Asthma Control During the Year After Bronchial Thermoplasty

ABSTRACT

Background Bronchial thermoplasty is a bronchoscopic procedure to reduce the mass of airway smooth muscle and attenuate bronchoconstriction. We examined the effect of bronchial thermoplasty on the control of moderate or severe persistent asthma.

Methods We randomly assigned 112 subjects who had been treated with inhaled corticosteroids and long-acting 2-adrenergic agonists (LABA) and in whom asthma control was impaired when the LABA were withdrawn to either bronchial thermoplasty or a control group. The primary outcome was the frequency of mild exacerbations, calculated during three scheduled 2-week periods of abstinence from LABA at 3, 6, and 12 months. Airflow, airway responsiveness, asthma symptoms, the number of symptom-free days, use of rescue medication, and scores on the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ) were also assessed.

Results The mean rate of mild exacerbations, as compared with baseline, was reduced in the bronchial-thermoplasty group but was unchanged in the control group (change in frequency per subject per week, -0.16±0.37 vs. 0.04±0.29; P=0.005). At 12 months, there were significantly greater improvements in the bronchial-thermoplasty group than in the control group in the morning peak expiratory flow (39.3±48.7 vs. 8.5±44.2 liters per minute), scores on the AQLQ (1.3±1.0 vs. 0.6±1.1) and ACQ (reduction, 1.2±1.0 vs. 0.5±1.0), the percentage of symptom-free days (40.6±39.7 vs. 17.0±37.9), and symptom scores (reduction, 1.9±2.1 vs. 0.7±2.5) while fewer puffs of rescue medication were required. Values for airway responsiveness and forced expiratory volume in 1 second did not differ significantly between the two groups. Adverse events immediately after treatment were more common in the bronchial-thermoplasty group than in the control group but were similar during the period from 6 weeks to 12 months after treatment.

Conclusions Bronchial thermoplasty in subjects with moderate or severe asthma results in an improvement in asthma control. (ClinicalTrials.gov number, NCT00214526 [ClinicalTrials.gov] .)

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Many of the variable symptoms of asthma are thought to be due to the contraction of airway smooth muscle, leading to bronchoconstriction.1,2 Increased airway smooth-muscle mass is a characteristic feature of asthma, particularly in persons with severe or fatal asthma.3,4 Bronchial thermoplasty is a novel intervention in which controlled thermal energy is delivered to the airway wall during a series of bronchoscopies, resulting in a prolonged reduction of airway smooth-muscle mass.5 In previous studies, we determined the amount and duration of energy to be delivered that result in modest thermal injury.5,6 The treatment in humans of airways between 3 and 10 mm in diameter led to clinically meaningful reductions in muscle-mediated narrowing of the airway and to the improvement of asthma symptoms.7,8 We report the results of the yearlong randomized, controlled Asthma Intervention Research (AIR) Trial, which examined the efficacy and safety of bronchial thermoplasty as a treatment for moderate or severe persistent asthma.

Methods

Subjects

Persons 18 to 65 years of age were eligible for enrollment if they had moderate or severe persistent asthma, defined according to the guidelines of the Global Initiative for Asthma,9 requiring daily therapy with inhaled corticosteroids equivalent to a dose of 200 µg or more of beclomethasone and long-acting 2-adrenergic agonists (LABA), at a dose of 100 µg or more of salmeterol (Serevent, GlaxoSmithKline) or the equivalent, to maintain reasonable asthma control. Inclusion criteria were airflow obstruction, assessed as a prebronchodilator forced expiratory volume in 1 second (FEV1) of 60 to 85% of the predicted value, and airway hyperresponsiveness, defined by a provocative concentration of methacholine required to lower the FEV1 by 20% (PC20) of less than 8 mg per milliliter, as well as stable asthma during the 6 weeks before enrollment. Stable asthma was defined as an absence of unscheduled physician visits for asthma care, unchanged use of asthma medication for maintenance therapy, and stable use of rescue medication (4 puffs or fewer of a short-acting bronchodilator at a dose of 100 µg per puff delivered by a metered-dose inhaler [albuterol or the equivalent]) during 24 hours for symptom relief.

One other criterion in addition to fulfilling the definition of moderate or severe asthma was worsening asthma control after abstention from LABA at baseline for 2 weeks, documented by either an increase of at least 0.5 in the score on the Asthma Control Questionnaire (ACQ)10 (on a scale of 0 to 6, with higher numbers indicating worse control), or a decline of 5% in the average morning peak expiratory flow (PEF) during the second week of abstinence, as compared with the mean morning PEF during the week immediately before LABA therapy was withdrawn. Subjects were excluded if they had had three or more lower respiratory tract infections requiring antibiotics during the previous 12 months or a respiratory tract infection within the previous 6 weeks.

Study Design

This randomized, controlled trial was conducted at 11 centers in four countries. During the 4-week baseline period, subjects continued to receive maintenance therapy with inhaled corticosteroids and LABA for the first 2 weeks, and LABA were then withheld for the next 2 weeks. Therapy with inhaled corticosteroids and LABA was resumed for the treatment period, which lasted for at least 6 weeks and usually no more than 9 weeks, with a subsequent 12-month follow-up period. The study design is shown in Figure 1. All subjects were seen in follow-up at 3 months while receiving treatment with inhaled corticosteroids and LABA. They were asked to refrain from using LABA after this point, unless they had a severe exacerbation (an event requiring treatment with oral corticosteroids, as judged by the investigator, or a decrease in the morning PEF, for 1 or more days, of more than 30% below the average baseline morning PEF recorded during the week immediately preceding withdrawal from LABA therapy), or if they were judged by the investigator to have poor asthma control that required the resumption of LABA. For those subjects whose asthma could be controlled without LABA, evaluations were performed after 6 and 12 months of treatment with inhaled corticosteroids alone. Subjects who needed to resume LABA therapy before the visits at 6 and 12 months were evaluated at those assessment