Bronchial Thermoplasty: Which Patients Will Respond?

by Lauren LeBano

Asthma specialists are the gatekeepers to bronchial thermoplasty and are charged with identifying the patients who are most likely to benefit from this nonpharmacologic treatment modality. To assist clinicians in making this determination, Mario Castro, MD, MPH, presented on bronchial thermoplasty at the annual meeting of the American College of Allergy, Asthma, and Immunology in San Diego, California.¹

GINA Guidelines

The Global Initiative for Asthma (GINA) guidelines² are the most up-to-date and helpful in guiding treatment decisions, Dr. Castro explained. “What we’re focusing on in consideration of bronchial thermoplasty is patients who fit into the category of Step 5 therapy,” he said.
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Bronchial thermoplasty was approved by the FDA in 2010 for the treatment of severe asthma.³ The procedure aims to permanently modify smooth muscle in the airway wall via controlled radiofrequency ablation.

The GINA guidelines recommend that asthma specialists evaluate Step 5 patients with severe asthma. The guidelines list several options for treating these patients, including low-dose oral corticosteroids, add-on therapies without phenotyping, therapies that are guided by phenotyping, and nonpharmacologic therapies.

The guidelines mention bronchial thermoplasty as a nonpharmacologic intervention that is appropriate for selected patients. “We’re starting to develop that data on how to exactly select patients who would respond best to bronchial thermoplasty,” said Dr. Castro. He added that 4 clinical trials have been conducted on bronchial thermoplasty and that a fifth is underway and following up patients for 5 years.

Clinical Trials

The Asthma Intervention Research 2 (AIR2) trial randomized participants to receive bronchial thermoplasty or a sham procedure, and the AIR2 Extension study followed only the 190 patients who received active treatment in the AIR2 trial for 5 years.^4,5 Results of the AIR2 trial showed that bronchial thermoplasty led to increased quality of life for patients, a 32% decrease in severe asthma exacerbations, and an 84% reduction in emergency department (ED) visits. In addition, over a 5-year period there was a significant and sustained reduction in severe exacerbations requiring systemic corticosteroids.

“What this demonstrates to me is [bronchial thermoplasty] is one of the few disease-modifying treatments we have, and that you can do a one-time treatment and this effect is sustained over a 5-year period of time,” said Dr. Castro.

However, he cautioned that there is a short-term cost to bronchial thermoplasty that should be discussed with patients. In over half of patients, asthma symptoms increase with each bronchial thermoplasty treatment, though the symptoms usually resolve within a week. Hospitalizations also increase at first, but both hospitalizations and ED visits decrease after 1 year. Thus, the benefits of bronchial thermoplasty are seen in the long term, not the short term.

Assessing Patients

When assessing whether a patient is a candidate for bronchial thermoplasty, asthma specialists should first confirm whether the diagnosis of severe asthma is accurate. “I turn down 1 out of 3 patients, on average, because really they do not have severe asthma,” said Dr. Castro. Instead, these patients may have (Continued on the next page)

vocal cord dysfunction, bronchiectasis, or another condition that might explain their symptoms.

According to FDA indications, bronchial thermoplasty is appropriate for adult patients with asthma who are aged 18 years or older, and who have inadequate control of symptoms despite being treated with a combination of high-dose inhaled corticosteroids and a long-acting beta agonist.³

Before suggesting bronchial thermoplasty, asthma specialists need to demonstrate that patients have adhered to previous therapies such as inhaled corticosteroids, long-acting beta-agonists, or biologic therapy. In addition, specialists should confirm that patients are not responding to standard-of-care medications in Step 5 and 6 therapy, and that there are no contraindications for bronchial thermoplasty.

Dr. Castro noted that he considers additional criteria when evaluating his own patients. He considers patients as candidates for bronchial thermoplasty if they have an exacerbator phenotype, defined as 2 or more exacerbations in the past year. Data have shown that the exacerbator phenotype is more likely to be responsive to bronchial thermoplasty. He also determines whether patients are unresponsive to biologic therapy or are not candidates for biologic therapy before making a bronchial thermoplasty referral.

Predicting Patient Response to Bronchial Thermoplasty

Some recent studies have provided more insight into which patients are likely to benefit from bronchial thermoplasty. Dr. Castro highlighted a study by Chakir and colleagues that analyzed 17 patients before and after bronchial thermoplasty. Study results showed that there was a significant decrease in airway smooth muscle and that there was a greater decrease in smooth muscle in patients who had a greater percent of smooth muscle at baseline.⁶ “In other words, the more smooth muscle you have at baseline, the more likely it is going to decrease post bronchial thermoplasty,” said Dr. Castro.

A study by Pretolani and colleagues supports this view on smooth muscle modulation and also examines nerve cell expression.⁷ The researchers demonstrated that patients showed significant reduction in nerve-ending receptors after treatment with bronchial thermoplasty. Nerve-ending receptors are intermingled with smooth muscle, explained Dr. Castro, so it is logical that bronchial thermoplasty would affect both smooth muscle and nerve endings.

Dr. Castro and colleagues presented data on predicting response to bronchial thermoplasty at the American Thoracic Society meeting. “Interestingly, we found that patients who had a shorter duration of asthma were more likely to respond to bronchial thermoplasty, suggesting that patients with longer duration probably have more extensive remodeling that would not respond to bronchial thermoplasty,” said Dr. Castro.

Data also showed other predictors of response to bronchial thermoplasty, in terms of reduction of medication dose. These predictors were a lower quality of life, higher oral corticosteroid dose, and more exacerbations requiring prednisolone in the prior year.

Putting into Practice

By focusing on guidelines and data, asthma specialists have an opportunity to bring bronchial thermoplasty to the appropriate patients. Close collaboration with colleagues is also important when incorporating bronchial thermoplasty into practice, Dr. Castro noted.

He emphasized that bronchial thermoplasty should involve a team approach with the bronchoscopist and the asthma specialist. Building a bronchial thermoscopy program requires having access to patients with severe asthma, so cultivating strong partnerships with referring colleagues is key.

Asthma specialists should also be aware that they might need to be persistent in pursuing preauthorizations for the procedure. Dr. Castro estimates that it may take 2 or 3 appeals before insurance companies offer approval.

The combination of persistence, collaboration, and evidence-based decision-making is important to sound practice of bronchial thermoplasty. “I think [bronchial thermoplasty] should be reserved for Step 5 patients who have seen an asthma specialist, have solidified the diagnosis, and are adherent. You’ve tried the therapies and they’re not responding and are not well controlled. Those are the appropriate patients for bronchial thermoplasty,” said Dr. Castro.

References

1. Castro M. Bronchial thermoplasty: where to position in practice. Presented at: American College of Allergy, Asthma, and Immunology; November 2016; San Diego, CA.

2. Global Strategy for Asthma Management and Prevention (2016 Update). Global Initiative for Asthma. http://ginasthma.org. Accessed January 31, 2017.

3. FDA approves new device for adults with severe and persistent asthma. Silver Spring, MD: U.S. Food and Drug Administration; April 27, 2010. http://www.fda.gov. Accessed January 31, 2017.

5. Castro M, Rubin AS, Laviolette M, et al. Effectiveness and safety of bronchial thermoplasty in the treatment of severe asthma. Am J Respir Crit Care Med. 2010;181(2):116-124.

5. Wechsler ME, Laviolette M, Rubin AS, et al. Bronchial thermoplasty: long-term safety and effectiveness in patients with severe persistent asthma. J Allergy Clin Immunol. 2013;132(6):1295-1302.e3.

6. Chakir J, Haj-Salem I, Gras D, et al. Effects of bronchial thermoplasty on airway smooth muscle and collagen deposition in asthma. Ann Am Thorac Soc. 2015;12(11):1612-1618.

7. Pretolani M, Bergquvist A, Thabut G, et al. Effectiveness of bronchial thermoplasty in patients with severe refractory asthma: Clinical and histopathologic correlations. J Allergy Clin Immunol. 2016 Sep 5. pii: S0091-6749(16)30896-X. doi: 10.1016/j.jaci.2016.08.009.