capsaicin cough reflex sensitivity (C-CS). These indices were compared between patients with and without Bio/BT introduction, and multivariate logistic regression analysis was performed to determine the association of the 4 definitions with treatment needs for Bio/BT.

Results

Patients who were introduced to Bio/BT had heightened C-CS, heavier smoking history, and a greater prevalence of diabetes mellitus than those without (p < 0.05). Poor asthma control (ACT < 20), frequent exacerbations (≥2/yr), and admissions (≥1/yr) were relevant to the future use of Bio/BT in the multivariate regression analysis. Type 2-related biomarkers including absolute eosinophil counts were higher in patients in the Bio introduction group than in the BT introduction group. Meanwhile, there was no significant difference of the 4 characteristics of severe uncontrolled asthma definition between patients in the Bio and those in the BT groups.

Conclusion

Although multiple factors such as treatment cost and asthma phenotypes affect treatment decision-making, the definition of poor asthma control, frequent exacerbations and admission by the ERS/ATS guidelines were important factors for an additional intensive treatment for severe uncontrolled asthma.

Trial registration

UMIN Clinical Trials Registry: UMIN000024734.

SUBMITTER: Nishiyama H

PROVIDER: S-EPMC9066086 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Characteristics of the European Thoracic Society/American Thoracic Society severe asthma definition as a determinant of future use of biologics/bronchial thermoplasty.

Nishiyama Hirono H Kanemitsu Yoshihiro Y Fukumitsu Kensuke K Takeda Norihisa N Kurokawa Ryota R Tajiri Tomoko T Ito Keima K Yap Jenifer Maries Go JMG Fukuda Satoshi S Uemura Takehiro T Ohkubo Hirotsugu H Maeno Ken K Ito Yutaka Y Oguri Tetsuya T Takemura Masaya M Niimi Akio A

Asia Pacific allergy 20220414 2

<h4>Background</h4>International guidelines define severe uncontrolled asthma. Biologics or bronchial thermoplasty (Bio/BT) are recommended for such patients.<h4>Objectives</h4>To determine which definitions of severe uncontrolled asthma are associated with an additional Bio/BT treatment in patients with severe uncontrolled asthma.<h4>Methods</h4>Consecutive 107 asthmatics (including 15 patients for whom Bio/BT was introduced within 3 months after examination), classified as treatment step 4 acc ...[more]

PMID: 35571548

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Project description:PurposeBronchial thermoplasty is approved in many countries worldwide as a non-pharmacological treatment for severe asthma. This review summarizes recent publications on the selection of patients with severe asthma for bronchial thermoplasty, predictors of a beneficial response and developments in the procedure and discusses specific issues about bronchial thermoplasty including effectiveness in clinical practice, mechanism of action, cost-effectiveness, and place in management.ResultsBronchial thermoplasty is a treatment option for patients with severe asthma after assessment and management of causes of difficult-to-control asthma, such as nonadherence, poor inhaler technique, comorbidities, under treatment, and other behavioral factors. Patients treated with bronchial thermoplasty in clinical practice have worse baseline characteristics and comparable clinical outcomes to clinical trial data. Bronchial thermoplasty causes a reduction in airway smooth muscle mass although it is uncertain whether this effect explains its efficacy since other mechanisms of action may be relevant, such as alterations in airway epithelial, gland, and/or nerve function; improvements in small airway function; or a placebo effect. The cost-effectiveness of bronchial thermoplasty is greater in countries where the costs of hospitalization and emergency department are high. The place of bronchial thermoplasty in the management of severe asthma is not certain, although some experts propose that bronchial thermoplasty should be considered for patients with severe asthma associated with non-type 2 inflammation or who fail to respond favorably to biologic therapies targeting type 2 inflammation.ConclusionBronchial thermoplasty is a modestly effective treatment for severe asthma after assessment and management of causes of difficult-to-control asthma. Asthma morbidity increases during and shortly after treatment. Follow-up studies provide reassurance on the long-term safety of the procedure. Uncertainties remain about predictors of response, mechanism(s) of action, and place in management of severe asthma.

Project description:BackgroundBronchial thermoplasty (BT) is a bronchoscopic treatment for severe asthma, of which the working mechanism and responder profile are partly unknown. The aim of this study is to analyse whether BT alters airway inflammation by epithelial gene expression, inflammatory cell counts and cytokines, and whether this relates to treatment response.MethodsIn this clinical trial, 28 severe asthma patients underwent bronchoscopy before and after treatment to obtain bronchial brushes and bronchoalveolar lavage fluid (BALF) from treated and untreated airways. RNA was extracted from bronchial brushes for transcriptome analysis, and BALF cells and cytokines were analysed. Asthma quality of life questionnaires were used to distinguish responders from non-responders. We compared results before and after treatment, between treated and untreated airways, and between responders and non-responders.ResultsGene expression of airway epithelium related to airway inflammation gene set was significantly downregulated in treated airways compared to untreated airways, although this did not differ for patients before and after treatment. No differences were observed in cell counts and cytokines, neither from the untreated compared to treated airways, nor before and after treatment. At baseline, compared to non-responders, the expression of genes related to glycolysis in bronchial epithelium was downregulated and both BALF and blood eosinophil counts were higher in responders.ConclusionLocal differences in gene sets pertaining to epithelial inflammatory status were identified between treated and untreated airways after treatment, not resulting in changes in differential cell counts and cytokine analyses in BALF. Secondly, baseline epithelial glycolysis genes and eosinophil counts in BALF and blood were different between responders and non-responders. The observations from this study demonstrate the potential impact of BT on epithelial gene expression related to airway inflammation while also identifying a possible responder profile.

Project description:BackgroundBronchial thermoplasty regulates structural abnormalities involved in airway narrowing in asthma. In the present study we aimed to investigate the effect of bronchial thermoplasty on histopathological bronchial structures in distinct asthma endotypes/phenotypes.MethodsEndobronchial biopsies (n = 450) were collected from 30 patients with severe uncontrolled asthma before bronchial thermoplasty and after 3 sequential bronchial thermoplasties. Patients were classified based on blood eosinophils, atopy, allergy and smoke exposure. Tissue sections were assessed for histopathological parameters and expression of heat-shock proteins and glucocorticoid receptor. Proliferating cells were determined by Ki67-staining.ResultsIn all patients, bronchial thermoplasty improved asthma control (p < 0.001), reduced airway smooth muscle (p = 0.014) and increased proliferative (Ki67 +) epithelial cells (p = 0.014). After bronchial thermoplasty, airway smooth muscle decreased predominantly in patients with T2 high asthma endotype. Epithelial cell proliferation was increased after bronchial thermoplasty in patients with low blood eosinophils (p = 0.016), patients with no allergy (p = 0.028) and patients without smoke exposure (p = 0.034). In all patients, bronchial thermoplasty increased the expression of glucocorticoid receptor in epithelial cells (p = 0.018) and subepithelial mesenchymal cells (p = 0.033) and the translocation of glucocorticoid receptor in the nucleus (p = 0.036). Furthermore, bronchial thermoplasty increased the expression of heat shock protein-70 (p = 0.002) and heat shock protein-90 (p = 0.001) in epithelial cells and decreased the expression of heat shock protein-70 (p = 0.009) and heat shock protein-90 (p = 0.002) in subepithelial mesenchymal cells. The effect of bronchial thermoplasty on the expression of heat shock proteins -70 and -90 was distinctive across different asthma endotypes/phenotypes.ConclusionsBronchial thermoplasty leads to a diminishment of airway smooth muscle, to epithelial cell regeneration, increased expression and activation of glucocorticoid receptor in the airways and increased expression of heat shock proteins in the epithelium. Histopathological effects appear to be distinct in different endotypes/phenotypes indicating that the beneficial effects of bronchial thermoplasty are achieved by diverse molecular targets associated with asthma endotypes/phenotypes.

Dataset Information

Characteristics of the European Thoracic Society/American Thoracic Society severe asthma definition as a determinant of future use of biologics/bronchial thermoplasty.

Background

Objectives

Methods

Results

Conclusion

Trial registration

Publications

Characteristics of the European Thoracic Society/American Thoracic Society severe asthma definition as a determinant of future use of biologics/bronchial thermoplasty.

Similar Datasets

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