Bronchial thermoplasty: A new treatment for severe refractory asthma

Asthma now has a new treatment, but it isn’t for everybody. Called bronchial thermoplasty, it is reserved for patients whose asthma is severe and refractory, as it involves three sessions of bronchoscopy, each lasting up to 1 hour, during which the smooth muscle layer is methodically ablated from the airway using radiofrequency energy.^1,2

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The US Food and Drug Administration (FDA) has approved bronchial thermoplasty,³ and although it does not cure asthma or completely eliminate its symptoms, patients with severe asthma that was not well controlled with medical therapy who underwent this procedure in clinical trials subsequently had fewer symptoms, enjoyed better quality of life, and needed less intensive health care (such as emergency room visits) than patients who did not undergo the procedure.^4–6

Here, we present an overview of the pathophysiology of severe refractory asthma and the clinical trials of bronchial thermoplasty, its current protocols, and the status of this new treatment.

WHAT IS SEVERE REFRACTORY ASTHMA?

Asthma is a chronic inflammatory condition of the airways characterized by episodic symptoms of breathlessness, cough, and wheezing, which can wax and wane over time. Approximately 8.2% of the general population is affected.⁷

Our understanding of the pathophysiology of asthma has improved over the past 20 years, and with the publication of clinical guidelines from the National Asthma Education and Prevention Program in 1991,⁸ 1997,⁹ and 2002,¹⁰ outcomes have improved. Most people with asthma can control their symptoms if they adhere to anti-inflammatory therapies and avoid triggers. Yet 5% to 10% of asthma patients have severe refractory disease, and asthma accounts for nearly half a million hospitalizations every year.¹¹

The latest guidelines, published in 2007, emphasize the importance of assessing the severity of asthma, including the patient’s impairment (symptoms and limitations) and risk (likelihood of exacerbations).¹²

Workshop consensus definition of severe refractory asthma

A consensus group convened by the American Thoracic Society¹³ defined asthma as severe and refractory if the patient meets at least one of the following major criteria:

• Takes oral corticosteroids continuously or nearly continuously (> 50% of year)
• Takes high-dose inhaled corticosteroids.

In addition, the patient must meet at least two minor criteria, ie:

• Takes a controller medication such as a long-acting beta-agonist, theophylline, or a leukotriene antagonist every day
• Takes a short-acting beta agonist every day or nearly every day
• Has persistent airway obstruction, ie, a forced expiratory volume in 1 second (FEV₁) less than 80% of predicted, or a peak expiratory flow that has a diurnal variability greater than 20%
• Has one or more urgent care visits for asthma per year
• Needs three or more oral corticosteroid “bursts” per year
• Has prompt deterioration when the dose of oral or inhaled corticosteroid is reduced by 25% or less
• Has had a near-fatal asthma event in the past.

Compared with people with mild asthma, people who have severe refractory asthma tend to be older, have fewer allergies, and make more use of intensive and urgent health care.¹⁴

Asthma is due to both inflammation and bronchoconstriction

The pathophysiology of asthma involves both chronic airway inflammation and bronchoconstriction, the latter characterized by a greater response to methacholine. Histologic findings include excessive mucus secretion, epithelial cell injury, and smooth muscle hypertrophy. These changes can lead to persistent airflow obstruction that can be difficult to control with medical therapies.¹²

Bronchoconstriction can be reversed temporarily with bronchodilators, but no longlasting therapy to reduce it has been available until now. Bronchial thermoplasty targets this gap in asthma management.

STUDIES OF BRONCHIAL THERMOPLASTY

Radiofrequency ablation has been used to treat other medical conditions such as lung cancer and cardiac arrhythmias.^15,16 Its use to treat asthma by eradicating smooth muscle cells from the airway wall began with studies in animals.¹ Later, studies were done in people without asthma,² then in patients with mild to moderate asthma,¹⁷ and finally in patients with moderate to severe refractory asthma.^4–6

These studies helped clarify which type of patients would be appropriate candidates and the outcomes to be anticipated, including adverse events.

Early studies

Danek et al,¹ in a study in nonasthmatic dogs, found that thermoplasty at 65°C or 75°C (149°F or 167°F) attenuated the airway’s response to methacholine up to 3 years after treatment. As early as 1 week after treatment, airway smooth muscle was seen to be degenerating or absent, and the effect was inversely proportional to airway responsiveness.

Adverse effects of the procedure were cough, inflammatory edema of the airway wall, retained mucus, and blanching of the airway wall at the site of catheter contact. Three years later, there was no evidence of smooth muscle regeneration.

Miller et al² next performed a feasibility study in eight patients, mean age 58 ± 8.3 years, who were scheduled to undergo lung resection for lung cancer. Five to 20 days before surgery, the investigators performed thermoplasty at 55°C or 65°C (131°F or 149°F) in three to nine sites per patient, 1 cm from known tumors but within areas to be resected. There were no significant adverse events such as hemoptysis, respiratory infections, or excess bronchial irritation.