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Bronchial thermoplasty (BT) is a treatment for moderate-to-severe asthma in which the airway smooth muscle layer is targeted directly using thermal ablation. Although it has been shown to be safe and effective in long-term follow-up, questions remain about its mechanism of action, patient selection, and optimization of protocol based on structural phenotype. Using a cohort of 20 subjects who underwent thermoplasty and assessment by computed tomography (CT), we demonstrate that response to BT can be feasibly predicted based on pretreatment airway dimensions that inform a subject-specific computational model. Analysis revealed the need for CT assessment at total lung capacity, rather than functional residual capacity, which was less sensitive to the effects of BT. Final model predictions compared favorably with observed outcomes in terms of airway caliber and asthma control, suggesting that this approach could form the basis of improved clinical practice.

Asthma continues to be a prevalent respiratory disease that affects lives within the United States and worldwide. Clinical asthma guidelines based on scientific evidence on testing and therapeutic interventions are needed to control this disease better. To meet this need, the NAEPP (National Asthma Education and Prevention Program) and GINA (Global Initiative for Asthma) were formed to assist with best practice diagnosis and treatments for asthma. This paper reviews the subtle differences and similarities between the most recent recommendations put forth by NAEPP 2020 and GINA 2021, mainly examining the six selected topics, as well as methodology, guidance on emerging topics, and implementation.In December 2020, the National Asthma Education and Prevention Program Coordinating Committee released their focused update on fraction of exhaled nitric oxide, indoor allergen mitigation, inhaled corticosteroids, long-acting muscarinic antagonists, allergen immunotherapy, and bronchial thermoplasty. The Global Initiative for Asthma comprehensive document is published annually as a framework for all nations. Therefore, it is timely to consider the National Asthma Education and Prevention Program Coordinating Committee 2020 in relation to the GINA 2021.The comparison provides a better understanding of evidence-based recommendations for asthma. The NAEPP 2020 and GINA 2021 will equip providers with the knowledge to provide their patients with the best and most updated asthma care.

The 2020 National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group (NAEPP [2020 Focused Asthma Update]) guidelines and the Global Initiative for Asthma (GINA) 2021 strategy report are compared in this Rostrum article. The methodologies of each publication are described. Subsequently, 4 different selected pharmacological recommendations are compared in the 2 documents: step 1 for children 0 to 4 years of age with viral-induced wheezing, step 2 in ages 12 years and older with the intermittent use of inhaled corticosteroid, steps 3 and 4 with single-inhaler maintenance and reliever therapy with inhaled corticosteroids-formoterol (SMART), and steps 3, 4, and 5 with add-on long-acting muscarinic antagonist therapy. Nonpharmacological recommendations are also considered and contrasted, including for exhaled nitric oxide, environmental control, immunotherapy, and bronchial thermoplasty. Similarities and differences in these 2 documents are highlighted, and recommendations are made about harmonizing the approaches where possible.

Background The effects of bronchial thermoplasty (BT) on smooth muscle (SM) and nerves in small airways are unclear. Methods We recruited 15 patients with severe refractory asthma, who received BT treatment. Endobronchial optical-coherence tomography (EB-OCT) was performed at baseline, 3 weeks' follow-up and 2 years' follow-up to evaluate the effect of BT on airway structure. In addition, we divided 12 healthy beagles into a sham group and a BT group, the latter receiving BT on large airways (inner diameter >3 mm) of the lower lobe. The dogs’ lung lobes were resected to evaluate histological and neuronal changes of the treated large airways and untreated small airways 12 weeks after BT. Results Patients receiving BT treatment had significant improvement in Asthma Control Questionnaire (ACQ) scores and significant reduction in asthma exacerbations. EB-OCT results demonstrated a notable increase in inner-airway area (Ai) and decrease in airway wall area percentage (Aw%) in both large (3rd-to 6th-generation) and small (7th-to 9th-generation) airways. Furthermore, the animal study showed a significant reduction in the amount of SM in BT-treated large airways but not in untreated small airways. Protein gene product 9.5 (PGP9.5)–positive nerves and muscarinic receptor 3 (M3 receptor) expression in large and small airways were both markedly decreased throughout the airway wall 12 weeks after BT treatment. Conclusions BT significantly reduced nerves, but not SM, in small airways, which might shed light on the mechanism of lung denervation by BT.

Asthma is a complex, heterogeneous chronic airway disease with high prevalence of uncontrolled disease. New therapies, including biologics, are now available to treat T2 high asthma. Treatment of T2 low asthma remains a challenge. Asthma guidelines need be to updated to incorporate new therapeutics.

Background: Asthma is a heterogeneous disease with differences in onset, severity, and inflammation. Bronchial epithelial cells (BECs) contribute to asthma pathophysiology.Objective: We determined whether transcriptomes of BECs reflect heterogeneity in inflammation and severity in asthma, and whether this was affected in BECs from patients with severe asthma after their regeneration by bronchial thermoplasty.Methods: RNA sequencing was performed on BECs obtained by bronchoscopy from healthy controls (n = 16), patients with mild asthma (n = 17), patients with moderate asthma (n = 5), and patients with severe asthma (n = 17), as well as on BECs from treated and untreated airways of the latter (also 6 months after bronchial thermoplasty) (n = 23). Lipidome and metabolome analyses were performed on cultured BECs from healthy controls (n = 7); patients with severe asthma (n = 9); and, for comparison, patients with chronic obstructive pulmonary disease (n = 7).Results: Transcriptome analysis of BECs from patients showed a reduced expression of oxidative phosphorylation (OXPHOS) genes, most profoundly in patients with severe asthma but less profoundly and more heterogeneously in patients with mild asthma. Genes related to fatty acid metabolism were significantly upregulated in asthma. Lipidomics revealed enhanced levels of lipid species (phosphatidylcholines, lysophosphatidylcholines. and bis(monoacylglycerol)phosphate), whereas levels of OXPHOS metabolites were reduced in BECs from patients with severe asthma. BECs from patients with mild asthma characterized by hyperresponsive production of mediators implicated in neutrophilic inflammation had decreased expression of OXPHOS genes compared with that in BECs from patients with mild asthma with normoresponsive production. BECs obtained after thermoplasty had significantly increased expression of OXPHOS genes and decreased expression of fatty acid metabolism genes compared with BECs obtained from untreated airways.Conclusion: BECs in patients with asthma are metabolically different from those in healthy individuals. These differences are linked with inflammation and asthma severity, and they can be reversed by bronchial thermoplasty.

Severe asthma is associated with frequent hospital visits and impact in quality of life as well as healthcare associated costs. Limited treatment modalities exist to assist in reduction of frequent exacerbations in patients with severe asthma who are already on maximum inhaler therapy. As supporting data becomes more robust, novel treatments have gained attention such as bronchial thermoplasty and immune-directed therapies.Based on review of recent studies, bronchial thermoplasty poses itself as a potential intervention for severe asthma, demonstrating a decrease in asthma exacerbations with long term clinical effect and safety profile at the expense of temporary uncontrolled asthma symptoms for the first six weeks following the procedure.In select patients with severe asthma, bronchial thermoplasty is a well tolerated and effective treatment to reduce asthma exacerbation.

Background:. The effectiveness of bronchial thermoplasty (BT) has been reported in patients with severe asthma. This study compared the effects of BT and cryoballoon ablation (CBA) therapy on the airway smooth muscle (ASM). Methods:. Eight healthy male beagle dogs were included in this experiment. In the preliminary experiment, one dog received BT treatment for both lower lobe bronchus, another dog received CBA treatment for 7 s on the upper and lower lobe of right bronchus, and 30 s on the left upper and lower lobe. The treatments were performed twice at an interval of 1 month. In subsequent experiments, the right lower lobe bronchus was treated with BT, and the left lower lobe bronchus was treated with CBA. The effects of treatment were observed after 1 (n = 3) month and 6 months (n = 3). Hematoxylin-eosin staining, Masson trichrome staining, and immunohistochemical staining were used to compare the effects of BT and CBA therapy on the ASM thickness, collagen fibers synthesis, and M3 receptor expression after treatment. One-way analysis of variance with Dunnett post hoc test was used to analyze the differences among groups. Results:. In the preliminary experiment, the ASM ablation effect of 30-s CBA was equivalent to that of 7-s CBA (ASM thickness: 30.52 ± 7.75 μm vs. 17.57 ± 15.20 μm, P = 0.128), but the bronchial mucociliary epithelium did not recover, and large numbers of inflammatory cells had infiltrated the mucosal epithelium at 1-month post-CBA with 30-s freezing. Therefore, we chose 7 s as the CBA treatment time in our follow-up experiments. Compared with the control group (35.81 ± 11.02 μm), BT group and CBA group (13.41 ± 4.40 μm and 4.81 ± 4.44 μm, respectively) had significantly decreased ASM thickness after 1 month (P

Despite the availability of effective medications, the majority of pediatric and adult patients with persistent asthma have uncontrolled symptoms. This has been attributed to patient nonadherence and poor self-management, but clinicians also contribute through inaccurate assessment of asthma and lack of familiarity with best practice guidelines for medication management. Thus, improving patient outcomes will require improving clinical management by health care providers, including utilization of evidence-based practice guidelines. In this report, we briefly summarize key points of the national guidelines for asthma management and delineate important changes enacted by 2020 Expert Panel Report-4 updates. These include revised recommendations on the use of fractional exhaled nitric oxide testing, indoor allergen mitigation, bronchial thermoplasty, adjunctive immunotherapy, and important modifications to medication management that are likely to have widespread impact on prescribing throughout the United States. In particular, for all patients aged five years and older taking stepwise therapy levels 3-4, it is now recommended to use Single Maintenance and Reliever Therapy, whereas the use of intermittent inhaled corticosteroids (ICSs) administered at the same time as short-acting beta agonist is recommended for step 2 to reduce symptom burden, improve control, and minimize total ICS dose.

The inability to assess and measure changes to the airway smooth muscle (ASM) in vivo is a major challenge to evaluating asthma and its clinical outcomes. Bronchial thermoplasty (BT) is a therapy for asthma that aims to reduce the severity of excessive bronchoconstriction by ablating ASM. Although multiple long-term clinical studies of BT have produced encouraging results, the outcomes of BT treatment in practice have been variable, and questions remain regarding the selection of patients. Previously, we have demonstrated an imaging platform called orientation-resolved optical coherence tomography that can assess ASM endoscopically using an imaging catheter compatible with bronchoscopy. In this work, we present results obtained from a longitudinal BT study performed using a canine model (n = 8) and with the goal of investigating the use of orientation-resolved optical coherence tomography (OR-OCT) for measuring the effects of BT on ASM. We demonstrate that we are capable of accurately assessing ASM both before and in the weeks following the BT procedure using blinded matching to histological samples stained with Masson’s trichrome (P < 0.0001, r(2) = 0.79). Analysis of volumetric ASM distributions revealed significant decreases in ASM in treated airways (average cross-sectional ASM area: 0.245 ± 0.145 mm(2) pre-BT and 0.166 ± 0.112 mm(2) 6 wk following BT). These results demonstrate that OR-OCT can provide clinicians with the feedback necessary to better evaluate ASM and its response to BT, and may potentially play an important role in phenotyping asthma and predicting which patients are most likely to respond to BT treatment. NEW & NOTEWORTHY The inability to assess ASM in vivo is a significant hurdle in advancing our understanding of airway diseases such as asthma, as well as evaluating potential treatments and therapies. In this study, we demonstrate that endoscopic OR-OCT can be used to accurately measure changes to ASM structure following BT. Our results demonstrate how this technology could occupy an important role in asthma treatments targeting ASM.

Methods BT10+ was an international, multicentre, follow-up study of participants who were previously enrolled in the AIR, RISA, and AIR2 trials and who had 10 or more years of follow-up since bronchial thermoplasty treatment. Data on patient demographics, quality of life, lung function, CT scans (AIR2 participants only), severe exacerbations, and health-care use during the previous year were collected at the BT10+ 10-year outcomes study visit. The primary effectiveness endpoint was durability of the thermoplasty treatment effect, determined by comparing the proportion of participants who had severe exacerbations during the first and fifth years after bronchial thermoplasty treatment with the proportion of participants who had severe exacerbations during the 12-month period before the BT10+ visit. The primary safety endpoint was the absence of clinically significant post-treatment respiratory image changes after bronchial thermoplasty, defined as bronchiectasis or bronchial stenosis as confirmed by pulmonary volumetric highresolution CT scan at the BT10+ visit (AIR2 participants only). All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03243292. The last patient was enrolled on Dec 11, 2018. The last patient completed follow-up on Jan 10, 2019.Findings The BT10+ study enrolled 192 (45%) of the 429 participants who were enrolled in the AIR, RISA, and AIR2 trials. The BT10+ participants comprised 136 who received bronchial thermoplasty (52% of the 260 participants who received bronchial thermoplasty in the original trials), and 56 sham or control participants (33% of 169 from the original trials). 18 (32%) sham or control participants received bronchial thermoplasty after the previous trials concluded. The participants included in BT10+ were followed for 10?8?15?6 years (median 12?1 years) post-treatment. Baseline characteristics were similar between participants enrolled in BT10+ and those not enrolled. Participants treated with bronchial thermoplasty had similar proportions of severe exacerbations at the BT10+ visit (34 [25%] of 136 participants) compared with 1 year (33 [24%] of 135 participants; difference 0?6%, 95% CI ?9?7 to 10?8) and 5 years (28 [22%] of 130 participants; difference 3?5%, ?6?7% to 13?6) after treatment. Quality of life measurements and spirometry were similar between year 1, year 5, and the BT10+ visit. At the BT10+ study visit, pulmonary high-resolution CT scans from AIR2 participants treated with bronchial thermoplasty showed that 13 (13%) of 97 participants had bronchiectasis. When compared with baseline high-resolution CT scans, six (7%) of 89 participants treated with bronchial thermoplasty who did not have bronchiectasis at baseline had developed bronchiectasis after treatment (5 classified as mild, 1 classified as moderate). Participants treated with bronchial thermoplasty after the original study and participants in the sham or control group also had reductions in severe exacerbations at the BT10+ visit compared with baseline.Summary Background Bronchial thermoplasty is an endoscopic treatment for uncontrolled asthma. Previous randomised clinical trials have shown that bronchial thermoplasty reduces severe exacerbations in people with asthma. However, the long-term efficacy and safety of bronchial thermoplasty beyond 5 years is unknown. The BT10+ study aimed to investigate the efficacy and safety of bronchial thermoplasty after 10 or more years of follow-up. Methods BT10+ was an international, multicentre, follow-up study of participants who were previously enrolled in the AIR, RISA, and AIR2 trials and who had 10 or more years of follow-up since bronchial thermoplasty treatment. Data on patient demographics, quality of life, lung function, CT scans (AIR2 participants only), severe exacerbations, and health-care use during the previous year were collected at the BT10+ 10-year outcomes study visit. The primary effectiveness endpoint was durability of the thermoplasty treatment effect, determined by comparing the proportion of participants who had severe exacerbations during the first and fifth years after bronchial thermoplasty treatment with the proportion of participants who had severe exacerbations during the 12-month period before the BT10+ visit. The primary safety endpoint was the absence of clinically significant post-treatment respiratory image changes after bronchial thermoplasty, defined as bronchiectasis or bronchial stenosis as confirmed by pulmonary volumetric high resolution CT scan at the BT10+ visit (AIR2 participants only). All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT03243292. The last patient was enrolled on Dec 11, 2018. The last patient completed follow-up on Jan 10, 2019. Findings The BT10+ study enrolled 192 (45%) of the 429 participants who were enrolled in the AIR, RISA, and AIR2 trials. The BT10+ participants comprised 136 who received bronchial thermoplasty (52% of the 260 participants who received bronchial thermoplasty in the original trials), and 56 sham or control participants (33% of 169 from the original trials). 18 (32%) sham or control participants received bronchial thermoplasty after the previous trials concluded. The participants included in BT10+ were followed for 10middot8-15middot6 years (median 12middot1 years) post-treatment. Baseline characteristics were similar between participants enrolled in BT10+ and those not enrolled. Participants treated with bronchial thermoplasty had similar proportions of severe exacerbations at the BT10+ visit (34 [25%] of 136 participants) compared with 1 year (33 [24%] of 135 participants; difference 0middot6%, 95% CI -9middot7 to 10middot8) and 5 years (28 [22%] of 130 participants; difference 3middot5%, -6middot7% to 13middot6) after treatment. Quality of life measurements and spirometry were similar between year 1, year 5, and the BT10+ visit. At the BT10+ study visit, pulmonary high-resolution CT scans from AIR2 participants treated with bronchial thermoplasty showed that 13 (13%) of 97 participants had bronchiectasis. When compared with baseline high-resolution CT scans, six (7%) of 89 participants treated with bronchial thermoplasty who did not have bronchiectasis at baseline had developed bronchiectasis after treatment (5 classified as mild, 1 classified as moderate). Participants treated with bronchial thermoplasty after the original study and participants in the sham or control group also had reductions in severe exacerbations at the BT10+ visit compared with baseline.Interpretation Our findings suggest that efficacy of bronchial thermoplasty is sustained for 10 years or more, with an acceptable safety profile. Therefore, bronchial thermoplasty is a long-acting therapeutic option for patients with asthma that remains uncontrolled despite optimised medical treatment. Funding Boston Scientific. Copyright (c) 2021 Elsevier Ltd. All rights reserved.

Bronchial thermoplasty (BT) is a treatment for moderate-to-severe asthma, which generally improves quality-of-life scores but not conventional measures of lung function. Newer methodologies have begun to demonstrate the underlying physiological changes and elucidate the mechanism of action. We postulated that systematic, computed tomography (CT)-based assessment of the response of

Bronchial asthma is characterized by chronic airway inflammation, which manifests clinically as variable airway narrowing (wheezes and dyspnea) and cough. Long-standing asthma may induce airway remodeling and become intractable. The prevalence of asthma has increased; however, the number of patients who die from it has decreased (1.3 per 100,000 patients in 2018). The goal of asthma treatment is to control symptoms and prevent future risks. A good partnership between physicians and patients is indispensable for effective treatment. Long-term management with therapeutic agents and the elimination of the triggers and risk factors of asthma are fundamental to its treatment. Asthma is managed by four steps of pharmacotherapy, ranging from mild to intensive treatments, depending on the severity of disease; each step includes an appropriate daily dose of an inhaled corticosteroid, which may vary from low to high. Long-acting β2-agonists, leukotriene receptor antagonists, sustained-release theophylline, and long-acting muscarinic antagonists are recommended as add-on drugs, while anti-immunoglobulin E antibodies and other biologics, and oral steroids are reserved for very severe and persistent asthma related to allergic reactions. Bronchial thermoplasty has recently been developed for severe, persistent asthma, but its long-term efficacy is not known. Inhaled β2-agonists, aminophylline, corticosteroids, adrenaline, oxygen therapy, and other approaches are used as needed during acute exacerbations, by selecting treatment steps for asthma based on the severity of the exacerbations. Allergic rhinitis, eosinophilic chronic rhinosinusitis, eosinophilic otitis, chronic obstructive pulmonary disease, aspirin-exacerbated respiratory disease, and pregnancy are also important conditions to be considered in asthma therapy.

Background Bronchial thermoplasty (BT) is a novel bronchoscopic intervention for severe persistent asthma. An increase in transient respiratory adverse events associated with BT were noted over the treatment periods, however, these events appear sporadic and should not always recur in a single individual and BT-related pneumonia has rarely been reported. Case presentation We present a case of uncontrolled severe asthma who developed puzzling pneumonia sequentially after each session of BT procedures. After each operation of three sequential BT procedures, she developed cough and purulent expectoration when her chest radiology showed new infiltrates right in the treatment regions. After empirical use of antibacterial agents plus physiotherapy and postural sputum drainage, her symptoms vanished and chest imaging resumed normal. Conclusion The originality of our case report is related to the recurrence of pneumonia after three sequential BT procedures. To date, similar report has not been available in the literature. We hope to prompt alerts for post-BT respiratory infections, although most of them, along with other adverse events, are mild and tractable.

Introduction: Bronchial thermoplasty (BT) improves asthma-related quality of life and decreases the number of asthma exacerbations. However, the effectiveness of BT in the treatment of severe asthma with smoking history is unclear because previous studies have excluded patients with smoking history of more than 10 pack-years. Objective: The aim of the study was to clarify the effectiveness and safety of BT for severe asthma with smoking history. Methods: We retrospectively reviewed patients who received BT and compared its effectiveness and safety with and without smoking history. Results: Seven patients were assigned to the smoking group and 9 to the nonsmoking group. Before BT, despite Global Initiative for Asthma step 4 or 5 treatment including oral corticosteroids (OCS) or monoclonal antibody drugs, most patients in both groups had asthma-related symptoms every day (85.7 vs. 77.8%; p = 0.475) and frequent asthma exacerbations. After BT, in the smoking group, 3 patients could discontinue or reduce OCS and all 3 patients treated with monoclonal antibody drugs could discontinue them. In the smoking group, 6 patients (85.7%) experienced a reduction in the rate of symptoms, of which 3 patients (42.9%) had a disappearance of symptoms, similar to the nonsmoking group. BT was effective in 5 patients (83.3%) in the smoking group and 6 patients (75.0%) in the nonsmoking group. There were no severe complications. Conclusions: BT was found to be effective and safe for treatment of severe asthma with smoking history. Our results suggest that BT may be a therapeutic option for asthma-chronic obstructive pulmonary disease overlap.

Since the publication of a sham-controlled, randomized trial (AIR2) and subsequent marketing approval by the US Food and Drug Administration, we have significantly advanced our understanding of bronchial thermoplasty (BT)'s scientific basis, long-term safety, clinical efficacy and cost-effectiveness. In particular, the last 2 years have witnessed multiple research publications on several of these counts. In this review, we critically appraise our evolving understanding of BT's biologic underpinnings and clinical impact, offer an evidence-based patient workflow guide for the busy pulmonologist and highlight both current challenges as well as potential solutions for the researcher and the clinician.

ObjectivesBronchial thermoplasty (BT) is a device-based treatment for subjects ≥18 years with severe asthma not well controlled with inhaled corticosteroids and long-acting beta-agonists. The Bronchial Thermoplasty Global Registry (BTGR) collected real-world data on subjects undergoing this procedure.DesignThe BTGR is an all-comer, prospective, open-label, multicentre study enrolling adult subjects indicated for and treated with BT.SettingEighteen centres in Spain, Italy, Germany, the UK, the Netherlands, the Czech Republic, South Africa and AustraliaParticipantsOne hundred fifty-seven subjects aged 18 years and older who were scheduled to undergo BT treatment for asthma. Subjects diagnosed with other medical conditions which, in the investigator’s opinion, made them inappropriate for BT treatment were excluded.Primary and secondary outcome measuresBaseline characteristics collected included demographics, Asthma Quality of Life Questionnaire (AQLQ), Asthma Control Test (ACT), medication usage, forced expiratory volume in one second and forced vital capacity, medical history, comorbidities and 12-month baseline recall data (severe exacerbations (SE) and healthcare utilisation). SE incidence and healthcare utilisation were summarised at 1 and 2 years post-BT.ResultsSubjects’ baseline characteristics were representative of persons with severe asthma. A comparison of the proportion of subjects experiencing events during the 12 months prior to BT to the 2-year follow-up showed a reduction in SE (90.3% vs 56.1%, pConclusionsThe BTGR demonstrates sustained improvement in clinical outcomes and reduction in asthma medication usage 2 years after BT in a real-world population. This is consistent with results from other BT randomised controlled trials and registries and further supports improvement in asthma control after BT.Trial registration numberNCT02104856.

Background Bronchial thermoplasty (BT) is a novel endoscopic therapy for severe asthma. Traditionally it is performed in three separate treatment sessions, targeting different portions of the lung, and each requires an anaesthetic and hospital admission. Compression of treatment into 2 sessions would present a more convenient alternative for patients. In this prospective observational study, the safety of compressing BT into two treatment sessions was compared with the traditional 3 treatment approach. Methods Sixteen patients meeting ERS/ATS criteria for severe asthma consented to participate in an accelerated treatment schedule (ABT), which treated the whole left lung followed by the right lung four weeks later. The short-term outcomes of these patients were compared with 37 patients treated with conventional BT scheduling (CBT). The outcome measures used to assess safety were (1) the requirement to remain in hospital beyond the electively planned 24-h admission and (2) the need for re-admission for any cause within of 30 days of treatment. Results The total number of radiofrequency activations delivered in the ABT group was similar to CBT (187 ± 21 vs 176 ± 40, p = 0.326). With ABT, 11 in 31 admissions (37.9%) required prolonged admission due to wheezing, compared to 5.4% with CBT (p = 0.0025). The mean hospital length of stay with ABT was 1.8 ± 1.3 days, compared to 1.1 ± 0.4 days (p Conclusion This study demonstrates that ABT results in greater short-term deterioration in lung function associated with a greater risk of prolonged hospital and ICU stay, predominantly affecting females. Therefore, in females, these risks need to be balanced against the convenience of fewer treatment sessions. In males, it may be an advantage to compress treatment.

Purpose of review The field of interventional pulmonology has ushered in a wave of innovations for individuals with obstructive airways disease in whom established medical therapies have failed. Leading the charge are bronchial thermoplasty for severe refractory asthma and uni-directional valves for severe emphysema with hyperinflation: both have received regulatory approvals in the United Kingdom and United States. With the commissioning of these novel treatments comes new challenges relating to implementation, positioning within therapeutic algorithms, honing of patient selection, and establishing long-term safety and benefits beyond 5 years. Recent findings This review summarises the evidence for their safety and efficacy, predictors of therapeutic response, mechanism(s) of action and emerging data supporting the durability of outcomes out to at least ten years. Summary It is anticipated the experience of treating increasing numbers of patients, the adoption of international registries, and ongoing research evaluations will serve to optimise these therapies for future generations of patients.

KEY TAKEAWAYS • The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group provides updated recommendations for 6 topics related to the management of individuals with asthma. • The classification of asthma severity and asthma control, as well as the concept of utilizing a stepwise approach to pharmacologic treatment, were not updated from the Expert Panel Report 3, released in 2007. • However, important updates in preferred therapies for intermittent and persistent asthma at treatment steps 1 through 5 were suggested. • Recommendations regarding biologic therapy were not included in the 2020 update, as only evidence and US Food and Drug Administration approvals through October 2018 were considered. • The most recent 2021 Global Initiative for Asthma guidelines are not included in this review but can be used in a complementary manner to assist primary care clinicians to optimize decisions regarding the care of patients with asthma.

Breathlessness is a subjective symptom that may stem from a number of pathological and functional aetiologies. Consequently, clinicians are often faced with the challenge of navigating between the tensions of Occam9s razor (parsimonious aetiology) or Hickam9s dictum (multiple diagnoses). We report a case of a 36-year-old woman with a lifelong history of episodic breathlessness caused at various times by dysfunctions of lung parenchyma (emphysema) and airway smooth muscle (asthma), skeletal muscle (filamin-C fibrillary myopathy) and cardiac muscle (cardiomyopathy). We illustrate the utility of the modern diagnostic toolbox in the assessment, understanding and management of complex dyspnoea (including the use of inflammometry, inhaled-gas magnetic resonance imaging-guided bronchial thermoplasty, and genetic testing), and also demonstrate the importance of interdisciplinary data interpretation in establishing accurate aetiologic diagnoses.

Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best-defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non-type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point-of-care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.

Bronchial thermoplasty (BT), which delivers thermal radiofrequency to the bronchial wall, is an effective therapy for patients with severe persistent uncontrolled asthma. We herein report the case of a 47-year-old man who underwent BT for uncontrolled severe asthma. After BT, his asthma control, asthma-related quality of life, and pulmonary function improved. Furthermore, a histologic examination of transbronchial biopsy specimens revealed a decrease in goblet cell hyperplasia and the smooth muscle mass as well as in the subepithelial basement membrane thickness. BT can be effective for patients with severe uncontrolled asthma and mucus hypersecretion.

Bronchial Thermoplasty (BT) is indicated in patients suffering from severe and symptomatic bronchial asthma despite maximal medical therapy. However, treatment of the right middle lobe (RML) bronchus is currently not recommended. The aim of this study was to investigate the safety and efficacy of BT if the RML bronchus is included. BT was performed in 17 consecutive patients, quality of life and pulmonary function were characterized before and 90 days after BT completion. Furthermore, we performed a clean-up bronchoscopy following every BT. This study was approved by the IRB of the University of Essen (No. 17-7356 BO) and registered as a retrospective observational study at the German Clinical Trials Registry (No. DRKS 00011550). The median baseline values of FEV1 and Asthma Questionnaire of Life Quality (AQLQ) were 1.33 l (0.91; 1.73) and 3.01 (2.76; 3.61), respectively, and significantly improved 90 days after treatment with FEV 1 at 1.75 l (p-value 0.002) and AQLQ 3.8 (p-value

We investigated the clinical characteristics of refractory asthma associated with the effectiveness of bronchial thermoplasty (BT). We retrospectively evaluated data from 10 patients who underwent BT between June 2016 and December 2017 at Okayama Medical Center. The following were measured before and 6 months post-BT: forced expiratory volume in 1.0 s (FEV1), fractional exhaled nitric oxide (FeNO), immunoglobulin E (IgE) level, blood eosinophil counts (Eosi), Asthma Quality of Life Questionnaire (AQLQ) score, and preventive medication use. At baseline, the mean post-bronchodilator FEV1 was 80.9% of the predicted value (range 45.6-115.7%). All patients were being treated with moderate- or high-dose inhaled corticosteroids and long-acting β2 agonists. The AQLQ improved from 4.26±1.67 at baseline to 5.59±0.94 at 6 months post-BT (p 0.5 points post-BT. For both allergic and eosinophilic asthmatics following mepolizumab, BT was not useful. BT was effective for non-allergic and non-eosinophilic or allergic asthmatics, but insufficient for both allergic and eosinophilic following mepolizumab.

Background Bronchial thermoplasty (BT) is a novel technique used in the treatment of subjects with severe refractory asthma. Radiofrequency is provided to airway walls during bronchoscopy in order to reduce airway remodeling. Several clinical studies have reported an improvement in subjects’ symptoms following BT. However, how BT affects the airway architectures and inflammatory mediators in the airways has not been yet fully elucidated. Methods Fourteen subjects with severe asthma were recruited in this study according to the criteria of ATS severe asthma definition. The study subjects undertook bronchial biopsy during the bronchoscopy procedure at baseline and 6 weeks after the initial BT treatment. The obtained samples were stained with antibodies for α-smooth muscle actin (α-SMA); protein gene product (PGP) 9.5, a specific nerve marker; von Willebrand factor (vWF), a marker for blood vessels; interleukin-17A (IL-17A) and transforming growth factor-β1 (TGF-β1). Results The expression of α-SMA and PGP9.5 were significantly reduced post-BT. There was no significant difference in the number of blood vessels between baseline and post-BT. In addition, BT did not affect the production of IL-17A and TGF-β1 in the airways. The changes in the expression of α-SMA and PGP9.5 had no significant correlation with the improvement of pulmonary function. Conclusion and Clinical Relevance: This study suggests that BT reduces airway smooth muscle mass and the airway innervation without affecting vasculature and the production of inflammatory mediators in the airways of subjects with severe asthma.

Background Severe asthma and chronic obstructive pulmonary disease (COPD) can be challenging to manage, particularly when the clinical features may be similar. With the increased availability of advanced therapies for both entities, it is more important than ever to diagnose and phenotype accurately to inform appropriate treatment decisions. This case highlights the use of endobronchial biopsies to allow for histological evaluation of airways disease, and in particular the role of airway smooth muscle mass as an additional biomarker that could facilitate the diagnostic process. Case presentation A 65 year old woman presented with a diagnosis of severe COPD on the background of previous smoking and mild childhood asthma. Despite taking maximal inhaled pharmacotherapy, she had frequent exacerbations requiring corticosteroids and remained dyspnoeic on mild exertion. Lung function tests showed severe obstruction on spirometry (forced expiratory ratio 43%, forced expiratory volume in 1 s 47% predicted), and single breath Diffusing Capacity for Carbon Monoxide was moderately reduced at 45% predicted. Computed tomography revealed hyperinflation without marked emphysema. Quantitative CT for emphysema distribution demonstrated a relatively small lung fraction of 9.35% with

Bronchial thermoplasty (BT) is one of the novel approved modalities in treating severe asthmatics to overcome their exacerbating symptoms such as increased anxiety. The purpose of this study was to evaluate anxiety level among severe asthmatics while undergoing BT procedure. This was an observational study where subjects self-evaluated their overall anxiety level using the burns anxiety inventory (BAI) questionnaire at baseline and prior to each of three BT treatments (broncho thermoplasty procedure 1, broncho thermoplasty procedure 2, and broncho thermoplasty procedure 3). The BAI questionnaire consisted of three different categories with each category having specific symptoms. Categories were grouped as: Anxious feelings, Anxious thoughts, and Physical symptoms. Subjects' Asthma Control Tests were also collected for analysis before and after the BT procedure. A total of 17 subjects with a mean age of 55.9 ± 14.5 years participated in the study. Fifty three percent were females (n = 9) and 41.2% (n = 7) were on prescribed anxiety medications. There was a significant drop in the patients' overall BAI anxiety level over time, P .0001, in Anxious feelings (P = .0001), anxious thoughts (P = .001), and physical symptoms (P = .025). When analyzing the change in anxiety level among those who were not on prescribed anxiety medications, significant drop in overall anxiety level and in the subcategories were also noted. (P .05). In addition, ACT scores showed a significant improvement (post vs pre) (18.5 ± 4.0 vs 13.3 ± 6.3, P = .03; Cohen's d = 0.73). This study shows the effectiveness of BT in decreasing severe asthmatic anxiety levels from baseline to last BT treatment and this benefit was mostly noted in those who were not on any anxiety medications. A limitation of this study is that all subjects were recruited from a single center. Therefore, to further validate the study findings, a multi-center study needs to be conducted with a larger sample size.

Background Bronchial 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. Methods Endobronchial 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. Results In all patients, bronchial thermoplasty improved asthma control (p 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. Conclusions Bronchial 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.

Bronchial thermoplasty is a device-based treatment for subjects ≥ 18 years of age with severe asthma poorly controlled with inhaled corticosteroids and long-acting beta-agonists. The Post-FDA Approval Clinical Trial Evaluating Bronchial Thermoplasty in Severe Persistent Asthma (PAS2) study collected data on patients with severe asthma undergoing this procedure.What are the 5-year efficacy and safety results in patients with severe asthma who have undergone bronchial thermoplasty?This was a prospective, open-label, observational, multicenter study conducted in the United States and Canada. Subjects 18 to 65 years of age who were taking inhaled corticosteroids ≥ 1,000 μg/d (beclomethasone or equivalent) and long-acting beta-agonists ≥ 80 μg/d (salmeterol or equivalent) were included. Severe exacerbations, hospitalization, ED visits, and medication usage were evaluated for the 12 months prior to and at years 1 through 5 posttreatment. Spirometry was evaluated at baseline and at years 1 through 5 posttreatment.A total of 284 subjects were enrolled at 27 centers; 227 subjects (80%) completed 5 years of follow-up. By year 5 posttreatment, the proportion of subjects with severe exacerbations, ED visits, and hospitalizations was 42.7%, 7.9%, and 4.8%, respectively, compared with 77.8%, 29.4%, and 16.1% in the 12 months prior to treatment. The proportion of subjects on maintenance oral corticosteroids decreased from 19.4% at baseline to 9.7% at 5 years. Analyses of subgroups based on baseline clinical and biomarker characteristics revealed a statistically significant clinical improvement among all subgroups.Five years after treatment, subjects experienced decreases in severe exacerbations, hospitalizations, ED visits, and corticosteroid exposure. All subgroups demonstrated clinically significant improvement, suggesting that bronchial thermoplasty improves asthma control in different asthma phenotypes.ClinicalTrials.gov; No.: NCT01350336; URL: www.gov.

Bronchial thermoplasty (BT) is an endoscopic therapy used for the treatment of refractory asthma. Some predictive factors, for example the number of activations and severity of disease at baseline, have been used to determine the effectiveness of BT in treating patients with asthma. The aim of the present study was to comprehensively analyze RNA samples from the airway bronchial tissues of patients with severe asthma treated by BT, and to characterize each patient as a BT responder or non-responder.Eight patients with severe asthma scheduled to undergo BT and bronchus biopsies were recruited before the procedures were conducted. Extracted RNA samples from bronchial tissues were sequenced and differential gene expression analysis was carried out.Results/discussion: Subjects with Asthma Quality of Life Questionnaire score changes ≥0.5 for a period of 12 months were considered BT responders. Non-responders had score changes0.5 for 12 months. Histopathology findings were similar to those reported previously, and no significant differences in the expression of α-smooth muscle actin and protein gene product 9.5 were observed between responders and non-responders. Transcriptome analysis at baseline identified 67 genes that were differentially expressed between responders and non-responders, including

Bronchial thermoplasty (B.T.) is a therapeutic bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle mass. Immediate complications of B.T. include acute exacerbation of bronchial asthma, upper and lower respiratory tract infection, hemoptysis, among others. Our study assessed these immediate adverse events and the changes in forced expiratory volume in one second (FEV1%) measured four hours after each procedure from baseline. The study also aimed to examine the number of activations during each cycle of treatment and its correlation to the corresponding change in FEV1% from baseline.A case-series analysis of 17 patients who underwent B.T. between 2014 and 2019 was done. Demographic, clinical characteristics, including pre and post-BT FEV1% measures, and the number of activations were obtained.Acute exacerbation of asthma was the commonest complication accounting for 33%, 57%, and 75% after BT1, BT2, and BT3, respectively. There was deterioration in FEV1% after each treatment phase, the most significant being in BT3. There was no correlation between the number of heat activations with the change in FEV1% from baseline.The number of activations in B.T. does not correlate with the immediate deterioration in FEV1%, although exacerbation of asthma is the commonest complication post-B.T.

Rationale Bronchial thermoplasty is a mechanical therapeutic intervention that has been advocated as an effective treatment option for severe asthma. The mechanism is promoted as being related to the attenuation of airway smooth muscle which has been shown to occur in the short-term. However, long-term studies of the effects of bronchial thermoplasty on airway remodeling are few with only limited assessment of airway remodeling indices. Objectives To evaluate the effect of bronchial thermoplasty on (a) airway epithelial and smooth muscle cells in culture, and (b), airway remodeling in patients with severe asthma who have been prescribed bronchial thermoplasty up to 12-months post-treatment. Methods The distribution of heat within the airway by bronchial thermoplasty was assessed in a porcine model. Culture of human airway smooth muscle cells and bronchial epithelial cells evaluated the impact of thermal injury. Histological evaluation and morphometric assessment were performed on bronchial biopsies obtained from severe asthma patients at baseline, 6-weeks, and 12-months following bronchial thermoplasty. Results Bronchial thermoplasty resulted in heterogenous heating of the airway wall. Airway smooth muscle cell cultures sustained thermal injury, whilst bronchial epithelial cells were relatively resistant to heat. Airway smooth muscle and neural bundles were significantly reduced at 6-weeks and 12-months post-treatment. At 6-weeks post treatment, submucosal collagen was reduced, and vessel density increased, with both indices returning to baseline at 12-months. Goblet cell numbers, submucosal gland area and subbasement membrane thickness, were not significantly altered at any timepoint examined. Conclusions Bronchial thermoplasty primarily affects airway smooth muscle and nerves with the effects still present at 12-months post-treatment.

Objective: To investigate the efficacy and safety of bronchial thermoplasty (BT) in clinical practice in adults with severe, refractory asthma. Methods: Prospective, single-center, open, observational study comprising patients with uncontrolled asthma (asthma control questionnaire (ACQ) >1.5) and/or frequent exacerbations despite treatment with at least high dose inhaled corticosteroids plus a second controller. Efficacy outcomes was change from baseline 4, 8, 12 and 24 months in FEV1, FVC and FEV1/FVC ratio, asthma control questionnaire (ACQ) score and asthma quality of life score (mini-AQLQ). Results are presented as median with interquartile ranges (IQR). The following were recorded as adverse events: Un-scheduled health care contacts, rescue courses of oral corticosteroid (OCS) and/or antibiotics for exacerbation for exacerbations/respiratory tract infections (RTI). Results: Six-teen patients were enrolled (nine males, median age 50 years; 14 followed for 24 months). Compared to baseline, an improvement in FEV1, FVC, FEV1/FVC ratio, mini-AQLQ and ACQ was observed, i.e.FEV1 (IQR) 1.98 L (1.65-2.45) vs. 2.45 L (2.09-2.93) (p = 0.006), FVC (IQR) 3.23 L (2.76-4.05) vs. 3.75 L (3.22-4.36) (p = 0.041), FEV1/FVC 0.60 (IQR: 0.55-0.70) vs. 0.66 (IQR: 0.63-0.71) (p = 0.016), mini-AQLQ 4.0 (IQR: 3.2-4.9) vs. 5.6 (IQR 4.5-6.5) (p = 0.008, and ACQ 2.9 (IQR: 2.1-3.7) versus 1.5 (IQR 1.0-2.4) (p = 0.004). On the other hand, an increase was observed in unscheduled visits (p = 0.005), as well as use of OCS and antibiotics (p = 0.009 and p = 0.003, respectively). Conclusion: BT in adults with severe asthma improved ACQ, mini-AQLQ and lung function, but resulted in an increased frequency of unscheduled doctor-visits and rescue courses of OCS and antibiotics.

There have been considerable advances in our understanding of asthmatic airway inflammation, resulting in a paradigm shift of classifying individuals on the basis of either the presence or the absence of type 2 (T2) inflammatory markers. Several novel monoclonal antibody therapies targeting T2 cytokines have demonstrated significant clinical effects including reductions in acute exacerbations and improvements in asthma-related quality of life and lung function for individuals with T2-high asthma. However, there have been fewer advancements in developing therapies for those without evidence of T2 airway inflammation (so-called non-T2 asthma). Here, we review the heterogeneity of molecular mechanisms responsible for initiation and regulation of non-T2 inflammation and discuss both current and potential future therapeutic options for individuals with non-T2 asthma.

In recent years, many bronchoscopic techniques have been developed in chronic obstructive airway inflammatory diseases, including asthma, COPD and emphysema. The main techniques with available data from randomised controlled trials are: 1) bronchial thermoplasty in asthma; 2) valves, coils and thermal vapor ablation in emphysema; and 3) targeted lung denervation in COPD. The objectives of this article are to describe the levels of evidence for efficacy and safety, long-term follow-up results beyond 1 year, and current recommendations for clinical practice from international guidelines for each technique.

The 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group was coordinated and supported by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health. It is designed to improve patient care and support informed decision making about asthma management in the clinical setting. This update addresses six priority topic areas as determined by the state of the science at the time of a needs assessment, and input from multiple stakeholders: Fractional Exhaled Nitric Oxide TestingIndoor Allergen MitigationIntermittent Inhaled CorticosteroidsLong-Acting Muscarinic AntagonistsImmunotherapy in the Treatment of Allergic AsthmaBronchial Thermoplasty A rigorous process was undertaken to develop these evidence-based guidelines. The Agency for Healthcare Research and Quality’s (AHRQ) Evidence-Based Practice Centers conducted systematic reviews on these topics, which were used by the Expert Panel Working Group as a basis for developing recommendations and guidance. The Expert Panel used GRADE (Grading of Recommendations, Assessment, Development and Evaluation), an internationally accepted framework, in consultation with an experienced methodology team for determining the certainty of evidence and the direction and strength of recommendations based on the evidence. Practical implementation guidance for each recommendation incorporates findings from NHLBI-led patient, caregiver, and clinician focus groups. To assist clincians in implementing these recommendations into patient care, the new recommendations have been integrated into the existing Expert Panel Report-3 (EPR-3) asthma management step diagram format.

Bronchial thermoplasty (BT) had been reported to improve the symptoms of severe asthma. However, the exertional responses of BT based on the mechanisms have not been elucidated. A 57-year-old man and a 60-year-old woman underwent BT due to intractable severe asthma. We evaluated the therapeutic effects of BT using cardiopulmonary exercise testing (CPET). After BT, the exercise time during CPET substantially prolonged reducing exertional dyspnea in the former (good), but not in the latter (poor). In the good responder, the high air remaining in the lung after expiration (i.e., inspiratory tidal volume minus expiratory tidal volume) during CPET decreased after BT. In contrast, in the poor responder, the high air remaining after expiration during exercise was not obtained before BT. Further investigations are necessary to confirm that the presence or absence of the exertional wasted ventilation on CPET may be informative to evaluate the therapeutic effects of BT. J. Med. Invest. 67 : 386-390, August, 2020.

Background Despite demonstrated symptomatic benefit from bronchial thermoplasty (BT), the underlying pathophysiological benefits have been uncertain. The purpose of the present study was to relate clinical benefit after BT to changes in lung physiology, focusing on ventilation homogeneity assessed using multiple breath nitrogen washout (MBNW), and how this may be affected by changes in airway volume and resistance. Methods Consecutive patients (n = 21) with severe asthma scheduled for BT, were evaluated at baseline, 6 weeks and 6 months after completion of treatment. Assessments included the Asthma Control Questionnaire (ACQ), medication usage, exacerbation frequency, spirometry, plethysmography and MBNW. Eighteen of these patients underwent detailed CT evaluation for the estimation of airway volume at baseline and then after the left lung had received BT treatment but prior to right lung treatment. Data are mean ± STDEV. Results Patients responded to BT with an improvement in ACQ from 3.4 ± 0.8 at baseline to 2.0 ± 1.1 at 6 months (p Airway volume measured by CT scanning significantly increased after treatment. The FEV1 improved from 1.34 ± 0.65 l to 1.52 ± 0.76 l (p = 0.024). The Residual Volume fell from 2.87 ± 0.89 l to 2.71 ± 0.93 l (p = 0.008) and Total Airway Resistance (Raw) from 10.58 ± 6.56 to 7.64 ± 3.74 cmH2O.s.l−1 (p = 0.020). The Lung Clearance Index (LCI) was 187 ± 63% predicted at baseline and improved after treatment from 12.7 ± 3.3 to 11.8 ± 2.4 (p = 0.049). The improvement in LCI correlated with the improvement in Raw (r = 0.463, p = 0.035). Conclusion Clinical benefit after BT is accompanied by improvements in lung physiology, including normalisation of lung homogeneity that seems to be driven by airway dilation and reduced resistance.

BackgroundFungal infections are rarely reported as a complication of bronchial thermoplasty (BT) in patients without immunosuppressive comorbidity.Case presentationA 19-year-old woman college student was admitted to our hospital owing to uncontrolled severe asthma despite using the maximum dose of steroid inhalation. She experienced asthmatic attacks more frequently while cheerleading, which is an extracurricular activity. She received BT because she wanted to continue cheerleading. After the second BT session, she developed more sputum and cough. During the third session, white secretion and saccular bronchodilation appeared in the left lower bronchus. Aspergillus fumigatus was detected in the culture of the bronchial lavage sample, and saccular bronchodilation in the affected bronchus was observed on computed tomography (CT). Five months after the start of oral itraconazole, her subjective symptoms as well as her CT findings improved. Her asthma condition improved enough for the patient to continue cheerleading without exacerbation.ConclusionsIt is necessary to consider the possibility of respiratory tract infections including fungal infections after BT. Detailed observations of the entire bronchus and sample collection for microbial culture are highly recommended.

Bronchial thermoplasty has been developed over the past fifteen years and is the first endoscopic technique approved in the management of severe asthma. This procedure uses radiofrequency applied to the airway wall to target bronchial smooth muscle. Patients treated in randomized controlled trials have experienced significant decreases in the use of rescue medications, urgent care visits, and exacerbations rate. The lack of reliable predictive markers of response to this expensive, minimally-invasive technique currently makes it a last-line treatment option. We review the principles and supposed mechanisms of action of this treatment, the results from the main trials and clinical registry data and discuss the place of bronchial thermoplasty in the current management of severe asthma. We also discuss perspectives to better characterize the mechanisms of action and identify the responder phenotype, the main challenge of current studies.

Rationale: Adverse events have limited the use of bronchial thermoplasty (BT) in severe asthma. Objectives: We sought to evaluate the effectiveness and safety of using (129)Xe magnetic resonance imaging ((129)Xe MRI) to prioritize the most involved airways for guided BT. Methods: Thirty subjects with severe asthma were imaged with volumetric computed tomography and (129)Xe MRI to quantitate segmental ventilation defects. Subjects were randomized to treatment of the six most involved airways in the first session (guided group) or a standard three-session BT (unguided). The primary outcome was the change in Asthma Quality of Life Questionnaire score from baseline to 12 weeks after the first BT for the guided group compared with after three treatments for the unguided group. Measurements and Main Results: There was no significant difference in quality of life after one guided compared with three unguided BTs (change in Asthma Quality of Life Questionnaire guided = 0.91 [95% confidence interval, 0.28–1.53]; unguided = 1.49 [95% confidence interval, 0.84–2.14]; P = 0.201). After one BT, the guided group had a greater reduction in the percentage of poorly and nonventilated lung from baseline when compared with unguided (−17.2%; P = 0.009). Thirty-three percent experienced asthma exacerbations after one guided BT compared with 73% after three unguided BTs (P = 0.028). Conclusions: Results of this pilot study suggest that similar short-term improvements can be achieved with one BT treatment guided by (129)Xe MRI when compared with standard three-treatment-session BT with fewer periprocedure adverse events.

Monoclonal antibodies targeting IgE or the type-2 cytokines interleukin (IL)-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma, respectively. However, these therapies are not appropriate for 30–50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, “type-2 low” asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, yet poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristics of type-2 low asthma and summarise current knowledge on the underlying pathobiological mechanisms, which includes neutrophilic airway inflammation often associated with smoking, obesity and occupational exposures and may be driven by persistent bacterial infections and by activation of a recently described IL-6 pathway. We review the evidence base underlying existing treatment options for specific treatable traits that can be identified and addressed. We focus particularly on severe asthma as opposed to difficult-to-treat asthma, on emerging data on the identification of airway bacterial infection, on the increasing evidence base for the use of long-term low-dose macrolides, a critical appraisal of bronchial thermoplasty, and evidence for the use of biologics in type-2 low disease. Finally, we review ongoing research into other pathways including tumour necrosis factor, IL-17, resolvins, apolipoproteins, type I interferons, IL-6 and mast cells. We suggest that type-2 low disease frequently presents opportunities for identification and treatment of tractable clinical problems; it is currently a rapidly evolving field with potential for the development of novel targeted therapeutics.