Severe asthma at COVID-19 time: what is new on biologic therapies.

I In recent years a number of emerging new therapies have become available for the treatment of severe asthma among which bronchial thermoplasty is the only nonpharmacologic intervention that has been approved by the United States Food and Drug Administration in 2010. Although bronchial thermoplasty has great promise for the patient with severe asthma and is now within the therapeutic armamentarium of the allergist-immunologist, the modality has paradoxically raised both excitement and curiosity but also questions as to when and how to recommend its use as well as concerns relating to any potential harm that may be associated with the procedure. In the interest of assisting the allergist-immunologist in the decision-making process for the use of this new treatment modality, two separate articles by Dunn and Wechsler ME and Iyler and Lim are presented in this issue of the Proceedings that offer opposing viewpoints on the role of bronchial thermoplasty in a pro/con debate format. In addition, employing a novel publication format, each author was given an opportunity to make rebuttal comments to each other’s presentation which are printed below in this editorial. It is our hope that this information will be useful and will assist the allergist-immunologist in making the best therapeutic decisions for the patient with severe asthma.

/pdf/bronchial-thermoplasty-quo-vadis-3z87h6dt15.pdf

Bronchial thermoplasty: Quo vadis?

Asthma is a complex inflammatory disorder of the airways characterized by airway hyper-responsiveness and variable, reversible, airflow obstruction Bronchial thermoplasty (BT) is a new modality for treating asthma It targets airway smooth muscles (ASM) by delivering a controlled specific amount of thermal energy (radiofrequency ablation) to the airway wall through a dedicated catheter The use of bronchial thermoplasty has been widely discussed for its potential in the treatment of asthma, since it seems to be able to reduce the symptoms of asthma The definitive study for BT (AIR2 trial) employed a randomized, double-blind, sham-controlled design and enrolled 288 subjects with severe persistent asthma from 30 US and international centers The results of the AIR2 trial demonstrated clinically significant benefits of BT compared with the sham group at one year post-treatment, including an improvement in asthma-related quality of life, 32% reduction in severe exacerbations, 84% reduction in emergency department visits for asthma symptoms, and a 66% reduction in time lost from work/school/other daily activities because of asthma symptoms Preclinical work showed that ASM is reduced after BT by at least 3 years after treatment The recent article from the ARI2 trial study group analyses the long-term safety and effectiveness of BT in patients with severe persistent asthma and demonstrates the 5-year durability of the benefits of BT in the control of symptoms and safety It supports the evidence that reduction in asthma attacks, ER visits, and hospitalizations for respiratory symptoms are maintained for at least 5 years There is a pressing need to understand the underlying mechanism(s) of BT and how the delivered heat is translated into clinical benefit This necessitates additional investigation to identify disease and patient characteristics that would enable accurate phenotyping of positive responders to avoid unnecessary procedures and risks

Bronchial thermoplasty in severe asthma: food for thoughts.

Introduction: No studies correlated ultrasonographic evaluation with doppler technique of subglottic stenoses with endoscopic measures. Aims and Objectives: The diagnosis of subglottic stenoses can be challenging and delayed. The gold standard is flexible bronchoscopy, which assesses the mobility of the vocal cords, the location, length and size of the stenosis. Ultrasonography isn’t frequently part of the diagnostic process, least of all doppler technique. Methods: We enrolled 22 patients with subglottic stenoses and 22 control patients. They underwent a bronchoscopic evaluation of the size of the tracheal lumen and subsequent ultrasonographic examination of the neck with doppler technique, both in inspiration and expiration, before and after the treatment. Results: We observed a significant difference between ultrasonographic doppler evaluation before and after the endoscopic treatment (Fig. 1), both in inspiration and expiration (p&lt;0,001). Also, the difference between the tracheal lumen of the two populations was statistically significant.&nbsp;We observed no differences between ultrasonographic and endoscopic measures, both in inspiration (p=0,640) and expiration (p=0,067). Conclusions: Diagnosing and evaluating subglottic stenoses via ultrasounds with doppler technique strongly correlates with endoscopic measures. The use of doppler may ease this process, especially in case of doubt. Figure 1

Comparison between endoscopic and ultrasonographic evaluation of subglottic stenoses

Background: Absence of collateral ventilation (CV) in the target lobe is essential for effective endobronchial Zephyr Valve (ZV) treatment in emphysema patients. Closure of the fissure gap with AeriSeal Foam (AF) with successful ZV treatment has been reported (Ing A et al. J Bronchol Interven Pulmonl. 2020;27(1):e14). CONVERT is a multicenter, single arm study to confirm this finding (NCT04559464). Aims and Objectives: Evaluate AF to occlude collateral channels to convert a CV+ lung lobe to having little to no CV. A secondary objective is ZV treatment in the CV- converted patients. Methods: Study will enroll 140 subjects with Chartis® confirmed CV+ status. Up to 40mL AF may be delivered over 2 sessions per a unique fissure defect. CV assessed at 45 days post-AF and if CV-, treatment with ZV. Typical clinical outcomes will be assessed at 3 and 6 months post-ZV. Results: 32 subjects (16M/16F), mean±SD; age 65.2±7.0 yrs; post-BD FEV1 31.9±9.1% pred.; RV 224±38% pred. have been enrolled and treated with AF (21 in one session; 11 in 2 sessions - 6wk apart) across all lobes (11 RUL, 5 RLL, 12 LUL, 4 LLL). 83% of the subjects completing the first stage have successfully converted and treated with ZV. Enrollment and follow-up are ongoing. AEs to date include post-AF acute inflammatory response, 37.5%; lobar pneumonitis 12.5%; cough 9%; COPD exacerbations 9%. All AEs managed with standard of care. Conclusions: AF can safely and effectively occlude collateral channels and convert a CV+ lobe to having little to no CV. Emphysema patients with a defined fissure gap in the target lobe may have an option for BLVR with ZV after closure of the fissure gap with AeriSeal Foam.

CONVERT Trial: Collateral ventilation conversion by closure of fissure defect with AeriSeal Foam for BLVR with Zephyr valves

A Case Report Novel Use of Aeriseal System to Convert Collateral Ventilation Status to Enable Bronchoscopic Lung Volume Reduction (BLVR) with Zephyr Valves in a Patient with Severe Emphysema

M Bezzi

Papers

Bronchial thermoplasty in severe asthma: food for thoughts.

Comparison between endoscopic and ultrasonographic evaluation of subglottic stenoses

CONVERT Trial: Collateral ventilation conversion by closure of fissure defect with AeriSeal Foam for BLVR with Zephyr valves

A Case Report Novel Use of Aeriseal System to Convert Collateral Ventilation Status to Enable Bronchoscopic Lung Volume Reduction (BLVR) with Zephyr Valves in a Patient with Severe Emphysema

Ultrasonographic Evaluation of Subglottic Stenoses: A Preliminary Analysis