Bronchial Thermoplasty Improves Ventilation Heterogeneity Measured by Functional Respiratory Imaging in Severe Asthma

Figures & data

Figure 1 Timeline and methodology. (A) Timeline for treatment and assessment. (B–C) Functional respiratory imaging derived regional ventilation map showing (B) homogeneous ventilation in a healthy subject, and (C) ventilation heterogeneity in a subject with severe asthma. (D) Schematic representation of expected changes in the ventilation histogram before (solid line) and after (dotted line) BT. The diagram illustrates a reduction in spread or standard deviation in the post-BT histogram, signifying a reduction in ventilation heterogeneity after BT.

Abbreviations: ACQ, asthma control questionnaire; BT, bronchial thermoplasty; CT, computed tomography of the chest; LLL, left lower lobe; LUL, left upper lobe; RLL, right lower lobe; RUL, right upper lobe.

Table 1 Patient Characteristics

Demographic	Participants (N=18)
Age (years)	59.8 ± 14.7
Male/Female	7 (39) / 11 (61)
BMI (kg/m^2)	31.9 ± 7.1
Smoking status
Never smoker	10 (56)
Ex-smoker	8 (44)
Blood eosinophils (x10^9/L)	0.1 (IQR 0.0–0.2)
Serum immunoglobulin E (IU/mL)	29.5 (IQR 9–299)
Asthma biologic at time of 1^st BT session*
None	13 (72)
Mepolizumab	3 (17)
Benralizumab	2 (11)

Notes: Values are presented as mean ± standard deviation, median (IQR) or number (%). *Some patients in this study underwent bronchial thermoplasty prior to the availability of mepolizumab, benralizumab and dupilumab in Australia.

Table 2 Key Clinical Outcomes Pre and Post BT

Clinical Variable	Baseline	12-months	p
ACQ	3.3 (2.7–4.2)	1.9 (1.1–2.7)	<0.001
SABA usage (puffs/day)	11 (8–20)	2.5 (1.3–6.8)	<0.001
Maintenance OCS (mg/day)	7.5 (5–25)	4.5 (0–10)	0.002
OCS-requiring exacerbations*	2 (1–3.8)	0 (0–1.8)	0.01

Notes: *Refers to the number of OCS-requiring exacerbations in the preceding 6 months from baseline and 12-month follow-up assessments.

Abbreviations: ACQ, asthma control questionnaire; BT, bronchial thermoplasty; OCS, oral corticosteroids; SABA, short-acting beta-agonist.

Table 3 Lung Function Pre and Post BT

Lung Function Variable	Baseline	12-months	p
Pre-bronchodilator FEV1 (% predicted)	45.7 ± 14.0	51.4 ± 15.6	0.02
Pre-bronchodilator FVC (% predicted)	73.0 ± 14.1	76.2 ± 15.9	0.34
Pre-bronchodilator FEV1/FVC (FER, %)	50.9 ± 12.0	52.2 ± 10.8	0.58
RV (% predicted)	152.3 ± 40.3	147.3 ± 60.2	0.50
TLC (% predicted)	103.0 ± 18.0	103.7 ± 25.3	0.77
RV/TLC	0.53 ± 0.11	0.51 ± 0.12	0.08
KCO (% predicted)	90.8 ± 28.7	90.1 ± 24.2	0.80

Abbreviations: BT, bronchial thermoplasty; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity; FER, forced expiratory ratio; KCO, mean diffusion capacity of the lung for carbon monoxide per unit lung volume; RV, residual volume; TLC, total lung capacity.

Table 4 Kurtosis, Skewness and CT-Derived Ventilation Values at V1, V2 and V3

Kurtosis	V1	V2	V3	p
Left lung	0.06 ± 0.70	0.22 ± 0.81	0.01 ± 0.42	0.45
Right lung	0.49 ± 1.68	0.22 ± 1.15	0.33 ± 0.87	0.79
Skewness	V1	V2	V3	p
Left lung	−0.26 ± 0.33	−0.30 ± 0.38	−0.20 ± 0.19	0.51
Right lung	−0.48 ± 0.35	−0.42 ± 0.34	−0.45 ± 0.36	0.86
CT ventilation values	V1	V2	V3	p
Left lung	1.36 ± 0.10	1.38 ± 0.15	1.36 ± 0.10	0.66
Right lung	1.36 ± 0.10	1.39 ± 0.16	1.39 ± 0.11	0.64

Notes: V1, baseline; V2, 4-week post treatment of left lung; V3, 12-month post treatment of right lung.

Figure 2 IQD values reported at the lung level across various timepoints. Bars and error bars represent mean and standard deviation. Open circle represents individual data-points. (A) Mean IQD significantly decreased after treatment of the left lung, with treatment effect persisting up to 12 months after BT. (B) There was a trend towards a significant decrease in IQD after treatment of the right lung, with no other significant changes noted across timepoints.

Abbreviations: IQD, interquartile distance of the ventilation histogram; V1, baseline; V2, 4-week post treatment of left lung; V3, 12-month post treatment of right lung; LL, left lung; RL, right lung.

Figure 3 Graphical illustration of ventilation maps at various timepoints from a representative patient. A decrease in ventilation heterogeneity is apparent visually by more regions nearing average ventilation (green and yellow), rather than interspersed regions of high (red) and low (blue) ventilation. Note the improvement in ventilation heterogeneity of the left lung between V2 and V1, and of the right lung between V3 and V2. V1, baseline; V2, 4-week post treatment of left lung; V3, 12-month post treatment of right lung.