Original article
Intervention
Persistence of effectiveness of bronchial thermoplasty in patients with severe asthma

https://doi.org/10.1016/j.anai.2011.03.005Get rights and content

Background

Bronchial thermoplasty (BT) has been demonstrated to be safe and effective in the treatment of severe persistent asthma out to at least 1 year. Preclinical studies have demonstrated that the reduction in airway smooth muscle after bronchial thermoplasty persists out to at least 3 years.

Objectives

To examine the persistence of effectiveness of BT 2 years posttreatment in subjects with severe asthma.

Methods

Subjects participating in the long-term safety follow-up phase of the Asthma Intervention Research 2 (AIR2) Trial were evaluated by comparing the proportion of subjects who experienced exacerbations, adverse events, or healthcare utilization during the first year (year 1) after BT treatment with the proportion of subjects who experienced the same during the subsequent 12 months (year 2).

Results

Severe exacerbations, respiratory adverse events, emergency department visits for respiratory symptoms, and hospitalizations for respiratory symptoms (proportion of subjects experiencing and rates of events), and stability of pre- and post-bronchodilator forced expiratory volume in 1 second (FEV1), were comparable between years 1 and 2. The proportion of subjects experiencing severe exacerbations in year 2 after BT was 23.0%, compared with 30.9% in year 1.

Conclusions

The reduction in the proportion of subjects experiencing severe exacerbations after BT is maintained for at least 2 years. Bronchial thermoplasty provides beneficial long-term effects on asthma outcomes in patients with severe asthma.

Trial Registration

clinicaltrials.gov, Identifier: NCT00231114.

Introduction

Asthma is a major public health problem, affecting approximately 24.6 million people and accounting for an estimated 14.7 million lost workdays for adults annually in the United States.1 The collective cost of the disease is estimated at more than $19.0 billion per year.2 Etiological factors involved in asthma include increased mucus, airway inflammation, and excessive and hyperresponsive airway smooth muscle.3 Because airway smooth muscle plays a key role in the bronchoconstriction causing airway obstruction, it provides a potential target for therapy. Bronchial thermoplasty (BT) delivered with the Alair System is designed to reduce the excess smooth muscle present in the airway walls of patients with severe asthma.4, 5

Results from a multi-center, randomized, double-blind, sham-controlled clinical trial (Asthma Intervention Research 2 [AIR2] Trial) in subjects with severe asthma demonstrated that over the 12-month period following treatment, BT-treated subjects experienced improved asthma control, indicated by a 32% reduction over sham in severe exacerbations, 84% reduction over sham in emergency department visits for respiratory symptoms, and 66% reduction over sham in days lost from work/school/other daily activities because of asthma, as well as an improvement in asthma-related quality of life.5 The long-term safety of this novel procedure has been reported over a 3- to 5-year period,6, 7 but long-term persistence beyond 1 year in subjects with severe asthma has not been reported. We now report data on the persistence of effectiveness of BT at 2 years posttreatment based on the BT-group subjects who participated in the follow-up phase of the AIR2 Trial.

Section snippets

Study Objective

The objective of this study was to evaluate the persistence of effectiveness beyond 1 year of BT in subjects with severe persistent asthma. Persistence of effectiveness was based on a non-inferiority design comparing the proportion of subjects experiencing severe exacerbations.8

Study Design

The AIR2 Trial was a prospective, randomized, sham-controlled study that evaluated the effectiveness and safety of BT in addition to standard of care (inhaled corticosteroid and long-acting β2-agonist), and compared this

Results

Of one hundred ninety (190) subjects randomized to the BT group at the beginning of the AIR2 Trial, 181 subjects completed follow-up evaluations at 12 months, and 166 subjects (92% of year 1 subjects) completed the follow-up evaluations at 2 years. Fifteen subjects did not complete the year 2 evaluation: 9 were lost to follow-up, 2 were withdrawn from study by the investigator (1 had terminal colon cancer, and the other was noncompliant with scheduled visits), 2 withdrew voluntarily for

Discussion

Bronchial thermoplasty is a device-based procedure that involves application of controlled heat to reduce the mass of the airway smooth muscle, using a Food and Drug Administration–approved device indicated for treating severe asthma.10 It has been evaluated in a series of studies involving subjects with mild to severe-refractory asthma.5, 6, 11, 12 The results of the AIR2 Trial demonstrated clinically significant benefits of BT compared with the sham group at 1 year posttreatment, including an

Acknowledgments

Members of The AIR2 Trial Study Group were as follows:

Australia: Royal Adelaide Hospital: M. Holmes, H. Jersmann, P. Robinson, K. Herewane; Sir Charles Gairdner Hospital: M. Phillips, S. Morey; Brazil: Irmandade Santa Casa de Miserico′rdia de Porto Alegre: A.S. Rubin, M. Cavalcanti, P. Soares; Hospital São Lucas da PUCRS: J. Fiterman, V. Tonietto, F. Maraschin, F. Kahan, D. Cavalet Blanco; Faculdade da Medicina do ABC: E. Fiss, C. Rufino, S. Squassoni; Hospital Universitario Clementino Fraga

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Disclosures: M.C. received $10,001-$50,000 from Asthmatx, $1,001-$5,000 from Schering, $1,001-$5,000 from Electrocore, and $1,001-$5,000 from BMS in consultancy fees; $5,001-$10,000 from Genentech in advisory board fees; $50,001-$100,000 from AstraZeneca, $10,001-$50,000 from Boehringer Ingelheim, $10,001-$50,000 from Pfizer, $5,001-$10,000 from Genentech, and $5,001-$10,000 from Merck in lecture fees; more than $100,001 from Asthmatx, more than $100,001 from Amgen, more than $100,001 from Centocor, more than $100,001 from Ception, more than $100,001 from Genentech, more than $100,001 from GlaxoSmithKline, more than $100,001 from MedImmune, more than $100,001 from Merck, and more than $100,001 from Novartis in industry-sponsored grants; and $1,001-$5,000 from Elsevier in royalties. A.S.R. received $5,001-$10,000 from Boehringer Ingelheim in advisory board fees, $1,001-$5,000 from AstraZeneca, $1,001-$5,000 from Novartis and $ $1,001-$5,000 from GSK in lecturefees, and more than $100,001 from Asthmatx, Inc. in institutional industry sponsored grants. M.L. received $1,001-$5,000 from Merck Frosst, up to $1,000 from Asthmatx, and $1,001-$5,000 from Nycomed, $1,001-$5,000 from Novartis in lecture fees for CMA and more than $100,001 from Asthmatx, more than $100,001 from Merck Frosst, $50,001-$100,001 from MedImmune, $50,001-$100,000 from Broncus, $50,001-$100,000 from Novartis, and more than $100,001 from GlaxoSmithKline in industry-sponsored grants for clinical trials. NAH received more than $100,001 from Asthmatx, more than $100,001 from Boehringer Ingelheim, more than $100,001 from GlaxoSmithKline, more than $100,001 from Genentech, more than $100,001 from Novartis, $40,000-$50,000 from Genentech and $40,000-$50,000 from Pfizer in industry-sponsored grants. $1,001-$5,000 each from GSK, Novartis and Genentech; $5,001-$10,000 from Pfizer and Nycomed in consultancy/advisory board fees; $50,001-$100,000 from GlaxoSmithKline, $10,001-$50,000 from AstraZenecca in lecture fees. B.A. is an employee of QST Consultations which was paid more than $100,001 from Asthmatx in consultancy fees. G.C.'s spouse/life partner a clinical scientist for and full-time employee of Boehringer Ingelheim, received $10,001-$50,000 from Asthmatx in consultancy fees, $1,001-$5,000 from Boehringer Ingelheim as an advisory board member; $1,001-$5,000 from GlaxoSmithKline, $1,001-$5,000 from Actelion, and $1,001-$5,000 fromNovartis in lecture fees; and more than $100,001 from Asthmatx in industry sponsored grants for clinical trial operating expenses.

Funding Sources: This study was funded by Asthmatx, Inc.

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