Plethysmography-derived gas trapping lacks utility in predicting response to bronchial thermoplasty.

There is a paucity of literature on measurable baseline parameters predicting response and guiding selection for bronchial thermoplasty. This study examines whether baseline gas trapping, as assessed by plethysmography, is associated with a response to bronchial thermoplasty at 12 months. 43 consecutive patients with severe asthma (mean±sd age 57.6±13.3 years) were evaluated at baseline and 12 months post bronchial thermoplasty. Data collected at both time points included spirometry, body plethysmography and four clinical outcome measures, namely Asthma Control Questionnaire (ACQ) score, annual exacerbation frequency, maintenance oral corticosteroid requirement and short-acting ß-agonist use. At baseline, participants had severe airflow obstruction (forced expiratory volume in 1 s 49.1±15.8%) with marked gas trapping (residual volume (RV) 150.3±40.8%, RV/total lung capacity (TLC) 51.3±10.5%), poor symptom control (ACQ 3.3±1.0) and frequent exacerbations (median 4, interquartile range 8). 12 months after bronchial thermoplasty, significant improvements were observed in all four clinical outcome measures. However, baseline RV and RV/TLC were not significantly associated with changes in ACQ nor any other clinical outcome measure, and changes in RV and RV/TLC did not significantly correlate with a change in any clinical outcome measure. Plethysmography-derived gas trapping does not demonstrate utility in predicting response and guiding selection for bronchial thermoplasty. An improvement in gas trapping was not associated with positive clinical outcomes, suggesting that this may not be the dominant mode of action of bronchial thermoplasty in generating clinical improvement.

Safety of delivering bronchial thermoplasty in two treatment sessions.

BACKGROUND: Bronchial thermoplasty (BT) is a novel endoscopic therapy for severe asthma. Traditionally it is performed in three separate treatment sessions, targeting different portions of the lung, and each requires an anaesthetic and hospital admission. Compression of treatment into 2 sessions would present a more convenient alternative for patients. In this prospective observational study, the safety of compressing BT into two treatment sessions was compared with the traditional 3 treatment approach. METHODS: Sixteen patients meeting ERS/ATS criteria for severe asthma consented to participate in an accelerated treatment schedule (ABT), which treated the whole left lung followed by the right lung four weeks later. The short-term outcomes of these patients were compared with 37 patients treated with conventional BT scheduling (CBT). The outcome measures used to assess safety were (1) the requirement to remain in hospital beyond the electively planned 24-h admission and (2) the need for re-admission for any cause within of 30 days of treatment. RESULTS: The total number of radiofrequency activations delivered in the ABT group was similar to CBT (187 ± 21 vs 176 ± 40, p = 0.326). With ABT, 11 in 31 admissions (37.9%) required prolonged admission due to wheezing, compared to 5.4% with CBT (p = 0.0025). The mean hospital length of stay with ABT was 1.8 ± 1.3 days, compared to 1.1 ± 0.4 days (p < 0.001). ICU monitoring was required on 5 occasions with ABT (16.1%), compared to 0.9% with CBT (p = 0.002). Subgroup analysis demonstrated that females were more likely to require prolonged admission (OR 11.6, p = 0.0025). The 30-day hospital readmission rate was similar for both groups (6.4% vs 5.4%, p = 0.67). All patients made a complete recovery after treatment with similar outcomes at the 6-month follow-up reassessment. CONCLUSION: This study demonstrates that ABT results in greater short-term deterioration in lung function associated with a greater risk of prolonged hospital and ICU stay, predominantly affecting females. Therefore, in females, these risks need to be balanced against the convenience of fewer treatment sessions. In males, it may be an advantage to compress treatment.

Bronchial thermoplasty reduces ventilation heterogeneity measured by multiple breath nitrogen washout.

BACKGROUND: Despite demonstrated symptomatic benefit from bronchial thermoplasty (BT), the underlying pathophysiological benefits have been uncertain. The purpose of the present study was to relate clinical benefit after BT to changes in lung physiology, focusing on ventilation homogeneity assessed using multiple breath nitrogen washout (MBNW), and how this may be affected by changes in airway volume and resistance. METHODS: Consecutive patients (n = 21) with severe asthma scheduled for BT, were evaluated at baseline, 6 weeks and 6 months after completion of treatment. Assessments included the Asthma Control Questionnaire (ACQ), medication usage, exacerbation frequency, spirometry, plethysmography and MBNW. Eighteen of these patients underwent detailed CT evaluation for the estimation of airway volume at baseline and then after the left lung had received BT treatment but prior to right lung treatment. Data are mean ± STDEV. RESULTS: Patients responded to BT with an improvement in ACQ from 3.4 ± 0.8 at baseline to 2.0 ± 1.1 at 6 months (p < 0.001). Steroid requiring exacerbations fell from 3.1 ± 2.9 in the 6 months prior to BT to 1.4 ± 1.7 following BT (p < 0.001). Significant reductions in maintenance oral steroid dosing and short acting beta agonist use were observed. Airway volume measured by CT scanning significantly increased after treatment. The FEV1 improved from 1.34 ± 0.65 l to 1.52 ± 0.76 l (p = 0.024). The Residual Volume fell from 2.87 ± 0.89 l to 2.71 ± 0.93 l (p = 0.008) and Total Airway Resistance (Raw) from 10.58 ± 6.56 to 7.64 ± 3.74 cmH2O.s.l-1 (p = 0.020). The Lung Clearance Index (LCI) was 187 ± 63% predicted at baseline and improved after treatment from 12.7 ± 3.3 to 11.8 ± 2.4 (p = 0.049). The improvement in LCI correlated with the improvement in Raw (r = 0.463, p = 0.035). CONCLUSION: Clinical benefit after BT is accompanied by improvements in lung physiology, including normalisation of lung homogeneity that seems to be driven by airway dilation and reduced resistance.

Bronchial thermoplasty reduces airway resistance.

BACKGROUND: The mechanism for symptomatic improvement after bronchial thermoplasty (BT) is unclear, since spirometry reveals little or no change. In this study, the effects of BT on airway resistance were examined using two independent techniques. METHODS: Eighteen consecutive patients, with severe asthma (57.6 ± 14.2 years) were evaluated by spirometry and plethysmography at three time points: (i) baseline, (ii) left lung treated but right lung untreated and (iii) 6 weeks after both lungs were treated with BT. At each assessment, total and specific airway resistance (Raw, sRaw) were measured. High resolution CT scans were undertaken at the first two assessments, and measurements of lobar volume, airway volume and airway resistance were made. The Asthma Control Questionnaire (ACQ) was administered at each assessment. RESULTS: The baseline ACQ score was 3.5 ± 0.9, and improved progressively to 1.8 ± 1.2 (p < 0.01). At baseline, severe airflow obstruction was observed, FEV1 44.8 ± 13.7% predicted, together with gas trapping, and elevated Raw at 342 ± 173%predicted. Following BT, significant improvements in Raw and sRaw were observed, as well as a reduction in Residual Volume, increase in Vital Capacity and no change in FEV1. The change in Raw correlated with the change in ACQ (r = 0.56, p < 0.05). CT scans demonstrated reduced airway volume at baseline, which correlated with the increased Raw determined by plethysmography (p = - 0.536, p = < 0.05). Following BT, the airway volume increased in the treated lung, and this was accompanied by a significant reduction in CT-determined local airway resistance. CONCLUSION: Symptomatic improvement after BT is mediated by increased airway volume and reduced airway resistance.

Measuring the effects of bronchial thermoplasty using oscillometry.

BACKGROUND AND OBJECTIVE: Bronchial thermoplasty (BT) has been consistently shown to reduce symptoms, exacerbations and the need for reliever medication in patients with severe asthma. Paradoxically, no consistent improvement in spirometry has been demonstrated. It has been suggested that this is due to a reduction in peripheral resistance in small airways, not captured by spirometry. Therefore, in this study, we evaluate the response to BT using oscillometry. METHODS: A total of 43 patients with severe asthma from two centres were evaluated at baseline, 6 weeks and 6 months post BT, using spirometry, plethysmography and oscillometry, in addition to medication usage, exacerbation frequency and the Asthma Control Questionnaire (5-item version) (ACQ-5). RESULTS: The mean age was 58.4 ± 11.2 years, forced expiratory volume in 1 s (FEV1 ) 55.5 ± 20.1% predicted, forced expiratory ratio 53.0 ± 14.5% and FEV1 response to salbutamol was 14.0 ± 14.5%. Following BT, the group responded to treatment with an improvement in ACQ-5 from 2.9 ± 0.9 at baseline to 1.7 ± 1.1 at 6 months (P < 0.005). There was an 81% reduction in exacerbation frequency (P < 0.001) and 50% of patients were weaned completely from maintenance oral corticosteroids. No changes after treatment were observed in spirometry but the residual volume reduced from 147 ± 38% to 139 ± 39% predicted (P < 0.01). Baseline oscillometry demonstrated high levels of resistance at 5 Hz with normal resistance at 20 Hz, indicating resistance in the small airways was elevated, but no changes were observed in any oscillometry parameter after BT treatment. CONCLUSION: Lung impedance measured with oscillometry did not change following BT despite marked clinical improvements in patients with severe asthma.

Bronchial thermoplasty reduces gas trapping in severe asthma.

BACKGROUND: In randomized controlled trials, bronchial thermoplasty (BT) has been proven to reduce symptoms in severe asthma, but the mechanisms by which this is achieved are uncertain as most studies have shown no improvement in spirometry. We postulated that BT might improve lung mechanics by altering airway resistance in the small airways of the lung in ways not measured by FEV1. This study aimed to evaluate changes in measures of gas trapping by body plethysmography. METHODS: A prospective cohort of 32 consecutive patients with severe asthma who were listed for BT at two Australian university hospitals were evaluated at three time points, namely baseline, and then 6 weeks and 6 months post completion of all procedures. At each evaluation, medication usage, symptom scores (Asthma Control Questionnaire, ACQ-5) and exacerbation history were obtained, and lung function was evaluated by (i) spirometry (ii) gas diffusion (KCO) and (iii) static lung volumes by body plethysmography. RESULTS: ACQ-5 improved from 3.0 ± 0.8 at baseline to 1.5 ± 0.9 at 6 months (mean ± SD, p < 0.001, paired t-test). Daily salbutamol usage improved from 8.3 ± 5.6 to 3.5 ± 4.3 puffs per day (p < 0.001). Oral corticosteroid requiring exacerbations reduced from 2.5 ± 2.0 in the 6 months prior to BT, to 0.6 ± 1.3 in the 6 months after BT (p < 0.001). The mean baseline FEV1 was 57.8 ± 18.9%predicted, but no changes in any spirometric parameter were observed after BT. KCO was also unaltered by BT. A significant reduction in gas trapping was observed with Residual Volume (RV) falling from 146 ± 37% predicted at baseline to 136 ± 29%predicted 6 months after BT (p < 0.005). Significant improvements in TLC and FRC were also observed. These changes were evident at the 6 week time period and maintained at 6 months. The change in RV was inversely correlated with the baseline FEV1 (r = 0.572, p = 0.001), and in patients with a baseline FEV1 of < 60%predicted, the RV/TLC ratio fell by 6.5 ± 8.9%. CONCLUSION: Bronchial thermoplasty improves gas trapping and this effect is greatest in the most severely obstructed patients. The improvement may relate to changes in the mechanical properties of small airways that are not measured with spirometry.