Airway Inflammation after Bronchial Thermoplasty for Severe Asthma

Denner, Darcy R.; Doeing, Diana; Hogarth, D. Kyle; Dugan, Karen; Naureckas, Edward T.; White, Steven R.

doi:10.1513/annalsats.201502-082oc

Cited by 88 publications

(79 citation statements)

References 57 publications

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“…Moreover, several studies using endobronchial biopsies in humans with asthma have demonstrated consistent reductions in ASM following BT. [124][125][126] Other effects on airway remodeling include decreased type 1 collagen deposition and a reduction in reticular basement membrane thickness which persist longterm. 124,126 Bronchial epithelial structure, however, is not modified.…”

Section: Discussionmentioning

confidence: 99%

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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RATIONALE: While severe asthma affects approximately 5% of all individuals with asthma, this small minority of individuals accounts for a large proportion of the asthma-related costs. Greater understanding of the pathophysiology of asthma combined with the emergence of novel biologic therapies for severe asthma supported the need for a thorough review of the diagnosis, investigation, phenotyping, and management of severe asthma. OBJECTIVES: We aimed to propose a practical approach to distinguish uncontrolled asthma due to inadequate asthma management from severe asthma despite optimal asthma management. Moreover, based on emerging scientific evidence, we sought to provide guidance for characterizing individuals with severe asthma and considering a phenotype-specific management. We also aimed to review other novel new potential therapeutic approaches. METHODS: We systematically reviewed the relevant literature focusing on randomized controlled trials and when available, systematic reviews of randomized controlled trials. The proposed key messages, based on scientific evidence and expert opinion, were agreed upon by unanimous consensus. MAIN RESULTS: We defined severe asthma and outlined its significant impact from the societal and patient perspectives. We outlined a practical approach to distinguish severe from uncontrolled but not severe asthma, based on stepwise investigation and management of potential reasons for uncontrolled asthma. After reviewing the current evidence we concluded that: 1) Several biomarkers (e.g. sputum or blood eosinophil count, total IgE, or FeNO) can help identify potential responders to new therapeutic options; 2) Tiotropium may be considered as an add-on therapy for individuals 12 years of age and over with severe asthma uncontrolled despite combination ICS/LABA therapy; 3) The chronic use of macrolides may decrease asthma exacerbations in individuals 18 years of age and over with severe asthma independent of their inflammatory profile; 4) Children aged 6 years and older and adults who are sensitized to at least one relevant perennial allergen and who remain poorly controlled asthmatics despite high dose ICS and a second controller can benefit from the addition of anti-IgE therapy to reduce asthma exacerbations; due to the known risk of side effects associated with high-dose ICS in children, omalizumab should also be considered in children and adolescents who repeatedly exacerbate or have poor control when therapy is stepped down from high-dose to moderate-dose ICS and at least one other controller; 5) Anti-IL5 therapies may be considered for adults 18 years of age and over with severe eosinophilic asthma who experience recurrent asthma exacerbations in spite of high doses of ICS in addition to at least one other controller; and 6) Although bronchial thermoplasty has shown a decrease in asthma exacerbations in one study, its role in the treatment of severe asthma remains uncertain. CONCLUSIONS: After reviewing existing and emerging therapies for severe asthma, we developed ke...

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Section: Discussionmentioning

confidence: 99%

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

FitzGerald

Lemière

Lougheed

et al. 2017

Canadian Journal of Respiratory, Critical Care, and Sleep Medic

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“…Owing to the fact that ASM secretes proinflammatory compounds, any effective reduction of ASM by BT would play an immediate role in the downregulation of those mediators in the airway wall. Disappointingly, current studies have already shown that neutrophilic asthma-related cytokines, including IL-17 and TNF-α, were not significantly changed after BT intervention [39]. Also, no benefits have been found in the percentage of neutrophils in bronchi biopsies with BT treatment [40].…”

Section: Treatment Of Neutrophil-dominant Severe Asthmamentioning

confidence: 82%

Targeting Neutrophils in Severe Asthma via Siglec-9

Chen

Bai

Han

et al. 2018

Int Arch Allergy Immunol

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Severe asthma comprises only 5% of patients with asthma, but the burden it brings to the social health system accounts for more than half of all asthmatics. Clinical evidence shows that severe asthma is often linked to the recruitment and activation of neutrophils in the airways. However, the underlying molecular and immunological mechanisms of neutrophilia in severe asthma are not clear and currently available drugs exert only limited effects on neutrophilic inflammation. Great efforts are underway to address the mystery of neutrophilic inflammation in chronic respiratory disorders. Sialic acid-binding immunoglobulin-like lectins (Siglecs) are members of the immunoglobulin gene family. Of note, Siglec-9 is uniquely expressed by human neutrophils and monocytes, as well as a minor population of natural killer cells. Engaging this structure with antibodies or glycan ligands results in programmed cell death in human neutrophils. Intriguingly, the administration of Siglec-E antibody abolished the recruitment of neutrophils in mouse models of neutrophilic pulmonary inflammation in vivo. Given that neutrophils are probably a major culprit in the generation and perpetuation of inflammation, targeting Siglec-9 could be beneficial for the treatment of severe asthma, chronic obstructive pulmonary disease, and related pulmonary disorders characteristic of neutrophilia.

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“…: assessed using different asthma symptom questionnaires (Asthma Control Questionnaire [12,16], Asthma Control Test [15] and Asthma Control Scoring System [13,14] versus 52%) and hospitalisations (15.3% versus 4.2%) in the 12 months prior to bronchial thermoplasty, had more subjects with chronic sinus disease (30.4% versus 18.4%) and had a larger number assessed as having severe asthma (94.7% versus 82.1%). Previous observation studies have also noted that patients treated with bronchial 3thermoplasty in clinical practice have more severe disease than those recruited to AIR and AIR2 trials [12][13][14][15][16][17][18] (table 2). The British Thoracic Society (BTS) Difficult Asthma Registry and Hospital Episodes Statistics database of 59 patients with severe refractory asthma undergoing bronchial thermoplasty in clinical practice between 2011 and 2015 reported that bronchial thermoplasty patients were, on average, older, and had worse baseline forced expiratory volume in 1 s (FEV1) and lower AQLQ scores compared with published clinical trials [19].…”

mentioning

confidence: 90%

“…Published information on the effectiveness of bronchial thermoplasty in clinical practice is limited to a few small case series from Australia, Canada, France, the UK and the USA (table 2) [12][13][14][15][16][17][18], and from a UK national registry [19]. In this issue of the European Respiratory Journal, CHUPP et al [11], describe the interim 3-year results of the Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) study, which is a prospective, open-label, multicentre, observational post-market study mandated by the FDA to evaluate the durability of the treatment effect, and the short and long-term efficacy and safety of the procedure.…”

mentioning

confidence: 99%

How effective is bronchial thermoplasty for severe asthma in clinical practice?

Thomson

Chanez

2017

Eur Respir J

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@ERSpublications Bronchial thermoplasty can be effective in patients who often have features of more severe asthma than in AIR2 http://ow.ly/Qv5730cTIuBCite this article as: Thomson NC, Chanez P. How effective is bronchial thermoplasty for severe asthma in clinical practice? Eur Respir J 2017; 50: 1701140 [https://doi.org/10.1183/13993003.01140-2017.Bronchial thermoplasty is an intervention developed for the treatment of asthma through the delivery of radio frequency energy to the airways [1,2]. Evidence for the efficacy and safety of bronchial thermoplasty in severe asthma is based on the results of three randomised controlled trials [3][4][5]. Two trials compared bronchial thermoplasty with usual care, the Asthma Intervention Research (AIR) trial [3] and the Research in Severe Asthma (RISA) trial [4], whereas the third trial (AIR2) compared bronchial thermoplasty with a sham procedure [5]. The AIR2 trial reported improved asthma quality of life questionnaire (AQLQ) scores, reduced severe exacerbations and decreased emergency department visits in the post-bronchial thermoplasty treatment period [5]. Bronchial thermoplasty was associated with a short-term increase in asthma-related symptoms and hospital admissions for asthma during the treatment phase [3][4][5]. Follow-up observational studies to date support the long-term safety of the procedure, based on unchanged rates of respiratory adverse events, lung function, serial computed tomography scans and rates of hospital admissions or emergency department visits in years 2-5 following the AIR [6], RISA [7] and AIR2 trials [8]. A Cochrane systematic review of the trials concluded that there was a modest clinical benefit in asthma quality of life and a reduction in exacerbation rates 12 months after bronchial thermoplasty [9]. In 2010, the Food and Drug Administration (FDA) gave premarket approval for the Alair bronchial thermoplasty system (Boston Scientific, Marlborough, MA, USA) as a treatment for severe persistent asthma in patients 18 years and older whose asthma is not well controlled with inhaled corticosteroids and a long-acting β-agonist [10]. Bronchial thermoplasty is also approved for the treatment of asthma in the European Union and in many countries worldwide.

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Airway Inflammation after Bronchial Thermoplasty for Severe Asthma

Cited by 88 publications

References 57 publications

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Recognition and management of severe asthma: A Canadian Thoracic Society position statement

Targeting Neutrophils in Severe Asthma via Siglec-9

How effective is bronchial thermoplasty for severe asthma in clinical practice?

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