Original articleInterventionSafety of bronchial thermoplasty in patients with severe refractory asthma
Introduction
Asthma affects more than 300 million people worldwide.1 In the United States, approximately 5% to 10% of the 23 million people with asthma have severe persistent asthma based on continued symptoms despite treatment with current guideline recommended treatment.2 Poorly controlled or uncontrolled asthma is associated with a significant social and economic burden through its effect on the patient's quality of life and health care utilization.[3], [4], [5], [6], [7], [8], [9]
Bronchial thermoplasty (BT) (delivered by the Alair Bronchial Thermoplasty System; Asthmatx Inc, Sunnyvale, California) is a new treatment option for patients with severe persistent asthma. The benefits of BT up to 1 year were initially demonstrated in 3 randomized controlled clinical trials with no safety concerns up to 1-year follow-up.[10], [11], [12] Longer-term follow-up of patients receiving BT in the Asthma Intervention Research 2 (AIR2) Trial has demonstrated the persistence of effectiveness and an acceptable safety profile up to at least 2 years.13 The Research in Severe Asthma (RISA) Trial (ClinicalTrials.gov identifier NCT00214539), a randomized controlled study involving 32 patients with severe refractory asthma, demonstrated that patients were able to safely tolerate BT and the treatment resulted in improvements in Asthma Quality-of-Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) scores and reduction in rescue β-agonist use compared with the control group.12 The potential disease-modifying effects of BT are believed to result from reduction in airway smooth muscle.
Longer-term safety data up to 5 years after BT have been reported from the feasibility study for a cohort of BT-treated patients with mild to severe asthma[14], [15] and for patients with moderate to severe asthma from the Asthma Intervention Research (AIR) Trial.16 The present study adds to information on the long-term safety data of BT by reporting on the 5-year safety data in a population that might be expected to be at highest risk of adverse events (AEs).
Section snippets
Study Participants
Fourteen of the 15 patients randomized to the BT group in the RISA Trial provided written, informed consent to participate in a 5-year follow-up study on completion of their 12-month evaluation. One patient who did not consent to participate in the extension study had died 3 years after the last BT treatment. The family refused to provide permission for medical record review, and so no further details were available. Exclusion criteria for participation in the RISA extension study were
Demographics and Clinical Characteristics
Fourteen of the 15 patients in the BT group participated in the extension study. The demographic and clinical characteristics of the 14 patients in the extension study, all with severe refractory asthma, are presented in Table 1.
Patient Disposition
All 14 patients completed follow-up evaluations at 3 years, and 12 patients completed follow-up evaluations at 4 years (1 patient was reported as having died during year 4 from a recreational drug overdose unrelated to the patient's asthma; 1 patient missed the year 4
Discussion
Previously published data from the Trial12 demonstrated that at 22 weeks after BT, significant improvements were seen in BT-treated patients vs controls in rescue medication use (−26.6 ± 40.1 vs −1.5 ± 11.7 puffs per 7 days, P<.05), prebronchodilator FEV1 percent predicted (14.9% ± 17.4% vs −0.94% ± 22.3%, P = .04), ACQ scores (−1.04 ± 1.03 vs −0.13 ± 1.00, P = .02), and AQLQ scores (1.21 ± 1.05 vs 0.15 ± 0.75, P = .003). Risks associated with BT procedures include the transient worsening of
Acknowledgments
Members of the RISA Trial Study Group included are as follows: coinvestigators and study coordinators―Canada: McMaster University: P. Nair, S. Goodwin, S. Keogh, M. Kjarsgard; Laval University: S. Martel, L-P. Boulet, N. Lampron, L. Trepanier; United Kingdom: University of Glasgow: S. Bicknell, R. Chaudhuri, J. Lafferty; University of Manchester: C. Prys-Picard, G. Fletcher, A. Fletcher; Newcastle University: B. Higgins, T. Small; University of Leicester: P. Halder, A. Charalambou, M. Bourne,
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Disclosures: In the last 5 years Dr Pavord has received speaker's honoraria or honoraria for attending advisory panels of between $1 and $5,000 from Astra Zeneca, Boehringer Ingelheim, GSK, MSD, Schering-Plough, Novartis, Dey, Napp, and Boston Scientific. He has received sponsorship to attend international scientific meetings from Boehringer Ingelheim, GSK, Astra Zeneca, and Napp. Neither Dr Pavord nor any member of his family has any shares in pharmaceutical companies. Dr Thomson has received more than $100,001 from Asthmatx, more than $100,001 from Glaxo SmithKline, $10,001 to $50,000 from Novartis, and more than $100,001 from Synairgen in industry-sponsored grants for clinical trials; received less than $1,000 from Asmacure, less than $1,000 from Boston Scientific, less than $1,000 from Chiesi, and $1,001 to $5,000 from Respivert for participating in advisory boards and/or as consultancy fees; and received less than $1,000 from AstraZeneca, less than $1,000 from Chiesi, less than $1,000 from Glaxo SmithKline, and less than $1,000 Novartis in lecture fees for CMA. Dr Niven has received between $1 and $5,000 from the following companies as a lecturer in sponsored meetings or an advisory board member in the last 5 years: GSK, Asthmatx, Chiesi, Astra Zeneca, Vectura, and Novartis. Dr Niven has also received patient-dependent fees for research clinical trials paid to the University Hospital of South Manchester. Dr Corris has received between $1 and $5,000 from the following companies as a lecturer in sponsored meetings or an advisory board member in the last 5 years: Pfizer, Bayer, Actelion, Boehringer, and Novartis. Dr Chung has received $1,001 to $5,000 from GSK, $1,001 to $5,000 from Novartis, and $1,001 to $5,000 from Gilead for participation at advisory board meetings; $1,000 to $5,000 each from GSK, Novartis, and Merck in lecture fees; and $1,001 to $5,000 each from Novartis and Boehringer Ingelheim in travel grants to attend international meetings. Mr Cox's spouse/life partner is a clinical scientist for and full-time employee of Boehringer Ingelheim; received $10,001 to $50,000 from Asthmatx in consultancy fees, $1,001 to $5,000 from Boehringer Ingelheim as an advisory board member, $1,001 to $5,000 from GlaxoSmithKline, $1,001 to $5,000 from Actelion, and $1,001 to $5,000 from Novartis in lecture fees; and received more than $100,001 from Asthmatx in industry-sponsored grants for clinical trial operating expenses. Mr Armstrong is an employee of QST Consultations, which was paid more than $100,001 from Asthmatx in consultancy fees. Dr Shargill is a full-time employee of Asthmatx, a Boston Scientific Company, and holds stock ownership or options in Boston Scientific. Dr Laviolette received financial support for industry-sponsored clinical trials from Novartis, Glaxo SmithKline, AstraZeneca, Centecor, and Boston Scientific Corporation.
Funding Sources: This study was sponsored by Asthmatx, a Boston Scientific Company, Sunnyvale, California.