In vivo evaluation of the effectiveness of bronchial thermoplasty with computed tomography

Abstract

A recent study has reported that the application of thermal energy delivered through a bronchoscope (bronchial thermoplasty) impairs the ability of airway smooth muscle to shorten in response to methacholine (MCh)(Danek CJ, Lombard CM, Dungworth DL, Cox PG, Miller JD, Biggs MJ, Keast TM, Loomas BE, Wizeman WJ, Hogg JC, and Leff AR. J Appl Physiol 97: 1946-1953, 2004). If such a technique is successful, it has the potential to serve as a therapy to attenuate airway narrowing in asthmatic subjects regardless of the initiating cause that stimulates the smooth muscle. In the present study, we have applied high-resolution computed tomography to accurately quantify the changes in airway area before and after a standard MCh aerosol challenge in airways treated with bronchial thermoplasty. We studied a total of 193 airways ranging from 2 to 15 mm in six dogs. These were divided into treated and control populations. The MCh dose-response curves in untreated airways and soon-to-be-treated airways were superimposable. In contrast, the dose-response curves in treated airways were shifted upward at all points, showing a significantly decreased sensitivity to MCh at both 2 and 4 wk posttreatment. These results thus show that treated airways have significantly increased luminal area at any dose of inhaled MCh compared with untreated airways. The work in this study thus supports the underlying concept that impairing the smooth muscle may be an effective treatment for asthma.

Effect of bronchial thermoplasty on airway distensibility

“…Thus, prior to lung inflation, the treated airways were less responsive to the same dose of Mch, while the response of untreated airways remained unchanged over the 5-week interval (16¡2 at 3 weeks and 16¡1% at 5 weeks versus 15¡1% pre-treatment of their initial maximum size, respectively). These results show that the previously reported reduced Mch responsiveness, performed only at FRC [3], cannot be eliminated at higher lung volumes.…”

“…The technique was recently proposed as an innovative treatment to attenuate airway narrowing in asthma [2]. In another recent study, high-resolution computed tomography (HRCT) was used to accurately quantify the changes in airway area before and after a standard Mch aerosol challenge in canine airways treated with bronchial thermoplasty [3]. These study results showed that treated airways had significantly increased lumenal area at any dose of inhaled Mch when compared to untreated airways.…”

Airway smooth muscle dynamics: a common pathway of airway obstruction in asthma

“…By reducing the mass of smooth muscle in the walls of conducting airways (intralobar bronchi with diameters .3 mm), COX et al [127] showed in a group of mild-tomoderate asthmatics, that the treatment was effective in reducing AHR and asthma exacerbation, and that the reduction persisted throughout the 2 yrs following the procedure, during which the subjects were monitored. The direct effect of bronchial thermoplasty on airway calibre during methacholine challenge was assessed by BROWN et al [129,130] and COX et al [127], who found that the decrease in ASM resulting from thermoplasty led to an increased airway calibre at any dose of inhaled methacholine, compared with the untreated airways. One cautionary note here is that airway calibre data relies on imaging that can detect only a limited number of airways per subject, with these being primarily larger airways.…”

Bronchial thermoplasty: a non‐pharmacological approach

“…There was no significant difference in the adverse event between groups. Treated subjects had clinically and statistically significant improvements over baseline in rescue medication use, prebronchodilator FEV 1 % predicted, and the Asthma Quality of Life Questionnaire (AQLQ) and Asthma Control Questionnaire (ACQ) scores in the stable steroid (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) phase of this study. Persistent improvement in the asthma symptoms and decrease in the use of rescue medication were seen in BT group up to 1 year.…”

“…In another animal study, Brown et al (18) used computed tomography (CT) to quantify the effect of Mch on treated and untreated groups. They found that dose response curve to Mch challenge was shifted upwards at all points, concluding that the treated group has significantly larger luminal area as compared with the untreated group at all points.…”