Emerging imaging techniques target bronchial thermoplasty

CHICAGO – Advanced imaging techniques may play an increasing role in targeting the delivery of bronchial thermoplasty in severe, uncontrolled asthma.

"It’s off-label at this point, but I think this is where we’re going with this therapy," Dr. Mario Castro said at the annual meeting of the American College of Chest Physicians. "Perhaps we can do a better job to target this therapy, just like phenotyping our patients [for novel biologic agents]."

Reconstruction of the airway and parenchyma using diagnostic software during an inspiratory computed tomography (CT) scan allows clinicians to measure all of the lung airways in a systematic way, said Dr. Castro, director of the asthma and airway translational research unit, Washington University School of Medicine, St. Louis.

In the case of a 50-year-old patient with severe persistent asthma, the technique revealed a clearly remodeled airway with a 63% average wall area, but also areas of great heterogeneity in all segmental airways. "What we find is that some airways are remodeled more than others," Dr. Castro said.

The university also now images its patients by combining inhaled hyperpolarized helium gas with magnetic resonance imaging from the apex all the way to the base of the lung. A color algorithm CT mask imposed on the MRI images allows the team to quantify ventilation defects before and after bronchial thermoplasty.

Earlier this year, Dr. Castro’s colleague, Dr. Ajay Sheshadri, reported that patients with severe asthma have a significantly higher baseline ventilation defect percentage (VDP) than healthy subjects (mean 24.4% vs. 3.5%; P = .003). VDP improved by about 7% overall after bronchial thermoplasty (P = .10), with some patients having a marked improvement in VDP, while others did not, Dr. Castro said.

Baseline characteristics were analyzed in an effort to identify responders, and "we were very surprised to find that sputum eosinophilia was the one that trended best in predicting a change in ventilation defect score," he added.

Biopredictors of bronchial thermoplasty response are also being evaluated in a prospective study of patients with severe refractory asthma, led by Dr. Castro, currently recruiting approximately 190 patients at five U.S. sites (NCT01185275).

Dr. Castro’s team is also using xenon gas instead of helium with MRI, because it is more readily available and less expensive. Other groups are using confocal CT to evaluate airways for bronchial thermoplasty, he noted.

Dr. Castro stressed that 13 years of cumulative experience have shown that bronchial thermoplasty is safe and effective, but that careful initial evaluation of candidates remains essential. The American Thoracic Society and European Respiratory Society are expected to release new guidelines early next year for the initial evaluation of all severe asthmatics that recommend six tests, including blood work, spirometry, immunoglobulin E assessment with skin prick tests or an immunoabsorbent assay, and multidetector CT to evaluate for other conditions mimicking asthma.

"With this basic evaluation in our center, we find about one out of every three patients are really not pure asthma; they’re asthma mixed with significant bronchiectasis or no asthma at all, or they have underlying emphysema from prior smoke exposure," said Dr. Castro. "So it is very important that we take a step back with these patients and look."

During a discussion following the presentation, Dr. Castro said he would use bronchial thermoplasty to treat patients with incomplete reversibility of airflow obstruction, but does not advocate repeat treatments because of the potential for additional injury.

"What we do advocate is that we extensively treat all the airways that we can access, and that you treat with continuous therapies," he said. "The average activations in the lower, lower [airway] is around 60, but in some cases I’ve done up to around 140-150 activations, just because they’ve had an extensive bronchial tree that I needed to treat. ... If you have a nonresponder, even 5 years out, I wouldn’t treat because I think smooth muscle is probably not their main problem," he added.

Dr. Castro reported research support, lecturing, and consulting for numerous firms including Boston Scientific, maker of the Alair bronchial thermoplasty system.

[email protected]

CHICAGO – Advanced imaging techniques may play an increasing role in targeting the delivery of bronchial thermoplasty in severe, uncontrolled asthma.

"It’s off-label at this point, but I think this is where we’re going with this therapy," Dr. Mario Castro said at the annual meeting of the American College of Chest Physicians. "Perhaps we can do a better job to target this therapy, just like phenotyping our patients [for novel biologic agents]."

Reconstruction of the airway and parenchyma using diagnostic software during an inspiratory computed tomography (CT) scan allows clinicians to measure all of the lung airways in a systematic way, said Dr. Castro, director of the asthma and airway translational research unit, Washington University School of Medicine, St. Louis.

In the case of a 50-year-old patient with severe persistent asthma, the technique revealed a clearly remodeled airway with a 63% average wall area, but also areas of great heterogeneity in all segmental airways. "What we find is that some airways are remodeled more than others," Dr. Castro said.

The university also now images its patients by combining inhaled hyperpolarized helium gas with magnetic resonance imaging from the apex all the way to the base of the lung. A color algorithm CT mask imposed on the MRI images allows the team to quantify ventilation defects before and after bronchial thermoplasty.

Earlier this year, Dr. Castro’s colleague, Dr. Ajay Sheshadri, reported that patients with severe asthma have a significantly higher baseline ventilation defect percentage (VDP) than healthy subjects (mean 24.4% vs. 3.5%; P = .003). VDP improved by about 7% overall after bronchial thermoplasty (P = .10), with some patients having a marked improvement in VDP, while others did not, Dr. Castro said.

Baseline characteristics were analyzed in an effort to identify responders, and "we were very surprised to find that sputum eosinophilia was the one that trended best in predicting a change in ventilation defect score," he added.

Biopredictors of bronchial thermoplasty response are also being evaluated in a prospective study of patients with severe refractory asthma, led by Dr. Castro, currently recruiting approximately 190 patients at five U.S. sites (NCT01185275).

Dr. Castro’s team is also using xenon gas instead of helium with MRI, because it is more readily available and less expensive. Other groups are using confocal CT to evaluate airways for bronchial thermoplasty, he noted.

Dr. Castro stressed that 13 years of cumulative experience have shown that bronchial thermoplasty is safe and effective, but that careful initial evaluation of candidates remains essential. The American Thoracic Society and European Respiratory Society are expected to release new guidelines early next year for the initial evaluation of all severe asthmatics that recommend six tests, including blood work, spirometry, immunoglobulin E assessment with skin prick tests or an immunoabsorbent assay, and multidetector CT to evaluate for other conditions mimicking asthma.

"With this basic evaluation in our center, we find about one out of every three patients are really not pure asthma; they’re asthma mixed with significant bronchiectasis or no asthma at all, or they have underlying emphysema from prior smoke exposure," said Dr. Castro. "So it is very important that we take a step back with these patients and look."

During a discussion following the presentation, Dr. Castro said he would use bronchial thermoplasty to treat patients with incomplete reversibility of airflow obstruction, but does not advocate repeat treatments because of the potential for additional injury.

"What we do advocate is that we extensively treat all the airways that we can access, and that you treat with continuous therapies," he said. "The average activations in the lower, lower [airway] is around 60, but in some cases I’ve done up to around 140-150 activations, just because they’ve had an extensive bronchial tree that I needed to treat. ... If you have a nonresponder, even 5 years out, I wouldn’t treat because I think smooth muscle is probably not their main problem," he added.

Dr. Castro reported research support, lecturing, and consulting for numerous firms including Boston Scientific, maker of the Alair bronchial thermoplasty system.

[email protected]

CHICAGO – Advanced imaging techniques may play an increasing role in targeting the delivery of bronchial thermoplasty in severe, uncontrolled asthma.

"It’s off-label at this point, but I think this is where we’re going with this therapy," Dr. Mario Castro said at the annual meeting of the American College of Chest Physicians. "Perhaps we can do a better job to target this therapy, just like phenotyping our patients [for novel biologic agents]."

Reconstruction of the airway and parenchyma using diagnostic software during an inspiratory computed tomography (CT) scan allows clinicians to measure all of the lung airways in a systematic way, said Dr. Castro, director of the asthma and airway translational research unit, Washington University School of Medicine, St. Louis.

In the case of a 50-year-old patient with severe persistent asthma, the technique revealed a clearly remodeled airway with a 63% average wall area, but also areas of great heterogeneity in all segmental airways. "What we find is that some airways are remodeled more than others," Dr. Castro said.

The university also now images its patients by combining inhaled hyperpolarized helium gas with magnetic resonance imaging from the apex all the way to the base of the lung. A color algorithm CT mask imposed on the MRI images allows the team to quantify ventilation defects before and after bronchial thermoplasty.

Earlier this year, Dr. Castro’s colleague, Dr. Ajay Sheshadri, reported that patients with severe asthma have a significantly higher baseline ventilation defect percentage (VDP) than healthy subjects (mean 24.4% vs. 3.5%; P = .003). VDP improved by about 7% overall after bronchial thermoplasty (P = .10), with some patients having a marked improvement in VDP, while others did not, Dr. Castro said.

Baseline characteristics were analyzed in an effort to identify responders, and "we were very surprised to find that sputum eosinophilia was the one that trended best in predicting a change in ventilation defect score," he added.

Biopredictors of bronchial thermoplasty response are also being evaluated in a prospective study of patients with severe refractory asthma, led by Dr. Castro, currently recruiting approximately 190 patients at five U.S. sites (NCT01185275).

Dr. Castro’s team is also using xenon gas instead of helium with MRI, because it is more readily available and less expensive. Other groups are using confocal CT to evaluate airways for bronchial thermoplasty, he noted.

Dr. Castro stressed that 13 years of cumulative experience have shown that bronchial thermoplasty is safe and effective, but that careful initial evaluation of candidates remains essential. The American Thoracic Society and European Respiratory Society are expected to release new guidelines early next year for the initial evaluation of all severe asthmatics that recommend six tests, including blood work, spirometry, immunoglobulin E assessment with skin prick tests or an immunoabsorbent assay, and multidetector CT to evaluate for other conditions mimicking asthma.

"With this basic evaluation in our center, we find about one out of every three patients are really not pure asthma; they’re asthma mixed with significant bronchiectasis or no asthma at all, or they have underlying emphysema from prior smoke exposure," said Dr. Castro. "So it is very important that we take a step back with these patients and look."

During a discussion following the presentation, Dr. Castro said he would use bronchial thermoplasty to treat patients with incomplete reversibility of airflow obstruction, but does not advocate repeat treatments because of the potential for additional injury.

"What we do advocate is that we extensively treat all the airways that we can access, and that you treat with continuous therapies," he said. "The average activations in the lower, lower [airway] is around 60, but in some cases I’ve done up to around 140-150 activations, just because they’ve had an extensive bronchial tree that I needed to treat. ... If you have a nonresponder, even 5 years out, I wouldn’t treat because I think smooth muscle is probably not their main problem," he added.

Dr. Castro reported research support, lecturing, and consulting for numerous firms including Boston Scientific, maker of the Alair bronchial thermoplasty system.

[email protected]